Phosphorus Chemistry. Proceedings of the 1981 International Conference 9780841206632, 9780841208476, 0-8412-0663-5

Table of contents :
Title Page......Page 1
Copyright......Page 2
ACS Symposium Series......Page 3
FOREWORD......Page 4
PdftkEmptyString......Page 0
PREFACE......Page 5
1 Phosphorus-Carbon Compounds with pπ-pπ Bonds Opening Lecture......Page 7
2 Selective Bond Formation of Organophosphorus Acids with Functional Groups of Biological Importance......Page 16
3 Chemical Synthesis and Biological Properties of the 5'-Terminus of Eukaryotic Messenger Ribonucleic Acids (mRNA)......Page 19
4 Triphenylphosphane-diethylazodicarboxylate: A Useful System for Directed Structural Variation of Carbohydrates......Page 22
Literature cited......Page 25
5 Synthetic Application of Element OrganicSubstituted Phosphorus Ylides......Page 26
Literature cited:......Page 29
6 Mono-, Di-, and Multi-Ylides in Organometallic Chemistry......Page 30
7 Synthetic and Spectroscopic Investigations Involving α-Heterosubstituted Phosphonate Carbanions......Page 38
Literature Cited......Page 41
8 A New Approach to Activation of Hydroxy Compounds Using Pentacoordinated Spirophosphoranes......Page 42
Literature Cited......Page 47
9 Synthetic Applications of α-Amino Substituted Phosphine Oxides......Page 48
REFERENCES......Page 51
10 Reactions of Aziridines, 4-Oxazolines, and Their Derivatives with Alkylidene Phosphoranes and Phosphorus(III) Nucleophiles......Page 52
References......Page 55
11 Phosphonates Containing Sulfur and Selenium: Synthesis, Reactions, and New Applications......Page 56
Literature Cited......Page 59
12 Umpolung of α,β-Ethylenic Ketones and Aldehydes by Phosphorus Groups......Page 60
Literature Cited.......Page 63
13 Monomeric Metaphosphates in Enzymic and in Enzyme-Model Systems......Page 64
Enzymology......Page 65
Literature Cited......Page 67
14 Stereoelectronic Effects in Phosphate Esters......Page 68
LITERATURE CITED......Page 74
15 Stereospecific Synthesis and Assignment of Absolute Configuration at Phosphorus in Nucleoside 3'- and 5'-O-Arylphosphorothioates and Nucleoside Cyclic 3',5'-Phosphorothioates......Page 75
Literature Cited......Page 79
16 The Stereochemistry of Chiral Cyclic Phosphorus Esters Do Theories of Bond-Forming and Bond-Breaking Processes Fit the Facts?......Page 80
Literature Cited......Page 84
17 The Stereochemical Course of the Alkaline Hydrolysis of 1,3,2-Oxazaphospholidine-2-thiones......Page 85
Literature Cited......Page 88
18 Hydrolysis of Adenosine 5'-Triphosphate An Isotope-Labeling Study......Page 89
Literature Cited......Page 93
19 Nucleoside Phosphorothioates for the Study of Enzyme Mechanisms......Page 94
Myosin ATPase......Page 95
Literature Cited......Page 96
20 Chiral [16O, 17O, 18O] Phosphate Monoesters for Determining the Stereochemical Course of Phosphokinases......Page 97
Literature Cited......Page 101
21 Syntheses and Configurational Assignments of Thymidine 3'- and 5'-(4-Nitrophenyl [17O, 18O] Phosphates)......Page 102
Acknowledgements......Page 106
Literature Cited......Page 107
22 The Mechanism of Aldehyde-Induced ATPase Activities of Kinases......Page 108
Literated Cited......Page 111
Binding Studies......Page 112
Kinetic and Thermodynamic Studies......Page 114
Literature Cited......Page 117
24 The Role of Histidine Residues and the Conformation of Bound ATP on ATP-Utilizing Enzymes......Page 118
Literature Cited......Page 123
25 [18O/16O]31P-NMR Studies of Phosphoryl Transfer Enzymes......Page 124
Literature Cited......Page 126
26 Potential Antiviral Nucleotides......Page 128
Literature Cited......Page 131
27 Phosphinomethanes: Synthesis and Reactivity......Page 132
28 Preparation and Synthetic Reactions of α- Alkoxyallyl Phosphorus Ylides......Page 136
LITERATURE CITED......Page 139
29 α-Phosphorylated Carbanions: Synthetic Features......Page 140
LITERATURE CITED......Page 143
30 A New Synthesis of Indoles......Page 144
31 Alkylation by Way of Monomeric and Polymeric Alkoxyphosphonium Salts......Page 147
Literature Cited......Page 150
32 Some Preparative and Mechanistic Aspects of the Chemistry of Phosphoric Acid and Thiophosphoric Acid Chloride Betaines......Page 151
Literature Cited......Page 154
33 "Activated" Phosphoranes for the Cyclodehydration and Chlorination of Simple Diols......Page 155
Literature Cited......Page 158
34 N-Alkylation of Organophosphorus Amides A New, Convenient Route to Primary and Secondary Amines......Page 159
LITERATURE CITED......Page 162
35 Phosphoric Amide Reagents......Page 163
36 Reversible Masking of Acetylcholinesterase by Covalent Phosphorylation in the Presence of a Novel Cyclic Phosphate Ester......Page 167
References......Page 170
37 α-Aminophosphonous Acids: A New Class of Biologically Active Amino Acid Analogs......Page 171
REFERENCES......Page 174
38 Phosphonodipeptides......Page 175
References:......Page 178
39 Some Aspects of the Chemical Synthesis of Oligodeoxyribonucleotides......Page 179
Literature Cited......Page 182
40 Coupling of Fatty Diazomethylketones with Organophosphorus Acids An Approach to Glycerophospholipid Analog Synthesis......Page 183
Literature Cited......Page 186
41 Design of Organophosphorus Reagents for Peptide Synthesis......Page 187
42 The Nature of the Energy Transduction Links in Mitochondrial Oxidative Phosphorylation......Page 193
Literature Cited......Page 197
43 ADP Hydrolysis Promoted by Cobalt(III)......Page 198
Literature Cited......Page 202
44 PMR Measurements of Chair-Twist Conformational Equilibria for Diastereomeric P-Derivatives of Thymidine Cyclic 3',5'-Monophosphate Possible Implications for Naturally Occurring Cyclic Nucleotides......Page 204
LITERATURE CITED......Page 207
45 Phosphonate Inhibitors of Carboxypeptidase A......Page 208
LITERATURE CITED......Page 211
46 "Illicit Transport" Systems for Organophosphorus Antimetabolites......Page 212
Literature Cited......Page 215
47 The Preparation of Phosphorus Esters and Thioesters from White Phosphorus......Page 216
LITERATURE CITED......Page 219
48 Thermal Rearrangement and Condensation of O,O-Dimethyl-O-phenylphosphorothionate......Page 220
Literature cited......Page 223
49 Synthesis and Reactivity of (Silylamino)phosphines......Page 224
Literature Cited......Page 227
50 Addition of Lithium Dialkylcuprates to α,β-Unsaturated Phosphoryl Compounds Nucleophilic Properties of Adducts......Page 228
Literature Cited:......Page 231
51 Phosphorylated Ketenes......Page 232
Literature Cited......Page 235
52 Preparation and Properties of N-(Hydroxycarbonylmethyl)aminomethyl Alkyl- and Arylphosphinic Acids and Derivatives......Page 236
Literature Cited......Page 238
53 Some Aspects of Aminoalkylphosphonic Acids Synthesis by the Reductive Amination Approach......Page 239
Literature Cited......Page 242
Phosphorus Hydrides......Page 243
Polycyclic Organylphosphanes......Page 245
Literature Cited......Page 247
Experimental......Page 248
Results and Discussion (5, 6)......Page 249
Literature Cited......Page 251
56 NMR Characterization of Homologous Cyclic Phosphoramides......Page 252
Notes and References......Page 255
57 Synthesis and Chemical Behavior of Some Bicyclophosphanes......Page 256
REFERENCES......Page 259
58 Reactions of 2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-Disulfide......Page 260
59 Small Rings with Tervalent Phosphorus......Page 263
Literature Cited......Page 266
60 The Unexpected Formation of 1,2-Oxaphosphol-3-ene 2-Oxides in the Reaction of Diacetone Alcohol with Phosphonous Dihalides......Page 267
Literature Cited......Page 270
61 Dihydrophenophosphazines via the Interaction of Diarylamines and Phosphorus Trichloride: Applications and Limitations......Page 271
Literature Cited......Page 274
62 Contributions to the Chemistry of N-Phosphoryl Phosphazenes......Page 275
Literature Cited......Page 278
63 Conjugation in Phosphazenes: Pyrrylphosphazenes and Phosphazenyl Carbanions......Page 279
Literature Cited.......Page 284
64 Structure, Conformation, and Basicity in Cyclophosphazenes and Related Compounds......Page 285
Literature cited......Page 288
65 Phosphazene Rings and High Polymers Linked to Transition Metals or Biologically Active Organic Species......Page 289
References......Page 292
66 Polymerization of Hexachlorocyclotriphosphazene......Page 293
Literature Cited......Page 298
67 Alkenylfluorocyclotriphosphazenes......Page 299
Literature Cited......Page 302
68 The Reactions of Halophosphazenes with Organometallic Reagents......Page 303
Literature Cited......Page 307
69 1,2-Bis(dichlorophosphino)alkanes......Page 308
LITERATURE CITED......Page 311
70 Products of Peracid Oxidation of S-Alkyl Phosphorothiolate Pesticides......Page 312
Literature Cited......Page 315
71 Research on Organophosphorus Insecticides, Synthesis of O-Alkyl O-Substituted Phenyl Alkylphosphonothioates......Page 316
Literature Cited......Page 319
72 Introduction of Phosphorus into the Polyethyleneterephthalate Molecule......Page 320
LITERATURE CITED......Page 324
73 Selected Novel Trivalent Organophosphorus Processing Stabilizers for Polyolefins......Page 325
Polypropylene (Profax 6801, Hercules Inc.) Multiple Extrusion At 500°F (260°C)......Page 327
REFERENCES CITED......Page 328
Polycondensation of 2-Chloroalkyl Phosphates and Phosphonates......Page 329
Copolycondensation......Page 330
Applications as Flame Retardants......Page 331
LITERATURE CITED......Page 332
Phosphate Fibers......Page 333
Animal Studies......Page 334
Literature Cited......Page 337
Mechanism of formation of fluorapatite from apatitic tricalcium phosphate and calcium fluoride in the solid state.......Page 338
Apatites with large amounts of fluoride ions : the B-type carbonated fluorapatite.......Page 339
Literature cited......Page 341
Sample Preparation......Page 342
Photo-Coloring (Photochromism)......Page 343
Literature Cited:......Page 346
78 A Gel Chromatographic Study on the Interactions of Long-Chain Polyphosphate Anions with Magnesium Ions......Page 347
Literature Cited......Page 350
79 Phosphaalkenes, R2C=PR', and Phosphaalkynes, RC≡P......Page 351
Literature Cited......Page 356
Phosphinyl Radicals as Ligands......Page 359
Pentamethylcyclopentadienyl-Substituted Phosphenium Ions......Page 360
Literature Cited......Page 361
81 31P NMR Investigations on Dicoordinated Phosphorus Compounds in P(II) = C-P(III) Systems......Page 363
NMR Investigations......Page 364
Results and Discussion......Page 366
Literature Cited......Page 368
82 Synthesis and Properties of Phosphaalkenes......Page 369
Literature Cited......Page 372
1,3-Benzazaphospholes......Page 373
Carbosilylated Phospha-Alkenes......Page 374
Dialkylamino Alkylidene Phosphines......Page 375
Literature Cited......Page 376
84 Reactions of 2,4,6-Tri(t-butyl)phenyllithium with Phosphorus Halides......Page 377
Literature Cited......Page 379
85 Synthesis of New Dicoordinated Phosphorus Compounds with a P(III)=N Bond......Page 381
Litterature cited :......Page 384
86 Cyano Anions of Dicoordinated, Tricoordinated, Tetracoordinated, Pentacoordinated, and Hexacoordinated Phosphorus......Page 385
87 Preparation, Reactions, and Structures of Some N,N'-Dimethylurea-Bridged Phosphorus Compounds......Page 391
Literature cited......Page 394
88 A Stable Monocyclic Triarylalkoxyhydridophosphorane A 10-P-5 Species with an Apical P-H Bond......Page 395
Literature Cited......Page 399
89 Monocyclic Phosphoranide and Phosphoranoxide Anions P(V) Oxyphosphorane Carbanion — P(IV) Ylide Alkoxide Tautomerism......Page 400
Literature Cited......Page 402
90 Selectivity in Reactions of Tricyclic Phosphatranes......Page 404
Literature Cited......Page 407
91 The Perfluoropinacolyl Group: A Stabilizing Substituent for Unusual Phosphites and Phosphoranes......Page 408
92 Tartaric Acid in Phosphorus Chemistry: Phosphor Emetics and Oligomers......Page 412
LITERATURE CITED......Page 416
93 Nucleophilic Substitution at Pentacoordinated Phosphorus Addition-Elimination Mechanism......Page 417
Literature Cited:......Page 420
Stabilities......Page 421
Insolubility of Protonated Chelates......Page 422
Polyphosphates as Ligands......Page 423
Literature Cited......Page 424
95 Transition VIB Metal π-Complexes of λ3- and λ5-Phosphorins and Some of Their Reactions......Page 425
Literature cited......Page 428
96 Synthesis of Transition Metal Phosphoranides Conversion of Bicyclic Phosphoranes into Phosphoranides and Phosphane Adducts with Transition Metal Derivatives......Page 430
Literature Cited......Page 433
97 Secondary Phosphino Macrocyclic Ligands......Page 434
Literature Cited.......Page 436
98 Dicoordinated and Tricoordinated Acyclic Phosphazenes as Complex Ligands......Page 438
Experimental Procedure......Page 441
Discussion......Page 442
Literature Cited......Page 445
100 Structural and Magnetic Investigation on Transition Metal Complexes with Tripodal Polytertiary Phosphines......Page 446
Chromium, Molybdenum, and Tungsten Derivatives......Page 448
Iron Carbonyl Derivatives......Page 449
Literature Cited......Page 451
102 New Aspects of the Coordination Chemistry of Carbonyl Phosphines......Page 452
Literature Cited......Page 456
Synthesis of chiral aminophosphines from natural aminoacids.......Page 457
Asymmetric C-C bond formation catalysed by metallic complexes with chiral amino-phosphines as ligands.......Page 459
Literature cited......Page 460
104 31P NMR Studies of Catalytic Intermediates in Triphenylphosphine Rhodium Complex Hydroformylation Systems......Page 461
Literature Cited:......Page 467
105 New Data on the Mechanism of the Perkow-Arbuzov Reaction......Page 468
Literature cited......Page 471
106 Structure and Reactivity of Quasiphosphonium Intermediates......Page 472
Literature cited......Page 475
107 Reactions of Triorganosilyl Halides with Esters of Tricoordinated and Tetracoordinated Phosphorus......Page 476
Literature Cited......Page 479
108 Halogenolysis of the Phosphorus-Sulfur Bond in Thioloesters of Organic Phosphorus Thioacids......Page 480
Literature Cited......Page 483
109 Isotope Effects in Amination Reactions of Chlorocyclophosphazenes......Page 484
Literature Cited......Page 487
110 Zwitterionic σ-Complexes: Their Role as Intermediates in Phosphorylation of Aromatics by Phosphorus Compounds......Page 488
σ-Complexes of PIII with derivatives of TNB......Page 489
Nucleophilic phosphorylation of 5-nitropyrimidines......Page 490
Literature Cited......Page 491
111 Use of X-Ray Structural Results on Phosphorus Compounds in Modeling Reaction Mechanism......Page 492
Literature Cited......Page 496
112 Ligand Effects on the Reaction of Alkoxide Ions with Organophosphorus Derivatives Containing Multiple Leaving Groups......Page 497
Literature Cited......Page 500
113 Methanolysis of a Phosphate Ester......Page 501
Literature Cited......Page 504
114 Reactivity of Tricoordinated Phosphorus Compounds A Mechanistic Study with a Variety of Substrates......Page 505
Literature cited......Page 508
115 A New Stereospecific Synthesis of a P(III) Organophosphorus Ester......Page 509
Literature Cited......Page 511
116 A Single Crystal X-Ray Diffraction Analysis of (1R,1'S)-1,1'-Ethylenebis(1,2,3,4-tetrahydro-4,4-dimethyl-1-phenylphosphinolinium) Diperchlorate......Page 512
Literature Cited......Page 516
117 Stereochemical Investigation of Chiral Onium Hexaarylphosphates......Page 517
LITERATURE CITED......Page 520
Results and Discussion......Page 521
Literature Cited......Page 524
Results......Page 525
Literature cited......Page 528
Experimental.......Page 529
Results.......Page 530
References......Page 532
121 Application of the 18O Shift on the 31P NMR Spectrum to the Elucidation of Biochemical Phosphate Transfer Mechanisms......Page 533
Studies on Purine Nucleoside Phosphorylases......Page 534
Position of Bond Cleavage or Formation in Some Other Phosphate Transfers......Page 536
Literature Cited......Page 537
122 Phospholipase A2 Hydrolysis of Phospholipids: Use of 31P NMR to Study the Hydrolysis, Acyl Migration, Regiospecific Synthesis, and Solubilization of Phospholipids......Page 538
123 Photolytic Rearrangement of Phosphorus, Germanium, and Silicon Azides: Evidence for New Hybridized Species......Page 542
Literature cited :......Page 545
124 Diphenylphosphinous Acid by UV Irradiation of Aroyl Diphenyl Phosphines......Page 546
References......Page 549
125 Chemical Model Showing Three Phenomena: Phosphorane→Ylide, Ylide → Phosphorane, and Phosphorane Ylide......Page 550
Literature cited......Page 553
Phosphonomethylphosphinates with Aldehydes......Page 554
Bis(Phosphonomethyl)phosphinates with Aldehydes......Page 555
Discussion......Page 556
Literature Cited......Page 557
127 Structure-Reactivity Studies on Oxygen-Containing Phosphorus-Based Ligands......Page 558
Literature Cited......Page 561
Restricted Rotation......Page 562
Molecular Structures......Page 563
Solvolytic Behavior......Page 564
Literature Cited......Page 565
POSTER PRESENTATIONS......Page 566
B......Page 574
D......Page 575
H......Page 576
N......Page 577
P......Page 578
R......Page 580
S......Page 581
T......Page 582
Z......Page 583

Citation preview

Phosphorus Chemistry Proceedings of the 1981 International Conference Louis D. Quin,

EDITOR

Duke University John G. Verkade,

EDITOR

Iowa State University

Based on the International Conference on Phosphorus Chemistry at Duke University, Durham, North Carolina, June 1-5, 1981.

ACS

SYMPOSIUM

SERIES

AMERICAN CHEMICAL SOCIETY WASHINGTON, D. C. 1981

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

171

Library of Congress CIP Data International Conference on Phosphorus Chemistry (1981: Duke University) Phosphorus chemistry. (ACS symposium series, ISSN 0097-6156; 171) "Based on the International Conference on Phosphorus Chemistry at Duke University, Durham, North Carolina, June 1-5, 1981." Includes bibliographies and index. 1. Phosphorus—Congresses. I. Quin, Louis D., 1928. II. Verkade, John G., 1935. III. American Chemical Society. IV. Title. V. Series. QD181.P1I57 546'.712 81-14956 ISBN 0-8412-0663-5 AACR2 ACSMC8 171 1-640 1981 Copyright © 1981 American Chemical Society All Rights Reserved. The appearance of the code at the bottom of the first page of each article in this volume indicates the copyright owner's consent that reprographic copies of the article may be made for personal or internal use or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center, Inc. for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to copying or transmission by any means—graphic or electronic—for any other purpose, such as for general distribution, for advertising or promotional purposes, for creating new collective work, for resale, or for information storage and retrieval systems. The citation of trade names and/or names of manufacturers in this publication is not to be construed as an endorsement or as approval by ACS of the commercial products or services referenced herein; nor should the mere reference herein to any drawing, specification, chemical process, or other data be regarded as a license or as a conveyance of any right or permission, to the holder, reader, or any other person or corporation, to manufacture, reproduce, use, or sell any patented invention or copyrighted work that may in any way be related thereto. PRINTED IN THE UNITED STATESOFAMERICA

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

A C S Symposium Series M . Joan Comstock, Series Editor

Advisory Board David L. Allara

James P. Lodge

Kenneth B. Bischoff

Marvin Margoshes

Donald D . Dollberg

Leon Petrakis

Robert E. Feeney

Theodore Provder

Jack Halpern

F. Sherwood Rowland

Brian M . Harney

Dennis Schuetzle

W. Jeffrey Howe

Davis L. Temple, Jr.

James D . Idol, Jr.

Gunter Zweig

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

FOREWORD The ACS S Y M P O S I U a medium for publishing symposia quickly in book form. The format of the Series parallels that of the continuing A D V A N C E S I N C H E M I S T R Y SERIES except that in order to save time the papers are not typeset but are reproduced as they are submitted by the authors in camera-ready form. Papers are reviewed under the supervision of the Editors with the assistance of the Series Advisory Board and are selected to maintain the integrity of the symposia; however, verbatim reproductions of previously published papers are not accepted. Both reviews and reports of research are acceptable since symposia may embrace both types of presentation.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PREFACE

D

uring the first week of June 1981 some 400 chemists actively engaged in research on phosphorus chemistry gathered at Duke University,

Durham, North Carolina for the continuation of a series of International Conferences on Phosphorus Chemistry. These chemists came from 29 different nations.

During the two decades that these International C o n -

ferences have been held, the meetings have taken place in Europe, thus making the Durham Conference the first of its kind in the United States. The growth of the activit and throughout the world,

years

diminution in this activity is in sight, for new discoveries are constantly being made that open up fresh channels of research. Phosphorus chemistry as a field can only be partially categorized by the traditional lines of organic and inorganic compounds.

In modern phosphorus chemistry increasing

attention is also being paid to biological involvement of phosphorus compounds.

In designing the 1981 Conference, papers describing research in

all of these aspects of phosphorus chemistry were included, marking the first time this has been done in any of the international conferences.

The

Durham meeting therefore attracted a broad variety of participants and papers, from both academic

and industrial research laboratories; the

opportunities for interaction among persons of diverse backgrounds were abundant. The program was unique in another sense: with the exception of the opening lecture by Professor Rolf Appel, the oral presentations were of equal length (25 minutes) and all chemists, regardless of age and stature, had an equal opportunity for gaining a place on the oral program. Investigators with research results that were insufficient to fill the alloted time period were encouraged to make use of the poster medium.

A further

stipulation was that only new research results should be presented; review papers or extensive literature discussions were discouraged. This volume contains the manuscripts provided by 128 of the participants in the oral part of the program. ( A few papers on the original program were not delivered).

T o publish a volume at a reasonable price

with such a large number of papers required a severe restriction in the length of the manuscripts; authors were asked to present their results in "Communication to the Editor" style in a maximum of four pages of text. The authors have complied faithfully with this request, and the Editors

xv

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

thank them all for the care with which they prepared their papers.

The

Editors also are grateful to the foreign authors for their excellent efforts in preparing their manuscripts in English.

With a collection of papers of

such diversity in topic and geographic origin, the style is more varied than is normal for such a symposium volume, but these variations do not interfere with the quality of the chemical discussions, and the Editors chose not to enforce strict adherence to detailed uniformity. The

127 posters on the program presented another fascinating array

of research results.

It is unfortunate that space limitations do not permit

the inclusion of the abstracts of these presentations in this volume.

How-

ever, the titles and addresses of the authors are provided on pages 623-630 for

the convenience of those who may wish to contact the authors for

copies of their abstracts. A

feature of the Conferenc

recognizing the signal accomplishment chemistry, Nobel Laureate Professor Georg Wittig and Professor Frank H . Westheimer.

Papers in these special sessions were solicited by Professor

Hans-Jurgen Bestmann and Professor Steven Benkovic, respectively.

The

work of Professor Wittig in the use of phosphorus compounds in organic synthesis, which among other contributions was responsible for his receiving the Nobel Prize in Chemistry in 1979, was recognized by the session "New Organic Synthetic Methods Based on Reagents Containing Phosphorus." The noteworthy accomplishments of Professor Westheimer on the mechanistic aspects of phosphate ester chemistry stimulated the session "Biochemistry of Phosphorus Compounds." This Conference was

enthusiastically

supported by the American

scientific community; the chemical industry, the U.S. National Science Foundation, and the Petroleum Research Fund, all made contributions that ensured

an adequate

financial

base, and many chemists worked

diligently on the numerous tasks that are associated with such an undertaking. The Editors express their deep appreciation to all. LOUIS D .

QUIN

Duke University Durham, North Carolina JOHN G. V E R K A D E

Iowa State University Ames, Iowa June 29, 1981.

xvi

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

1 Phosphorus-Carbon Compounds with pπ-pπ Bonds Opening Lecture R. APPEL Anorganisch Chemisches Institut der Universität, 5300 Bonn, Gehard-Domagk-Strasse 1, FRG

In this lecture some new routes to phosphorus-carbon com­ pounds with P-C multipl vestigations on reactions of tertiary phosphanes with chlorinated carbon compounds, such as tetrachloromethane, hexachloroethane, phosgene, and isocyanide dichlorides are reported. Furthermore some stereochemical problems concerning this type of compound will be discussed. Action of tetrachloromethane on trimethylsilyl-substituted methyl-diphenylphosphanes causes quantitative chloroform elimina­ tion with formation of trimethylsilylated (TMS) methylenechloro­ -diphenylphosphoranes. Heating the b i s t r i m e t h y l s i l y l substituted

compound causes spontaneous gas evolution of TmsCl at 120°C. The product i s identified by elemental analysis, molecular mass de­ termination, and the characteristic 31p nmr s h i f t . I t is a greenish-yellow l i q u i d which can be distilled i n vacuo without decomposition. The general a p p l i c a b i l i t y of this synthesis, based upon migration of an organyl substituent from phosphorus to the ylid-carbon i s restricted so far to P-aryl substituted com­ pounds. Another route to a number of theoretically interesting com­ pounds of two-coordinate phosphorus i s the reaction of P-trimethy l s i l y l - s u b s t i t u t e d phosphanes with phosgene. The reaction pro­ ceeds v i a several isolable intermediates. The first i s the phosphino-substituted methylene-phosphane, which is generated by silyl-group migration from phosphorus to oxygen. Treatment with further phosgene then causes further elimination of CO and chlorotrimethylsilane, yielding a compound with a P-P bond which 0097-6156/81/0171-0001$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2

PHOSPHORUS CHEMISTRY

4PhPTms

2

+ 2C1 C0

4

T

m

s

C

1

2PhP= C-PPhTms

2

+

ci co

TmsCljCO

2

Ψ

OTms PhP—C —PPh 1 I I PhP — C — PPh i OTms no l o n g e r shows t h e c h a r a c t e r i s t i n a t e p h o s p h o r u s . An x - r a r i e d o u t by Dr. H a l s t e n b e r g a n d P r o f e s s o r H u t t n e r a t K o n s t a n z , showed t h a t i t i s t h e f i r s t 2,3,5,6-tetraphosphabicyclo[2.2.0]h e x a n e , w h i c h c o n t a i n s a n a s y m m e t r i c and d i s t o r t e d b i c y c l o h e x a n e s k e l e t o n w i t h two s e t s o f e q u i v a l e n t p h o s p h o r u s atoms i n d i f f e r ­ ent environments. Thus f a r t h e b i c y c l o h e x a n e s k e l e t o n c a n o n l y be o b t a i n e d i n t h e r e a c t i o n o f COCI2 w i t h p h e n y l - b i s ( t r i m e t h y l silyl)phosphane. I n i t i a l l y t-butyl-bis(trimethylsilyl)phosphane indeed r e a c t s analogously t o g i v e t h e p h o s p h i n o - s u b s t i t u t e d m e t h y l e n e p h o s p h a n e , w h i c h c a n be i s o l a t e d a s a p u r e s u b s t a n c e a n d w h i c h c a n be c o n v e r t e d t o t h e P-H p h o s p h i n e by m e t h a n o l . What happens i n t h e s e c o n d s t e p w i t h f u r t h e r p h o s g e n e , h o w e v e r , d e ­ pends v e r y much upon t h e r a t e o f a d d i t i o n . I f theaddition oc­ c u r s v e r y s l o w l y a t -80°, t h e f i v e - m e m b e r e d r i n g s y s t e m w i t h a C-C d o u b l e bond i s f o r m e d , w h i l e r a p i d m i x i n g o f s o l u t i o n s o f b o t h components i n t h e m o l a r r a t i o 1:1 a f f o r d s a f i v e membered r i n g c o n t a i n i n g f o u r p h o s p h o r u s atoms b r i d g e d by a CO m o i e t y . TmsO

OTms \

c

/ t-Bu-P "

t-Bu-p

c

\

/

P-t-Bu

t-Bu-P

X

p-jt-Bu

\ P-t-Bu

N

P / ~ ~ c ' " I II _t-Bu 0 The r e a c t i o n o f p h e n y l ( b i s t r i m e t h y l s i l y l ) p h o s p h i n e w i t h p h e n y l i s o c y a n i d e d i c h l o r i d e , t h e a z a - a n a l o g u e o f phosgene y i e l d s tetraphosphahexadiene according t o elemental a n a l y s i s , c r y o s c o p i c m o l e c u l a r mass d e t e r m i n a t i o n , a n d 31p nmr s t u d i e d . To u n d e r s t a n d t h e i n t e r e s t i n g s t r u c t u r a l p r o b l e m o f t h i s compound, we must l o o k i n d e t a i l a t t h e 31p m r s p e c t r u m . A t a m b i e n t t e m p e r a t u r e t h e s u b s t r u c t u r e o f an AA XX 4 - s p i n system i s observed. The downf i e l d s i g n a l s a t 258 ppm a r e a s s i g n e d t o t h e t w o - c o o r d i n a t e p h o s ­ p h o r u s a n d t h e u p f i e l d m u l t i p l e t a t -12.3 ppm a r i s e s f r o m t h e t r i v a l e n t phosphane m o i e t y . Between b o t h g r o u p s t h e r e i s a n

f

f

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

1.

APPEL

Phosphorus-Carbon

4PhPTms + 2Cl C=NPh 2

2

Compounds

with p ^ p *

Bonds

3

PhNTms ! -4TmsCl > 2PhP=C-PPhTms + Cl C=NPh 2

- 2TmsCl - PhNC

PhNTms PhNTms \ / PhP=C-P-P-C=PPh ι ι PhPh

d i f f u s e a b s o r p t i o n a t 115.7 ppm which sharpens on heating to 60°C while the other s i g n a l s broaden. The s i g n i f i c a n c e of the broad s i g n a l can be e l u c i d a t e d by c o o l i n g to -70°C. In a d d i t i o n to the two sharp m u l t i p l e t s already mentioned, a second 4-spin A A X X system appears, the l e f t h a l f i n d i c a t i n g two-coordinate phosphorus and the r i g h t , a t -3.2 ppm., the diphosphane Ρ atoms. Renewed heating to ambient temperature r e s u l t s i n coalescence of the two inner m u l t i p l e t s at 115 ppm. Thus the process i s r e v e r ­ sible. On f u r t h e r c o o l i n g to about -80°C, however, the outer m u l t i p l e t s l a b e l l e d 5a t o t a l l y disappear. The reason f o r t h i s i s p r e c i p i t a t i o n due to i n s u f f i c i e n t s o l u b i l i t y . Low temperature f i l t r a t i o n of the c r y s t a l s and r e d i s s o l v i n g them a t 30° again gives the complete 31p nmr spectrum as before. F i r s t l y , according to elemental a n a l y s i s and molecular mass determination, the com­ pound i s homogeneous, that i s to say, the broad a b s o r p t i o n i s f

f

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

4

c a u s e d by an i s o m e r . F u r t h e r m o r e t h e s p l i t t i n g i n t o a s e c o n d AA'XX s y s t e m a t -70° i n d i c a t e s a d i a s t e r e o m e r i c t e t r a p h o s p h a hexadiene, s i n c e both the c h a r a c t e r i s t i c m u l t i p l e t s of diphosphane- and m e t h y l e n e p h o s p h a n e - p h o s p h o r u s c a n be i d e n t i f i e d . An e x p l a n a t i o n , which e l u c i d a t e s the r e v e r s i b l e temperature-depen­ d e n t c o a l e s c e n c e o f t h e i n n e r s i g n a l s and a l s o r a t i o n a l i z e s why o n l y one s t e r e o i s o m e r d i s p l a y s t h i s phenomenon i s now g i v e n . A t t e m p t s t o e x p l a i n t h e c o a l e s c e n c e by m i g r a t i o n o f t h e s i l y l g r o u p b e t w e e n t h e n i t r o g e n and p h o s p h o r u s atom o r by a r o ­ t a t i o n a r o u n d t h e C-N o r P=C d o u b l e - b o n d a r e n o t s u p p o r t e d by the e x p e r i m e n t a l d a t a . We came t o t h e c o n c l u s i o n t h a t a p e r i c y c l i c r e a c t i o n o c c u r s , w h i c h i s a n a l o g o u s t o t h e Cope r e a r r a n g e ­ ment f o r h e x a d i e n e - 1 , 5 . I n a [ 3 . 3 ] - s i g m a t r o p i c r e a c t i o n o f t h e tetraphosphahexadiene, breaks with simultaneou new P-P bond. The o r i g i n a l nmr s i g n a l s o f t h e Ρ atoms w i t h t h e c o o r d i n a t i o n number 2 and 3 must c o l l a p s e i n t h e m i d d l e b e c a u s e the r e a r r a n g e m e n t i s a s y m m e t r i c a l one and b e c a u s e i t o c c u r s on the nmr t i m e s c a l e . The f a c t t h a t o n l y one d i a s t e r e o m e r shows c o a l e s c e n c e c a n be e x p l a i n e d a s f o l l o w s . As i s w e l l known, s y m m e t r i c a l , d i f f e r e n t l y s u b s t i t u t e d d i p h o s p h a n e s w h i c h a r e com­ p a r a b l e t o o u r t y p e i n s u b s t i t u t i o n have two c e n t e r s o f c h i r a l i t y . T h e i r s y n t h e s i s u s u a l l y y i e l d s a 1:1 p r o p o r t i o n o f t h e meso f o r m and r a c e m i c m i x t u r e , w h i c h c a n be c h a r a c t e r i z e d by t h e i r d i f f e r ­ ent 31p nmr s h i f t s . I n o u r c a s e t h e o u t e r s e t o f m u l t i p l e t s must be a s s i g n e d t o one d i a s t e r e o m e r and t h e i n n e r s e t t o t h e o t h e r . From t h e o b s e r v a t i o n t h a t t h e s p e c t r u m o f t h e c r y s t a l s f i l t e r e d a t l o w t e m p e r a t u r e shows two s i g n a l g r o u p s a g a i n a t room t e m p e r a t u r e , we must c o n c l u d e t h a t t h e c o n f i g u r a t i o n a l e q u i l i b r i u m between t h e meso f o r m and r a c e m i c m i x t u r e i s p r o m p t l y a c h i e v e d . The f a s t exchange i n t h e ^ l p nmr s p e c t r u m o f one i s o m e r a t room t e m p e r a t u r e , w h i c h i s n o t o b s e r v e d f o r i s o m e r 5 a , l e a d s t o the c o n c l u s i o n t h a t o n l y one f o r m f u l f i l l s t h e s t e r e o c h e m i c a l d e ­ mands o f t h e C o p e - r e a r r a n g e m e n t . T h i s i s the racemic m i x t u r e as shown. I f t h i s i s c o r r e c t , t h e c r y s t a l s f i l t e r e d a t l o w t e m p e r a ­ t u r e , w h i c h show no c o a l e s c e n c e , s h o u l d be t h e meso f o r m . The x-ray a n a l y s i s of these c r y s t a l s v e r i f i e s t h i s a s s e r t i o n s i n c e the s u b s t i t u e n t s a t t h e P-P bond a r e i n d e e d t r a n s t o one a n o t h e r . Of c o u r s e , we must be c a r e f u l when t r a n s f e r r i n g c o n c e p t i o n s f r o m c a r b o n compounds t o o t h e r e l e m e n t s . N e v e r t h e l e s s t h e r e a r e i n t e r a c t i o n s between e l e c t r o n s o f t h e 2p and e l e c t r o n s o f t h e 3p l e v e l which i s c o n s i d e r a b l y higher. T h e r e f o r e we l o o k e d f o r f u r t h e r p r o o f o f t h i s h y p o t h e s i s . The f o l l o w i n g e x p e r i m e n t seemed t o be a l i n k i n g one between t h e f i e l d s o f c a r b o n and p h o s ­ p h o r u s c h e m i s t r y . We t r e a t e d s u c c i n i c a c i d d i c h l o r i d e w i t h b i s ( t r i m e t h y l s i l y l ) s i l y l p h e n y l phosphane. A c c o r d i n g t o o u r h y p o t h e ­ s i s a p r i m a r y h a l o s i l a n e c o n d e n s a t i o n f o l l o w e d by a s i l y l m i g r a ­ t i o n and f o r m a t i o n o f t h e P=C d o u b l e b o n d , and f i n a l l y a [3.3]s i g m a t r o p i c rearrangement to the diphosphane should occur. In the 31p nmr s p e c t r u m . We o b s e r v e a h a l o s i l a n e c o n d e n s a t i o n t o 1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

1.

APPEL

Phosphorus-Carbon

2ΡΗΡτ

PhCEP -TmsCl

2

-HCl s p e c t r o m e t e r d i r e c t l y c o n n e c t e d t o t h e p y r o l y s i s a p p a r a t u s , we r e a d i l y s u c c e e d e d i n s y n t h e s i z i n g t h e m e t h i n e p h o s p h a n e on a p r e ­ p a r a t i v e s c a l e and c h a r a c t e r i z e d i t f u r t h e r . The PC t r i p l e bond i n t h e p h o s p h a - a l k y n e h a s been c o n f i r m e d b y i t s c h a r a c t e r i s t i c •^C and P nmr d a t a a s w e l l a s by s t e p w i s e H C l a d d i t i o n . The phospha-alkene i s obtained f i r s t , which i s transformed t o benz y l d i c h l o r o p h o s p h a n e by a s e c o n d m o l e o f H C l . By ^ P nmr s p e c ­ t r o s c o p i c s t u d i e s we c o u l d show t h a t b e n z y l d i c h l o r o p h o s p h a n e c a n be d e h y d r o c h l o r i n a t e d by t e r t i a r y a m i n e s i n r e v e r s a l o f i t s f o r ­ mation r e a c t i o n . I n a d d i t i o n t o the Ε isomer, t h e Ζ isomer i s a l s o formed. Y e t H C l a d d i t i o n t o t h e phospha-alkyne does n o t p r o d u c e any t r a n s - c o m p o u n d . T h i s c a n be e x p l a i n e d i n t e r m s o f a s t e r e o s p e c i f i c c i s - a d d i t i o n t o t h e t r i p l e bond. 3 1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

1.

APPEL

Phosphorus-Carbon

Compounds

with ρπ-ρ*· Bonds

The d i r e c t vacuum p y r o l y s i s o f b e n z y l d i c h l o r o p h o s p h a n e a l s o y i e l d s some p h o s p h a - a l k y n e i n a d d i t i o n t o a l a r g e amount o f u n i ­ d e n t i f i e d side products. In a d d i t i o n to the phenylphosphaa c e t y l e n e w h i c h has a h a l f - l i f e o f 7 m i n u t e s a t 0°C, we c o u l d p r e p a r e t h e c o n s i d e r a b l y more s t a b l e t r i m e t h y l s i l y l d e r i v a t i v e w h i c h has a h a l f - l i f e a t room t e m p e r a t u r e o f 50 m i n u t e s . The _t-butyle d e r i v a t i v e i s e n t i r e l y s t a b l e , as Becker reported recent iy. To sum up, we c a n s t a t e t h a t t o d a y a s u r p r i s i n g l y g r e a t num­ b e r o f s t a b l e compounds w i t h PC d o u b l e bonds i s known. A t t h e moment we have s e v e r a l methods f o r t h e f o r m a t i o n o f t h i s d o u b l e bond. I n a d d i t i o n t o t h e d e h y d r o h a l o g e n a t i o n o f h a l o g e n o p h o s p h i n e s , t h e t h e r m a l e l i m i n a t i o n o f t r i m e t h y l c h l o r o s i l a n e and t h e e l i m i n a t i o n of h e x a m e t h y l d i s i l o x a n e l i m i n a t i o n , the s i l y l grou o x y g e n , n i t r o g e n , o r s u l f u r o f a n α-carbonyl o r h e t e r o c a r b o n y l f u n c t i o n s u b s e q u e n t t o i n i t i a l TmsCl a d d i t i o n t o o r c o n d e n s a t i o n with silylphosphanes. M o s t i m p o r t a n t l y , t h e r e i s no l o n g e r a n y reason f o r the p r e p a r a t i v e chemist to b a l k a t 2ρ -3ρ i n t e r a c ­ tions. V e r y c l e a r l y t h e l ^ C nmr s p e c t r a s u p p o r t t h i s v i e w , s i n c e t h e y beyond any d o u b t show t h a t t h e c a r b o n i n t h e m e t h y l i d e n e p h o s p h a n e s i s s p ^ - h y b r i d i z e d and s p - h y b r i d i z e d i n t h e p h o s p h a alkynes. The e x i s t e n c e o f Ε and Ζ i s o m e r s a t t h e PC d o u b l e bond can a l s o be demonstrated. Moreover, the f l u c t u a t i n g s t r u c t u r e of the tetraphosphahexadiene i s a b s o l u t e l y analogous to p u r e l y o l e f i n i c compounds. Whether t h e hopes w i l l be f u l f i l l e d t h a t t h e s e s t u d i e s o f t h e l a s t f i v e y e a r s have t u r n e d t h e f i r s t p a g e s o f a new c h a p t e r o f p h o s p h o r u s - c a r b o n c h e m i s t r y s t i l l r e m a i n s t o be s e e n . W h e t h e r , f o r i n s t a n c e , i t w i l l be p o s s i b l e t o c o n s t r u c t c o n j u ­ g a t e d PC s y s t e m s s u i t a b l e f o r D i e l s - A l d e r r e a c t i o n s , i s n o t y e t certain. E x p l o r a t i o n of the c o o r d i n a t i o n chemistry o f these new s p e c i e s may a l s o p r o v e f r u i t f u l . π

R E C E I V E D July 13,

π

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2 Selective Bond Formation of Organophosphorus Acids with Functional Groups of Biological Importance L. HORNER, R. GEHRING, and H.-W. FLEMMING Institut für Organische Chemie der Universität Mainz, Johann-Joachim-Becher-Weg 18-20, D-6500 Mainz, FRG

A knowledge of the interaction of nucleophiles with the phosphorylating agent, (modified in its reactivity by the use of different leaving-groups bonding of biologically important groups (e.g. OH, NH , SH) to organophosphorus acids in a controlled manner. The following variations were investigated: 2

Phosphinic acid derivatives, Phosphonic acid derivatives, Phosphoric acid derivatives X = Cl, F, CN, N , OC H NO (p); for RYH: Y = O, NR, S 3

6

4

2

The relative reactivities were determined by means of competition with different nucleophiles RYH and RY'H.

Examples: X = Cl (a); X = F (b); X = N (c); X = CN (d); X = OC H NO (p) (e) 3

6

4

RYH = n-BuNH ; RY'H = n-BuOH 2

(a) P-YR = Amide (94 %); P-Y'R = Ester (2 %) (b) P-YR = Amide (0 %); P- Y'R = Ester ( 87 %) 0097-6156/81/0171-0013$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2

14

(c)

PHOSPHORUS CHEMISTRY

P-YR

= Amide (~80 %);

P-Y'-R

(d)

P-YR

= Amide (0 %);

(e)

P-YR

= Amide (0 %); P-Y'R = Ester (~90 %)

P-Y'-R

= Ester (~20 %)

= Ester (~90 %)

X = Cl (a); X = N (b); X = CN (c) 3

RYH = n-BuNH ; RY'Η = n-BuSH 2

(a)

P-YR

= Amide (~90 %); S-ester (trace)

(b)

P-YR

= Amide (~80 %); S-ester (~20 %)

(c)

P-YR

= Amide (trace); S-ester (~90 %)

With X = F and OC H NO : no reaction 6

4

2

Three products are philes are situated i n the same molecule (e.g. ethanolamine, cysteamine, serine and cysteine).

® = (C H ) P(0) 6

5

2

Several s e l e c t i v i t y studies were also carried out for serine (important i n the active s i t e of many enzymes) and for cysteamine and cysteine (also i n view of their b i o l o g i c a l importance). S e l e c t i v i t y i n the reaction of serine-N-butylamide with Ph P(0)X (X = CI or F ) :

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2.

HORNER E T A L .

Organophosphorus

Acids

of Biological

Importance

15

S e l e c t i v i t y i n the r e a c t i o n of cysteamine with diphenylphosp h i n i c a c i d cyanide : HS-CH -CH -NH 2

2

2

HS-CH -CH-NH 2

2

C0 CH 2

+ Ph P(0)CN

> Ph P(0)-S-CH -CH -NH

2

2

+ Ph P(0)CN 2

2

> Ph P(0)-S-CH -CH-NH

2

C0 CH

3

2

2

3

2

Diphenylphosphoric a c i d d e r i v a t i v e s ( C ^ O ) P (0)X 2

CN,

2

(X = C l , F, N

OC^H^N0 (p))are as s e l e c t i v e as the corresponding 2

2

3

phosphinic

acid derivatives ( C ^ ) Corresponding competition r e a c t i o n s (BuNH , BuOH, BuSH) were a l s o c a r r i e d out with the diphenylthiophosphinic a c i d d e r i v a t i v e s Ph P(S)X (X = C l , F, CN). 2

2

Organophosphorus compounds bearing a f l u o r e s c e n t group were s p e c i f i c a l l y introduced i n t o the a c t i v e s i t e s of the s e r i n e - e n zymes ^-Chymotrypsin, T r y p s i n and B u t y r y l c h o l i n - e s t e r a s e using the agents _2, 3 > and 4_. This was shown using e l e c t r o p h o r e s i s .

NMe.

2

OMe 4

R = so ci 2

R = EtOP(0)F

(dansylchloride) 2

= PhP(0)F

3

= PhP(0)-OC H N0 (p) 6

4

2

The compounds 2, 3 and 4 are e f f e c t i v e i n h i b i t o r s o f s e r i n e enzymes ( oC -Chymotrypsin, T r y p s i n , B u t y r y l c h o l i n - e s t e r a s e and A c e t y l c h o l i n e s t e r a s e (only 4) . RECEIVED

July 13, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

3 Chemical Synthesis and Biological Properties of the 5'-Terminus of Eukaryotic Messenger Ribonucleic Acids (mRNA) TSUJIAKI HATA, MITSUO SEKINE, IWAO NAKAGAWA, KAZUO YAMAGUCHI, SHINKICHI HONDA, TAKASHI KAMIMURA, and KAZUKO YAMAGUCHI Department of Life Chemistry, Tokyo Institute of Technology, Nagatsuta, Midoriku, Yokohama227,Japan KIN-ICHIRO MIURA National Institute of Genetics,

In contrast to prokaryotic mRNAs, mRNAs from various eukaryotic cells and viruses have been found to contain a terminal 7-methylguanosine (mG) residue linked from its 5'-position through a triphosphate bridge which was presented commonly as shown in the following Scheme 1 . 7

0097-6156/81/0171-0017$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

18

PHOSPHORUS CHEMISTRY

We first describe the synthesis of unsymmetrical α,γ-dinucleoside triphosphates involving 7-methylguanosine. For the construction of the terminal cap structure, there might be two possible reac­ tion modes where an activatable protecting group (X) was intro­ duced into a nucleotide by direct displacement with phosphate hydroxyl group (Method A) and by pyrophosphorylation between Xp and pN (Method B). Method A:

As the former type of reaction, we have developed the triphosphate bond formation by means of phosphinothioyl bromide as shown in the following scheme.

The latter requires a phosphorylating species possessing an acti­ vatable protecting group for the preparation of the starting mate­ rial (XppN). Now, we found a convenient method for the synthesis of this type of pyrophosphorylating reagent by the reaction of methyl phosphorodichloridate with thiophenol in pyridine. A prom­ ising capping reagent, P -S-phenyl P -7-methylguanosine-5'-pyrophosphorothioate, was synthesized as described below. 1

2

The phenylthio group could serve as the temporary protecting group which was easily activated by treatment with silver acetate, silver nitrate or iodine. By the above methods, we synthesized several kinds of unsymmetrical α,γ-dinucleoside triphosphates in­ volving methylated or nonmethylated cap structures. The abovementioned methods have been also applied to the synthesis of cap structure containing oligoribonucleotides. Furuich and Miura discovered the terminal structure of cytoplasmic polyhedrosis virus (CPV) mRNA which was represented as m G 'pppAmpGpU-·· In order to confirm the structure by chemical synthesis and investi­ gate the function and the mechanism of its formation in vitro m G *pppAm, m G 'pppAmG, and mG'pppAmpGpU were synthesized by utilizing the present capping reactions and the phosphotriester approach. However, we have felt during the investigation that 7methylguanylic acid and its derivatives used for the construction 7

7

5

7

5

7

5

5

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

3.

HÂTA E T A L .

Eukaryotic

Messenger Ribonucleic Acids

19

of the cap structure should be appropriately protected because of their extreme instability and poor s o l u b i l i t y . In most of mosaic virus mRNAs, there exsists the common terminal structure of m G pppGpU-·· In order to elucidate its biological meaning, we tried the synthesis of this part by using monomethoxytrityl and dimethoxytrityl groups as the highly lipophilic protecting groups of N -amino functions of guanosine and 7-methylguanosine. Consequently, mGpppGpU was obtained i^good yield and some related compounds of m G pppGpUpU and m G ppGp(J were also synthesized in a simmilar manner. We have tested some of biological properties of the cap structure by employing unusual man-made cap analogues which were synthesized by the above methods. Here, we shall describ position of guanosine residu F i r s t , the methylation of guanosine moiety of the cap struc ture with S-adenosylmethionine (SAM) was examined. When only GTP was added as a substrate to the in vitro RNA synthesizing system of CPV in the presence of SAM, GTP was not methylated. However, GTP and ATP were added to the same system, m G^pppA and m G pppApG were formed. On the basis of the above facts, chemically synthesized G 'pppA was added as a substrate in place of GTP and ATP, m G pppA was obtained expectedly. In this case no methylation took place of 2'-0H of adenosine moiety. In the same system G^pppG was not methylated. Therefore, the cap structure of CPV was formed as follows: 7

5

2

7

7

5

7

5

7

7

5

5

7

5

GTP

+

5

G pppA 7

5

m G pppA

5

•> G pppA

ATP -

7

5

m G 'pppA

+ SAM —*

+ GTP

7

5

m G pppApG

, On the other hand, mRNAs from reovirus were represented as m G pppGmpUν. In the in vitro RNA synthesizing system of reovirus, G pppG was methylated selectively at the 7-position of one of two guanosine residues, but any methylation is not caused for G pppA. This shows that the methylation enzymes either in CPV or in reovirus recognized s t r i c t l y the structure of the con­ fronting nucleoside residues. Next, we examined the structural requirement for the con­ fronting phosphate bridge in the methylation. The CPV system as described previously was employed. It was found that G ppppA and G ppA were methylated imper­ fectly about 50% relative to G pppA in the presence of SAM and no methylation was observed in the case of G pA. 7

5

5

5

5

5

5

/

5

R E C E I V E D J u l y 7,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

4 Triphenylphosphane-diethylazodicarboxylate: A Useful System for Directed Structural Variation of Carbohydrates E. ZBIRAL, H. H. BRANDSTETTER, and E. MARK Institute for Organic Chemistry, University of Vienna, A-1090 Vienna, Austria

Nucleophilic s u b s t i t u t i o strates with HX initiated by a c t i v a t i o o e hydroxy -group by means of TPΡ/DEAD first developed by Hitsunobu (1) are being increasingly utilized (1,2). This p r i n ­ c i p l e has been seldom applied until now in the field of carbohydrates. In order to diminish h y d r o p h i l i c i t y , the mono- and b i s - t - b u t y l d i m e t h y l s i l y l e t h e r derivatives of a series of carbohydrates were prepared, which repre­ sent very useful substrates with two or even three free OH groups f o r r e a l i z i n g a series of i n t e r e s t i n g transformations by means of TPP/DEAD or TPP/DEAD/HX. The methyl-β-glucopyranoside 1a can be transformed in t h i s way e x c l u s i v e l y to the 3-desoxy-3-X-allose derivatives 2a-2d (X = N , Br, J, p-NO -C H COO) (figure 1), whereas the corresponding methyl- -D­ -glucopyranoside 1b gives e x c l u s i v e l y the analogous 4-desoxy-4-X-galactose derivatives 3a-3d. This useful s u b s t i t u t i o n reaction e s p e c i a l l y by means of TPP/DEAD/ can be applied also to the methyl-2-acetamido-63

2

6

4

Figure 1. ( t - b u t y l d i m e t h y l s i l y l ) - 2 - d e s o x y - -D-glucopyranoside 4 and methyl-2-acetamido-3,6-bis-O-(t-butyldimethyls i l y l ) - 2 - d e s o x y - -D-glucopyranoside 5. The former i s 0097-6156/81/0171-0021$05.00/ 0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

22

PHOSPHORUS CHEMISTRY

transformed to the methyl-2-acetamido-3-azido-6-O(t-butyldimethylsilyl)-2,3-didesoxy-oc-D-allopyranoside 6.whereas the l a t t e r goes over to the corresponding galactose derivative J . When la., Vb and 4 are treated with TPP/D~:AD alone the preparatively useful 3,4-anhydro-galactose derivatives 8 (methyl~3,4-anhydro2,6-bis-C-(t-butyldimethylsilyl)-B-D-galactopyranosid), 9 (methyl-3,4-anhydro-2,6-bis-C-(t-butyldimethylsilyl)-D-galactopyranosid) and K) (methyl-acetamido-3# 4anhydro-6-0-(t-butyldimethylsilyl)-?-desoxy- oL -Dgalactopyranoside) a r i s e . Under s i m i l a r conditions m e t h y l - 6 - C - ( t - b u t y l d i m e t h y l s i l y l ) - oC-D-glucopyranoside 11 y i e l d s the methyl-2,3-anhydro-6-0-(t-butyldi­ me t h y l s i l y l ) - o c - a l l o p y r a n o s i d 12. which can be sub­ jected a d d i t i o n a l l y means of TPF/Dl'AD/HJNj resp. p-i^-CôZl^CQOH without any opening of the oxirane function by i l l . Kethy1-2,3-anhydro-4-azido-6-0-(t-butyldimethylsilyl)-4-desoxyot D-gulopyranoside 13a and methyl-2,3-anhydro-6-0-(tbutyldimethylsilyl)-4-0-(p-nitrobenzoyl)- ot -D-gulo­ pyranoside 13b are formed. The transformations of 2,6-0-bissilyl-methyl-oCD-mannopyranoside are represented i n figure 2. The predominating product i s the methyl-3,4-anhydro-talopyranoside 1j| even when TPP/DEAD/HII3 i s used. Obviously the s u b s t i t u t i o n process leading to the altro-sugar 16 i s greatly hindered by the w e l l known 1,3-diaxial i n t e r a c t i o n . A l l the epoxy sugars 8, J_C and 1£ serve as very useful s t a r t i n g points for further i n t e r e s t i n g s t r u c t u r a l modifications by opening the epoxide r i n g with EX (£, J5).

Figure 2. The behaviour of the :;-1,4-gluconolactone d e r i v a ­ t i v e JJ7 towards TrP/DIAD/ILX i s summarized i n figure 3· The exclusive a c t i v a t i o n of the Oil group at C5 using one equivalent ΤΡΓ/DF.AD followed by a s u b s t i t u t i o n by :,X opens an i n t e r e s t i n g approach to the L-1,4-idonolactone derivative 1_8 whereas the a c t i v a t i o n of the second Oil group at C3 y i e l d s by an e l i m i n a t i o n process

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

4.

ZBIRAL E T A L .

Structural

Variation

of

23

Carbohydrates

the u n s a t u r a t e d s u g a r l a c t o n e 1 2 · By a p p l y i n g s u c h procedures to the analogous ? "5-bis-0-(t-butyldimethyls i l y l ) - e t h e r d e r i v a t i v e o f D - 1 , A - g a l a c t o n o l a c t o n e 20 the c o r r e s p o n d i n g L - a l t r o n o l a c t o n e d e r i v a t i v e s 21a (X = h j ) and 21b (X = p - ï ^ - C g l i / C C O ) o n t h e one a n d 2,6-bis-0-(t-butyldimethylsilylT-5-C-p-nitrobenzoyl-Lerythro-hex-2-en-1,4-lactone 22_ o n t h e o t h e r h a n d a r e r e s u l t i n g , A s i m i l a r p a t t e r n c a n be o b s e r v e d i n the case o f the 2 , 6 - b i s - 0 - ( t - b u t y l d i m e t h y l s i l y l ) - e t h e r f

>SiO-i HO-f

=

*

S

i

°lx

TPP/DEA H 19

°

S

i

-

Figure 3.

d e r i v a t i v e o f L - m a n n o n o l a c t o n e 2£. By o m i s s i o n o f HX t h e o l e f i n s u g a r l a c t o n 2J- ( 2 , 6 - b i s - G - ( t - b u t y l d i ­ methylsilyl )-3-desoxy-L-erythro-hex-2-en-1,4-la.ctone) i s formed w i t h o u t any involvement o f the C5-0H. I n c o n t r a s t the D-1,4-gulonolactone d e r i v a t i v e 2j? i s t r a n s f o r m e d i n t o t h e 3 , 6 - a n h y d r o - D - g u l o n o l a c t o n e 26 (figure 4)·

Figure 4.

The 4 , 9 - b i s - O - a n d 4,8,9-tris-O-t-butyldimethyls i l y l e t h e r d e r i v a t i v e s 2J_ a n d 2 8 o f t h e b i o l o g i c a l l y important neuraminic acid represent useful starting p o i n t s f o r t h e s y n t h e s i s o f t h e new s t r u c t u r a l l y v a r i e d n o n u l o s o n i c a c i d d e r i v a t i v e s 29 ( f i g u r e 5 ) 30 a n d 2l ( f i g u r e 6 ) . O p e n i n g o f t h e o x i r s n e r i n g o f 29 w i t h HI.jleads to the 8-desoxy-8-azido-neuraminic p c i d d e r i v a t i v e 30 w h i c h c o r r e s p o n d s completely 28. B y t h e r e a c t i o n o f t h e t r i s - s i l y l e t h e r d e r i v a t i v e 28 w i t h TPP/DEAD/MW5 a n i n t e r e s t i n g r e s u l t w a s o b s e r v e d

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

24

PHOSPHORUS

CHEMISTRY

( f i g u r e 6). The p r i m a r y a c t i v a t e d OH group o f 07 i s a t t a c k e d o b v i o u s l y as a r e s u l t o f i d e a l s t e r e o e l e c t r o n i c c o n d i t i o n s by t h e acetamido group o f 05· As a consequence o f t h i s n e i g h b o u r i n g group p a r t i c i p a t i o n an i n v e r s i o n o f t h e c o n f i g u r a t i o n o f 07 l e a d i n g t o t h e D-glycero-L-altro-5-(5 -methy1-1-N-tetr? zolo)-nonulos o n i c a c i d d e r i v a t i v e J5J_ o c c u r e d . 1

Figure

6.

Literature cited 1. O. Mitsunobu, Synthesis 1981, 1-28 2. Η.Η. Brandstetter, E. Z b i r a l , Helv.Chim.Acta 1978, 61, 1832, 1980, 63, 327 3. Ε. Mark, Ε. Z b i r a l , Η.Η. Brandstetter, Mh.Chem. 1980, 111, 289. RECEIVED June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

5 Synthetic Application of Element Organic Substituted Phosphorus Ylides H. J. BESTMANN Institut für Organische Chemie der Universität Erlangen-Nürnberg, Henkestrasse 42, 8520 Erlangen, FRG

The trimethylsilylated ylides 1 (1), easily generated from t r i methylchlorosilane and ylides nylsilanes 3 (2,3). The vinylphosphonium silanolates 4 are also formed. Compounds 3 are versatile reagents for further reactions (4). The ylide 1 (with R =H) reacts with aldehydes 2 to give the dienes 9. The oxidation of 1 with the adduct 6, from triphenylphosphite and ozone, gives access to a general synthesis of acylsilanes (trimethylsilylketones) 8 (2). The silylated ylides 1 react to form phosphonium salts 7 with halogen compounds. The salts 7 can be desilylated by fluoride ions. The disubstituted ylides 10 formed can be converted in statu nascendi with aldehydes 11 into the tris-substituted olefin 12 (2,3). In the case of R =I, vinyl 1

3

0097-6156/81/0171-0025$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

26

PHOSPHORUS CHEMISTRY

iodides 12, R =I, are obtained (2). Using deuterated halogen compounds R X (and R =H) partially selectively deuterated pheromones can be obtained by this method (5). Recent results show, that (tert. butyl-dimethylsilyl)-methylene phosphorane 1 (R =H, and tert. butyl-dimethylsilyl instead of Me Si) gives a Wittig reaction which affords a vinyl silane with terminal double bond in high yields (2). 3

3

1

1

3

The hexaphenylcarbodiphosphorane 13 (6) can be understood as an elementorganically substituted ylide with a particular character. It reacts with S to form CS 14, which immediately reacts further with one more molecule of 13 via a betaine intermediate as described previously (7) to make thioketenylidene triphenylphosphorane 15 (8). 8

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

5.

BESTMANN

Substituted

Phosphorus

27

Ylides

Compound J_3 reacts with 2 moles of acetylene dicarboxylic ester 16 via a twofold cycloaddition and a subsequent electrocyclic ring opening reaction (9) to form the a l i è n e bisylid 18 (8). The radialene 20 is formed (8) from 13 and f 1 uorenylideneTetene 17. Compound Improbably reacts f i r s t with J_7 to give the phosphacumulene ylTJe 19. (10) » from which a pentatetraen is formed with 17. This then reacts with 19 to give a cycloaddition yielding 20 (9]7 Phosphorus y l i d e s T l combine with BH 22 to yield adducts 23 (11), which rearrange thermally to give the monoalkyl boranetriphenylphosphane adducts 24. On further heating these disproportionate to trialkylboranes £ 9 and the adduct from BH and t r i phenylphosphane 30 (12). 3

3

FT

R

ι ΐ θ

ι ι Φ

R -C-PPh

i i

+ B H — - R -C-PPh

0

0

θ BH 21

22

—

0

25

R-C-BH 2

P P h

3

R-CH=CH-R

q

26

23~

2 R Η

R 1 ι ι R -C-B(CH-CH -R)

R 1

( R - C ) B + PPh 3~ 3 I H

1

R -C-B-PPh

?

H Cl 27

BH

Q

3

I 1

I H

30

29

28

1. CO 2. H 0 2

R 1 ι

25

26

2

R 1 »

R 1

R -CH-C(CH-CH -R) 2

R ·

I.NaOCH,

R-C-B-CH-CH -R 9

1 I1 •R'-C-C-C-C-R

I II I 1

2

H Cl

OH

32

31

2.DCME

Η 0 ΗΗ 33

We were able to direct the rearrangement 23—24 so that no dis­ proportion into 29 and 3 £ occurred (13). The adducts 24 are stable and can now be used for hydroboration reactions whereby a suitable method for the elimination of t r i phenylphosphane from complex 24 must be used. This can be achieved with benzyl-iodide 2 £ . On a c o i ­ tion of the iodo compound 25 and an olefin 26 to a solution of 24 in tetrahydrofuran, the benzyl-triphenylphosphoniurn iodide precTP pitates and the free R-BH adds to the olefin 26 forming the t r i 2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

28

alkylborane 27 (13). The latter can be converted into tertiary alcohols υ by subsequent treatment with CO and H^O- (14). The reaction of 2A_ and HC1 yields alkylchloroborane t r i phenylphosphane complexes 28» which can be converted with olefins in the presence of benzyl iodide 25 (15). The dialkylchloroboranes 32 thus formed can be transformed into ketones 31 with sodium methyl ate and then the DCME-technique of H.C. Brown (16). These last results combine the Wittig ylide chemistry with Brown s hydroboration reaction. We hope that a preparatively i n ­ teresting ylide-borane chemistry will arise from this new "alloy". I thank my coworkers, named in the references, for their enthusiastic engagement in the solution of our common problems. ;

Literature cited: 1 Seyferth, D.; Singh, G. J. Am. Chem. Soc. 1965, 87, 4156. Schmidbaur, H.; Tronich, W. Chem. Ber. 1967, 100, 1032. 2 Bestmann, H.J.; Bomhard, A. unpublished. 3 Bestmann, H.J. Pure and Appl. Chem. 1980, 52, 771. 4 Colvin, E.W. Chem. Soc. Rev. 1978, 7, 15. 5 Bestmann, H.J.; Hirsch, L. unpublished. 6 Ramirez, F.; Desai, N.B.; Hansen, B . ; Mc Kelvie, N. J. Am. Chem. Soc. 1961, 83, 3539. 7 Matthews, C . N . ; Birum, G.H. Tetrahedron Lett. 1966, 5707. Matthews, C . N . ; D r i s c o l l , J.S.; Birum, G.H. Chem. Comm. 1966, 736. 8 Bestmann, H.J.; Öchsner, H. unpublished. 9 Bestmann, H.J.; Rothe, O. Angew. Chem. 1964, 76, 569; Angew. Chem. Int. Ed. Engl. 1964, 3, 512. 10 Bestmann, H.J. Angew. Chem. 1977, 89, 361; Angew. Chem. Int. Ed. Engl. 1977, 16, 349. 11 Hawthorne, F.M. J. Am. Chem. Soc. 1961, 83, 367. 12 Köster, R.; Rickborn, B. J. Am. Chem. Soc. 1967, 89, 2782. 13 Bestmann, H.J.; Sühs, K . ; Röder, Th. unpublished. 14 Brown, H.C. "Organic Synthesis via Boranes" John Wiley Sons, New York, Chichester, Brisbane, Toronto, 1975. 15 Bestmann, H.J.; Röder, Th. unpublished. 16 Brown, H.C.; Ravindran, N . ; Kulkarni, S.U. J. Org. Chem. 1979, 44, 2417. RECEIVED

June 30,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

6 Mono-, Di-, and Multi-Ylides in Organometallic Chemistry HUBERT SCHMIDBAUR Anorganisch-Chemisches Institut der Technischen Universität München, Lichtenbergstrasse 4, D-8046 Garching, FRG

The ylid function i ed in the various theoretica with a combination of donor and acceptor capacity - or as a set of adjacent nucleophilic and electrophilic centers at carbon and phosphorus, respectively. The situation is not unlike the characteristics of the carbonyl group, one of the most important reactive functions in classical organic chemistry. Following the pioneering work by G. Wittig (1) and his collaborators, the synthetic potential of phosphorus ylids - and the reaction with carbonyl compounds in particular - has been widely exploited and the literature witnesses an ever increasing range of new preparative uses (2). In most of these reactions the PC bond of the ylid is cleaved and formally a carbene moiety is exchanged with a corresponding part of the substrate. In contrast, the majority of the reactions of ylids with acceptor sites centered at metals or metalloids occur with conservation of the PC bond and lead to organometallic/organometalloidal products containing M-C-P bridges (3,4,5,). Depending on the nature of M, these carbon bridges between phosphorus and heteroatoms may show CH acidity and may be deprotonated when exposed to strong bases or to an excess of ylid, which acts as a transylidating agent.

Bonding in the resulting products again depends strongly on the nature of M, and cases with the character of metallated ylids RP=CH-M- are also known (3) as are their phosphoniumcarbene metal counterparts R P + P-CH=M (6,7,8). A second feature, also uncommon in reactions of ylids with organic substrates, is the additional ylidation of the substituents at phosphorus (3,4,5). This alternative provides for an enormous variety of bridged and chelated metal complexes, amply described in a large number of papers in recent years. 3

2-

3

0097-6156/81/0171-0029$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS

30

CHEMISTRY

R e c e n t a d v a n c e s i n t h e a u t h o r ' s l a b o r a t o r y emerged f r o m a s e a r c h f o r m e t a l c o m p l e x e s w i t h c h i r a l c e n t e r s a t t h e P-C*-M b r i d g e , w i t h s p i r o c y c l i c c e n t e r s generated from c y c l o p r o p y l i d e s , f o r m u l t i f u n c t i o n a l i t y o f c y c l i c and n o n - c y c l i c y l i d s and t h e i r c o m p l e x e s w i t h weak a c c e p t o r m e t a l s , s u c h a s t h e a l k a l i and e a r t h a l k a l i n e m e t a l s , o r t h e d and d t r a n s i t i o n m e t a l s . Only r e ­ p r e s e n t a t i v e e x a m p l e s c a n be g i v e n , and t h e r e a d e r i s r e f e r r e d t o r e l a t e d papers quoted f o r f u r t h e r r e f e r e n c e . I n t r o d u c t i o n o f C h i r a l i t y (A. M o r t l , B. Z i m m e r - G a s s e r ) . There a r e examples s c a t t e r e d i n t h e l i t e r a t u r e , where t h e y l i d i c d o n o r c e n t e r becomes c h i r a l o n p r e s e n t i n g a d a t i v e bond t o t h e metal. Perhaps the s i m p l e s t case i s the s u b s t i t u t i o n product o f (C H ) P=CHCH with N i ( C 0 ) ( 9 ) : (CO) Ni-*CH(CH )-P(C H ) . A m e t a l b r i d g i n g c a s e i s r e p r e s e n t e d by t h e u r a n i u m compound [(C H ) UCH (CH)P(C H ) A pronounced c h i r a l i t y l i d c o m p l e x e s i s t o be e x p e c t e d f r o m p r o p e l l e r - t y p e l i g a n d s w i t h a C rotation axis. I n a f i r s t attempt t o s y n t h e s i z e p e r t i n e n t e x a m p l e s , a s p i r o b i c y c l i c y l i d e 1 was d e s i g n e d (11) and c o n v e r t e d i n t o a n o v e l l i t h i o - d e r i v a t i v e 2, w h i c h o n r e a c t i o n w i t h m e t a l h a l i d e s y i e l d s m u l t i - s p i r o complexes o f unusual geometries: 5

6

1 1

5

5

3

2

3

1 0

4

2

6

5

3

3

6

1 x

3

2

2

_3 i s o b t a i n e d a s y e l l o w c r y s t a l s , w h i c h have t h e l i g a n d d o n o r c e n t e r s i n a DD, L L c o n f i g u r a t i o n , y i e l d i n g a c e n t r o s y m m e t r i c m o l e c u l e ( 1 2 ) . I n F i g u r e 1 t h e s q u a r e p l a n a r a r r a y o f CH g r o u p s a r o u n d t h e N i atom and t h e p a d d l e - t y p e p o s i t i o n o f t h e p h o s p h o r i nane r i n g s - a l l i n a c h a i r c o n f o r m a t i o n - a r e i m m e d i a t e l y o b v i o u s . The C h e m i s t r y o f P h o s p h o n i u m C y c l o p r o p y l i d s (A. S c h i e r ) . A s m a l l number o f c y c l o p r o p y l i d s a r e known i n t h e l i t e r a t u r e ( 1 3 , 14,) b u t t h e i r c o o r d i n a t i o n c h e m i s t r y h a s n o t b e e n d e v e l o p e d . F o r a d e t a i l e d s t u d y o f t h e e f f e c t o f t h e c y c l o p r o p y l r i n g on t h e donor p r o p e r t i e s o f y l i d s a s e r i e s o f s i m p l e s p e c i e s was p r e p a r e d i n t h e p u r e , s a l t - f r e e s t a t e and c h a r a c t e r i z e d by m u l t i p l e - r e s o n a n c e experiments (14, 1 5 ) . -

-

γ

γ

Α

χ-

Δ

4

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

6.

SCHMIDBAUR

Figure

1.

Molecular

Ylides in Organomeiallic

structure

31

Chemistry

of the nickel complex diffraction (121

3 as determined

by

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

x-ray

32

PHOSPHORUS CHEMISTRY

The f u l l y c y c l o p r o p y l a t e d y l i d 4 i s a f l u x i o n a l molecule e x h i b i t ­ ing r a p i d α-proton exchange (15). Moreover, low temperature NMR s p e c t r a i n d i c a t e a pyramidal s t r u c t u r e of the carbanion i n triphenylphosphonium c y c l o p r o p y l i d 6, and an X-ray d i f f r a c t i o n a n a l y s i s of the c r y s t a l l i n e s o l i d con­ firms t h i s r e s u l t (14). Contrary to e a r l i e r p r e d i c t i o n s , c y c l o p r o p y l i d s are thus found to be the f i r s t c l a s s of y l i d s to con­ t a i n non-planar carbanions with an unusual y l i d i c bonding ( F i g . 2 ) . They form s t a b l e metal complexes, as i l l u s t r a t e d by a gold complex (p: + Ph P 3

Ni

7

PP PPh

Open-chain Double- an Milewski-Mahrla). In compounds of the type R P=CH-PR (8) an a d d i t i o n a l phosphine donor center i s d i r e c t l y attached to the b a s i c y l i d carbon atom (16, 17). Novel d e r i v a t i v e s of these l i g a n d s are, e.g., n i c k e l complexes 9 c o n t a i n i n g the NiCPCP five-membered r i n g (18). 3

2

CH 3

2

2

w

//i( H LC ^ 22

2

/ PPh +

2

Ni

CH Ph P/'

H

\\_ PPh

v

8

3

C

2

PPho PPh

Ph P II CH

Ph P

C

2

H

\ V-'/ — Ρ P h

CH L i * The c r y s t a l s t r u c t u r e of 9 has been determined and a c e n t r o symmetrical r e c t a n g u l a r c o o r d i n a t i o n geometry was found around the N i atom ( F i g . 3). A l l PC bonds of the r i n g s show p a r t i a l y l i d i c c h a r a c t e r . The geometry of the corresponding Ni-complex c o n t a i n ­ ing the six-membered r i n g s NiCPCPC, d e r i v e d from the carbodiphosphorane was e s t a b l i s h e d i n previous s t u d i e s (19). Four-membered r i n g s NiCPC (20) and MiPCP (21) were detected i n y l i d and diphosphinomethanide complexes, r e s p e c t i v e l y . I t appears t h e r e f o r e that a whole s e r i e s of organometallic complexes with a l t e r n a t i n g C/P r i n g members i s now a v a i l a b l e , c l o s e l y r e l a t e d to some of the S/N complexes of metals (22). For r e l a t e d examples of a l k a l i complexes see (22, 23). C y c l i c M u l t i p l e - y l i d s (Th. Costa and B. Milewski-Mahrla). C y c l i c double y l i d s with a l i p h a t i c r i n g members occur s o l e l y as carbodiphosphoranes (24, 25). The r e l a t e d benzo-heterocycle exists as a 1 , 3 - b i s - y l i d 1Q, however, and i s e a s i l y transformed i n t o a c y c l i c d i p h o s p h o n i u m - t r i p l e - y l i d 1_1 (26). T h i s anion forms a l a r g e v a r i e T y of complexes with u n i - and b i v a l e n t metals. Among these are a l k a l i and a l k a l i n e e a r t h metals, but a l s o Zn, Cd, Mn, Fe, Co and others. 2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

SCHMIDBAUR

Figure

2,

Ylides in Organometallic

Molecular

Chemistry

structure of triphenylphosphonium cyclopropylid mined by x-ray diffraction (14).

6 as deter-

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

Figure

3.

Molecular

structure

of the nickel complex diffraction (\%).

9 as determined

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

by

x-ray

6.

SCHMIDBAUR

Figure

4.

Ylides

Molecular

in Organometallic

35

Chemistry

structure of the manganese complex mined by x-ray diffraction (26)-

12 (Μ - Mn) as deter­

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

36

Two c r y s t a l s t r u c t u r e s have been determined so f a r (25, 2 6 ) , t h e most recent r e s u l t showing the Mn(II) complex to be a quasi-sandwich compound with the metal being attached predominantly to the b e n z y l i c carbon atoms ( 2 6 ) . As i n the Cd(II) complex, the com­ pound has a C a x i s ( F i g . 4 ) through the metal. 2

The c o o r d i n a t i o n spher strongly tetrahedron. A f t e r the d and d cases (Cd(II) and Mn(II), r e ­ s p e c t i v e l y ) , a number of other s t r u c t u r e s w i l l have to be e l u c i d a ­ ted, before the metal-ligand bonding can be p r o p e r l y understood. The author i s indebted to Drs. U. Schubert and C.Kruger for vita: a s s i s t a n c e with X-ray s t u d i e s . Support by Deutsche Forschungsgemein schaft,Fonds der Chemischen Industrie,and Hoechst AG,Knapsack i s g r a t e f u l l y acknowledged. 1 0

5

1. Wittig,G.,Accounts Chem.Res. 1974, 7, 6. 2. Bestmann,H.J.,Zimmermann,R.,Fortschr. Chem.Forsch.1971, 20, 1. 3. Schmidhaur, Η . , Accounts Chem. Res. 1975, 8, 62. 4. Schmidbaur, Η., Pure & Applied Chem. 1978, 50, 19. 5. Schmidbaur, Η., Pure & Applied Chem. 1980, 52, 1057. 6. Cramer,R.Ε.,Maynard,R.B.,Gilje,J.W.,J.Amer.Chem.Soc.1981, in press. 7. Baldwin,J.C.,Keder,Ν.L.,Strouse,C.E.,Kaska,W.C., Z. Naturforsch. 8. Schwartz,J.,Gell,K.I.,J.Organometal. Chem.1979, 184,Cl; Inorgan. Chem.l981, in press. 9. üger,C.,Angew.Chem.Int.Ed.Engl. 1972, 12, 387. 10.Cramer,R.Ε.,Maynard,R.B.,Gilje,J.W.,Inorg.Chem.1980,19, 2564. 11.Schmidbaur, Η . , M ö r t l , A . , Z.Naturforsch. 1980, 35b, 990. 12.Schmidbaur, H.,Mörtl A.,Zimmer-Gasser,Β.,Chem. Ber. 1981,in press. 13.Bestmann,H.J.,Hartung,H.,Pils,I., Angew.Chem.Int.Ed.Engl.1965,4,957. 14.Schmidbaur,Η.,Schier,A.,Milewski-Mahrla,Β.Chem.Ber.1981,inpress. 15.Schmidbaur,H.,Schier,A.,Chem.Ber. 1981, in press. 16.Schmidbaur,Η.,Tronich,W.,Chem.Ber. 1968, 101, 3545. 17.Issleib,K.,Lindner,R.,Lieb.Ann.Chem.1967,707,(1967),ref.therein. 18.Schmidbaur,H.,Deschler,U.,Milewski-Mahrla,B.Angew.Chem.1981,in press. 19.Schmidbaur, H.,Gasser,O.,Krüger,C.,Sekutowsla,J.C.,Chem. Ber. 1977, 1 1 0 , 3 5 1 7 . 2 0 . K a r s c h , H . H . , Schmidbaur,H. Chem.Ber. 1974, 107, 3684. 21.Bassett,J.-M.,Mandl,J.R., Schmidbaur, H.Chem.Ber.1980, 113, 1145. 22.Schmidbaur,H.,Deschler,U.,Zimmer-Gasser,B.,Neugebauer,D., Schubert, U.,Chem. Bar. 1980 113, 902 23.Schmidbaur,H.,Deschler,U., Zimmer-Gasser,B., Milewski-Mahrla, Β . , Chem.Ber. 1981, 114, 608. 24.Schmidbaur,Η., Costa,T.,Chem.Ber. 1981, in press. 25.Schmidbaur,Η., C o s t a , Τ . , M i l e w s k i - M a h r l a , Β . , Schubert, U . , Angew. Chem.Int.Ed. Engl. 1980, 19, 555. 26. Schmidbaur,H.,Costa,Τ.,Milewski-Mahrla, B . , Chem. Ber.1981, in press. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

7 Synthetic and Spectroscopic Investigations Involving α-Heterosubstituted Phosphonate Carbanions HANS

ZIMMER

Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221

α-Heterosubstitute ducted abstraction of a proton from a variety of substituted ethyl (or diphenyl) phosphonic acid esters

di­

(R=Et, Ph; R'=alkyl or a r y l groups; X=NHAr, Nalk , Cl, OSiMe and 2

3

OC(O)Ph-4-NO .) 2

The reaction of I (X-NHAr) with aromatic aldehydes, II, leads to enamines which easily hydrolyze to give deoxybenzoins. Thus, reactions of I with ortho-nitrosubstituted upon hydrolysis and subsequent reduction of the n i t r o group to an amino group leads to formation of indols. Similarly, reactions of I with ortho­ -methoxysubstituted I I followed by hydrolysis of the enamine and ether cleavage yields benzofurans. 1

1

1

Carbanions of type I derived of ortho-nitrocinnamaldehyde lead i n an analogous sequence to 2-benzylquinoline. 2

0097-6156/81/0171-0037$05.00/0

© 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

38

The reactions of I with phenylpropargylaldehyde leads to the expected yne-enamine which upon heating to about 50ºC in solution undergoes secondary reactions with the main one being a c y c l i z a tion to 2-phenyl-4-benzylquinolines. 1

Anions of type I (R'=aromatic, X=Cl) lead to formation of substituted vinyl chlorides, o abstraction step are used, to acetylenes 1

With I (X-Nalk ; R'=H) the intermediate hydroxyphosphonate(III) is rather stable and undergoes the expected cycloelimination only poorly or not at all. However, III upon acidification undergoes a semi-pinacol type rearrangement to give aldehydes 2

3

In reactions with I (R'=aromatic; X=OCOCH , OCOPh-4-NO ) enol ethers were obtained. 3

2

3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

7.

ziMMER

οί-Heterosubstituted

Phosphonate

39

Carbanions

A t o t a l l y d i f f e r e n t course was observed with type I anions (R= aromatic or a l i p h a t i c ; X=OSiMe~); the expected t r i m e t h y l s i l y l s u b s t i t u t e d enol ethers were not obtained. Instead, a f t e r a 1 , 4 - 0 . 0 - t r i m e t h y l s i l y l m i g r a t i o n a n d ^ s p l i t t i n g o f f of ( R O ) ~ ° " benzoins or a c y l o i n e s were obtained. 0 R P

2

θ (R0) P(0)C0SiMe + R R"CH=0I

4P\

(RO) P 2

f

C - 0 - SiMe,

9

1

3

R

C - 0 Li » R

f

M

0 R\

R\^

H 0

n/

R ÎOSiMe. 1

In a l l r e a c t i o n s i n v o l v i n g I (X - NHAr) and R an o r t h o - s u b s t i tuted benzaldehyde no condensation r e a c t i o n was observed. An Xray s t r u c t u r e of such an α-heterosubstituted carbanion shows that the c a r b a n i o n i c s i t e o f such anions i s r a t h e r e f f e c t i v e l y s h i e l d e d against a t t a c k by an e l e c t r o p h i l e . The intermediacy of enamines i n the r e a c t i o n i n v o l v i n g (E|(j)) P(0) CHNalk i s c u r r e n t l y questioned. I t was thought that a P-NMR study o f the r e a c t i o n could solve t h i s question, The f o l l o w i n g observations were made. Η θ \ Ph Ph (EtO), Ρ - CH - NR NR (Et0) Ρ CH 2

n

9

n

\\

0 R

C H

9

0

(A)

(B)

C H

- ~ 2 ^ -CH CH^

0 U

2

M

(EtO) ^J? - C - 2

»

P

h

V

P

h

Ç

Η,0 3

?

h

\/l

Φ

y

C—η I

Η

0

0 (EtO) P-0~ (D) A had a chemical s h i f t o f 22.4 6;upon a d d i t i o n o f base presence of β was i n d i c a t e d by a chemical s h i f t o f 49.6 6 . A d d i t i o n of PhXO to g y i e l d e d the expected adduct Ç w i t h a chemical s h i f t of 3 2 . / δ . Quenching o f Ç with 1 e q u i v a l e n t o f H^O gave the expected hydro+

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

40

PHOSPHORUS CHEMISTRY

xyphosphonate d e r i v e d o f Q (29.66). Upon s t a n d i n g f o r 12 h o u r s o n l y t r a c e s o f D ( c h e m i c a l s h i f t -1.36 i d e n t i c a l w i t h a u t h e n t i c m a t e r i a l ) was o b s e r v e d . A l s o t h e s h a r p p e a k s due t o Β a n d C h a d disappeared. The l a c k o f β i s t a k e n a s a n i n d i c a t i o n t h a t o n l y t r a c e s o f a n enamine a r e f o r m e d u n d e r t h e s e c o n d i t i o n s . Acknowledgement: R e s u l t s f o r t h i s p r e s e n t a t i o n a r e t a k e n f r o m t h e Ph.D. t h e s e s b y D.M. Nene, R.E. K o e n i g k r a m e r , P.D. Seemuth a n d t h e proposed Ph.D. t h e s i s b y M.R. Crenshaw.

Literature Cited 1. 2. 3. 4.

Koenigkramer, R . E . , Zimmer, Hans. J. Org. Chem. 1980, 45, 3994. Nene, D.M. Ph.D. Thesis Universit f Cincinnati 1976 Koenigkramer, R.E 1979. Broekhof, N . L . J . M . , Jonkers, F . L . Van der Gen, A. Tetrahedron Letters, 1979, 2433.

RECEIVED September 14, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

8 A New Approach to Activation of Hydroxy Compounds Using Pentacoordinated Spirophosphoranes J. I. G. CADOGAN B. P. Research Centre, Chertsey Road, Sunbury-on-Thames, Middlesex, TW16 7LN, England I. GOSNEY, D. RANDLES, and S. YASLAK Department of Chemistry, Universit 3JJ, Scotland

There are several examples in the literature of activation of hydroxy compounds by various organophosphorus compounds. For example, in the presence of pyridine, n-butyltriphenoxyphosphonium bromide (1) activates carboxylic acids towards reaction with amines or phenols to give, respectively, amides or esters (1). Such condensation reactions are also promoted by certain trivalent phosphorus compounds, e.g. triphenyl phosphite (2) or diphenyl ethylphosphonite (3), or to a lesser extent by phosphonate esters, e.g. diphenyl n-butylphosphonate (3). "Bates' reagent," μ-oxobis[tris(dimethylamino)phosphonium] bis-tetra-f1uoroborate (2) may also be used to activate the carboxyl function towards amide bond formation during peptide synthesis (4) and to bring about the Beckmann rearrangement of ketoximes (5). We wish to report a new approach to condensation reactions of hydroxy compounds related to the Ritter reaction, the Beckmann rearrangement and peptide formation based on easily accessible pentaco-ordinate spirophosphoranes of the type (3) (6 - 9). Thus, reaction of equimolar amounts of 2-phenyl-2,2'­ spirobis(1,3,2-benzodioxaphosphole) (3a) (6) and benzhydrol under anhydrous conditions in boiling acetonitrile gave N-benzhydrylacetamide (40%), bis(benzhydryl)ether (30%) and 2-phenyl-1,3, 2-benzodioxaphosphole (4) which was identified by spectroscopic comparison with an authentic sample prepared from phenylphosphonic dichloride and catechol (10). The formation of N-benzhydrylacetamide from benzhydrol and acetonitrile constitutes a Ritter reaction (11) which, in this case, is accomplished under extraordinarily mild, and above all neutral conditions. Usually, such reactions are carried out in 0097-6156/81/0171-0041$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

42

PHOSPHORUS CHEMISTRY

concentrated sulphuric acid. The formation of the by-product, bis(benzhydryl) ether, may be inhibited and the yield of Ritter product greatly increased (to 84%) by slow addition of the alcohol to an excess of the phosphorane (3a) in boiling acetonitrile, other phosphoranes giving similar results. Re­ action as in Scheme 1 is assumed, whereby the f i r s t step (step A) involves nucleophilic substitution of benzhydrol for one of the catechol oxygens i n the phosphorane (3a) to give the phosphorane intermediate (5). This activates the alcohol toward nucleophilic attack by either the solvent, acetonitrile (step Β ) , or another molecule of benzhydrol (step C) to give, respectively, N-benzhydrylacetamide or bis(benzhydryl) ether. Nucleophilic attack on the intermediate (5) has a direct analogy in the reaction shown in Schem 2 i whic (6) a powerful methylating agen phenols (12J. Equimolar quantities of benzhydrol and the phosphorane (3a) were also reacted in dimethyl sulphoxide solution. Apart from bis(benzhydryl) ether (18%) and catechol monobenzhydryl ether (39%), a small amount of benzophenone (17%) was obtained. It was shown that, in the absence of phosphorane, benzhydrol is not oxidised to benzophenone by dimethyl sulphoxide. Reaction similar to that outlined in Scheme 1 is a l i k e l y p o s s i b i l i t y . Again, the alcohol is activated by reaction with the phosphorane toward nucleophilic attack, in this case by dimethyl sulphoxide. Significantly, oxidation of alcohols by dimethyl sulphoxide is usually carried out using the Pfitzner-Moffatt reagent (dicyclohexylcarbodiimide and anhydrous phosphoric acid in dimethyl sulphoxide) (13) whereas the reaction using the phosphorane (3a) is carried out under neutral conditions. Unfortunately, however, attempts to improve the y i e l d of benzophenone have hitherto fai led. Pentaco-ordinate spirophosphoranes of the type (3) are also capable of activating N-hydroxy functional groups towards Beckmann-type rearrangements. In a typical experiment, reaction of acetophenone oxime in boiling acetonitrile for several days in the presence of phosphorane (3a) afforded acetoacetanilide in 70% y i e l d . Here again, the conditions employed are much milder than the usual conditions required for the Beckmann rearrangement (e.g. phosphorus pentachloride, concentrated sulphuric acid, polyphosphoric acid), and are comparable to the conditions re­ quired using Bates' reagent (5.). Preliminary results show that pentaco-ordinate phosphoranes are practical reagents for the formation of the peptide link. Thus, application of the phosphorane (3b) (7) in the stringent Izumiya test (14)

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

8.

CADOGEN E T A L .

Activation

Scheme

L

of Hydroxy

43

Compounds

R = Ph CH. 2

(A)

ι

Me ^ acid workup

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

44

PHOSPHORUS CHEMISTRY

Scheme

2.

(Pho) PBu 3

n

R=MeC=

O; 2,4,6-trimeth

ylbenzoyl; Ph.

Br"

0) (Me N) P 2

3

/ 0 > X

P(NMe )3 2

2BF "

(3) a:R = Ph b:R = H ;

4

W

c:R=CI .d:R=PhO

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

8.

CADOGEN E T A L .

Activation

of Hydroxy

Compounds

45

Table 1. Degree of racemisation(l5) as measured by the Izumiya test. Coupling agent 20° 14days 60°, Iday 3

Ν - m e t h y l morpholine (NMM)-THF

20

50-60

23

60°7days

50-60

21

40°7days

50-60

12

40°4days

50-60

11

Iday

(Me N) P-0-P(NMe ) Et N 2BF " Ν MM DMF,20°(4_) poly Hunig base + HOBt 2

3

2

4

3

18

50-60

100°

Et N-THF

30

3

43 16 9 0

Ph P2

C

2. NHi+Cl

OH

R-

adducts with potassium hydride leads to completion of the HornerW i t t i g r e a c t i o n to provide the d e s i r e d enamines J_ i n high y i e l d s . Some r e p r e s e n t a t i v e r e s u l t s are compiled i n Table I . Table I : R

1

2

Conversion of R R CO i n t

Morpholin

Enamine J_

1

yield p-BrC^-

H

176- 7°

93%

137- 8°

p-CHaCeH^-

H

155- 8°

96%

68-70°

p-OCH C H^-

H

146- 7°

91%

84- 6°

C H -

H

168-70°

99%

73- 5°

H

167- 9°

H

oil

3

6

6

5

(E)-C H CH=CH6

5

(E)-C H CH=C(CH )2

C H 6

5

3

3

3

2

CH CH CH(CH CH )3

2

2

3

78-81°

90%

H

149-50°

83%

n

H

136- 7°

63%

1^^=1.4688

6

CH CH(CH )CH -

3

n£ =l.5057

not i s o l .

C H

5

72%

5

2 1

^ .4720

The r e s u l t s obtained by r e a c t i o n of 2_ with e n o l i z a b l e ketones are l e s s s a t i s f a c t o r y , because i n that case the anion a l s o a c t s as a base, converting p a r t of the carbonyl compound i n t o i t s l i t h i u m enolate. I t was a n t i c i p a t e d that the use of a l e s s s t r o n g l y b a s i c , but s t i l l s u f f i c i e n t l y n u c l e o p h i l i c anion could circumvent t h i s problem. Indeed, anion 4^ obtained from the corresponding ^-methyla n i l i n o s u b s t i t u t e d phosphine oxide as d e s c r i b e d b e f o r e , reacted smoothly with a l a r g e v a r i e t y of carbonyl compounds at -78° to a f f o r d , a f t e r quenching with ammonium c h l o r i d e , the adducts _5 i n v i r t u a l l y q u a n t i t a t i v e y i e l d s . The much lower b a s i c i t y of t h i s an­ i o n i s c l e a r l y r e f l e c t e d by the o b s e r v a t i o n that no s t a r t i n g mate­ r i a l i s recovered, even with h i g h l y e n o l i z a b l e ketones such as cyclopentanone and acetophenone. Conversion of the adducts _5 i n t o the #-me t h y l a n i l i n o enamines 6^ i s conveniently e f f e c t e d by t r e a t ­ ment with KOt-Bu i n THF at ambient temperatures. A number o r repre­ s e n t a t i v e examples i s compiled i n Table I I . Because aldehydes a l ­ ready gave good r e s u l t s with the morpholinosubstituted anion, only

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

9.

V A N DER G E N A N D BROEKHOF

R

1

R

2

0 Li II I / 1. P h P — C H — N 2

r C

v

Substituted

Phosphine

u H

3 (4) Ph

49

Oxides

> 0 j l - to C 0 , 0 q l - t r i e s t e r s w i l l provide the s t e r e o ­ chemical i n f o r m a t i o n . Thus i n p r a c t i c e , 1 and 4 or 7 and 10 w i l l predominate i n the P NMR spectrum but w i l l not be the e x c l u s i v e resonances. 1

1 7

1

1

1

1 7

1

3 1

1 7

1

1 7

1 6

1 8

3 1

1 6

8

1 6

a x

1 8

8

e (

1 6

a x

e

3 1

1

1 7

1

D-Glucose 6 [ ( S ) - d , 0 , d i p h o s p h a t e was c y c l i z e d w i t h diphenylphosphorochloridate and potassium t-butoxide and e s t e r i f i e d w i t h methyl i o d i d e . The c y c l i z a t i o n occurs with i n v e r s i o n of c o n f i g u r a t i o n at phosphorus s i n c e 7 and 10 predominated i n the P NMR spectrum; i t was p o s s i b l e to c a l c u l a t e that the s t e r e o s p e c i f i c i t y of the r e a c t i o n was i n excess of 94%. Adenosine 5 ' C ( S ) - 0 , 0 , d i p h o s p h a t e was s i m i l a r l y c y c l i z e d and e s t e r i f i e d , the c y c l i z a t i o n o c c u r r i n g with i n v e r s i o n o f c o n f i g u r a t i o n i n excess of 94% ( 2 ) . Adenosine 5 C y ( S ) - 0 , 0 , d l t r i p h o s p h a t e , prepared by the general method of s y n t h e s i s was incubated w i t h D-glucose and y e a s t hexokinase. The D-glucose 6 C 0 , 0 , d i p h o s p h a t e was shown to have the (i?)-configuration at phosphorus by P NMR spectroscopy a f t e r c y c l i z a t i o n and e s t e r i f i c a t i o n (4_). I ncubation of adenosine 5 ' C y ( S ) - d , 0 , d l t r i p h o s p h a t e w i t h adenosine 3'-phosphate and polynucleotide kinase (from Τι* i n f e c t e d E. ooli gave adenosine 3 , 5 * [ d , 0 , d l b i s p h o s p h a t e which was converted i n t o adenosine 5 C * d , 0 , 0lphosphate with nuclease Pi. A f t e r c y c l i z a t i o n and e s t e r i f i c a t i o n the P NMR spectrum showed the adenosine 5 C 0 , 0 , d i p h o s p h a t e to have the (/?)c o n f i g u r a t i o n at phosphorus ( 5 ) . Thus both yeast hexokinase and Ti* i n f e c t e d E.coli p o l y n u c l e o t i d e k i n a s e c a t a l y s e phosphoryl t r a n s f e r with i n v e r s i o n of c o n f i g u r a t i o n at phosphorus. Since ATP i s a common substrate f o r a l l phosphokinases, i t i s now p o s s i b l e to analyse the stereochemical course of any 3 1

1 6

1 7

1

1 7

1

1

1 6

1 7

1

3 1

1

,

1

1 7

1

1 7

1

1

1 7

8

3 1

1

1 6

1 7

1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

106

PHOSPHORUS CHEMISTRY

l6

17

18

Scheme 2. Cyclization of D-glucose 6[(S)- O O, (Diphosphate with retention of configuration at phosphorus followed by methylation should give 1-6, whereas cyclization with inversion of configuration at phosphorus should give 7-12 after methylation. t

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

20.

LOWE ET AL.

Stereochemical Course of

Phosphokinases

1 6

1 7

enzyme o f t h i s c l a s s by p r e p a r i n g the appropriate C ( 5 ) - 0 , 0 , 0 ] p h o s p h a t e e s t e r and enzymically t r a n s f e r r i n g the c h i r a l phosphoryl group to ADP. The A T P C Y - 0 , 0 , 0 ] t r i p h o s p h a t e ca then be used as a s u b s t r a t e f o r hexokinase and the D-glucose 6 C 0 , 0 , 0 ] p h o s p h a t e so formed, analysed f o r c h i r a l i t y at phosphorus as b e f o r e . I η t h i s way we have shown that phosphoryl t r a n s f e r c a t a l y s e d by Bacillus stearothermophïlus and r a b b i t s k e l e t a l muscle phosphofructokinase ( 6 ) , and r a b b i t s k e l e t a l muscle pyruvate kinase occurs with i n v e r s i o n of c o n f i g u r a t i o n a t phosphorus ( 7 ) . The simplest i n t e r p r e t a t i o n of these s t e r e o chemical r e s u l t s i s that phosphoryl t r a n s f e r occurs by an i n - l i n e ' mechanism i n the enzyme substrate ternary complexes. Stereochemical a n a l y s i i thu provin t b f considerabl importance f o r d e l i n e a t i n kinases . 18

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Literature Cited

1. 2. 3. 4. 5. 6. 7.

Cullis, P.M. and Lowe, G., J. Chem. Soc. Perkin Trans. 1, 1981 in press. Jarvest, R.L., Lowe, G. and Potter, B.V.L., J. Chem. Soc. Perkin 1, 1981 in press. Lowe, G., Potter, B.V.L., Sproat, B.S. and Hull, W.E., J. Chem. Soc. Chem. Comm., 1979, 733. Lowe, G. and Potter, B.V.L., Biochem. J . , submitted for publication. Jarvest, R.L. and Lowe, G., Biochem. J., submitted for publication. Jarvest, R.L., Lowe, G. and Potter, B.V.L., Biochem. J . , submitted for publication. Lowe, G., Cullis, P.M., Jarvest, R.L., Potter, B.V.L. and Sproat, B.S., Phil. Trans. R. Soc. Lond. 1981, B293, 75.

RECEIVED June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

21 Syntheses and Configurational Assignments of Thymidine 3'- and 5'-(4-Nitrophenyl [ O, O] Phosphates) 17

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SHUJAATH MEHDI, JEFFREY A. CODERRE, and JOHN A. GERLT Department of Chemistry, Yale University, New Haven, CT 06511

Determination of the stereochemical course of nucleophilic displacement reactions direct experimental metho reaction involves the formation of a covalent adduct between the enzyme and substrate. Whereas the classical approach to this problem has been to use chiral phosphorothioate esters which are analogs of the natural substrates (1,2), recent work reported by a number of laboratories has demonstrated that the syntheses and configurational assignments of oxygen chiral phosphate mono- and diesters are technically feasible (3-6). These recent advances allow the stereochemical course of phosphoryl and nucleotidyl transfer reactions to be investigated with oxygen chiral sub­ strates; such studies are desirable because the results obtained with the phosphorothioate analogs are mechanistically ambiguous due to the low rates at which these substrate analogs are pro­ cessed by enzymes. At present, stereochemical experiments em­ ploying both the phosphorothioate and oxygen chiral approaches have been performed on three enzymes: glycerol kinase from yeast (7,8), adenylate cyclase from Brevibacterium liquefaciens (9,10), and cyclic nucleotide phosphodiesterase from bovine heart (11,12). In each case, results were obtained which demonstrated that sul­ fur substitution does not alter the stereochemical course of the enzymatic reaction. To facilitate determination of the stereochemical course of both enzymatic and nonenzymatic hydrolyses of phosphodiesters, we have decided to prepare phosphodiesters which are [ 0, ]-chi­ ral so that the hydrolysis reactions can be performed in Η 0. We have previously reported the syntheses and configurational analyses of the diastereomers of cyclic 2-deoxyadenosine 3',5'[ 0, 0]monophosphate (13) and the stereochemical course of the hydrolysis of one of the diastereomers catalyzed by the cyclic nucleotide phosphodiesterase from bovine heart (12). I n t h i s 17

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communication we report the syntheses and c o n f i g u r a t i o n a l a s s i g n Current address: Department of Biochemistry and B i o p h y s i c s , U n i v e r s i t y of C a l i f o r n i a , San F r a n c i s c o , CA 94143 1

0097-6156/81/0171-0109$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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merits of the diastereomers of thymidine 3 - and 5 - ( 4 - n i t r o p h e n y l [ 0, 0 ] p h o s p h a t e s ) ; these oxygen c h i r a l phosphodiesters w i l l be used to determine the stereochemical course of r e a c t i o n s c a t a l y z e d by nucleases. The diastereomeric [ 0 ] - e n r i c h e d 4 - n i t r o p h e n y l e s t e r s of the P - a n i l i d a t e s of 3 -monomethoxytrityl thymidine and of 5 -monometho x y t r i t y l thymidine were prepared a c c o r d i n g to the procedures developed i n t h i s l a b o r a t o r y f o r the p r e p a r a t i o n of u n l a b e l l e d mat e r i a l s (14), except that [ 0 ] P O C l 3 was used to prepare the r e quired 4-nitrophenyl N-phenyl phosphoramidic c h l o r i d e ; the [ 0 ] enrichment of the l a b e l l e d POCI3 was 51%. The diastereomers were separated by short column chromatography on Merck s i l i c a g e l 60H. The [ 0 ] - P - a n i l i d a t e s were reacted s e p a r a t e l y with a 10-fold excess of 99% enriched C 0 2 and a f t e r removal of the monomethoxyt r i t y l groups, the product Amberlite XAD-2. The chemistr c h i r a l [ 0 , 0 ] - p h o s p h o d i e s t e r s which were obtained were i d e n t i c a l with a u t h e n t i c thymidine 4 - n i t r o p h e n y l phosphates u s i n g the c r i t e r i a of TLC and H NMR at 270 MHz; the P s p e c t r a at 32 MHz and at 81 MHz revealed the expected r a t i o of [ 0 , 0 ] - and [ 0, 0]-resonances. Although the c o n f i g u r a t i o n s of the u n l a b e l l e d P - a n i l i d a t e s have been assigned (14) and the r e a c t i o n of c y c l i c P - a n i l i d a t e s with C 0 (5) or [ T)]benzaldehyde (6) has been shown to proceed with the a n t i c i p a t e d r e t e n t i o n of c o n f i g u r a t i o n at phosphorus, we considered i t necessary to determine the c o n f i g u r a t i o n s of the ac y c l i c [ 0 , 0 ] - c h i r a l phosphodiesters. The r e q u i r e d c o n f i g u r a t i o n a l assignments have been accomplished by two independent methods. The most s t r a i g h t f o r w a r d method of c o n f i g u r a t i o n a l assignment i s to determine the c o n f i g u r a t i o n of the c y c l i c thymidine 3 , 5 [ 0, 0]monophosphate which can be obtained by t e r t - b u t o x i d e i n duced c y c l i z a t i o n of the 4-nitrophenyl e s t e r ; Borden and Smith have reported that t h i s i s a f a c i l e method f o r the p r e p a r a t i o n of 3 , 5 ' - c y c l i c n u c l e o t i d e s (15). The accepted p r i n c i p l e s of n u c l e o p h i l i c displacement r e a c t i o n s at phosphorus allow the p r e d i c t i o n that t h i s c y c l i z a t i o n r e a c t i o n should proceed w i t h i n v e r s i o n of c o n f i g u r a t i o n at phosphorus (16). A c c o r d i n g l y , we have converted each of the [ 0, 0 ] - c h i r a l a c y c l i c n u c l e o t i d e e s t e r s to c y c l i c thymidine 3 , 5 - [ 0 , 0]monophosphates u s i n g the c o n d i t i o n s des c r i b e d by Borden and Smith (15); c y c l i c n u c l e o t i d e s were obtained i n y i e l d s of 70% f o l l o w i n g p u r i f i c a t i o n by chromatography on DEAESephadex A-25. The c o n f i g u r a t i o n s of the c y c l i c thymidine 3 , 5 - [ 0 , 0 ] monophosphates can be c o n v e n i e n t l y assigned by 0 NOT. s p e c t r o s copy. We have p r e v i o u s l y reported that i n aqueous s o l u t i o n at 95° C the 0 NMR chemical s h i f t s of the phosphoryl oxygens of c y c l i c 2'-deoxyadenosine 3 , 5 - [ 0 , 0]monophosphate are s u f f i c i e n t l y d i f f e r e n t at 36.6 MHz such that two resonances can be r e solved i n a racemic mixture of the diastereomers, with the down1 7

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In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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f i e l d resonance being a s s o c i a t e d with the a x i a l l y p o s i t i o n e d [ 0 ] - n u c l e u s (13); i t i s u n l i k e l y that the i d e n t i t y of the h e t e r o c y c l i c base would i n f l u e n c e the chemical s h i f t s of the phosphoryl oxygens. One major resonance was observed i n the 0 NMR spectrum of each c y c l i c thymidine 3 » 5 - [ 0 » 0]monophosphate; the chemic a l s h i f t s were those expected i f the r e a c t i o n of the a c y c l i c Pa n i l i d a t e s with C 0 proceeded with the p r e d i c t e d r e t e n t i o n of c o n f i g u r a t i o n a t phosphorus. The c o n f i g u r a t i o n s of the c h i r a l [ 0, 0 ] - c y c l i c phosphodiesters were v e r i f i e d by conversion to a mixture of a x i a l and e q u a t o r i a l methyl e s t e r s and measurement of the [ 0 ] - p e r t u r b a t i o n s on the P NMR chemical s h i f t s , as prev i o u s l y described (12). Because the c o n f i g u r a t i o n a l assignments d e r i v e d from 0 NMR chemical s h i f t s r e l y o not been f i r m l y e s t a b l i s h e we have a l s o assigned the c o n f i g u r a t i o n s of the a c y c l i c 4 - n i t r o phenyl e s t e r s i n an unambiguous f a s h i o n . E t h a n o l i c s o l u t i o n s of the a c y c l i c e s t e r s were hydrogenolyzed i n the presence of Adam's c a t a l y s t and an excess of HC1. The r e d u c t i o n proceeds v i a C-0 bond cleavage and r e s u l t s i n the formation of [ 0 , 0 , 0 ] c h i r a l phosphate monoesters. C o n f i g u r a t i o n a l a n a l y s i s of these c h i r a l monoesters can be accomplished by c y c l i z a t i o n u s i n g r e a c t i o n s of known stereochemical course t o y i e l d a mixture of three types of c h i r a l c y c l i c thymidine 3 ,5 -monophosphate, i . e . , [ 0, 0 ] - , [ 0 , 0 ] - , and [ 0 , 0 ] - l a b e l l e d ; the c o n f i g u r a t i o n of the [ 0 , 0 ] - c h i r a l c y c l i c e s t e r present i n the mixture can be accomplished by measurements of the [ 0 ] - p e r t u r b a t i o n s on the P chemical s h i f t s of the a x i a l and e q u a t o r i a l methyl e s t e r s . In the absence of a p p r o p r i a t e enzymes (12), t h i s procedure must be c a r r i e d out chemically. We have s e l e c t e d a c t i v a t i o n by d i p h e n y l phosphorochloridate followed by t e r t - b u t o x i d e induced c y c l i z a t i o n to c a r r y out the r e q u i r e d r i n g c l o s u r e , s i n c e recent s t u d i e s have demonstrated that t h i s r e a c t i o n sequence i s accompanied by the p r e d i c t e d i n v e r s i o n of c o n f i g u r a t i o n (16) a t the c h i r a l phosphorus atom (4,12). Following hydrogenolysis, chemical a c t i v a t i o n and c y c l i z a t i o n , and methylation, measurements of the [ 0 ] - p e r t u r b a t i o n s on the P chemical s h i f t s of the methyl e s t e r s revealed that the c o n f i g u r a t i o n s of the a c y c l i c 4-nitrophenyl phosphates were those p r e d i c t e d i f the r e a c t i o n o f the a c y c l i c P - a n i l i d a t e s with C 0 proceeded with r e t e n t i o n of c o n f i g u r a t i o n a t phosphorus. Thus, the c o n f i g u r a t i o n s of the a c y c l i c [ 0 , 0 ] - c h i r a l 4-nitrophenyl e s t e r s can be considered t o be f i r m l y e s t a b l i s h e d . 17

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Determination of the stereochemical course of the r e a c t i o n s c a t a l y z e d by the exonucleases from snake venom and bovine spleen and by Staphylococcal nuclease i s i n progress. Acknowledgements T h i s research was supported by a grant from the N a t i o n a l I n s t i t u t e s of Health (GM-22350). The h i g h f i e l d NMR spectrometers

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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used i n t h i s research are supported by a grant from the N a t i o n a l Science Foundation (CHE-791620). J.A.G. i s the r e c i p i e n t of a Research Career Development Award from the N a t i o n a l I n s t i t u t e s of Health (CÂ-00499, 1978-83) and of a f e l l o w s h i p from the A l f r e d P. Sloan Foundation ( 1 9 8 1 - 8 3 ) . Literature Cited

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Eckstein, F. Acc. Chem. Res. 1979, 12, 204. Knowles, J. R. Annu. Rev. Biochem. 1980, 49, 877. Abbott, S. J.; Jones, S. R.; Weinman, S. Α.; Bockhoff, F. M.; McLafferty, F. W.; Knowles, J. R. J. Am. Chem. Soc. 1979, 101, 4323. Cullis, P. M.; Jarvest R L.; Lowe G.; Potter Β V L J. Chem. Soc., Chem Gerlt, J. Α.; Coderre, , , 4531. Baraniak, J.; Lesiak, K.; Sochacki, M.; Stec, W. J. J. Am. Chem. Soc. 1980, 102, 4533. Blättler, W. Α.; Knowles, J. R. J. Am. Chem. Soc. 1980, 102, 510. Pliura, D. H.; Schomburg, D.; Richard, J. P.; Frey, P. Α.; Knowles, J. R. Biochemistry 1980, 19, 325. Gerlt, J. Α.; Coderre, J. Α.; Wolin, M. S. J. Biol. Chem. 1980, 255, 331. Coderre, J. A.; Gerlt, J. A. J. Am. Chem. Soc. 1980, 102, 6594. Burgers, P. M. J.; Eckstein, F.; Hunneman, D. H.; Baraniak, J.; Kinas, R. W.; Lesiak, K.; Stec, W. J. J. Biol. Chem. 1979, 254, 9959. Coderre, J. Α.; Mehdi, S.; Gerlt, J. A. J. Am. Chem. Soc. 1981, 103, 1872. Coderre, J. Α.; Mehdi, S.; Demou, P. C.; Weber, R.; Traficante, D. D.; Gerlt, J. A. J. Am. Chem. Soc. 1981, 103, 1870. Gerlt, J. Α.; Mehdi, S.; Coderre, J. Α.; Rogers, W. O. Tetrahedron Lett. 1980, 2385. Borden, R. K.; Smith, M. J. Org. Chem. 1966, 31, 3247. Westheimer, F. H. in "Rearrangements in Ground and Excited States;" DeMayo, P., Ed.; Academic Press, New York, 1980; Vol. II, p. 229.

R E C E I V E D June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

22 The Mechanism of Aldehyde-Induced ATPase Activities of Kinases W. W. C L E L A N D and ALAN R. RENDINA Department of Biochemistry, University of Wisconsin, Madison, WI 53706

Kinases are enzymes which transfer the γ-phosphate of MgATP to various acceptors stereochemistry (1), w except that the acid-base catalyst which accepts the proton from the alcohol in the hexokinase (2) and fructokinase (3) reactions is a carboxyl group, while that for creatine kinase is a histidine (4). The ATPase activity induced by suitable aldehydes is thus a reaction of considerable interest. Such activity was first seen with glycerokinase (5), which phosphorylates L-glyceraldehyde at the 3 position, but in the presence of D-glyceraldehyde splits MgATP to MgADP and P with no evi­ dence of any intermediates being formed. It was thought at the time that the ATPase activity involved phosphorylation of the aldehyde hydrate to give the phosphate adduct of the aldehyde, which promptly decomposed. We have now found that this is not correct, and in this paper we will detail studies on 3 enzymes which show ATPase activites in the presence of aldehydes and on two which do not, and discuss the possible chemistry of the reaction. While checking a sample of 2,5-anhydromannose-6-P for fructose-6-P by incubating it with phosphofructokinase and MgATP, we discovered that this aldehyde, which is sterically hindered from forming an internal hemiacetal, induced an ATPase activity (6). Since aldehyde hydration shows a large inverse equilibrium isotope effect of 0.73 when the hydrogen on the carbonyl carbon is replaced by deuterium (7,8) , 2,5-anhydromannose-6-P-1-d will be 60% hydrated, compared to 52% hydration of the unlabeled aldehyde. If the free aldehyde were the activa­ tor, 48% of the unlabeled and 40% of the deuterated compound would be active, and a normal deuterium isotope effect of i

0.48/0.40 = 1.2 would be seen on V/K (the apparent f i r s t order rate constant) f o r the a c t i v a t o r , while i f the hydrate were the a c t i v e form, an i n v e r s e isotope e f f e c t o f 0.52/0.60 = 0.87 would be seen. The observed value of 1.23 ± 0.03 showed that the free aldehyde and not the hydrate was the a c t i v a t o r (6).

0097-6156/81/0171-0115$05.00/0 © 1981 American Chemical Society

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The absence of an isotope e f f e c t on the V f o r the ATPase r e a c t i o n , however, means that the hydraïe does not bind a p p r e c i a b l y i n the a c t i v e s i t e as a competitive i n h i b i t o r (when a competitive i n h i b i t o r i s present i n the v a r i a b l e s u b s t r a t e , there i s no e f f e c t on V/K, but V i s decreased). A normal isotope e f f e c t on V of 1.2 woïïîi be seen i f the hydrate and f r e e aldehyde had tBe same a f f i n i t y f o r the enzyme. The f a i l u r e of the hydrate to bind presumably r e f l e c t s s t e r i c r e s t r a i n t s i n the a c t i v e s i t e . Since the f r e e aldehyde and a water molecule would take up more space than the hydrate, these data suggest that the aldehyde-induced ATPase does not r e s u l t from i n d u c t i o n by the aldehyde of the proper conformation change to permit r e a c t i o n of MgATP with a bound water molecule. When we attempted to induce ATPase a c t i v i t b acetate kinase with r e d i s t i l l e from MgATP was seen. However a column of Dowex-l-Cl, or condensed from a stream of n i t r o g e n passing over an aqueous s o l u t i o n at n e u t r a l pH d i d not show t h i s a c t i v i t y , and we conclude that the i n i t i a l o b s e r v a t i o n was due to t r a c e s of a c e t i c a c i d . Acetaldehyde d i d c o m p e t i t i v e l y i n h i b i t acetate kinase, however, with a K. of 57 mM f o r unl a b e l e d and 49 mM f o r deuterated acetaldehyde. T h i s i n v e r s e isotope e f f e c t of 0.87 shows that the hydrate i s the i n h i b i t o r y species (acetaldehyde i s 60% hydrated and acetaldehyde-l-d w i l l be 67% hydrated, so that the Κ. of the deuterated species should be lower by the r a t i o 0*60/0.67 = 0.89). Since the a c t i v e s i t e of acetate kinase has room f o r both oxygens of acetate, i t i s not s u r p r i s i n g to f i n d that the hydrate of acetaldehyde i s bound i n the a c t i v e s i t e . The f a i l u r e of the hydrate to be phosphorylated (which would r e s u l t i n ATPase a c t i v i t y ) could be due to i n c o r r e c t geometry, or to the l a c k of an acid-base c a t a l y s t to accept the proton of the hydroxy1 group being phosphorylated. With 3-P-glycerate kinase, which a l s o c a t a l y z e s p h o s p h o r y l a t i o n of a carboxyl group by MgATP, D-glyceraldehyde-3-P d i d not induce ATPase a c t i v i t y . 2,5-Anhydromannose i s phosporylated at the 6-hydroxyl by f r u c t o k i n a s e as w e l l as by hexokinase (9). When we used f r u c t o kinase and hexokinase to check the concentrations of our 2,5anhydromannose p r e p a r a t i o n s (from ADP monitored by a pyruvate kinase, l a c t a t e dehydrogenase couple), more ADP was produced with f r u c t o k i n a s e , and the excess ADP was accompanied by an equal amount of i n o r g a n i c phosphate. 2,5-Anhydromannose i s thus inducing an ATPase a c t i v i t y by f r u c t o k i n a s e as w e l l as becoming phosphorylated. Because of the symmetry of 2,5-anhydromannose, when C-6 i s adsorbed i n the a c t i v e s i t e , phosphory­ l a t i o n occurs, while when C - l i s adsorbed, MgATP i s s p l i t to MgADP and P.. Since the two r e a c t i o n s are competitive, the product r a t i o equals the r a t i o of V/K values f o r the two react i o n s . Thus: (V/K) /(V/K) = [ADP] / [ A D P ] - 1. With p u r i f i e d 2,5-anhyaromannose the XATPase)/Xkmase) r a t i o X

X

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In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

22.

C L E L A N D A N D RENDINA

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Activities

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Kinases

117

was 0.13, and was constant from pH 5.5 to 9.4. Since V/K f o r the kinase r e a c t i o n decreases below a pK of 6 (3), the ATPase r e a c t i o n must show the same pH dependence. The (ATPase)/(kinase) r a t i o was higher f o r unlabeled 2,5-anhydromannose than f o r the deuterated compound by a f a c t o r of 1.22, while f o r the two compounds as s u b s t r a t e s f o r f r u c t o ­ kinase (ADP p r o d u c t i o n followed) the V/K isotope e f f e c t was 1.04 ± 0.02, and there was no V isotope e f f e c t . I f only the f r e e aldehyde i s an a c t i v a t o r f o r the ATPase a c t i v i t y , while the f r e e aldehyde and the hydrate have equal V/K values f o r the kinase r e a c t i o n , the p r e d i c t e d isotope e f f e c t on the (ATPase)/ (kinase) r a t i o i s 1.19, while that on the V/K f o r ADP produc­ t i o n i s 1.024. Thus, the aldehyde i s the a c t i v a t o r f o r f r u c t o ­ kinase as w e l l as f o r phosphofructokinase With g l y c e r o k i n a s e ceraldehyde shows the same pH p r o f i l e f o r the V/K of MgATP as the kinase a c t i v i t y , decreasing at low pH as the group which i s presumably the acid-base c a t a l y s t becomes protonated. Since the most l i k e l y chemical mechanisms f o r the aldehyde-induced ATPase r e a c t i o n s appeared to be metaphosphate cleavage of MgATP or d i r e c t phosphorylation of the aldehyde to give an unstable oxycarbonium i o n , we decided to run the ATPase r e a c t i o n i n the presence of methanol, which should react with metaphosphate to give methyl phosphate, or with a phosphorylated aldehyde to give a phosphoryl methyl a c e t a l . When [ P]-ATP^was incubated with D-glyceraldehyde and g l y c e r o k i n a s e i n 35% [ C]-methanol and the products chromatographed on Doygx-l wi|£ a borate gradient no compounds c o n t a i n i n g both C and Ρ were detected. In a s i m i l a r r e a c t i o n mixture, i n o r g a n i c phosphate and ADP were formed at equal r a t e s , and thus i t appears that i f metaphosphate or a phosphorylated aldehyde were formed, that they reacted with water ( e i t h e r trapped i n the a c t i v e s i t e , or being the f i r s t molecule to have access to the a c t i v e s i t e a f t e r r e a c t i o n ) i n t o t a l preference to methanol. The f a i l u r e to i s o l a t e a s t a b l e methanol and phosphatec o n t a i n i n g compound from ATPase r e a c t i o n s run i n the presence of methanol leaves the chemical mechanism of the ATPase reac­ t i o n i n doubt. The requirement f o r the proper p r o t o n a t i o n s t a t e of the acid-base c a t a l y s t i m p l i e s e i t h e r that the aldehyde i s phosphorylated to an oxycarbonium i o n , with the negative charge on the acid-base group s t a b i l i z i n g the p o s i t i v e charge on the oxycarbonium i o n , or that the conformation change which produces ATP cleavage r e q u i r e s i o n i z a t i o n of the acid-base catalyst. In the l a t t e r case, ATP could e i t h e r cleave to give metaphosphate or t r a n s f e r a phosphoryl group to a bound water molecule, although the f a i l u r e of the aldehyde hydrates to b i n d makes the b i n d i n g of water i n the a c t i v e s i t e l e s s l i k e l y , and such bound water would be expected to i n t e r f e r e with the normal kinase r e a c t i o n . Perhaps t h i s water i s bound i n such a way that i t has access to the reactants only a f t e r r e a c t i o n , but before they are r e l e a s e d i n t o s o l u t i o n .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

118

PHOSPHORUS CHEMISTRY

I t i s p o s s i b l e t o t e s t f o r p h o s p h o r y l a t i o n o f the aldehyde by seeing i f 0 i s transferrçg from the aldehyde to phosphate during the ATPase r e a c t i o n . 0 should have a h a l f l i f e i n the carbonyl group o f D-glyceraldehyde i n water a t 20° o f about 50 seconds (10), so by running the r e a c t i o n a t low temperature with a high lçgel o f enzyme and adding the aldehyde i n a small volume o f H^[ 0] i t should be p o s s i b l e t o c a r r y out such an experiment, and we hope to do so i n the near f u t u r e . Acknowledgement T h i s work was supported by NIH grant GM 18938. Literated Cited

1. 2. 3.

Knowles, J. R. Annu , , Viola, R. E.; Cleland, W. W. Biochemistry 1978, 17, 4111. Raushel, F. M.; Cleland, W. W. Biochemistry 1977, 16, 2176. 4. Cook, P. F.; Kenyon, G. L.; Cleland, W. W. Biochemistry 1981, 20, 1204. 5. Janson, C. A.; Cleland, W. W. J. Biol. Chem. 1974, 249, 2562. 6. Viola, R. E.; Cleland, W. W. Biochemistry 1980, 19, 1861. 7. Hill, E. A.; Milosevich, S. A. Tetrahedron Lett. 1976, 50, 4553. 8. Lewis, C. A.; Wolfenden, R. Biochemistry 1977, 16, 4886. 9. Raushel, F. M.; Cleland, W. W. J. Biol. Chem. 1973, 248, 8174. 10. Trentham, D. R.; McMurray, C. H.; Pogson, C. I. Biochem. J. 1969, 114, 19. RECEIVED July 12, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

23 Kinetic and Thermodynamic Studies of Yeast Inorganic Pyrophosphatase B A R R Y S. C O O P E R M A N Department of Chemistry, University of Pennsylvania, Philadelphia, P A 19104

Despite their widespread distribution and central importance to cellular metabolism pletely understood with respec especially when compared with what is known about more well studied enzymes, such as the serine proteases. Our goal is to obtain a detailed understanding of enzymatic catalysis of phosphoryl transfer and toward this end we have chosen to study yeast inorganic pyrophosphatase (PPase) as an example of a phosphoryl transfer enzyme. PPase is a dimer made up of identical subunits of molecular weight 32,000 daltons (1). Its covalent structure has been determined (2), two research groups have reported low-resolution crystal structures (3,4), and a high resolution structure determination is underway (D. Voet, personal communication). PPase catalyzes three different reactions, inorganic pyrophosphate (PPi) hydrolysis, H O-inorganic phosphate (Pi) oxygen exchange, and, considerably more slowly, PPi:Pi equilibration (5,6). PPase requires divalent metal ions for activity. The highest activity is conferred by Mg+, although substantial activity (>5% of that found with Mg+) is also found in the presence of Zn+ > Co = Mn+ (7). In this paper we report on recent findings of ours which have 1) demonstrated that PPase activity requires three divalent metal ions per subunit and 2) allowed formulation of a minimal kinetic scheme for PPase catalysis which accounts quantitatively for the three activities it manifests. 2

2

2

2

2+

2

Binding

Studies

I t had been p r e v i o u s l y shown by Rapoport et al. (8) that nat i v e PPase binds two d i v a l e n t metal ions ( M g , C o , M n ) per subunit. We have now used e q u i l i b r i u m d i a l y s i s t o extend these s t u d i e s , by measuring the e f f e c t o f added P i on Mn + and C o binding ( 9 ) . The r e s u l t s (Figure 1) demonstrate that i n the presence o f P i a t h i r d d i v a l e n t metal i o n i s bound per subunit. F o r Mn2+, one i n t r i n s i c d i s s o c i a t i o n constant c h a r a c t e r i z e s the b i n d 2+

2 +

2+

2

0097-6156/81/0171-0119$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2 +

120

PHOSPHORUS CHEMISTRY

Figure 1. Scatchard plots of metal ion binding to PPase as measured by equilibrium dialysis. A; Mn binding (a) no added Pi, enzyme concentration 7-42μΜ (O); φ) in the presence of 50 μ M Pi, enzyme concentration 7-36 μΜ (·); (c) in the presence of 4mM Pi, enzyme concentration 8-116μΜ (Π). Β: Co * binding (a)no added Pi, enzyme concentration 8-96μΜ (O); φ) in the presence of 2.5mM Pi, enzyme concentration 30-35μΜ (Π) (see Réf. 9). 2+

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

23.

COOPERMAN

Ύeast

Inorganic

Pyrophosphatase

121

ing i n the absence of P i , and another, lower by about t h r e e - f o l d , c h a r a c t e r i z e s the b i n d i n g i n the presence of P i . For Co +, e s s e n t i a l l y the same i n t r i n s i c d i s s o c i a t i o n constant c h a r a c t e ­ r i z e s the b i n d i n g i n both the presence and absence of P i . These s t u d i e s , along w i t h p a r a l l e l s t u d i e s on d i v a l e n t metal i o n e f ­ f e c t s on P i b i n d i n g (as measured by e q u i l i b r i u m d i a l y s i s p r o t e c ­ t i o n of a c t i v i t y against chemical m o d i f i c a t i o n , 31p and water proton r e l a x a t i o n r a t e s ) have allowed e v a l u a t i o n of a l l of the e q u i l i b r i u m constants i n Scheme I d e s c r i b i n g d i v a l e n t metal i o n (Mn or Co +) and P i b i n d i n g to PPase. 2

2 +

2

K i n e t i c and

Thermodynamic

Studies

We have combined the r e s u l t s of three d i f f e r e n t types of measurement, enzyme-boun and r a t e s of P P i h y d r o l y s i s PPase c a t a l y s i s shown i n equation ( 1 ) , and to evaluate the r a t e constants contained w i t h i n i t (10). We note that a l l constants are apparent f o r pH 7.0

( k l

7

1

H

1

?°*

(

k

3

\ MgE(MgPi)

6s-l

222s-l

(k )

(U)

2

k

< *> 740s-l

2

(k ) 464 -1 7

R

(1) 1.6

χ 105M-VI (k

6>

M

8

E

M

g

P

i

* 9 χ 10*M-1.-1

+

M

(k

tpi* MgPi* (pH

7.0,

+ Pi

8> 25°C)

and f u r t h e r that the complexes shown i n equation (1) are d e f i n e d w i t h respect to s t o i c h i o m e t r y but not with respect to r e l a t i v e p o s i t i o n i n g . Thus, f o r example, Mg2EMgPPi r e f e r s to a complex with three Mg and one P P i , and i s not meant to imply that MgPPi i s n e c e s s a r i l y bound as a complex to Mg2E. The major f e a t u r e s of equation (1) are: 1) the i m p l i e d r e ­ quirement f o r three bound metal ions per a c t i v e subunit; 2) the r e l e a s e of the e l e c t r o p h i l e P i ( i . e . , the phosphoryl group a t ­ tacked n u c l e o p h i l i c a l l y by H2O i n the forward d i r e c t i o n ) p r i o r to the r e l e a s e of the l e a v i n g group P i ; and 3) the numerical evalua­ t i o n of the r a t e constants. We now d i s c u s s each of these f e a ­ tures i n t u r n . Boyer and h i s co-workers have r e c e n t l y presented evidence that H20-Pi exchange proceeds v i a enzyme-bound P P i (denoted EPPi) formation from P i (6,11). Extending t h e i r r e s u l t s , we have i n v e s ­ t i g a t e d EPPi formation as a f u n c t i o n of MgPi c o n c e n t r a t i o n at d i f -

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

122

PHOSPHORUS CHEMISTRY

Scheme I. Relevant equilibria

Ε ^=

=3t EM Λ

EM^

(EM ) 3

/II

1

\ 4

iEMPi

Φ

• ΕΜ Ρ 3

/ι κ"

^ 3 Ρ

2

1

, Φ (ΕΡ ) 2

ΕΜΡ„

=^ΕΜ Ρ, 0

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

23.

COOPERMAN

Y east Inorganic

123

Pyrophosphatase

f e r e n t f i x e d l e v e l s of i M g ] f . These measurements r e q u i r e d development o f two methods f o r q u a n t i t a t i v e l y measuring P P i i n the presence of a ΙΟ^-ΙΟ^ molar excess of P i . The f i r s t i n v o l v e s the s e l e c t i v e e x t r a c t i o n i n t o i s o b u t a n o l from water o f 32pi as a phosphomolybdate complex l e a v i n g behind 32ppi i the aqueous s o l u t i o n . The second i n v o l v e s the separation of P P i from P i by two-dimensional t i c on polyethyleneimine p l a t e s . We found that the dependence o f EPPi formation on [MgPi] obeyed equation (2), where [ E P P i ] and [Ε]χ represent t h e t o t a l concentrations of EPPi and enzyme, r e s p e c t i v e l y , r e e

n

t

[Ε]

τ

[EPPi]

=

t

A [MgPi]

+

2

Β

+

c

(

2

)

[MgPi]

and that whereas the e m p i r i c a of [Mg2+] over t h e range studied (10-30mM), parameter A was approximately p r o p o r t i o n a l t o [Mg2+]. The q u a l i t a t i v e s i g n i f i ­ cance of t h i s r e s u l t was that enzyme forms c o n t a i n i n g e i t h e r two bound P i ' s or one bound PPi required one a d d i t i o n a l Mg2+ compared with enzyme forms c o n t a i n i n g one or no P i . Thus, the t h i r d metal ion which i s bound on P i a d d i t i o n (Figure 1) appears necessary f o r EPPi formation. Rates o f H20-Pi oxygen exchange were d e t e r ­ mined by measuring 18 0 r e l e a s e from 1^0-labeled P i using the nmr method of Cohn and Hu (12) , which r e s o l v e s the 31p peaks due t o the f i v e l ^ O - l a b e l e d and unlabeled s p e c i e s . We found that the exchange r a t e has e s s e n t i a l l y the same dependence on [MgPi] as does EPPi formation, thus p r o v i d i n g confirmatory evidence f o r the intermediacy of EPPi i n oxygen exchange. Further, we found, i n agreement with the r e s u l t s of Hackney (13), that the value of t h e p a r t i t i o n c o e f f i c i e n t f o r l ^ O - P i oxygen exchange, Pc, defined as the r a t e a t which enzyme-bound P i l o s e s water i n t h e exchange step d i v i d e d by the sum of t h i s r a t e and the r a t e o f r e l e a s e of P i to the medium, was much l e s s than one (we f i n d 0.23; Hackney r e ­ ports 0.30) and e s s e n t i a l l y independent o f MgPi c o n c e n t r a t i o n over a wide range. This r e s u l t r e q u i r e s that the P i c o n t a i n i n g t h e oxygen from H20 be r e l e a s e d f i r s t , s i n c e , were i t r e l e a s e d second, i t i s c l e a r from equation (1) that Pc should increase with i n c r e a s i n g MgPi u n t i l i t a t t a i n e d a l i m i t i n g value of 1.0. The eight r a t e constants i n equat ion (1) were evaluated using the f o l l o w i n g eight equations. The measured parameters A,B, and C i n equation (2) a l l o w e v a l u a t i o n o f K3 (k3/k4), K5 ( k / k ) , and K7 (ky/kg). Knowing these constants and p r e v i o u s l y determined values f o r the s o l u t i o n e q u i l i b r i u m of P P i ^ 2 P i and f o r Mg2+ binding t o P P i and P i allows c a l c u l a t i o n o f Κχ ( k / k ) , by c l o s i n g a thermodynamic loop. The remaining 4 equations (3-6) were p r o ­ vided by measuring Pc and enzyme-catalyzed r a t e s o f oxygen ex­ change and of P P i h y d r o l y s i s . An independent check on the v a l i ­ d i t y of the c a l c u l a t i o n i s provided by t h e good agreement 5

1

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

6

124

PHOSPHORUS

Pc=

c a t , hyd

4Pc

(3)

k k 3

5

cat,ex

Κ m, hyd

+ k (k +k +k ) y

3

4

(4) 3Pc

k [k k +k (k +k )] ?

3

5

2

4

5

(6)

k [ k ^ + k j (k +k +k ) ] ±

5

CHEMISTRY

3

4

5

1

of our c a l c u l a t e d value f o r k ( 6 s ~ l ) and t h e value of 5 s " which can be estimated from a measured value of P P i r e l e a s e from enzyme (6). The r a t e constant v a l u e s shown i n equation (1) lead t o t h e f o l l o w i n g c o n c l u s i o n s regarding the three r e a c t i o n s c a t a l y z e d by PPase; (1) f o r P P i h y d r o l y s i s a l l t h r e e steps f o l l o w i n g P P i b i n d i n g steps 3,5, and 7, a r e p a r t i a l l (2) f o r H20-Pi exchange e x c l u s i v e l y rate-determining; (3) f o r P P i : P i e q u i l i b r a t i o n , P P i r e l e a s e , step 2, i s e x c l u s i v e l y rate-determining. 2

Literature Cited

1. Heinrikson, R. L.; Sterner, R.; Noyes, C.; Cooperman, B. S.; Bruckmann, R. H. J. Biol. Chem. 1973, 248, 2521-8. 2. Cohen, S. A.; Sterner, R.; Keim, P. S.; Heinrikson, R. L.; J. Biol. Chem. 1978, 253, 889-97. 3. Bunick, G.; McKenna, G. P.; Scarbrough, F. E.; Uberbacher, E. C.; Voet, D. Acta Crystallog, Sect. B. 1978, 34, 3210-5. 4. Makhaldiani, V. V.; Smirnova, Ε. Α.; Voronova, A. A.; Kuranova, I. P.; Arutyunyun, E. G.; Vainshtein, Β. K.; Höhne, W. E.; Binwald, B.; Hansen, G. Dokl. Akad. Nauk SSSR 1978, 240 1478-81. 5. Cohn, M. J. Biol. Chem. 1958, 230, 369-79. 6. Janson, C. Α.; Degani, C.; Boyer, P. D. J. Biol. Chem. 1979 254, 3743-9. 7. Butler, L. G.; Sperow, J. W. Bioinorg. Chem. 1977, 7, 141-50. 8. Rapoport, Τ. Α.; Höhne, W. E.; Heitmann, P.; Rapoport, S. M. Eur. J. Biochem. 1973, 33, 341-7. 9. Cooperman, B. S.; Panackal, Α.; Springs, B.; Hamm, D. J. Biochemistry 1981, 20, in press. 10. Springs, B.; Welsh, Κ. M.; Cooperman, B. S. Biochemistry 1981, 20, in press. 11. Hackney, D. D.; Boyer, P. D. Proc. Natl. Acad. Sci. USA 1978, 75, 3133-7. 12. Cohn, M.; Hu, A. Proc. Natl. Acad. Sci. USA 1978, 75, 200-3. 13. Hackney, D. D. J. Biol. Chem. 1980, 255, 5320-8. R E C E I V E D June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

24 The Role of Histidine Residues and the Conformation of Bound ATP on ATP-Utilizing Enzymes 1

P. R. ROSEVEAR , G. M. SMITH, S. MESHITSUKA, and A. S. MILDVAN

1

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111 P. DESMEULES and G. L. KENYON Departments of Pharmaceutical Chemistry and Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143

Histidine residues often play important roles in the functioning of proteins. Thi poin cogently y fact that viruses, the most efficient organisms known, rarely if ever incorporate histidine into their coat proteins, but generally incorporate it into their enzymatic proteins (1). Proton NMR has long provided a method for monitoring the role of individual histidine residues in small proteins (2). Improvements in instrumentation (3) have prompted us to study by NMR the role of histidines in large phosphotransferase enzymes, a field to which Professor Westheimer has made profound mechanistic contributions. The enzymes we have studied are adenylate kinase (M 22,000), creatine kinase (M 82,000) and pyruvate kinase (M 237,000), and the roles detected for histidine are summarized in Figure 1. Creatine kinase was purified from rabbit muscle by the method of Kuby et al. (4). Rabbit muscle pyruvate kinase was purchased from Boehringer. Porcine muscle adenylate kinase was purchased from Sigma, and was further purified by gel filtration on Sephadex G-50. The enzymes were homogeneous as judged by their specific activities and by their migration as single components in sodium dodecyl sulfate gel electrophoresis. Proton NMR spectra at 250 MHz of 0.5-2.0mMenzyme sites in H O solution were obtained with a Bruker WM 250 MHz pulse FT spectrometer at 25°. At least 256 transients were accumulated over 8192 data points using 16 bit A/D conversion. Relaxation rates and histidine pK' values were determined by standard NMR methods (5 , 6 ). r

r

r

2

2

Creatine Kinase. Six of the s i x t e e n imidazole C-2 proton resonances and one imidazole C-4 proton resonance per subunit of t h i s dimeric enzyme (M =» 82,000) were detected. T i t r a t i o n s measuring t h e i r chemical s h i f t s as a f u n c t i o n o f pH* y i e l d e d pK values of 7.0, 7.1, 5.9, and 5.2 f o r h i s ( 2 ) , (3), (4) and (6), r e s p e c t i v e l y , and permitted the assignment of the C-4 resonance to h i s ( 3 ) (7). The pK of h i s ( 2 ) was unaffected by s a t u r a t i o n of the enzyme with c r e a t i n e but was increased by 0,6 - 0.7 u n i t s on s a t u r a t i o n with the phosphorylated substrates phosphocreatine or MgATP, i n r

f

f

•Current address: Department of Physiological Chemistry, The Johns Hopkins Medical School, Baltimore, MD 21205.

0097-6156/81/0171-0125$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

24.

ROSEVEAR E T A L .

ATP-Utilizing

127

Enzymes

q u a n t i t a t i v e agreement w i t h the r e s u l t s o f a k i n e t i c s t u d y o f t h e c r e a t i n e k i n a s e r e a c t i o n as a f u n c t i o n o f pH (β) i n d i c a t i n g t h a t h i s ( 2 ) i s the g e n e r a l a c i d / b a s e c a t a l y s t w h i c h deprotonates t h e g u a n i d i n i u m g r o u p o f c r e a t i n e a s i t i s p h o s p h o r y l a t e d b y MgATP. Because o f the p i t f a l l s i n pH-rate s t u d i e s a l o n e , as i n c i s i v e l y p o i n t e d o u t b y W e s t h e i m e r and c o - w o r k e r s ( 9 , 10) i n d e p e n d e n t i n v e s ­ t i g a t i o n s a r e n e c e s s a r y t o i d e n t i f y a c i d / b a s e c a t a l y s t s o n enzymes. f

The p K v a l u e s o f h i s (4) a n d h i s ( 6 ) o f c r e a t i n e k i n a s e , w h i l e too l o w t o f i t t h e k i n e t i c d a t a a s t h e g e n e r a l a c i d / b a s e c a t a l y s t , a l s o i n c r e a s e d (by 0.4 u n i t s ) i n r e s p o n s e t o t h e b i n d i n g o f t h e phosphorylated substrates. T i t r a t i o n s of creatine kinase with s u b s t r a t e s a t c o n s t a n t pH* (6.8) m o n i t o r i n g t h e c h e m i c a l s h i f t s o f h i s ( 2 ) o r h i s (6) y i e l d e d d i s s o c i a t i o n c o n s t a n t s f o r p h o s p h o c r e a t i n e (8.7 mM) a n d MgADP from k i n e t i c d a t a (8, 11 D i r e c t e v i d e n c e f o r the p r e s e n c e o f h i s ( 2 ) , h i s ( 3 ) and h i s ( 6 ) a t o r n e a r t h e a c t i v e s i t e was p r o v i d e d b y t h e p a r a m a g n e t i c e f f e c t s o f t h e s u b s t r a t e a n a l o g β,γ-bidentate Cr^+ATP o n t h e r e l a x a t i o n rates of t h e i r imidazole protons. The l/Τχ v a l u e s y i e l d e d d i s ­ t a n c e s o f 12 + 0.5 Â f r o m C r + t o t h e C-2 p r o t o n s o f h i s ( 2 ) a n d h i s ( 6 ) , c o n s i s t e n t w i t h h i s ( 2 ) f u n c t i o n i n g as the g e n e r a l a c i d / b a s e c a t a l y s t ( F i g u r e 2 ) , and w i t h h i s ( 6 ) i n t e r a c t i n g e l e c t r o s t a t i c a l l y w i t h the s u b s t r a t e s . H i s ( 3 ) i s somewhat f a r t h e r f r o m Cr3+ATP a n d i s s o p o s i t i o n e d t h a t i t s 0 4 p r o t o n i s o r i e n t e d t o w a r d t h e Cr3+, a t a d i s t a n c e o f 14 Â, The p r e s e n c e o f a g e n e r a l a c i d / b a s e c a t a l y s t a t t h e c r e a t i n e b i n d i n g s i t e , t o g e t h e r w i t h a r e c e n t measurement o f a s h o r t (y 6 Â ) d i s t a n c e f r o m Cr^+ADP t o t h e p h o s p h o r u s o f P - c r e a t i n e ( 1 3 ) , i m p l y a n a s s o c i a t i v e mechanism f o r t h e c r e a t i n e k i n a s e r e a c t i o n . Pyruvate Kinase. S i x o f t h e f o u r t e e n I m i d a z o l e C-2 p r o t o n r e s o n a n c e s a n d t h r e e i m i d a z o l e C-4 p r o t o n r e s o n a n c e s o f t h i s t e t r a m e r i c enzyme ( M 237,000) w e r e d e t e c t e d and t h e i r p K v a l u e s d e t e r ­ m i n e d . The s u b s t r a t e P - e n o l p y r u v a t e s e l e c t i v e l y d e c r e a s e d t h e p K o f o n e h i s t i d i n e ( h i s ( 3 ) ) by 0.4 u n i t s , f r o m a v a l u e o f 6.2 t o 5.8, o n l y i n t h e p r e s e n c e o f t h e c a t i o n a c t i v a t o r s Mg2+ a n d K+ (3). The m e t a l a c t i v a t o r s Mg2+ and K a l o n e p r o d u c e d s m a l l e r decreases i n the p K v a l u e o f h i s ( 3 ) s u g g e s t i n g t h a t the b i n d i n g of P - e n o l p y r u v a t e lowers the p K o f h i s ( 3 ) by s t r e n g t h e n i n g i t s i n t e r a c t i o n w i t h the metal a c t i v a t o r s . D i r e c t evidence f o r t h e p r o x i m i t y o f t h e d i v a l e n t c a t i o n t o h i s ( 3 ) was o b t a i n e d b y t h e p a r a m a g n e t i c e f f e c t s o f t h e a c t i v a t o r N i 2 + o n l/Τχ and 1/T2 v a l u e s o f t h e C-2 p r o t o n o f h i s ( 3 ) i n t h e p y r u v a t e k i n a s e - K + , Ni2+ com­ p l e x a t p H * 6.0. The c a l c u l a t e d N i - H d i s t a n c e o f 6 Â i s c o n ­ s i s t e n t w i t h a s e c o n d s p h e r e i m i d a z o l e c o m p l e x . The p r e s e n c e o f P - e n o l p y r u v a t e i n c r e a s e s t h e p a r a m a g n e t i c e f f e c t o f Ni2+ o n 1 / T o f t h i s p r o t o n b y a f a c t o r o f 8.7, s u g g e s t i n g d i r e c t c o o r d i n a t i o n o f h i s ( 3 ) b y Ni2+ i n t h e s u b s t r a t e c o m p l e x ( 1 4 ) . The p a r a m a g n e t i c s u b s t r a t e , $,γ-bidentate Cr3+ATP b r o a d e n s a l l o f t h e h i s t i d i n e C-2 r e s o n a n c e s . S p e c i f i c d i s p l a c e m e n t o f Cr3+ATP from the a c t i v e s i t e by P - e n o l p y r u v a t e r e s u l t e d i n the s e l e c t i v e narrowing not o n l y o f h i s ( 3 ) as e x p e c t e d , but a l s o o f h i s ( 2 ) , 3

f

r

f

+

f

f

2 +

1

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

24.

ROSEVEAR E T AL.

ΛΤΡ-Utilizing

129

Enzymes

demonstrating the presence o f both h i s C3) and h i s ( 2 ) a t the a c t i v e site. An i n t e r m o l e c u l a r negative n u c l e a r Overhauser e f f e c t (NOE) was detected between the C-2 proton of h i s (2) and the adenine H-2 proton of MgATP i n the pyruvate kinase-Mg +-ATP-Mg complex i n d i c a t i n g the p r o x i m i t y of h i s ( 2 ) to the adenine H-2 proton (Figure 1), Independent evidence f o r the presence of h i s (2) a t the n u c l e o t i d e b i n d i n g s i t e was provided by the s e l e c t i v e chemical m o d i f i c a t i o n of t h i s r e s i d u e with d i e t h y l pyrocarbonate as moni­ tored by NMR and by k i n e t i c s t u d i e s (14). Conformation of ATP on Pyruvate Kinase, C r e a t i n e Kinase, and Pro te i n Kinase. A fundamental problem i n the determination of the conformation o f f l e x i b l e enzyme-bound s u b s t r a t e s such as ATP by d i s t a n c e measurements from a paramagnetic r e f e r e n c e p o i n t i s that a weighted root-mean-sixth conformatio i detected (5,15) From the average conformatio the number and nature o r i s e to t h i s average. In the case o f the pyruvate kinase-meta1-ATP complex we have solved t h i s problem by determining the average conformation of bound ATP by two independent methods with d i f f e r ­ ing l o c a t i o n s of the r e f e r e n c e p o i n t s and with d i f f e r e n t observa­ t i o n frequencies (14, 16). Intramolecular negative NOE s were observed on the adenine H-8 proton of enzyme-bound MgATP upon the pre-irradiâtion of c e r t a i n o f the r i b o s e protons o f the bound n u c l e o t i d e . The magnitude o f the NOE s decreased i n the order 2 l H3 >> H4 , H5 , i n d i c a t i n g correspondingly i n c r e a s i n g d i s t a n c e s between the adenine H-8 and these r i b o s e protons. These e f f e c t s are c o n s i s t e n t with a previous determination of the g l y c o s i d i c t o r s i o n a l angle of pyruvate kinase-bound ATP based on the paramagnetic e f f e c t s of enzyme-bound Mn + on the Τχ of the protons of ATP, (X = 30 + 10° (16)) provided a 2 -endo r i b o s e conformation i s assumed. This agreement i n the n u c l e o t i d e conformations d e t e r ­ mined by the two methods, can be explained only by the e x i s t e n c e of a unique average conformation about the g l y c o s i d i c bond o f ATP on pyruvate kinase (14). P r e l i m i n a r y observations have a l s o been made, with c r e a t i n e kinase and bovine heart p r o t e i n k i n a s e , of negative N0E s on the adenine H-8 proton of bound metal-ATP, upon p r e - i r r a d i a t i o n o f the r i b o s e protons (17). The magnitude of the N0E s decreased i n the order H2 > H3 > H l , H4 , H s suggesting a 2 -endo r i b o s e pucker and a high a n t i - c o n f o r m a t i o n , d i f f e r i n g i n the g l y c o s i d i c t o r s i o n a l angle from that on pyruvate k i n a s e . The r e s u l t s w i t h p r o t e i n kinase are c o n s i s t e n t w i t h an independent determination of the conformation of bound metal-ATP based on d i s t a n c e s from Mn + (X =» 84 + 10° (18)), suggesting a unique aver­ age n u c l e o t i d e conformation on t h i s enzyme. 2

2+

1

1

H

f

>

H

?

%

T

f

f

2

f

f

f

f

f

f

f

f

T

2

Adenylate Kinase. As i n the pyruvate kinase-ATP complex, an i n t e r m o l e c u l a r negative NOE i s detected on adenylate k i n a s e between the C-2 proton o f h i s ( 3 6 ) and the adenine H-2 proton of bound MgATP, i n d i c a t i n g that h i s ( 3 6 ) i s very near the adenine H-2 proton of the bound MgATP s u b s t r a t e (Figure 1). His(36) had p r e v i o u s l y been assigned (19). C o n s i s t e n t with t h i s f i n d i n g , the paramagnetic

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

130

PHOSPHORUS

CHEMISTRY

3+

substrate analog α,3,γ-tridentate C r A T P s e l e c t i v e l y increases 1/Tl and 1/T of the C-2 proton of h i s ( 3 6 ) y i e l d i n g a Cr3+~lH d i s t a n c e of 11 + 1 Â, 2

Acknowledgement. I t i s a great pleasure f o r the authors to d e d i cate t h i s paper to Frank Westheimer. Though most of us have not had the p r i v i l e g e of working i n h i s l a b o r a t o r y , we are a l l h i s students n e v e r t h e l e s s , s i n c e we have learned so much from the c r i s p c l a r i t y and profound wisdom of h i s p u b l i c a t i o n s , h i s l e c t u r e s , and h i s comments on s c i e n c e and l i f e . This work was supported by Ν,Ι.Η. Grants AM-13351, CA-06927, RR-05539, CA-22780, RR-542, and AM-17323, N.S.F, Grant PCM-79-23154, and an a p p r o p r i a t i o n from the Commonwealth of Pennsylvania, Literature Cited

1. Dayhoff, M. O. "Atla Nat. Biomed. Res. Fdn.: Silver Spring, MD 1969; D-173. 2. Roberts, G. C. K.; Jardetzky, O. Adv. Prot. Chem. 1970, 24, 447. 3. Meshitsuka, S.; Smith, G. M.; Mildvan, A. S. J.B.C. 1981, 256, 4460. 4. Kuby, S. Α.; Noda, L.; Lardy, H. A. J.B.C. 1954, 209, 191. 5. Mildvan, A. S.; Gupta, R. K. Methods Enzymol. 1978, 49G, 322. 6. Meadows, D. L. Methods Enzymol. 1972, 26, 638. 7. Rosevear, P. R.; Desmeules, P.; Kenyon, G. L.; Mildvan, A. S. Fed. Proc. 1981, 40, 1872. 8. Cook, P. F.; Kenyon, G. L.; Cleland, W. W. Biochem. 1980, 20, 1204. 9. Frey, P. A.; Kokesh, F. C.; Westheimer, F. H. J.Am.Chem. Soc. 1971, 93, 7266. 10. Kokesh, F. C.; Westheimer, F. H. J.Am.Chem. Soc. 1971, 93, 7270. 11. Morrison, J. F.; James, E. Biochem. J. 1965, 97, 37. 12. Schimmerlik, M. I.; Cleland, W. W. J.B.C. 1973, 248, 8418. 13. Gupta, R. K. Biophys. J. 1980, 32, 225. 14. Meshitsuka, S.; Smith, G. M.; Mildvan, A. S. Int. J. Quantum Chem. 1981, (in press). 15. Jardetzky, O. Biochem. Biophys. Acta. 1980, 621, 227. 16. Sloan, D. L.; Mildvan, A. S. J.B.C. 1976, 251, 2412. 17. Rosevear, P. R.; Desmeules, P.; Kenyon, G. L.; Bramson, H. N.; Kaiser, E. T.; Mildvan, A. S. Abs. A.C.S. Mtg., Biol. Div. 1981. 18. Granot, J.; Kondo, H.; Armstrong, R. N.; Mildvan, A. S.; Kaiser, Ε. T. Biochem. 1979, 18, 2339. 19. McDonald, G. G.; Cohn, M.; Noda, L. J.B.C. 1975, 250, 6947. R E C E I V E D September 16, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

25 18

16

31

[ O/ O] P-NMR Enzymes

Studies of Phosphoryl Transfer

J. J. VILLAFRANCA, F. M. RAUSHEL, C. DEBROSSE, and T. D. MEEK

R.

P.

PILLAI,

M. S.

BALAKRISHNAN,

Department of Chemistry, The Pennsylvania State University, University Park, PA 16802

In 1978 Cohn and H 0 on the P-nmrspectru that replaces an 0, an upfield shift of 0.021 ppm results. Thus the chemical shift forHP 0 =is 0.084 ppm downfield from HP180=. Based on this observation it is obvious that any chemical event that potentially involves substitution or exchange of an 0 for 0 in phosphorus containing compounds can be followed by monitoring the P-nmrspectrum throughout the course of the reaction. This article describes experiments from my laboratory on two enzymes that catalyze phosphoryl transfer reactions and our use of the [ 0/ ] p-nmr methodology to detect intermediates in the enzymic reactions. Glutamine synthetase catalyzes the formation of glutamine from ATP, gluatmate, and ammonia. The other products are ADP and The reaction mechanism is though to proceed through a γ-glutamyl phosphate intermediate. We have shown that incubation of ADP, glutamine, and [ 0] i with glutamine synthetase resulted in the loss of 0 from the i (2). Analysis of the data showed that only one 0 was lost per encounter and that the rate constant for exchange was 5-7 times faster than net turnover of products. This was also demonstrated by Stokes and Boyer (3) using mass spectrometry. 18

31

16

16

4

4

18

16

31

18

160

31

18

18

p

P

18

CL #-l Η· — Ρ - · " I ·"

+

t

I R

I R

NH,

{

(IÎ

II I R

+ ADP

I R

+

II ADP-O-P-t" I t"

(I)

0097-6156/81/0171-0131$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

132

PHOSPHORUS CHEMISTRY

T h i s exchange r e a c t i o n i s explained by assuming that the above r e a c t i o n s are o c c u r r i n g on the enzyme s u r f a c e and that the γ-carboxyl of glutamate ( I I ) i s f r e e t o r o t a t e , thus a l l o w i n g , upon r e v e r s a l of the r e a c t i o n , the formation of γ-glutamyl phosphate ( I ) with an ^ 0 ± the bridge p o s i t i o n . Reaction of I with NH3 would then produce V± with only 3 atoms of ^ 0 i n s t e a d of the o r i g i n a l 4. Since a random d i s t r i b u t i o n of ^ 0 ± maintained a t a l l times, only one ^ 0 i s l o s t per encounter with the enzyme and thus must be d i s s o c i a t i n g from the enzyme f a s t e r than glutamine. Recently M i d e l f o r t and Rose (4_) introduced a p o s i t i o n a l i s o t o p e exchange technique that i s a l s o s u i t a b l e f o r study by the •^0 chemical s h i f t technique. B r i e f l y , t h i s technique f o l l o w s the exchange of l a b e l fro due t o r o t a t i o n a l equivalenc was f i r s t a p p l i e d t o glutamin synthetas n

Q

0 0 0 11 11 11 Ado-0-P-0-P-#-P-0~ 1 I I

o~

cr

or

0 0 11 % » + Glu = = è A d o - 0 - P - 0 > P - t + χ - G l u t o m y l - Ρ I I %

ο" o"

"rotation"

0 · II II A d o - O - P - O - P - 0 " + y-Glutomyl-P 7=^ I I 0" 0" v

0 · 0 II II II A d o - 0 - P - 0 - P - 0 - P - 0 ~ + Glu I I I 0" 0" 0"

ATP i s synthesized with 0 i n the 3 - γ bridge p o s i t i o n . In phosphate-containing species such as ATP where the phosphorus ( a , 3 , and γ) and oxygen (bridge and nonbridge) atoms are i n d i f f e r e n t environments the e f f e c t of ^ 0 s u b s t i t u t i o n on the 31p chemical s h i f t i s dependent on the oxygen environment. The s h i f t i s l a r g e s t f o r those oxygens with most double bond c h a r a c t e r . For the 3-P, the s h i f t per 0 atom i s 0.016 ppm f o r the 3 - γ bridge p o s i t i o n and 0.028 ppm f o r the 3 nonbridge p o s i t i o n . Presuming glutamine synthetase c a t a l y z e d the formation of γ-glutamyl-P from ATP and glutamate i n the absence of N H 3 , then ADP would be formed; because of r o t a t i o n a l equivalence i t would allow, upon the r e v e r s a l of the above r e a c t i o n s , the formation of ATP with 0 i n the nonbridge p o s i t i o n of the 3~Ρ· M i d e l f o r t and Rose found t h i s t o be the case f o r glutamine synthetase by mass s p e c t r a l a n a l y s i s of the 18O/16Q exchange and we have followed t h i s r e a c t i o n by nmr. We detected the l o s s of 0 from the γ-Ρ s i g n a l (the s t a r t i n g m a t e r i a l had 0 i n a l l four oxygens of the γ-Ρ) and the s h i f t of s i g n a l from the 3~Ύ bridge to 3 nonbridge p o s i t i o n as p r e d i c t e d above. Thus a l l l i n e s of evidence p o i n t t o formation of γ-glutamyl-P as a k i n e t i c a l l y competent intermediate i n c a t a l y s i s . 1 8

1 8

1 8

1 8

1 8

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

25.

VILLAFRANCA ET AL.

Phosphoryl

Transfer Enzymes

133

Carbamyl phosphate synthetase c a t a l y z e s the synthesis of carbamyl-P from HCO3"» glutamine, and 2 moles of ATP. The enzyme a l s o c a t a l y z e s the HC03""-dependent h y d r o l y s i s of ATP. Raushel and V i l l a f r a n c a (5) followed the exchange of 1^0 from the bridge to the nonbridge p o s i t i o n of [γ-18ο]ΑΤΡ a f t e r i n c u b a t i o n with enzyme and bicarbonate. The exchange r a t e was 0.4 times the r a t e of ADP formation. These r e s u l t s support the formation of carboxy phosphate as the f i r s t intermediate i n the c a t a l y t i c sequence. The r a t e of formation of intermediates i n the r e a c t i o n was a l s o s t u d i e d using r a p i d r e a c t i o n techniques by Raushel and V i l l a f r a n c a (6) and the data agree with the ^Ip-nmr s t u d i e s presented above. The p o s i t i o n a l isotope exchange has a l s o been measured with 31p-nmr i n the reverse r e a c t i o n of carbamyl phosphate synthetase : CarbamylCarbamyl phosphate was synthesized with 1^0 i n a l l oxygens except the carbonyl oxygen of carbon. The exchange of the bridge oxygen i n t o the carbonyl oxygen was followed by nmr and was evidence f o r the f o l l o w i n g s e r i e s of r e a c t i o n s

Ν Η

2

0 · II II - 0 - · - Ρ - · ~

Ο II ADP

4-

ADP

•·

II II N H - C - 0 - P - # ~ I 2

r

+

ATP

NH -C-CT

+

ATP

NH 4-

9

2

t"

These data support the formation of a second intermediate i n the r e a c t i o n pathway, v i z , carbamate (NH2CO2"") and i t s formation i s ~4 times f a s t e r than ATP formation f o r the reverse r e a c t i o n o u t l i n e d above. In c o n c l u s i o n the [18rj/16o] 3 1 p method i s a powerful technique f o r the study of r e a c t i o n intermediates i n phosphoryl t r a n s f e r r e a c t i o n s . Both the nature of the r e a c t i v e species as w e l l as the r a t e of formation and breakdown of the r e a c t i v e species on the enzyme can be e s t a b l i s h e d . Work supported by NIH grants AM-21785, AM-05996, GM-23529 and NSF Grant PCM-7807845. n m r

Literature Cited

1.

Cohn, M.; Hu, A. Proc. Natl. Acad. Sci. USA 1978, 200-3.

75,

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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PHOSPHORUS CHEMISTRY

2. Balakrishnan, M. S.; Sharp, T. R.; Villafranca, J. J. Biochem. Biophys. Res. Commun. 1978, 85, 991-8. 3. Stokes, B. O.; Boyer, P. D. J. Biol. Chem. 1976, 251, 5558-64. 4. Midelfort, C. F.; Rose, I. A. J. Biol. Chem. 1976, 251, 5881-7. 5. Raushel, F. M.; Villafranca, J. J. Biochemistry 1980, 19, 3170-4. 6. Raushel, F. M.; Villafranca, J. J. Biochemistry 1979, 18, 3424-9. R E C E I V E D June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

26 Potential Antiviral Nucleotides D. W. HUTCHINSON Department of Chemistry and Molecular Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom

In contrast to antibacterial agents, few clinically useful antiviral agents are in ing antiviral agent is th glycoprotein chemical events which take place when interferon interacts with susceptible cells are beginning to be understood. For example, one result of the interaction of interferon with cells is the increased synthesis of the 5'-triphosphate of adenylyl(2'-5') adenylyl(2'-5')adenosine (2-5A) together with the tetramer and higher oligomers (1). These unusual oligonucleotides are very effective inhibitors of protein synthesis in cell-free systems and can also activate a nuclease which degrades viral mRNAs. Many syntheses of 2-5A have been reported but most of these are multistage preparations involving the selective use of protecting groups and hence the final yields of 2-5A are usually very low. We find that the metal ion-catalysed oligomerisation of adenosine 5'-phosphoroimidazolidate (2) is a rapid and efficient route to the 5'-phosphate of the 'core' trinucleoside diphosphate of 2-5A. T h i s s y n t h e t i c method arose from s t u d i e s on the formation of o l i g o n u c l e o t i d e s under p r e b i o t i c c o n d i t i o n s when i t was observed that n u c l e o s i d e S'-phosphoroimidazolidates o l i g o ­ mer i s e i n the presence of d i v a l e n t metal i o n s . Thus, adenosine 5'-phosphoroimidazolidate i n the presence of l e a d ( I I ) ions g i v e s oligomers with mainly the thermodynamically more s t a b l e 2'-5' links. On the other hand, guanosine S'-phosphoroimidazolidate g i v e s 2'-5' l i n k e d oligomers i n the presence of l e a d ( I I ) ions but 3'-5' l i n k e d oligomers i n the presence of z i n c ( I I ) ions ( 3 ) . Presumably, the d i f f e r e n c e s i n linkage a r i s e from d i f f e r e n c e s i n the s t r u c t u r e s of the nucleotide-metal i o n complexes. In our hands, chromatographic s e p a r a t i o n of the oligomers from the l e a d ( I I ) c a t a l y s e d o l i g o m e r i s a t i o n followed by removal of 3'-5' l i n k e d oligomers by d i g e s t i o n w i t h RNase Τ2 and rechromatography i s a r a p i d , convenient, method of o b t a i n i n g the 5'-phosphate of the 'core' o l i g o n u c l e o t i d e of 2-5A. The 5'-phosphate can then be converted i n t o the triphosphate by standard methods. The enzyme which converts ATP i n t o 2-5A has been found i n a v a r i e t y

0097-6156/81/0171-0135$05.00/0 © 1981 American Chemical Society

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136

PHOSPHORUS

CHEMISTRY

of c e l l s and i t has been suggested that 2-5A may have hormonal p r o p e r t i e s ( 4 ) . We are c u r r e n t l y i n v e s t i g a t i n g the e f f e c t of the c o r e o l i g o n u c l e o t i d e on c e l l growth and v i r u s r e p l i c a t i o n . The use of 2-5A as an a n t i v i r a l agent i n animals does not seem to be f e a s i b l e at present as the h i g h l y charged o l i g o n u c l e o ­ t i d e i s not taken up by c e l l s to any extent and i s broken down r a p i d l y i n interferon treated c e l l s . We are l o o k i n g at the mode of a c t i o n of another c l a s s of s t a b l e phosphorus-containing a n t i v i r a l s which appear to be r e a d i l y taken up by c e l l s . These a n t i v i r a l compounds are phosphonoacetic (PAA) and phosphonoformic (PFA) a c i d s , analogues of pyrophosphoric a c i d . The a n t i v i r a l p r o p e r t i e s of PAA against Herpes Simplex v i r u s were discovered during r o u t i n e screening (5), and these compounds a l s o i n h i b i t i n f l u e n z v i r u r e p l i c a t i o (6) Whil the p r e c i s e mode of a c t i o present, they w i l l i n h i b i v i r u s e s . Two mechanisms f o r t h i s i n h i b i t i o n appear p l a u s i b l e . As enzymic r e a c t i o n s are i n theory r e v e r s i b l e , an analogue of a nucleoside triphosphate (e.g. I or I I ) may be formed i n which the β,γ-phosphoryl r e s i d u e s of the triphosphate moiety are replaced by PAA or PFA r e s i d u e s . We have prepared the ATP analogue of PAA. T h i s compound has, not unexpectedly, no e f f e c t on enzymes such as hexokinase which t r a n s f e r the γ-phosphoryl residue of ATP to a s u b s t r a t e . T h i s ATP analogue i s a l s o not a substrate RNA polymerase from E. ooli or from i n f l u e n z a v i r u s . Furthermore, the dTTP analogue i s not a substrate f o r the DNA polymerase of HSV ( 7 ) . We have been unable to prepare the ATP analogue of PFA(II) by the phosphoromorpholidate r o u t e . When we attempt t h i s p r e p a r a t i o n a l l we observe by TLC i s the r a p i d formation of AMP. We b e l i e v e that the ATP analogue i s formed but i t undergoes r a p i d i n t r a m o l e c u l a r breakdown to give a h i g h l y r e a c t i v e formyl phosphate. The d i f f e r e n c e i n s t a b i l i t y between (I) and ( I I ) i s s t r i k i n g , but i t has been observed that d i e t h y l 2-carboxymethylphenylphosphonate ( I I I ) undergoes h y d r o l y s i s by an i n t r a m o l e c u l a r route 10 times more slowly than d i e t h y l 2-carboxyphenylphosphonate(IV) at pH 3.0 and 79.5° (8). While we have not i n v e s t i g a t e d the e f f e c t of PAA and PFA analogues of n u c l e o s i d e triphosphate i n d e t a i l , we do not think that the i n h i b i t o r y e f f e c t of PAA and PFA i s due to the formation of these analogues. Rather we b e l i e v e that PAA and PFA a c t by complexing w i t h a pyrophosphate-binding s i t e i n enzymes, probably by c o - o r d i n a t i n g w i t h an e s s e n t i a l metal i o n such as z i n c . DNA and RNA polymerases are z i n c - r e q u i r i n g enzymes (9), and i t i s r e l e v a n t that reverse t r a n s c r i p t a s e , another z i n c - r e q u i r i n g enzyme (10), i s i n h i b i t e d by PFA (11). The s t a b i l i t y constants of some metal complexes of PAA are known (12). U n l i k e pyrophosphate, PAA does not form strong complexes w i t h magnesium i o n but does form strong complexes w i t h z i n c i o n . Bathocuproin(V) and 2 - a c e t y l p y r i d i n e thiosemicarbazone(VI), both good c h e l a t i n g agents f o r 1

?

5

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

HUTCHINSON

Potential

Antiviral

Nucleotides

A

Ad

> » > 2 - 5 A ii) P N a s e T iii) s e p a r a t e i

S


ether route has several unique advantages over existing methods: (a) the reaction conditions are effectively neutral and mild, (b) the stereoselectivity in the closure of both unsymmetrical and symmetrical diols to cyclic ethers is high, and (c) the isolation of the product(s) from triphenylphosphine oxide (TPPO) is convenient. We have systematically examined the facility with which DTPP promotes the cyclodehydration of simple diols to cyclic ethers: 1,3-propanediol (1) -> oxetane (2) (2-5%); 1,4-butanediol (3) -> tetrahydrofuran (4) (85%); 1,5-pentanediol (5) -> tetrahydropyran (6) (72%); 1,6-hexanediol (7) -> oxepane (8) (55-68%). Increased alkyl substitution at the carbinol carbon significantly diminishes the facility for cyclic ether formation. For example, a mixture of meso- and d,1-2,6-heptanediol gave only 6-10% of the cis- and trans-2,6-dimethyltetrahydropyrans when treated with DTPP. While diol 1 resists cyclodehydration with DTPP to oxetane, some 2,2-disubstituted 1,3-propanediols are readily converted to the appropriate oxetanes [e.g., 2-ethyl-2-phenyl-1,3-propanediol 3-ethyl3-phenyloxetane (78%)]. Treatment of diol 9 with DTPP gives starting material and ethyl ether 10 (32%) but no bicyclic oxetane. trans-2-Hydroxycyclohexyl 2-hydroxyethyl sulfide (11) reacts with DTPP affording 63% of trans-1,4-oxathiadecalin (12) and none of the corresponding cis isomer. These results indicate that the primary hydroxyl group undergoes preferential activation by DTPP and subsequent displacement as TPPO.

c X o » 9

a 10

>

c

11

0097-615 6/ 81 /0171-0165$05.00/ 0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

q 12

166

PHOSPHORUS CHEMISTRY

We have a l s o determined that the r e a c t i o n o f (Z)-2-bute.ne-l, 4 - d i o l with DTPP i n r e f l u x i n g dichloromethane (CH C1 ) a f f o r d s 2,5-dihydrofuran (85-87% GLC and 60% i s o l a t e d y i e l d ) . On the other hand, treatment of (E)-2-butene-l,4-diol with DTPP i n chloro­ form ( 6 1 ° , 18 h) gave a d i s t i l l e d m a t e r i a l (42%) whose E NMR spectrum was completely superimposable on an authentic sample of 3,4-epoxy-l-butene (13). This r e s u l t i s i n agreement with the r i n g closure p r e d i c t i o n s o f Baldwin where the 3 - e x o - t r i g cy­ c l i z a t i o n i s p r e d i c t e d t o be favored (2). 2

2

l

ff

,f

DTPP h

42%

Stereochemical informatio unsymmetrical d i o l s t o c y c l i c ethers could o b v i o u s l y have import ant consequences regarding u s e f u l , p r e p a r a t i v e routes t o c h i r a l c y c l i c ethers o f high enantiomeric p u r i t y . For example, dioxyphosphorane promoted cyclodehydration o f a c h i r a l d i o l can, i n p r i n ­ c i p l e , g i v e the enantiomeric ethers by e i t h e r of two stereochemic a l l y d i s t i n c t routes. Separate stepwise decomposition o f oxyphosphonium b e t a i n e s , A and B, although proceeded by a number o f e q u i l i b r i a could u l t i m a t e l y a f f o r d a nonracemic mixture of c y c l i c ethers. Ph P(OEt) + H0(CH ) CH(0H)R Λ

3

+ Ph

P

Λ

CΠ) 2

2

n

2 EtOH

+ J*

n

1

^u\/ \ *CH

2

\

^

Ph

*CHR

X\

3PS\

(n-1-3; R=Me,Ph)

(CH ) 2

n

. 0

Β

A

•

/A \ • (CH )—CHR

Pn P0 3

^

2

* The r e s u l t s (Table I) i n d i c a t e that the c o l l a p s e o f betaine Β a f f o r d i n g l a r g e l y r e t e n t i o n of stereochemistry at the c a r b i n o l car­ bon (91.8-96.4%) i s h i g h l y favored. While the length o f the hydro­ carbon chain does not appear to i n f l u e n c e the stereochemical course o f the c y c l o d e h y d r a t i o n , the % r e t e n t i o n a t the c h i r a l c a r ­ bon i s diminished s l i g h t l y when a phenyl group replaces a methyl group (Entry 1 and 4 ) . This may imply formation o f a b e n z y l i c carbocation with the expected l o s s o f stereochemical i n t e g r i t y . We have excluded pathways which might i n v o l v e concerted decom­ p o s i t i o n of dioxyphosphoranes to c y c l i c ethers with r e t e n t i o n o f stereochemistry at l e a s t f o r symmetrical 1,2-diols by examining the r e a c t i o n o f jd,l-2,3-butanediol with DTPP. The C NMR spectrum of the r e a c t i o n mixture i s c o n s i s t e n t only with the c i s epoxide e x h i b i t i n g resonances at δ 12.9 and 52.4 ppm. l â

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

33.

BASS ET A L .

Table I . Entry 1 2 3 4

Cyclodehydration

and Chlorination

of

167

Diols

Stereochemistry o f Cyclodehydration o f D i o l s w i t h DTPP %Optical Diol Purity C y c l i c Ether % Ret

(S)- (+)-l,2-Propanediol 00- (-)-l,3-Butanediol 00- (-)-l,4-Pentanediol (S)- ( + ) - l - P h e n y l - l , 2 ethanediol

2-Methyloxirane

96.4

100

2-Methyloxetane

95.6

100

2-Methyloxolane

93.8

1-Phenyloxirane

91.8

71.4

97.5

During the course o f our work with DTPP we became i n t e r e s t e d i n developing other u s e f u f o r d i o l s and t r i o l s , w i t chloromethane ( C C l ^ ) . When trans-1,2-cyclohexanediol i s t r e a t e d with equimolar TPP i n excess C C l ^ , a 88% y i e l d of t r a n s - 2 - c h l o r o c y c l o h e x a n o l can be r e a l i z e d w i t h no evidence ( H, C NMR, GLC) f o r t r a n s - 1 , 2 - d i chlorocyclohexane or c i s - 2 - c h l o r o c y c l o h e x a n o l . Since the trans c h l o r o h y d r i n c o u l d not a r i s e from simple displacement o f TPPO by c h l o r i d e i o n w i t h r e t e n t i o n o f stereochemistry ( 3 ) , we suspected the intermediacy o f cyclohexene oxide which could subsequently undergo r i n g opening by the h y d r o c h l o r i c a c i d (HC1) generated i n solution. T h i s was e a s i l y proven by r e p e a t i n g the r e a c t i o n i n the presence of s o l i d potassium carbonate and r e a l i z i n g a 86% y i e l d of cyclohexene oxide and no c i s o r t r a n s c h l o r o h y d r i n s . Treatment o f d i o l 1 w i t h TPP-CCl^ i n CH CN s o l v e n t g i v e s predominantly 3-chloropropanol (75%) and 1,3-dichloropropane (16%) but no oxetane. I t i s u n l i k e l y that some 3-chloropropanol i s a consequence o f r i n g opening of 2 with HCI s i n c e r e p e a t i n g the r e a c t i o n i n the presence o f K 2 C O 3 7 an BC1 scavenger, gave i d e n t i c a l results. We have observed that d i o l 3, c i s - 2 - b u t e n e - l , 4 - d i o l , and c i s i,2-bis(hydroxymethyl)cyclohexane r e a c t smoothly with TPP-CCli to a f f o r d 4 (78%), 2,5-dihydrofuran (65%), and c i s - 8 - o x a b i c y c l o [ 4 . 3 . 0 ] nonane ^84%). Reaction o f d i o l 5 with TPP-CCl^ i n CH3CN g i v e s 52% of 5-chloropentanol, 6 (11%), and 1,5-dichloropentane (25%) while d i o l 7 a f f o r d s 6-chlorohexanol (48%) and 1,6-dichlorohexane (39%). Comparisons of the ether : c h l o r o h y d r i n : d i c h l o r i d e product d i s t r i butions a r i s i n g from these simple d i o l s r e v e a l a trend f o r e f f i c i ency of chain c l o s u r e to 3 7 membered r i n g s where the formation of c y c l i c ethers appear to decrease i n order of the f o l l o w i n g r i n g size: 3 ~ 5 > 6 > 4 ~ 7 . In an attempt to prepare b i c y c l i c ether 12 by c y c l o d e h y d r a t i n g d i o l 11 with one equiv of TPP i n CCli+, we d i s c o v e r e d a r e g i o s p e c i f i c c h l o r i n a t i o n of the primary hydroxyl group a f f o r d i n g X

15

3

f

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

168

PHOSPHORUS CHEMISTRY

trans-2-hydroxycyclohexyl 2 - c h l o r o e t h y l s u l f i d e (14) i n 70% y i e l d . Formation o f 14 may r e s u l t from c h l o r i d e displacement of TPPO o r c h l o r i d e capture of a t h i i r a n i u m i o n formed by neighboring s u l f e n y l s u l f u r displacement o f TPPO. The r e l a t i v e l y s m a l l amount of 12 (6%) formed i n t h i s r e a c t i o n may r e s u l t from (a) i n t r a m o l e c u l a r c y c l i z a t i o n of 14, capture of a t h i i r a n i u m i o n by the hydroxyl group, or (c) betaine (e.g., B) c o l l a p s e to ether 12 and TPPO.

ci+

d(V âfpC!v (Xv 11

14 1 eq TPP 2 eq TPP

i+

co

15

70% 39%

12

0% 48%

6% 13%

When d i o l 11 i s allowed t o r e a c t with 2 equiv of TPP-CCl^, c h l o r o h y d r i n 14 and 12 are formed as w e l l as t r a n s - 2 - c h l o r o c y c l o h e x y l 2c h l o r o e t n y l s u l f i d e (15) i n 48%. The evidence seems firm that f o r mation o f 15 must a r i s e from the intermediacy o f a t h i i r a n i u m i o n which allows f o r r e t e n t i o n of c o n f i g u r a t i o n during the HO -* CI conversion at Οχ. T h i s i s f u r t h e r supported by the f a c t that trans-2-thiomethyl cyclohexanol under s i m i l a r r e a c t i o n c o n d i t i o n s (1 eq TPP i n CCl^) gives o n l y trans-2-thiomethylcyclohexyl c h l o ­ r i d e (62% by C NMR). By c o n t r a s t , the r e a c t i o n of trans-2methoxycyclohexanol with TPP-CCl^ gives e x c l u s i v e l y cis-2-methoxyc y c l o h e x y l c h l o r i d e a r i s i n g from c h l o r i d e displacement of TPPO with complete i n v e r s i o n o f stereochemistry at . Our present f i n d i n g s corroborate the r e s u l t s o f B i l l i n g t o n and Golding where i t was de­ termined that the r e a c t i o n between CH SCH *CH 0H and TPP-CCl^ gave a mixture (1:1) o f CH S*CH CH C1 and CH SCH *CH CI (*CH = C en­ r i c h e d methylene carbon)(4). TPP=triphenylphosphine; DTPP=diethoxytriphenylphosphorane; TPP0= triphenylphosphine oxide ; GLC= g a s - l i q u i d chromatography. 1 3

3

2

2

1 3

3

2

2

3

2

2

2

Acknowledgement i s made to the N a t i o n a l Science Foundation (CHE 78-05921) and Research Corporation f o r support o f t h i s research. Literature Cited

1. 2. 3. 4.

Chang, B. C.; Conrad, W.; Denney, D. B.; Denney, D. Z.; Edelman, R.; Powell, R. L.;White, D. W. J. Am. Chem. Soc. 1971, 93, 4004. Baldwin, J. E. J. C. S. Chem. Commun.1976, 734. Jones, L. A.; Sumner, C. E.; Franzus, B.; Haung, T. T.-S.; Snyder, Ε. I. J. Org. Chem. 1978, 43, 2821. Billington, D. C.; Golding, B. T. J. C. S. Chem. Commun. 1978, 208.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

34 N-Alkylation of Organophosphorus Amides A New, Convenient Route to Primary and Secondary Amines A. ZWIERZAK Institute of Organic Chemistry, Technical University (Politechnika), Zwirki 36, 90-924 Łódź 40, Poland

Gabriel synthesis, cal approach to primary tion of a suitably protected ammonia derivative with subsequent removal of the phthaloyl group from nitrogen. Despite its wide applicability this procedure suffers, however, from several drawbacks: (i) hydrazinolysis is unsuitable for deprotection in the presence of some functional groups (i.e. carbonyl or carboalkoxyl group); (ii) deprotection cannot be carried out under non-hydrolytic conditions; (iii) direct synthesis of secondary amines is not possible. It is well documented that the phosphorus-nitrogen bond in organophosphorus amides can be easily and effectively cleaved under acidolytic conditions using gaseous hydrogen chloride in benzene |1| or tetrahydrofuran |2|:

This particular feature of P-N bond containing compounds can be utilized for synthetic purposes by using "phosphoryl protection" in the synthesis of amines based on alkylative procedures. The solution of this problem introducing two new reagents, i.e. diphenylphosphinic amide (I) and sodium N-(t-butyloxycarbonyl) diethyl phosphoroamidate (II) as useful synthetic equivalents of an amino moiety is the subject of this communication.

Diphenylphosphinic amide (I) can be readily prepared in 70% yield from diphenylphosphinic chloride by a modified procedure described by Russian workers |3|. Amide (I) is a crystalline material (m.p. 166-167°), perfectly stable at ambient temperature for indefinite periods of time. Sodium hydride in benzene easily converts amide (I) into its sodium 0097-6156/81/0171-0169$05.00/0

© 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

170

PHOSPHORUS

CHEMISTRY

d e r i v a t i v e whi ch c a n be t h e n d i r e c t i y a l k y l a t e d i n b o i 1 i ng benzene. A l k y l a t i o n i s n o t s e l e c t i v e , however, even when an e q u i m o l a r amo­ u n t o f t h e c o r r e s p o n d i ng h a l i de i s s l o w l y added t o t h e N a - s a l t o f ( I ) . Owing t o t r a n s m e t a l a t i o n and s u b s e q u e n t a 1 k y l a t i o n o f t h e N - a l k y l d e r i v a t i ves ( I I I ) m i x t u r e s c o n t a i n i n g 25-50% o f Ν,N-dia 1ky1d i pheny1phosph i n i c amides ( I V ) a r e a l w a y s formed : Ph P(0)NH 2

(I)

0

NaH/benzene^O ^

2

p h 2

p

( 0 ) N H R

+

(m)

*

p^pfo)^ (IV)

R e c e n t l y i t was f o u n d t h a t d i p h e n y l p h o s p h i n i c amide ( I) c a n be s e l e c t i v e l y mono- o r d i a l k y l a t e d under t h e c o n d i t i o n s o f p h a s e transfer catalysis. Monoalkylatio tem c o n s i s t i n g o f 50% aqueou zene i n t h e p r e s e n c e o f 5 m o l - I o f t e t r a - n - b u t y l a m m o n i urn h y d r o g e n s u l f a t e as c a t a l y s t . Alky1 bromides a r e the a l k y l a t i n g agents o f c h o i c e . D i a l k y l a t i o n o r f u r t h e r a l k y l a t i o n o f m o n o a l k y l d e r i v a t i ve ( I I I ) c a n be r e a d i 1 y a c c o m p l i shed under s i m i l a r c o n d i t i o n s when benzene i s r e p l a c e d by boi1î ng t o i u e n e . The f o l l o w i ng scheme i l l u ­ s t r a t e s both p o s s i b i 1 i t i e s : 1°R-Br/PTC benzene, 8 0 Ph.P(0)NH m U

i

o >

Ph P(0)NHR 2

(HI) ^sJ R-Br(2m)/PTC t o l u e n e , 110° Q

Ph P(0)NR 2

2

(IV) When p r i m a r y a l k y l b r o m i d e s a r e used a s a l k y l a t i n g a g e n t s t h e y i e l d s o f ( I I I ) and ( I V ) a r e h i g h (80-95%). A l l c r u d e p r o d u c t s a r e s p e c t r o s c o p i c a l l y homogeneous (^P-NMR) and f r e e f r o m any u n d e s i r a b l e i m p u r i t i e s . M o n o a l k y l a t i o n o f ( I ) c a n be a l s o a c c o m p l i shed by means o f s e c o n d a r y a l k y l bromi des when c o n v e n t i o n a l 1 i q u i d - 1 i q u i d PTC s y s t e m i s r e p l a c e d by t h e s o l i d - 1 i q u i d o n e . Powdered s o d i urn h y d r o x i d e - p o t a s s i u r n c a r b o n a t e i n b o i 1 i n g benzene i n t h e p r e s e n c e o f 10 m o l - % o f t e t r a - n - b u t y l a m m o n i urn h y d r o g e n s u l f a t e as c a t a l y s t was f o u n d t o be t h e s y s t e m o f c h o i ce f o r t h e préparât i o n o f N - a l k y l d i pheny1phosph i n i c amides (V) c o n t a i n i n g s e c o n d a r y a l k y 1 g r o u p s 1i nked t o n i t r o g e n :

(Ο

(v)

A l t h o u g h t h e m o n o a l k y l d e r i v a t i v e s (V) a r e formed i n r e a s o n a b l e y i e l d s (40-60%) t h e y c a n n o t be s u b j e c t e d t o f u r t h e r a l k y l a t i o n by t h e same g e n e r a l p r o c e d u r e i n v o l v i n g t h e use o f s e c o n d a r y o r p r i ­ mary a l k y l bromi d e s . T h i s m a r k e d l y r e d u c e d r e a c t i v i t y i s p o s s i b l y due t o s t e r i c r e a s o n s .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

34.

zwiERZAK

N-Alkylaîion

of Organophosphorus

171

Amides

Due t o i t s r e m a r k a b l e a c i d l a b i 1 i t y t h e p r o t e c t i n g d i p h e n y l p h o s p h i n i c g r o u p c a n be a l m o s t q u a n t i t a t i v e l y removed f r o m t h e a l k y l a t i o n p r o d u c t s ( I I I ) , ( I V ) o r (V) by t r e a t m e n t o f t h e l a t t e r w i t h g a s e o u s HC1 i n t e t r a h y d r o f u r a n a t room t e m p e r a t u r e | 2 | : HC1/THF r . t . ; 12h

9

Ph P(0)NHR 2

R-NH

£

CI

(VI)

(UI),(V) Ph P(0)NR

3

HC1/THF r . t . ; 12h

2

R NH 2

2

CI

(VII)

(IV)

The a l k y l a t i o n - d e p r o t e c t i o n t w o - s t e p p r o c e d u r e c a n be u t i 1 i z e d f o r t h e préparât i o n o f h y d r o c h l o r d a r y ( V I I ) amines t h u s o f f e r i n tional variants o f Gabriel synthesis. P h a s e - t r a n s f e r c a t a l y s e d N - a l k y l a t i o n o f diphenylphosphîηic amide ( I ) i s t o t a l l y u n s u i t a b l e i n t h e c a s e o f e a s i l y h y d r o l y s a b l e o r g a n i c h a l i des , e s p e c i a l 1 y t h o s e c o n t a i η i ng add i t i o n a l f u n c t i o n a l g r o u p s ( i . e . c a r b o n y 1 o r c a r b o a l k o x y l ) w h i c h decompose r e a d i 1 y i n s t r o n g l y a l k a l i ne med i urn. To c i rcumvent t h e d i f f i c u l t y c o n n e c t e d w i t h s i m u l t a n e o u s mono- and d i a l k y l a t i o n o f ( I ) under a n h y d r o u s conditions, N-(t-butyloxycarbony1) d i e t h y l phosphoroamîdate ( X ) , a d o u b l y - p r o t e c t e d ammonia d e r i v a t i v e , was d e v i s e d a s a u s e f u l and s u p e r i o r s u b s t i t u t e o f p h t h a l i mi de i n t h e G a b r i e l - t y p e s y n t h e s i s o f ami n e s . Compound (X) i s r e a d i 1 y a v a i 1 a b l e by a s i m p l e t w o - s t e p p r o c e ­ d u r e i n v o l v i ng t r a n s f o r m a t i o n o f d i e t h y l phosphoroamî d a t e ( V I M ) i n t o t h e c o r r e s p o n d i n g i s o c y a n a t e | 4 J ( I X ) fο11 owed by a d d i t i o n o f t-butanol t o the carbonyl group:

( E t

„

) 2 P m

„„

2

icocivcc,,, -s-o°

(VIII)

t E t 0 ) / ( 0 ) N C 0

» W f r

(IX)

(Et0) P(0)NHC00Bu 2

(X)

t

M

e

°^"

e

°

0

H

»

(Et0) P(0)N(Na)C00Bu

t

2

(M)

By t h e a c t i o n o f an e q u i v a l e n t amount o f sodiurn m e t h o x i d e i n metha­ n o l (X) c a n be q u a n t i t a t i v e l y c o n v e r t e d i n t o i t s s o d i urn s a l t ( I I ) , whi ch i s n o n - h y g r o s c o p i c a n d p e r f e c t l y s t a b l e a t a m b i e n t t e m p e r a ­ ture. 11 was f o u n d t h a t s o d i urn s a l t ( I I ) c a n be e a s i l y a n d c l e a n l y monoalkylated w i t h a v a r i e t y o f p o l y f u n c t i o n a l o r g a n i c h a l i d e s un­ d e r strîctly a n h y d r o u s c o n d i t i o n s . The r e a c t i o n s a r e g e n e r a l l y c a r ­ r i e d o u t i n r e f 1 u x i n g b e n z e n e i n t h e p r e s e n c e o f 10 mo\-% o f t e t r a n-buty1ammoni urn bromi de (TBAB) a s p h a s e - t r a n s f e r c a t a l y s t :

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

172

PHOSPHORUS

(Εί0) Ρ(0)Ν(Ν3)000Βυ

1

2

(II)

^ ^ η β ! ^ '

CHEMISTRY

(EtO)/(0)N(^COOBu

1

(XI)

N - A l k y l a t e d d e r i v a t i v e s ( X I ) a r e f o r m e d i n h i g h y i e l d s (80-95%) and need n o t a n y f u r t h e r p u r i f i c a t i o n . The r e a c t i o n i s r e s t r i c t e d to primary h a l i d e s but a c c o r d i n g t o o u r e x p e r i e n c e t h i s i s the o n ­ l y s e v e r e 1imi t a t i o n . C r u d e (X I) c a n be a l m o s t q u a n t i t a t i v e l y d e p r o t e c t e d by t r e a t m e n t w i t h g a s e o u s HC1 i n benzene o r t e t r a h y d r o f u r a n a t room t e m p e r a t u r e t o g i ve t h e c o r r e s p o n d i ng amine h y d r o c h l o r i des ( X I I ) . S e l e c t i ve removal o f Boc g r o u p i s a l so p o s s i b l e by means o f an e x c e s s o f t r i f 1 u o r o a c e t i c a c i d a t 0 , It a f f o r d s N - a l k y l d i e t h y l phosphoroamidates ( X I I I ) which a r e po­ t e n t i a l s t a r t i ng m a t e r i a nes 15.|.

The u s e o f s o d i urn s a l t ( I I ) i s s t r o n g l y recommended f o r n u c l e o p h i 1 î c ami n a t i o n o f p r i mary h a l i des u n d e r a n h y d r o u s cond i t i o n s . B o t h r e a g e n t s ( I ) a n d ( I I ) c a n be c o n s i d e r e d a s u s e f u l s u b s t i t u t e s o f p o t a s s i urn p h t h a l i m i d e , f r e e f r o m wel1 known préparâti ve i n c o n v e n i a n c e s i n v o l v i nq a p p l i c a t i o n o f t h e 1 a t t e r . LITERATURE CITED 1. 2. 3. 4. 5.

Skrowaczewska, Z . ; Mastalerz, P. Roczniki Chem. 1955, 2 9 , 4 1 5 . Zwierzak, A . ; Osowska, K. Angew.Chem.Int.Ed.Engl. 1976, 15, 302. Zhmurova, I . N . ; Voitsekhovskaya, I . Y . ; Kirsanov, A . V . Zh.Obshch. Khim. 1959, 29, 2 0 8 3 . Samaraj, L.I.; Derkatsch, G . I . Zh.Obshch.Khim. 1966, 3 6 , 1433. Zwierzak, A . ; Brylikowska-Piotrowicz, J . Angew.Chem. Int. Ed. Engl. 1977, 16 107.

RECEIVED June 30,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

35 Phosphoric Amide Reagents ERIK B. PEDERSEN Department of Chemistry, Odense University, DK-5230 Odense M, Denmark

In 1935 F r i c k e r showed that N-substituted amides could be prepared acids with a mixtur y phos phorus pentoxide [1]. The first report i n the literature on the reaction of hexamethylphosphoric triamide (HMPT) with organic molecules was given by Heider [2]. Carboxylic acids form stable (1:1) complexes with HMPT. They decompose at 200 C and transamidation products were isolated in high y i e l d s . By heating a series of p o t e n t i a l hydroxy h e t e r o c y c l i c compounds i n HMPT, the corresponding dimethylamino-heterocycles were produced. The yields for p o l y c y c l i c compounds were generally above 50%, as exemplified here by the synthesis of 2-dimethylaminoquinoline in 79% y i e l d [3]. It is generally found

that oxo groups i n h e t e r o c y c l i c compounds can be transformed d i r e c t l y into an amino-group by heating the oxo compound to 200 °C with an appropriate phosphoramide reagent [ 4 , 5 ] . However, the phosphoramides are not generally commercially a v a i l a b l e . So for laboratory preparations the method will be of minor importance only. The phosphorus pentoxide-amine mixtures, which can r e a d i l y be prepared i n an exothermic r e a c t i o n , were found to react analogously to phosphoramides. 0097-6156/81/0171-0173$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

174

PHOSPHORUS

CHEMISTRY

4-pyridone was u s e d a s a model compound f o r demon­ s t r a t i n g the p o s s i b i l i t y o f making a d i r e c t conver­ s i o n o f an oxo group i n t o an amino group by h e a t i n g at 210 C [ J5] . 2 - D i a l k y l a m i n o p y r i d i n e s w e r e simi­ l a r l y optained i n 16-39% y i e l d .

23-49% The correspondin mary amines and p h o s p h o r u s p e n t o x i d e were n o t easy to handle. Instead, a reagent mixture which was prepared from phosphorus pentoxide, primary amine hydrochloride, and Ν,N-dimethyIcyclohexylamine was u s e f u l a t 250 °C f o r t h e s y n t h e s i s o f N - s u b s t i t u t e d 2-aminoquinolines from the corresponding o x o com­ p o u n d [_7 ] .

RNH C1,P 0 3

0

6

Η

ι

1

2

5

Ν(0Η ) 3

2

NHR 31-86%

The corresponding 4-aminoquinolines were obtained in 42-98% y i e l d . In the synthesis o f 4-methyl-2quinolinamine which was p r e p a r e d i n 49% yield, using Ν,N-dimethyIcyclohexylamine as the tertiary amine component of the reaction mi χ t u r e , N-monoand Ν,N-dimethylated quino1inamines c o u l d a l s o be isolated i n 1 6 % and 3% y i e l d , respectively. I f t r i b u t y l a m i n e was u s e d a s t h e t e r t i a r y amine compo­ nent , the y i e l d o f 4-methyl-2-quinolinamine increa­ sed t o 6 8 % and N - b u t y 1 - 4 - m e t h y 1 - 2 - q u i n o l i n a m i n e was only formed i n 6% yield. In the latter reaction pure 4-methy1-2-quino1inamine was e a s i l y obtained by r e c r y s t a l l i z i n g t h e raw m a t e r i a l . The most s t r i k i n g similarity b e t w e e n HMPT a n d mixtures o f phosphorus pentoxide and d i a l k y l a m i n e s was f o u n d i n a new q u i n o l i n e s y n t h e s i s . 2 - D i a l k y 1 a m i n o q u i n o l i n e s were s y n t h e s i z e d i n 23-61% y i e l d

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

35.

PEDERSEN

Phosphoric

Amide

175

Reagents

by h e a t i n g a c e t a n i l i d e s a n d Ν,N-diethylformamide i n mixtures o f phosphorus pentoxide and dialkylamines [8] . S i m i l a r r e a c t i o n s w e r e o b t a i n e d using HCONEt^ P

HNR,

2°5
h C=N-CH

f

R

H P0 3

N

2

f

Ph

N

Method A (Ethanol) R

N

R f

-

C=0

+

Ph

CHNH H P0 / 3 2 2 Q

p

h

i) Η i i ) propylene oxide

x

Method Β (Ethanol) Method C (Dioxan)

o

o

κ

*° .C-PrH R" I OH NH f

0

Acid cleavage of the diphenylmethyl group could be achieved under a variety of conditions e.g. i) 49% HBr, 100°, 45 min., i i ) TFA/Anisole, reflux, 30 min. and the free aminophosphonous acid 8 then obtained by treatment of the hydrobromide salt with propylene oxide in ethanol, or simply by heating the trifluoroacetates in ethanol.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

37.

BAYLis E T A L .

a-Aminophosphonous

Acids

185

The f o l l o w i n g amino a c i d a n a l o g u e s were Amino a c i d [ M . P t . , Method ( y i e l d %)]

prepared:

Alanine [223-4°C, 0(45)] V a l i n e [201-5 C , A ( 6 9 ) , Β ( 4 9 ) ] Leucine [222-3°C, A ( 4 7 ) , B(78)] Phenylalanine [227-8°C, C (36)] M e t h i o n i n e [231 C , C ( 2 5 ) ] Glutamic a c i d [154°C, C (38)] The a n a l o g u e s o f s e r i n e a n d t y r o s i n e were p r e p a r e d from s u i t a b l y p r o t e c t e d hydroxy aldehydes and the tryptophan a n a l o g u e from i n d o l e p y r u v i c a c i d . A w i d e s e l e c t i o n o f o t h e r o-aminophosphonous a c i d a r o m a t i c and h e t e r o c y c l i The cr-aminophosphonous a c i d s c a n be r e s o l v e d by c l a s s i c a l procedures using the α-methylbenzylamine s a l t s o f N-benzyloxycarbonyl derivatives. We h a v e r e s o l v e d t h r e e c r - a m i n o p h o s phonous a c i d s ( a l a n i n e , v a l i n e a n d m e t h i o n i n e a n a l o g u e s ) a n d o b t a i n e d b o t h d - and _ l - e n a n t i o m e r s w i t h >99% o p t i c a l p u r i t y . A c r y s t a l structure determination o f a protected dipeptide d e r i v a t i v e o f (-)1-aminoethanephosphonous a c i d showed t h e (-)aminophosphonous a c i d t o have R s t e r e o c h e m i s t r y . D i - and o l i g o - p e p t i d e s w i t h a terminala-aminophosphonous a c i d r e s i d u e h a v e been p r e p a r e d b y c o u p l i n g w i t h N - h y d r o x y succinimide esters o f N-benzyloxycarbonylamino acids or peptides. R I ZNH-CH-COONSu

i)

a q . NaHCO^

f

+

f

R R R I ^0 i ) i i ) i i i ) I I ^0 H NCHP-H » H NCHC0NHCHP—H ^DH ^ 0 H p

i i ) HBr/HOAc

p

i i i ) propylene oxide

As w e l l a s p e p t i d e f o r m a t i o n t h e α - a m i n o p h o s p h o n o u s a c i d s u n d e r g o t h e t y p i c a l amine r e a c t i o n s o f a m i n o a c i d s . Further, t h e y c a n be o x i d i s e d t o t h e c o r r e s p o n d i n g a m i n o p h o s p h o n i c a c i d s without racemisation. F o r e x a m p l e , o x i d a t i o n o f t h e ( S , R) d i p e p t i d e 9 w i t h m e r c u r i c c h l o r i d e gave a phosphonic d i p e p t i d e i d e n t i c a l to Alaphosphin i n q u a n t i t a t i v e y i e l d , and s e r v e d to confirm the stereochemical assignments.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

186

PHOSPHORUS

CH

CHEMISTRY

CH.

0

HgCl

2

H NCHCONHCHP—H (S) (R) ^ O H 9

d

(9)

ALAPHOSPHIN

R

When o u r work o n s y n t h e s i s o f α - a m i n o p h o s p h o n o u s a c i d s was e s s e n t i a l l y c o m p l e t e a n d a p a t e n t f i l e d f, a b r i e f r e p o r t appeared^ d e s c r i b i n g t h e s y n t h e s i s o f t h r e e o-aminophosphonous a c i d s by a d d i t i o n o f hypophosphorous a c i d t o oximes. I n b i o l o g i c a l s t u d i e s w i t h i n CIBA-GEIGY t h e a l a n i n e , v a l i n e and methionine significant antibacteria a g a r medium. T h e v a l i n e a n d m e t h i o n i n e a n a l o g u e s a n d t h e d i p e p t i d e 9 possess i n v i v o a c t i v i t y and a l l t h r e e a r e e f f e c t i v e a g a i n s t e x p e r i m e n t a l i n f e c t i o n s i n t h e mouse. T h e a n t i b a c t e r i a l a c t i v i t y o f the v a l i n e analogue i s antagonised by v a l i n e , a n d t h i s a n d o t h e r p r e l i m i n a r y s t u d i e s i n d i c a t e t h a t t h e mode o f a c t i o n o f b o t h t h e v a l i n e a n a l o g u e a n d t h e d i p e p t i d e 9 i s by t r a n s p o r t i n t o t h e b a c t e r i a l c e l l f o l l o w e d by i n h i b i t i o n o f p r o t e i n s y n t h e s i s . This i s i n contrast to the phosphonic d i p e p t i d e Alaphosphin which a c t s by t r a n s p o r t i n t o the b a c t e r i a l c e l l and i n t r a - c e l l u l a r r e l e a s e o f t h e a l a n i n e mimectic which i n t e r f e r e s w i t h b a c t e r i a l c e l l w a l l synthesis. The parent aminophosphonic a c i d i s i t s e l f i n a c t i v e and c l e a r l y not transported i n t o the b a c t e r i a l celle. The phosphonous a n a l o g u e o f a l a n i n e a n d p e p t i d e s d e r i v e d from i t a l s o a f f e c t t h e g r o w t h o f p l a n t s a t l o w c o n c e n t r a t i o n s

REFERENCES 1. 2. 3. 4. 5.

U.S. Patent 3,160,632, 1964; Chem. Abstr. 62, 4053F Tyka, R., Tetrahedron Lett. 1970, 677 Schmidt, Η., Chem. Ber. 1948, 81, 477 Ger. Offen. 2,722,162, 1977; Chem. Abstr. 88, 105559 Khomutov, R.M., Osipova, T.I , Izv. Akad. Nauk SSSR, Ser. Khim. 1978, 1951 6. Atherton, F.R., Hall, M.J., Hassall, C.H., Lambert, R.W., Ringrose, P.S., Antimicrobial Agents and Chemotherapy, 1979, 696. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

38 Phosphonodipeptides LIDIA KUPCZYK-SUBOTKOWSKA, PAWEL KAFARSKI, JANUSZ KOWALIK, BARBARA LEJCZAK, PRZEMYSLAW MASTALERZ, and JÓZEF OLEKSYSZYN Institute of Organic and Physical Chemistry, Technical University of Wrocław, 50-370 Wrocław, Poland JERZY SZEWCZYK Department of Organic Chemistry, Technical University of Gdańsk, 80-952 Gdańsk, Poland

Peptides of aminoalkanephosphonic acids (Phosphonopeptides) 4, are now because some representatives of this class were found to repress bacterial growth at very low concentration levels .Literature data on the synthesis of dipeptides containing aminoalkylphosphonic acids are scarce and very little information i s avaiable οn blocking and de­ blocking of the phosphonate moiety . In this communication we report synthesis of dipep­ tides containing P-terminal aminoalkylphosphonic acids related structurally to glycine,alanine,nor-valine,va­ line,leucine,phenylglycine and phenylalanine,while the N-terminal residues include glycine,alanine,valine,leu­ cine,proline,methionine,beta-alanine,phenylalanine,ty­ rosine,lysine and glutamine. The peptides 3 were prepared by condensation of phtaloyl,N-carbobenzoxy,N-t-butoxycarbonyl or N-formylamino acids with 1-aminoalkanephosphonic acids as well as with their dialkyl or diphenyl esters /Scheme/. Special attention was payed on the efectiveness of the peptide bond formation and on the methods for selective and total removal of the blocking groups. The literature data on the preparation of phosphonodipeptides from 1-aminoalkanephosphonic acids showed that the yields of condensation reactions are usually small or moderate. Moreover,the use of bulky N-blocked amino acids drastically decreased the reaction y i e l d . Thus following Martell's method- we wre unsuccesful i n the preparation of dipeptides containing N-terminal valine or leucine,while peptides of phenylalanine were obtained i n 5-10% yield.Also the active ester method appeared to give small yields of the desired products. Our studies using p-nitrophenyl- and cyanomethyl esters of N-phtaloyl amino acids confirmed these observations. 1-3

3-9

3-5

0097-6156/81/0171-0187$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

188

PHOSPHORUS CHEMISTRY

R' X-NH-CH-COOH I

R

R

coupling R X-NH-CH-C-NH-C-P0,Y R R

deblocking R ι RgN-CH-C-NH—C-POjHg 2

(

R

X - OHC-

I

II 0

R

1

CgHjCHgOCO- , /CH^COCO- , phtaloyl

9

Y - Na,^g CH CH CH /CH / CH,C H #

R -

3#

3

2t

3

3

6

1

-

R 2

5

H.OTj.CHjOTg^./CHj/gCT./Cîîj/gCHCHg^gHçCHg, p-HO-C H^CH , CHjSCHgOTg ,

R

6

2

W C H g / ^ CHgCHgCONHg t

HJCHJ

H.CHj.CHjCHj^/CHj^OT./CHj/gCKCHg^CgHc.CgHgCHg and 2-aninoethanephosphonic acid

Although esters of amino acids are much more widely used i n peptide synthesis than the corresponding acids, the use of d i a l k y l 1-aminoalkanephosphonates was strongly limited because of lack of simple method for the

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

38.

KUPCZYK-SUBOTKOWSKA E T A L .

Phosphonodipeptides

189

esteriflcatlon of these acids.Also the Methods f o r preparation of these esters given i n the literature are rather complex and their yields are low. The simple method for the preparation of dialkyl 1-aminoalkanephosphonates discovered i n our laboratory— enabled us to solve that problem. Phosphonopeptldes 2. were prepared by condensation of N-blocked amino acids with dialkyl 1-aminoalkanephosphonates by means of dicyclohexylcarbodiimide ( DCC ) method.or preferably using the mixed carboxylie-carbonic anhydride ( ICA ) method. A l l the blocking groups were removed from the peptides £ by acldolysis with 45% hydrogen bromide i n glac i a l acetic acid solution i n the case of N-carbobenzoxy-,N-formy1 or N-t-butoxycarbony lective removal of N-blocklng groups was a l s o carried out.Thus î ^ c a r b o b e n z o x y - group was removed with hydrogen gas on palladium c a t a l y s t , Λ - p h t a l o y l by the action of hydrazine,while N-formyl or N-t-butoxycarbony1 with etheral or methanolic solutions of hydrogen chloride gas.Dialkyl esters of phosphonodipeptides obtained in this manner can be further used for oligopeptide syn­ thesis. If the racemlc form of amlnophosphonates were used mixtures of diastereoIsomers were obtained.We invented a method for their separation by column ion-exchange chromatography ( Dowex 50W X8,H form) .The chromatographically pure diastereoisomerlc phosphonodipeptides were obtained i n this manner. The other way for obtaining diastereoisomerlc dipep­ tides was the use of optically active dialkyl 1-aminoalkanephosphonated.They were prepared by the separation of dibenzoyl-L-tartaric salts of these esters. The u s e of dialkyl aminoalkanephosphonates seems to be the most preferable method for the synthesis of pho­ sphonodipeptides s o far. 1

Dlphenyl 1-aminoalkanephosphonates l 2 , Y « C , H - ) were not used for the phosphonopeptide synthesis yex.They appeare to be very exciting substrates because these esters can be very easily prepared by the method inven­ ted i n our laboratory l2 Coupling of N~carbobenzoxyamino acids with dlphenyl 1-aminoalkanephosphonates by the DCC method resulted i n the formation of mixtures of diastereoisomers en­ riched i n one of diastereoisomers,1.e. they appeare to form i n nonequimolar quantities.lt Is probably due to kinetic control of the reaction. On the other hand the MCA method gave a n equlmolar mixtures of diastereoiso­ mers. m

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

Q

190

PHOSPHORUS

CHEMISTRY

The main problem here Is removing the phenyl ester groups from the phosphonic moiety .We have found that convenient routes for deblocking are: h y d r o g é n a t i o n on Adams' catalyst and transesteriflcation methods f o l lowed by hydrogen bromide i n glacial acetic acid t r e atment. The best results ewre obtained i f transesteriflcation was carried out using potassium fluoridecrown ether-methanol system. References: 1./E.Bayer,K.H.Gugel,H.Hägele,H.Hagenmaier,S.Jessipow, W.A.Konig,H.Zähner,Helv.Chim.Acta,55,224/1972/ 2./Β.K.Park,A.Mirota,H.Sakai,Agric.Biol,Chem.,40,190 /1976/ 3./J.G.Allen,F.R.Atherton,M.J.Hall,C.H.Hassall, S.W.Holmes, .W.Lambert,N.J.Nisbet,P.S.Ringrose, Nature 272,56/1978/ 4./M.Hariharan,R.J.Motekaitis,A.E.Martell,J.Org.Chem., 40,470/1975/ 5./F.R.Atherton,H.J.Hall,C.H.Hassall,R.W.Lambert, P.S.Ringrose,Ger.Offen.,26.02.193 /1976/ 6./P.Kafarski,P.Mastalerz,Roczniki Chemii,51,433/1977/ 7./K.P.Poroshin,V.K.Buritchenko,Dokl.Akad.Nauk SSSR, 168,386/1964/ 8./W.F.Gilmore, M.A.McBride,J.Pharm.Sci.,63,1087/1974/ 9./K.Yamauchi,M.Kinoshita,M.Imoto,Bull Soc.Chem.Jap., 45,2528/1972/ 10./J.Kowalik,L.Kupczyk-Subotkowska,P.Mastalerz,Synthe­ s i s , i n press 11./J.Oleksyszyn,L.Kupczyk-Subotkowska,Synthesis ,985 /1979/ RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

39 Some Aspects of the Chemical Synthesis of Oligodeoxyribonucleotides COLIN B. REESE and LYDIA VALENTE Department of Chemistry, King's College, Strand, London WC2R 2LS, England

We report some recent studies on the synthesis of oligodeoxy­ ribonucleotides. We hav adaptors which were require of Biochemistry, Imperial College of Science and Technology, University of London, in connection with his studies on the cloning of cDNA (complementary deoxyribonucleic acids). The nucleotide sequences are d[AATTCGGTACCG], d[AATTCGAGCTCG] and d[AATTCGTCGACG] which are Eco RI -> Κpn I, Eco RI->Sst I and Eco RI->Pst I adap­ tors, respectively. These three dodecamers were prepared in satis­ factory yields from four fully-protected hexamers (d[Dbmb­ -ApApTpTpCpG-Px], d[Dbmb-GpTpApCpCpG-Px], d[Dbmb-ApCpCpTpCpG-Px] and d[Dbmb-TpCpGpApCpG-Px]. The system of abbreviations for pro­ tected oligodeoxynucleotides has been described previously (1). [o-Dibromomethylbenzoyl (2) and 9-phenylxanthen-9-yl (3) are abbre­ viated to Dbmb and Px, respectively. 6-N-(p-t-Butylbenzoyl)-2'­ -deoxyadenosine, 4-N-benzoyl-2'-deoxycytidine and 2-N-(p-t-butylphenylacetyl)-2'-deoxyguanosine residues are represented by A, C and G, respectively; phosphate residues which are protected by o­ -chlorophenyl groups are represented by p.]

0097-6156/81/0171-0191$05.00/ 0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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PHOSPHORUS CHEMISTRY

Scheme 1

Scheme 2 (a)

d[Obmb-ApApTpTpCpG-Vx] [Obmb-GpTpApCpCpG-T?x]

(b) d (c)

(12)

+ (23)

d[Obmb-ApApTpTpCpGp]

(12)

d[HO-GpTpApCpCpG-Px]

(13)

d[Dbmb-ApApTpTpCpGpGpTpApCpCpG-Px]

(14)

(d) (14)

d[AATTCGGTACCG] (15)

ReagentsÎ

( i ) ( a ) ( 2 ) / a c e t o n i t r i l e - p y r i d i n e , (b) E t N - H 0 ; (ii)(3)/ pyridine; (iii)(4)/pyridine; (iv)(a) s i l v e r perchlorate2,4,6-collidine/acetone-water (98:2 v / v ) , (b) morpholine; (ν) t o l u e n e - p - s u l f o n i c acid/CHCl -MeOH (95:5 v / v ) ; (vi) Ν ,Ν ,N_^,N -tetramethylguanidinium s y n - 4 - n i t r o benzaldoximate i n dioxan-water (1:1 v / v ) , 20°C, 24 h r ; ( v i i ) aqueous ammonia (d 0.88), 20°C, 48 h r ; ( v i i i ) a c e t i c acid-water (4:1 v / v ) , 20°C, 15 min. 3

2

3

1

1

3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

39.

REESE A N D VALENTE

Synthesis of

Oligodeoxyribonucleotides

193

The procedure used for the preparation of the fully-protected hexamers is indicated in Scheme 1. The nucleoside building blocks required (5) are prepared (1,2) by treating thymidine or appropriate N-acyl derivatives of 2'-deoxyribonucleosides (7) with o-dibromomethylbenzoyl chloride (1) in acetonitrile-pyridine solution. The resulting Dbmb-derivatives (5), which are obtained as crystalline solids in good isolated yields, are first treated with a two- to three-fold excess of o-chlorophenyl phosphorodi-(1,2,4triazolide) (2) (1^,4) in acetonitrile-pyridine and the products hydrolyzed with aqueous triethylamine to give the corresponding 3 (o-chlorophenyl) phosphates (6) in very high (usually { 90%) yields. The latter mononucleotide building blocks (6) are isolated as pure solid triethylammonium salts Q,3' -dinucleoside phosphates may be detected in the products When the mononucleotid 20 min, room temperature) thymidin appropriat N-acyl 2 -deoxyribonucleoside (7) in the presence of an excess (ca. 3 molecular equivalents) of 1-(mesitylene-2-sulfonyl)-3-nitro-l,2,4triazole (3, MSNT) (5,6) in pyridine solution, the corresponding 3 ->5 -partially-protected dinucleoside phosphates (8) are obtained in good yields (usually 60-70%). Phosphorylation occurs on the 5'-hydroxy function of (7) with a very high degree of regioselectivity and the small quantities of the isomeric 3'->3 -dinucleoside phosphates sometimes obtained are less polar and may readily be removed from the desired products (8) by short column chromatography (7) on silica gel. A partially-protected dinucleoside phosphate (d[HO-CpG-Px]) with a free 5'-hydroxy and a protected 3'-hydroxy function is also required. Treatment of the 5*-protected dinucleoside phosphates (8) with 9-phenyl-9-xanthenyl chloride (4, pixyl chloride) (3) in pyridine solution gives their 5'-0-pixyl derivatives in virtually quantitative yields. When the latter are treated first with silver perchlorate and 2,4,6-collidine in acetone-water (98:2 v/v) for ca. 1 hr at room temperature and the products then treated with morpholine, the 5'-Dbmb group (2) is removed and the desired dinucleoside phosphates (9) with protected 3 -terminal hydroxy functions are obtained in good yields. The appropriate 5'protected dinucleoside phosphates (8) are then phosphorylated with o-chlorophenyl phosphorodi-(1,2,4-triazolide) (2) and thereby converted into their 3'-(o-chlorophenyl) phosphates (10) in yields of ca. 90%. The latter (10) are then condensed, in the presence of an excess of MSNT (3) with the 3 -protected dinucleoside phosphates (9) to give fully-protected tetranucleoside triphosphates usually in good yields (ca. 70%). The corresponding partially-protected tetranucleoside triphosphates (11) are then obtained by removing the 5'-Dbmb protecting groups by the procedure described above. The desired fully-protected hexanucleoside pentaphosphates are then prepared in the same way by condensing dinucleotide blocks (10) with the appropriate partially-protected tetranucleoside triphos1

1

1

1

1

1

1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

194

PHOSPHORUS

CHEMISTRY

phates (11). MSNT (3) i s again used as the condensing agent and s a t i s f a c t o r y y i e l d s (ca. 60%) are u s u a l l y obtained. The p r e p a r a t i o n o f one o f the completely unblocked dodecamers ( 1 5 ; the Eco RI -> Kpn I adaptor) i s i l l u s t r a t e d i n Scheme 2. The f i n a l steps i n the p r e p a r a t i o n and unblocking o f the other two do­ decamers correspond e x a c t l y . In the f i r s t p l a c e , the hexamer block (d [Dbmb-ApApTpTpCpG-'Px] ) i s t r e a t e d (Scheme 2a) with toluene£-sulfonic a c i d i n chloroform-methanol (95:5 v/v) and the r e s u l t i n g hexamer with a f r e e 3 -hydroxy f u n c t i o n i s phosphorylated with ochlorophenyl p h o s p h o r o d i - ( 1 , 2 , 4 - t r i a z o l i d e ) t o give the correspond­ ing hexanucleotide block (12). The l a t t e r i s then condensed, i n the presence o f MSNT (3), with the product (13, Scheme 2b) obtained by removing the 5'-Dbmb p r o t e c t i n g group from the hexamer block (diDbmb-GpTpApCpCpG-Vx]), t o g i v e the f u l l y - p r o t e c t e d dodecamer (14, Scheme 2c). The y i e l good but the p u r i f i c a t i o tography on s i l i c a g e l proved sometimes t o be d i f f i c u l t . The removal o f the p r o t e c t i n g groups from (14) i s e f f e c t e d i n a t h r e e step process. The f u l l y - p r o t e c t e d o l i g o n u c l e o t i d e i s f i r s t t r e a t e d with a l a r g e excess (ca. 10 molecular e q u i v a l e n t s p e r phosp h o t r i e s t e r group) o f a 0.3 M-solution o f the Ν , Ν , N , N - t e t r a methylguanidinium s a l t o f syn-4-nitrobenzaldoxime (_5) i n dioxanwater (1:1 v/v) a t 20°C f o r 24 h r to unblock the i n t e r n u c l e o t i d e linkages. We now b e l i e v e (8) t h a t t h i s process i s complete i n a much s h o r t e r time. An ammonolysis step completes the removal o f the N-acyl and 5 -O-Dbmb p r o t e c t i n g groups. The f u l l y - u n b l o c k e d o l i g o n u c l e o t i d e i s obtained f o l l o w i n g the removal o f the p i x y l group by a c i d i c h y d r o l y s i s . 1

1

1

3

3

1

A l l three o f the f u l l y - u n b l o c k e d dodecamers underwent complete d i g e s t i o n t o give t h e i r monomeric components when they were t r e a t e d with C r o t a l u s adamanteus snake venom and spleen phosphodiesterases. T h e i r s t r u c t u r e s were f u r t h e r confirmed i n the usual way. We thank the Science Research C o u n c i l f o r generous f i n a n c i a l support.

Literature Cited 1. Chattopadhyaya, J. B.; Reese, C. B. Nucleic Acids Res. 1980, 8, 2039. 2. Chattopadhyaya, J. B.; Reese, C. B.; Todd, A. H. J. Chem. Soc. Chem., Commun. 1979, 987. 3. Chattopadhyaya, J. B.; Reese, C. B. J. Chem. Soc., Chem. Commun. 1978, 639. 4. Chattopadhyaya, J. B.; Reese, C. B. Tetrahedron Lett. 1979, 5059. 5. Reese, C. B.; Titmas, R. C.; Yau, L. Tetrahedron Lett. 1978, 2727. 6. Jones, S. S.; Rayner, B.; Reese, C. B.; Ubasawa, A.; Ubasawa, M. Tetrahedron 1980, 36, 3075. 7. Hunt, B. J.; Rigby, W. Chem. Ind. (London) 1967, 1868. 8. Reese, C. B.; Valente, L . , unpublished observations. RECEIVED

July 7, 1981. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

40 Coupling of Fatty Diazomethylketones with Organophosphorus Acids An Approach to Glycerophospholipid Analog Synthesis 1

DAVID A. MARSH and JOSEPH G. TURCOTTE Department of Medicinal Chemistry, University of Rhode Island, Kingston,RI02881

Intense interest in cell membrane architecture chemistry and function as a current frontie generated a concomitant interes ecular species of glycerophospholipids. Since naturally occurring phospholipids are multispecies and generally "non-separable ", and the chemical synthesis of individual molecular species is multistep, stereospecific, and low yield (overall), new appraoches to the synthesis of natural glycerophospholipids and/or analogs of glycerophospholipids suitable for biochemical, biophysical, and pharmacologic studies are needed. That derivatives of naturally occurring glycerophospholipids can exhibit significant physicochemical properties and pharmacologic activities, can be seen from studies on pulmonary surfactant (1), antihypertensive (2), and anticancer (3,4,5) phospholipid and lysophospholipid analogs. As an entry to an alternative approach to the synthesis of the spectrum of classes of glycerophospholipids and structurally related analogs, lipid dihydroxyacetone phosphate and phosphonate derivatives were considered. Published routes (6-9) to such derivatives are long and low yielding. For example, 1-palmitoyloxyhydroxyacetone phosphate [III, CH (CH ) COOCH COCH OP(O)(OH) ] can be synthesized (10) by direct phosphorylation (POCl ) of 1-palmitoyloxyhydroxyacetone [II, CH (CH ) COOCH COCH OH] , obtained (11) from the diazomethylketone [I, CH (CH ) COOCH COCHN ] precursor, the yield of III from II was 25% and from I, would be less than 15%. Alternatively, Hajra and Agranoff (10) found that the diazomethylketone _I could be reacted directly with phosphoric acid to give a 60% yield of 1-palmitoyloxyhydroxyacetone phosphate (III) in a single step. This direct coupling procedure could be a promising approach to glycerophospholipid synthesis provided that: the direct phosphorylation or phosphonylation of lipid d ia zome thyIke tones structurally related to molecules such as I_ has general applicability; facile reduction (12) of product ketones to corresponding secondary alcohols (racemic and/or optically active) can be accom3

2 14

2

2

2

3

3

2 l4

2

3

2 14

2

2

2

1

Current address: Department of Medicinal Chemistry, Massachusetts College of Pharmacy, Hampden Campus, Springfield,MA01119. 0097-6156/81/0171-0195$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

196

PHOSPHORUS

R1COCHN2 1

CHEMISTRY

H Q P Q ( R 2 ) R 3

IV

Π C 1

RxC0CH 0H I

R

PQ( 2)Ra —

2

y

R C0CH 0P0(R )R VIII 1

2

2

3

p l i s h e d ; subsequent a c y l a t i o n of such a l c o h o l s can be c o n t r o l l e d to give e s t e r s e s t e r i f i e d at what would be comparable to the sn-2 po­ s i t i o n of n a t u r a l g l y c e r o p h o s p h o l i p i d s . Because of the p o t e n t i a l s y n t h e t i c u t i l i t y of the d i r e c t cou­ p l i n g r e a c t i o n , a p r e l i m i n a r y i n v e s t i g a t i o n of i t s scope was made using l-diazo-2-heneicosanone [IV, R = C H ( C H ) 1 C H ] as a model compound ; l i t t l e a t t e n t i o n has been given to the d i r e c t s y n t h e s i s (10,12,13,14) of α-phospho-o α-phosphonoketone fro r e a c t i o f organophosphorus a c i d s wit study are summarized i n eicosanone r e a c t s with acids such as 2-phthalimidoethylphosphonic a c i d , 2-chloroethylphosphonic a c i d , chloromethylphosphonic a c i d , 3-bromopropylphosphonic a c i d , dioctadecyphosphoric a c i d , and d i benzylphosphoric a c i d to g i v e f a i r to good y i e l d s of the c o r r e ­ sponding d e r i v a t i v e s ; y i e l d s (Table I) have not been optimized. Most of the r e a c t i o n s were completed w i t h i n a few hours and i n each case the products ( V l l l a - V I I I f ) were able to be p u r i f i e d r e a d i l y by column chromatography ( S i l i c A R CC-7 ); t h i n - l a y e r chromatography of crude r e a c t i o n mixtures u s u a l l y showed the products s i g n i f i c a n t l y d i f f e r e n t i n R^ values from both s t a r t i n g m a t e r i a l s and s i d e - p r o d ­ ucts. D i a c i d i c phosphonates (Vla-VId), i . e . , those with two protons a v a i l a b l e f o r s u b s t i t u t i o n , had a tendency to y i e l d s i g n i f i c a n t amounts of b i s - s u b s t i t u t e d phosphonates [(RiC0CH 0) P0(R ) ] upon r e ­ a c t i o n w i t h IV. However, i t was found that c a r e f u l a d d i t i o n (Table I) of the α-diazoketone to the phosphonate a t r e a c t i o n tem­ perature minimized the formation of t h i s by-product; moreover, the b i s - s u b s t i t u t e d phosphonates could be converted to the correspond­ ing monoacids by r e f l u x i n g the former w i t h sodium i o d i d e i n methyl e t h y l ketone. In t h i s manner higher y i e l d s of phosphonates (e.g., V H I a - V I I I d ) c o u l d be obtained. Although the y i e l d s of α-phospho- and α-phosphonoketones were not optimized, the d i r e c t s y n t h e s i s (IV VIII) of these ketones from diazomethylketones and organophosphorus a c i d s can be expectx

3

2

7

2

CH 0C0Ri 2

J

CH Ri

2

2

2

CH 0C0Ri

2

2

I

J

2

I

CH0H

CH0H

CH 0P0(X)

CH 0P0(X)

CH 0P0(X)

CH 0P0(X)

IX

X

XI

XII OH

I

2

I

OH

I

*CH0C0R

CH Ri

I

2

2

I

OH

I

2

OH

CH0C0R

I

2

2

I

Ri,R = saturated or unsaturated f a t t y chains; X = OH, c h o l i n e , ethanolamine, s e r i n e , e t c . , or corresponding phosphonate i s o s t e r e s ; *S-configuration. 2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

3 2

6

3

3

2

a

2

6

2

3

2

6

0CH C H

5

3

1

EtAc

3.0

3.0

3

Dioxane

3

0.1

2

17

0.1

2

3

2

3

reflux

reflux

71.4

30.0

49.0

0CH (CH ) CH

reflux

Dioxane

0.3

2

2

0.8

2

3

VHIf

Ville

VHId

VIIIc

VHIb

CH CH CH Br

2

66.1

2.6 25°C

2

2

CH C1

2

CH C H C l

Product Villa

d

57.8

% Yield

EtAc

c

2.5

reflux

Temperature

2

10.0

Dioxane

Solvent

2

VHIa-VIIIf

18

45.0

c

b

14.9

IV

2

25°C

b

3

+ CH (CH ) C0CH 0P0(Ri)R

CH C12

28.8

VIa-VIf

Vla-VIf

+ HOPOCRjRa

0.6

2

2

IV

18

CH CH N(CO) C H4

R

2

e

3 2

P r e p a r e d by treatment of e i c o s a n o i c a c i d with o x a l y l c h l o r i d e followed by r e a c t i o n of the r e s u l t ant a c i d c h l o r i d e with diazomethane. ^Mmol. A d d i t i o n s of s o l u t i o n s of reactants u s u a l l y made a t ambient temperature. ^Per cent y i e l d s based on e i c o s a n o i c a c i d [CH (CH )îeCOOH ] as s t a r t i n g material. I n a t y p i c a l r e a c t i o n V i a was d i s s o l v e d i n 900 ml of dioxane ( r e f l u x ) and IV d i s s o l v e d i n 200 ml of dioxane was added dropwise. A f t e r r e f l u x f o r an a d d i t i o n a l 1 h r , the solvent was removed i n vacuo and CHC1 added. The p r e c i p i t a t e was f i l t e r e d , the f i l t r a t e concentrated, and the product chromatographed on S i l i c A R CC-7 (400 g ) : CHC1 ; CHCl /MeOH (19:1); CHCl /MeOH (10:1); CHCl /MeOH (5:1); CHCl /MeOH (1:1). The product e l u t e d i n the 1:1 CHCl /MeOH f r a c t i o n . Anal. C a l c d . f o r C H N 0 P : C,66.05; H, 8.94; N, 2.48; P, 5.49. Found : C, 65.81; H, 8.84; N, 2.33; P, 5.49. Structures of a l l r e a c t i o n products were confirmed by spectroscopy ( H NMR,IR) and elemental a n a l y s i s .

3

0CH C eHs

Vlf

e

0(CH ) CH

Vie

a

OH

VId

2

OH

Vic

1 7

OH

VIb

2

OH

Ri

Via

Acid

3

CH (CH ) COCHN

PHOSPHONATES AND PHOSPHATES DERIVED FROM l-DIAZO-2-HENEICOSANONE

TABLE I

198

PHOSPHORUS

CHEMISTRY

ed to have advantages over the a l t e r n a t i v e s y n t h e t i c route (IV V V I I I ) . For example, i n the a p p l i c a t i o n of t h i s r e a c t i o n to g l y c e r o p h o s p h o l i p i d and glycerophosphonolipid analog synthesis the α-phosphonoketone V i l l a was synthesized i n 58% o v e r a l l y i e l d from eicosanoic a c i d (Table I) s t a r t i n g m a t e r i a l ; by comparison, the a l t e r n a t i v e 4-step route a f f o r d e d V i l l a i n 26% o v e r a l l y i e l d and required two chromatographic (column) p u r i f i c a t i o n s . Therefore, s t a r t i n g with any r e a d i l y a v a i l a b l e f a t t y a c i d , upon generation o f the a c i d c h l o r i d e and diazomethylketone i n s i t u , r e a c t i o n o f the l a t t e r c l a s s o f molecules with r e s p e c t i v e organophosphorus a c i d s , a f f o r d s an e s s e n t i a l l y one-chamber p r e p a r a t i v e route f o r l i p i d aphospho- and ce-phosphonoketones. This simple sequence provides a synthesis o f analogs (e.g., Χ, XII, r e s p e c t i v e l y ) o f g l y c e r o l y s o phospholipids (IX) and glycerophospholipid (XI) d related approach to the synthesi intermediates such as I I I

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

13. 14.

Turcotte, J. G.; Sacco, A. M.; Steim, J . M.; Tabak, S. A., Notter, R. H. Biochim. Biophys. Acta 1977, 488, 235. Turcotte, J . G. et al. J. Med. Chem. 1975, 18, 1184; Sen, S., Smeby, R. R., Bumpus, F. M., Turcotte, J. G., Hypertension 1979, 1, 427. Turcotte, J. G., Srivastava, S. P., Meresak, W. A., Rizkalla, Β. H., and Wunz, T. P. Biochim. Biophys. Acta 1980, 619, 604. Turcotte, J. G. et al. Biochim. Biophys. Acta 1980, 619, 619. Raetz, C. H. R., Chu, M. Y., Srivastava, S. P., Turcotte, J. G. Science 1977, 196, 303 Piantadosi, C.; Ishaq, K. S.; Wykle, R. L.; Snyder, F. Biochem. 1971, 10, 1417. Piantadosi, C.; Chae, K.; Ishaq, K. S.; Snyder, F. J. Pharm. Sci. 1972, 61, 971. Piantadosi, C.; Ishaq, K. S.; Snyder, S. J. Pharm. Sci. 1970, 59, 1201. Snyder, F; Blank, M. L.; Malone, B.; Wykle, R. L. J. Biol. Chem. 1970, 245, 1800. Hajra, A. K.; Agranoff, B. W. J . Biol. Chem. 1968,243, 1617. Schlenk, H.; Lamp, B. G.; DeHaas, B. W. J . Am. Chem. Soc. 1952, 74, 2550. Turcotte, J . G.; Pavanaram, S. K.; Yu, C-S.; Lee, H; Boyd, R. O.; Dadbhawala, K. R.; Marsh, D. A. Fed. Proc. (Abs) 1973, 32, 690; Marsh, D. A. Ph. D. Dissertation, University of Rhode Island, 1976. Rosenthal, A. F.; Chodsky, S. V. Chem. Commun. 1968, 1504. Silverman, J . B.; Babiarz, P. S.; Mahajan, K. P.; Buschek, J.; Fondy, T. P. Biochem. 1975, 14, 2252.

RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

41 Design of Organophosphorus Reagents for Peptide Synthesis R. RAMAGE, Β. ATRASH, and M. J. PARROTT Department of Chemistry, The University of Manchester Institute of Science and Technology, Sackville Street, Manchester M60 1QD, England

Two crucial aspects of the stepwise synthesis of peptides are the temporary protectio carboxylic acids to enabl amino protecting groups should be stable,except under specific mild cleavage conditions,and must not lead to diminished stereo­ chemical integrity of the protected α-amino acid during activation. Criteria for the choice of activation procedure adopted for the carboxylic acid function are no less stringent requiring rapid, highly efficient amide formation during the repetitive steps leading to the synthesis of polypeptides. One of the most successful classes of amino protecting groups is that based on the t-butyl urethane which may be cleaved by mild acid.Structural variation gives rise to groups susceptible to deprotection over a range of acid conditions.A disadvantage of this type of protection is the formation of carbenium ions during the deprotection process which can react with side chain functionality of cysteine,methionine,tryptophan or tyrosine leading to alkylated products.Although this can be mitigated by use of scavengers it was thought desirable to design another series of protecting groups which have the same propensity towards acid cleavage,but which occasion no deleterious side reactions during deprotection.lt was decided to investigate for this purpose the utility of the remarkable acid lability of the P-N bond in phosphinamidates.—Careful mechanistic researches have led to results which would suggest that acid-catalysed solvolysis of phosphinamidates can proceed via trigonal bipyramidal intermediates thus producing no reactive intermediates capable of entering side reactions.In order to maximise the effect of substituents it was judged that phosphinamidates would be capable of a wider range of reactivity towards acid hydrolysis than phosphoramidates which would also suffer from the disadvantages of offering two modes of fragmentation of the trigonal bipyramidal intermediate during solvolysis.Preliminary worklshowed that the Pt^PO.NHR group is more acid-labile than BuO.CONHR,therefore a series of protected amino acids were prepared using the readily accessible Ph^PO.Cl t

0097-6156/81/0171-0199$05.00/0 ©

1981

American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

200

PHOSPHORUS

CHEMISTRY

and these have now been i n c o r p o r a t e d i n t o a programme aimed towards the s y n t h e s i s of prohormones.Recent researches d i r e c t e d to the a p p l i c a t i o n o f phosphinamidates i n t h i s area have i n v o l v e d the mechanistic study of the a c i d - c a t a l y s e d methanolysis o f a s e r i e s o f phosphinamidates d e r i v e d from 3-phenylethyl amine i n c o r p o r a t i n g s u b s t i t u e n t s on phosphorus which were s e l e c t e d i n order to d e f i n e the optimum reagent f o r use i n peptide s y n t h e s i s . R P(0).NHCH CH Ph HCl/MeOH ^ ( Q ) ^ H^CH^H^h C l " 2

2

2

>

+

K i n e t i c r e s u l t s f o r a s e r i e s o f such r e a c t i o n s are given i n Table 1 and show an i n t e r e s t i n g combination of s t e r i c and e l e c t r o n i c e f f e c t s o f the s u b s t i t u e n t R.From X-ray d i f f r a c t i o n data on Ph P(0).N(Me)CH CH Ph i t could be seen that the geometry o f s u b s t i t u e n t s a t the n i t r o g e n atom i s non-planar and that only one phenyl r i n g was o r i e n t e Comparison of r a t e data R2=Ph ,R =Me and R =Me/Ph shows the l a t t e r to have the optimum balance o f s t e r i c e f f e c t (Me) and e l e c t r o n i c e f f e c t (Ph)for f a c i l e h y d r o l y s i s . T h e r a p i d onset of s t e r i c r e t a r d a t i o n may be seen from comparison of the r a t e s o f hydroLysis of dimethylphosphinamidates with the higher d i a l k y l analogues.Unfortunately the dimethyl s e r i e s proved too hygroscopic to be u s e f u l i n peptide s y n t h e s i s , however the diethylphosphinamides show promise f o r s i d e - c h a i n amino p r o t e c t i o n which r e q u i r e s r e l a t i v e l y g r e a t e r a c i d s t a b i l i t y . C a r b o x y l i c mixed anhydrides are very important f o r the r a p i d s y n t h e s i s o f peptides by the stepwise procedure,however the use o f c a r b o x y l i c mixed anhydrides,e.g.those d e r i v e d from p i v a l i c a c i d and a p r o t e c t e d amino a c i d ( 1 ) , s u f f e r s from two disadvantages. F i r s t l y , r e g i o s p e c i f i c i t y o f a t t a c k a t the d e s i r e d c a r b o x y l f u n c t i o n i s l a r g e l y determined by s t e r i c e f f e c t s and w i l l not be 100% f o r a l l c o u p l i n g reactions.Secondly,such mixed anhydrides have a propensity towards d i s p r o p o r t i o n a t i o n to symmetric anhydrides which i s h i g h l y u n d e s i r a b l e i n terms of r e a c t i o n e f f i c i e n c y . T h i s l a t t e r process can be depressed by o p e r a t i o n o f the r e a c t i o n at -15 °C, but with the concurrent decrease i n r e a c t i o n r a t e and,on l a r g e s c a l e manufacture,increased c o s t s . 2

2

2

2

2

2

2

2

Ç X.NH.CH.CO.O.COBut (I) K

J

2

f-

X.NH. CH. CO. 0. Ρ (0)R R1 r

(2) K

o

1

R R -> X.NH.CH.C0NH.OH.COOMe

l

J

H NCHC00Me R P(0)0H (3) With these c o n s i d e r a t i o n s i n mind i t was decided to i n v e s t i g a t e p h o s p h i n i c - c a r b o x y l i c mixed anhydrides i n peptide methodology^.Mechanistic c o n s i d e r a t i o n o f the r e a c t a n t s (2) and (3) and products shown above would suggest r e g i o s p e c i f i c nucleop h i l i c a t t a c k by the amine component due to the formation o f an amide bond with concomitant generation o f a new P-0 bond.As i n the study of phosophinamidates d i s c u s s e d above,a s e r i e s of phosphinic acids were s e l e c t e d f o r p r e p a r a t i o n o f the mixed anhydrides (2) because of the i n t i m a t e s t e r i c and e l e c t r o n i c ?

?

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981. 5

Table

1

2

2

Me,Ph

q-p

P h

Me

n-Bu

2

88. 0

22

52.8

32

36. 0

too

f a s jt

to

measure? by HPLC

94.7

17

68. 7

21

53.6

28

41. 0

153.5

520.0

4

326. 0

6

201 . 0

8

145. 0

13

27.0

75

15. 4

111

10.4

169

6. 8

26.1

78

14. 8

118

9.7

169

6. 8

2

45

8.0

°

197

37

5. 9

ο

287

4.0

373

3. 1

(PhCH )

2

k

k

2

30 k

ο k

25

2

E t

R

ο

8

12

2

43

44

144

\

Rate Constants (s" χ 10 ) and H a l f - l i v e s (min) f o r Acid C a t a l y s e d M e t h a n o l y s i s of Phosphinamidates R P(0)NHCH C H / h

1

202

PHOSPHORUS

Rate

Constants

1

(1.mol" .s"

Disproportionation Diphenylphosphinic-Amino

Amino Acid Z-Gly Z-Ala Z-Leu Z-Phe Z-Val Z-Ply

0

°

3.3 1.4 0.5 1.4 11.7 —

30

°

15.5 22.0 7.4 6.7 43.0 52.2

1

χ

5

10 )

CHEMISTRY

f o r the

of Acid

40

Anhydrides

°

49.2 62. 4 18.1 26.0 67.3 135.0

50

138 113 40 75 109 248

°

Time 10% (min) 74 143 390 170 17 56

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

41.

RAMAGE E TAL.

Organophosphorus

Reagents for Peptide Synthesis

o\° Ο

Φ

C

•Η

ε

οο ο ο t n ro r o οο Η Η OJ

Μ00

Η Η

σ>

h

ro

«Ή (R0KPC1 (R0) P=0 + R 0 3

2

De-alkylation by alkoxide ion increases the acidity of the medium and this accounts for the formation of dialkyl phosphonate in the later stages of the reaction. For these reasons, higher concentrations of alkoxide were used, firstly to increase the initial rate and secondly to preserve alkalinity throughout the reaction. With two equivalents of alkoxide, high yields of trialkyl phosphite were obtained within 1-2 h. at 25°. Again, the yield decreased with time owing to the subsequent oxidation, e.g. 82% tr ime thylpho sph i te and 76% t r i ethylphosphite after 1 h. When the reaction was carried out in the probe of a P NMR spectrometer, no evidence for the accumulation of intermediates was obtained (vide infra). These results establish the conditions for the formation of trialkyl phosphites in high yields. However attempts to distil the ester from the reaction mixture were unsuccessful as codistillation and some decomposition always occurred. Other workers who carried out similar experiments independently,! report a 50% yield of isolated trimethyl phosphite. Attention was turned to the analogous reaction of thiols. Here the subsequent oxidation can be neglected, and the products were readily separated by distillation. Again, low yields of triester were obtained when equivalent quantities of thioalkoxide and phosphorus were used.I. Evidence of incomplete conversion was obtained from the P NMR spectra of the reaction mixtures using 31

31

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

47.

BROWN

ET AL.

Phosphorus

Esters

and

Thioesters

233

ethane t h i o l . Three absorptions i n the r a t i o 2:1:1 were observed corresponding to t r i e t h y l p h o s p h o r o t r i t h i o i t e (δρ 114.1), d i e t h y l p h o s p h o r o c h l o r i d o d i t h i o i t e (δρ 184.5) and d i e t h y l t r i c h l o r o m e t h y l phosphonodithioite (δρ 121.6). The two intermediates probably a r i s e i n the l a t e r stages o f the r e a c t i o n when the t h i o a l k o x i d e c o n c e n t r a t i o n i s low. The presence o f these intermediates i s evidence o f the intermediate formation of the t r i c h l o r o m e t h y l anion, i n r e a c t i o n s of the following kind. DO"

(RS) P-P(SR) 2

2

— — » CCI.

(RS) P + (RS) PC1 — » ( R S ) P + (RS) P.CC1 3

2

3

+ CCI

2

+ Cl

3

These r e a c t i o n s occu by r e a c t i o n with tetrachloromethan reactions ,Ζ 4NaSR

+

CCI +

RSH

3

g

* CH(SR)

3

+

RSSR

+

4NaCl

The c h l o r i d o d i t h i o i t e does not r e a c t with n e u t r a l t h i o l , whereas the corresponding d i a l k y l p h o s p h o r o c h l o r i d i t e r e a c t s r a p i d l y with ethanol. Consequently the l a t t e r r e a c t i o n proceeds to completion even when the alkoxide has been n e u t r a l i s e d . With two equivalents o f t h i o a l k o x i d e , the t r i e s t e r only i s produced and t h i s can be d i s t i l l e d from the r e a c t i o n mixture i n high y i e l d (e.g. 97% from e t h a n e t h i o l and 82% from b u t a n e t h i o l ) . The f o l l o w i n g scheme i s suggested f o r the breakdown o f the Pi# molecule and the formation o f t r i e s t e r (X = 0, S ) .

1X1 P'

Ρ

— —

fx/F

IXI

—

Ρ

î

Ρ

t

^P

Ρ—XR II

RX

I

XR 4(RX) P * 3

2(RX) P—P(XR) 2

2

+

(RX) P — Ρ — Ρ — Ρ (XR) 2

2

U

XR III

The absence of detectable r e a c t i o n intermediates suggests that the i n i t i a l heterogeneous r e a c t i o n i s rate determining. The b i c y c l i c intermediate, I , gives the c y c l o t e t r a p h o s p h i t e I I with r e l e a s e of r i n g s t r a i n . C y c l i c molecules of t h i s k i n d have been i s o l a t e d from r e a c t i o n s o f elemental phosphorus, e.g. t e t r a a l k y l cyclotetraphosphines from the combined a c t i o n o f Grignard reagents and n - a l k y l bromides.JL

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

234

PHOSPHORUS

CHEMISTRY

The subsequent stages i n v o l v i n g tetraphosphine, triphosphine and diphosphine d e r i v a t i v e s proceed r a p i d l y owing t o the high r e a c t i v i t y o f the P-P bond. These r e a c t i o n s appear to be r e s t r i c t e d to s t r o n g l y b a s i c n u c l e o p h i l e s , as we found no r e a c t i o n with phenoxides and t h i o phenoxides. This l a c k o f r e a c t i v i t y i s a t t r i b u t e d to the r e v e r s i b i l i t y o f the n u c l e o p h i l i c s u b s t i t u t i o n , promoted by the increased l e a v i n g group a b i l i t y of the n u c l e o p h i l e , e.g. :-)

LITERATURE CITED 1. 2. 3. 4. 5. 6. 7. 8.

Rahut, M.M. Topics in Phosphorus Chemistry Vol. 1, p.1, Interscience, Ν.Y., 1964 Maier, L. Fortsch. Chem. Forsch. 1971, 19, 1 Brown, C.; Hudson R.F.; Wartew, G.A.; Coates, H. Phosphorus and Sulphur 1979, 6, 481 Burn, A.J.; Cadogan, J.I.G. J . Chem. Soc. 1963, 5788 Lehmann, H.A.; Schadow, H.; Richter, H.; Kurze, R.; Oertel, M. Ger. Patent, 127,188, 1977 Brown, C.; Hudson, R.F.; Wartew, G.A. J.Chem. Soc. Perk. I., 1979, 1979 Backer, J.H.; Stedehonder, P.L. Rec. Trav. Chim. 1933, 52, 437 Cowley, A.H.; Punnell, R.P. Inorg. Chem. 1966, 5, 1463

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

48 Thermal Rearrangement and Condensation of O,O-Dimethyl-O-phenylphosphorothionate HERBERT TEICHMANN Zentralinstitut für Organische Chemie der Akademie der Wissenschaften der DDR, DDR1199 Berlin-Adlershof, GDR GERHARD SCHRAMM Orthopädische Klinik der Medizinischen Akademie, Erfurt, DDR-50 Erfurt, GDR

I t i s now more than three decades that d i a l k y l arylphosphorothionate thion-methyl took a phorus p e s t i c i d e s . Owing to o c c a s i o n a l i n c i d e n t s i n production and h a n d l i n g , v a r i o u s e f f o r t s have been made in the past to e l u c i d a t e the thermal behaviour of such compounds ( c f . (1, 2, 3) and references c i t e d t h e r e i n ) . However, our knowledge of the r e a c t i o n s involved i s still f a r from being s a t i s f a c t o r y . With the aim of a better understanding of the thermal r e a r r a n gement and decomposition processes i n t h i s c l a s s of commercially h i g h l y important substances, the thermolysis of (MeO)2(PHO)PS (I) as a model compound has been reexamined. In the temperature range of 1 2 5 - 1 4 0 ° C two periods c l e a r l y can be d i s t i n g u i s h e d . During the first one which consumes about 70% of the t o t a l r e a c t i o n time, only 30% conversion of the thionate I takes p l a c e . So f a r the decrease of I follows an a u t o c a t a l y t i c law and corresponds quite w e l l to the increase of the i s o meric S-methyl t h i o l a t e I I . In the shorter and exothermic second p e r i o d i s o m e r i z a t i o n of I soon comes to completion. Here, however, the t h i o l o isomer II also r a p i d l y decomposes a f t e r reaching a maximum conc e n t r a t i o n of about 65%. The final product, free from I and I I , c o n s t i t u t e s a water s o l u b l e , hygroscopic substance of unchanged elemental composition, e x h i b i t ing strong a c i d i c r e a c t i o n and containing Me3^ions ( about h a l f o f the t o t a l s u l f u r ) and condensed phosphates. An i d e n t i c a l product i s obtained from pure I I a f t e r a much shorter heating time. The t h i o n o - t h i o l o rearrangement I-^II i s c a t a l y zed by II as w e l l as by decomposition products of I I : Me2S induces an 0 - d e a l k y l a t i o n / S - r e a l k y l a t i o n sequence ( 4 ) , and Me3S® acts as an a l k y l a t i n g agent s u p e r i o r 0097-6156/81/0171-0235$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

236

PHOSPHORUS

CHEMISTRY

to I or I I j S-alkylation of I-analogues with R3O® i n ­ stead of s a l t s t o form c r y s t a l l i n e trialIroxyalkylthiophosphonium s a l t s and dealkylation of them by Me2S to y i e l d II-analogues has been demonstrated before (5.» 6). Relative reaction times u n t i l t o t a l loss of I a% 135°C are (hours, approximately)1 with­ out catalyst 7; i n the presence of 1 equivalent of I I or of 0,06 equivalents of Me3S® SbClôP 2; i n the pre­ sence of 0,06 equivalents of Me2S 1; removing Me2S by passing through a stream of N2 18· Further evidence for c a t a l y s i s by I I arose from crossing experiments

(1).

Soon a f t e r t o t a l isomerization of I the decompo­ s i t i o n of i t s isome version of I I into th ces consists of two basic steps: dealkylation by Me2S to form the S-methyl-O-phenylphosphorothiolate anion I I I (eq. 3), and nucleophilic attack at phosphorus by the anion I I I t o give a S-methyl diphosphate which i s O-dealkylated to IV by the leaving group MeS® (eq. 1 ) . 0

es u

0 0 ^c£) 0 0 M u + MeS~κ , ι > MeO-P-0-P-SMe * ^O-P-0-P-SMe + Me S OPh OPh OPh OPh (1) IV

^ TT +11

M

0-P-SMe OPh III

M

2

Preparative application of t h i s condensation p r i n c i p l e has been shown (8) to y i e l d , e.g., 83°/> diphenyldiphosphate from I I and (MeO)(PhO)POOK after 5 hours r e f l u x i n BU2O. Analogous condensation of I I with IV or even higher condensed phosphorothiolate anions would enable a stepwise formation of longer chains. The Me2S produced i n every single condensation step must consume an equivalent amount of 0-methylester functions because no sulfur i s l o s t . Therefore, a f t e r isomerization of I , one h a l f of I I i s required for sulfonium s a l t formation, and a reasonable s t o i chiometry of the II-conversion r e s u l t s from the sum of equations (2) and (3). Since by reaction (3) a large supply of anion I I I i s offered, I I I w i l l be the dominant nucleophile f o r condensation with I I , and one may expect a large number of chains, i . e . , a low average condensation degree b. TLC on DEÂE c e l l u l o s e with 0.2 m HC1 permits the i o n i c species to be separated and thus the course of the thermolysis t o be followed. Besides an i n i t i a l t i n y uncertain spot (obviously (MeO)(PhO)P02® accord­ ing to Rp value), four different compounds emerge suc­ cessively: I I I , a f t e r i t IV, and f i n a l l y the s u l f u r -

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

TEiCHMANN A N D S C H R A M M

48.

Ο,Ο-Dimethyl-O-phenylphosphorothionale

237

Ο Ο Ο ιι II a ^O-P-SMe• O-P-SMe η MeO-P-SMe + Ο-Ρ OPh OPht OPh II III Ο Ο ιι II n O-P-SMe + n Me^S" η MeO-P-SMe + n Me2S OPh OPh II III Ο Ν

n Me S 2

(2)

(3)

0

Ο

Ο Θ " c O-P-SMe Ο - Ρ — O-P-SMe + OPh b III b = a + c = n

0 2n MeO-P-SMeOPh II

Ο

Θ

©

Ν

(4)

free diphosphate V and triphosphate VI. By P-NMR spectroscopy exactly the same components are identi­ f i e d . Phosphorus determinations in isolated spots of the f i n a l product are in l i n e with values obtained from integration of NMR signals (see table). 31

III IV 7

VI \\ ^ ;

Table: Thermolysis of I at 135°C, composition of f i n a l product $> of total Ρ * 3 1 Ρ (ppm) 1) from T K from P-NMR 15 14 1 s 29 62 65 P 12Î72(d);pB-18,05(d) ) 11 9 -18,26 ,x 12 13 pA-18,20(d);P -29,14(t) in CH C1 ) P bond to SMe; Jpp 26,4 Hz P terminal P; Jpp 17,7 Hz A

2

B

5

5

2

1

A

Hydrolytic s t a b i l i t y of the condensed species decreases i n the series V>VI >IV; the latter could not be isolated but was identified unambiguously by its hydrolysis products (eq. 5 , b = 1) in two dimen0

Η

0 - P — O-P-SMe + H 0-

OPh

2

v OPh

0

0

0

Η

fp-o OPh

θ

+

b = 2: V b = 3 : VI

M

O-P-SMe 1 OPh

+ 2 H® (5)

III

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

238

PHOSPHORUS

CHEMISTRY

sional TLC as w e l l as i n 31p-NMR spectra. Higher con­ densed t h i o l o oligophosphates must be regarded to be extremely sensitive to moisture and to act as precur­ sors of V and VI. I f the thermolysis temperature i s allowed to r i s e to 180°C and above, evolution of Me2S takes place with sulfur l o s s up to 60$· Simultaneously the content of V and VI and of other unidentified conden­ sation products increases markedly at the expense of IV· l o s s of Me3S® approximately p a r a l l e l s that of t h i o l o ester groups, however*, no MeO groups are detec­ table i n the H-NMR spectra. From these r e s u l t s one must conclude that the uncharged t h i o l o sulfur w i l l p r e v a i l over the anioni phile toward the Me3S θ

0 M 0-P— OPh

0 0 ι -P-SMe + Me S' -y^Me-f-O-P- 0-P-SMe OPh OPh OPh 0 II

3

Me S 2

b

(6) V

0 θ

0 il

M

0-P-SMe, 0-P OPhJb OPh L

Me S 2

+ 2 Me S

-μο-Ρ-

2

OPhJb+1 L

monomeric (b = 0) or oligomeric metaphosphate species open an alternative route for building up condensed phosphates even a f t e r t o t a l consumption of I I . Literature

cited

1. H i l g e t a g , G.; Schramm, G.; Teichmann, H . J. P r a k t . Chem. 1959, 8, 73. 2. Teichmann, Η . ; Lehmann, G. Sitzungsber. DAW Berlin Kl. Chem., Geol., B i o l . 1962, No. 5. 3. E n g e l , R. R . ; L i o t t a , D . J. Chem. Soc. C 1970, 523. 4. H i l g e t a g , G . ; Teichmann,H. Angew. Chem. i n t e r n a t . Edit. 1965, 4, 914. 5. Teichmann, H.; H i l g e t a g , G . Chem. B e r . 1963, 96, 1454. 6. Schulze, J. T h e s i s , Humboldt U n i v e r s i t y B e r l i n , 1971. 7. Teichmann, H . Angew. Chem. i n t e r n a t . E d i t . 1965, 4, 993. 8. H i l g e t a g , G . ; K r ü g e r , M . ; Teichmann, H . Z . Chem. 1965, 5, 180. RECEIVED July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

49 Synthesis and Reactivity of (Silylamino)phosphines R O B E R T H . NEILSON, H. R A N D Y O ' N E A L

P A T T Y W I S I A N - N E I L S O N , D A V I D W. M O R T O N , and

Department of Chemistry, Texas Christian University, Fort Worth, T X 76129

Compounds containing the Si-N-P linkage combine the structural and phorus with the reactivit bond. Indeed, much of the derivative chemistry and synthetic potential of these compounds, especially the (silylamino)phosphines such as (Me Si) NPMe2,is based on this difunctional character. We report here a general, "one-pot" synthesis of (silylamino)phosphines and describe their use in the preparation of several types of phosphorus-containing materials. Synthesis of (Silylamino)phosphines. In a typical preparation, addition of one molar equivalent of PCI to a stirred solution of LiN(SiMe ) in ether at -78°C followed by one or two equivalents of an alkyl Grignard or lithium reagent at 0°C gives the corresponding mono- or dialkylphosphine . This proce 3

3

2

3

(1)

n-BuLi

(2)

PCI3

>

(Me Si) NH 3

2

2

(Me Si) NPC1 3

2

R

RMgX > or R L i

(Me Si) N 3

2

2

CI

R

(MeoSi)oNPCl

2

= i-Pr,

t-Bu, CH SiMe

RMgX >(Me Si) NPR 3

R

2

2

2

= Me, E t , C H S i M e 2

0097-6156/81/0171-0239$05.00/0

©

1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

3

3

240

PHOSPHORUS CHEMISTRY

dure routinely affords high yields (ca 75%) and large quantities (ca 100-200 g) of the phosphine product. Moreover, the method has been generalized to include the use of other silylamines, PhPCl instead of PCI , and different organometallic reagents. Synthesis of Polyphosphazenes. We are investigat­ ing a new, direct synthesis of phosphazene polymers which involves the thermally-induced elimination of silanes from suitably constructed N-silylphosphinimines. As a route to linear polyphosphazenes, this method 2

Me SiN

-«N=PV-

Me SiX

3

3

o f f e r s the d i s t i n c t advantage of i n c o r p o r a t i n g the d e s i r e d p h o s p h o r u s s u b s t i t u e n t s d i r e c t l y i n t o an easily-prepared s t a r t i n g m a t e r i a l , thereby e l i m i n a t i n g the need f o r p r e p a r i n g the d i h a l o polymers (X2PN) . Many o f t h e " s u i t a b l y c o n s t r u c t e d " phosphinimines (1) a r e p r e p a r e d v i a t h e b r o m i n a t i o n o f ( s i l y l a m i n o ) phosphines. The P-bromo compounds a r e e a s i l y convert­ ed t o t h e c o r r e s p o n d i n g d i a l k y l a m i n o o r a l k o x y d e r i v a ­ tives . n

I

0°C (Me Si) NPRR 3

2

?

+ Br

>Me SiBr

2

+

3

Me S i N = P — R 3

R R,R

f

f

= Me, E t , P h , OCH2CF3

We f i n d t h a t t h e n a t u r e o f t h e l e a v i n g g r o u p ( X ) is important i n determining both the r e l a t i v e stability of t h e s t a r t i n g m a t e r i a l as w e l l as t h e degree o f o l i g o m e r i z a t i o n of t h e phosphazene products. For e x a m p l e , w h i l e t h e P-NMe a n d P-OMe p h o s p h i n i m i n e s are s t a b l e t o a t l e a s t 2 50°C, t h e P-Br a n a l o g u e s decompose a t lower t e m p e r a t u r e s (100-150°C) t o g i v e M e S i B r a n d c y c l i c p h o s p h a z e n e s ( R 2 P N ) w h e r e η = 3,4. Most s i g n i f i c a n t l y , however, p o l y m e r i c p h o s p h a ­ z e n e s ( £ ) a r e o b t a i n e d a l m o s t e x c l u s i v e l y when t h e l e a v i n g group i s OCH2CF . The p r o d u c t s a r e t h e f i r s t f u l l y characterized polyphosphazenes containing only d i r e c t P-C b o n d e d s u b s t i t u e n t s . These m a t e r i a l s a r e s o l u b l e film-forming or elastomeric polymers with m o l e c u l a r w e i g h t s i n t h e 50-70,000 r a n g e . The 2

3

n

3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

49.

NEILSON ET A L .

OCH CF 2

241

(Silylamino)phosphines

3

180-190°. C Me SiN=P—R > j 2-5 d a y s R R,R = Me,Et,Ph 3

Me SiOCH CF 3

2

1 I -4N=P> | R

+

3

f

f

1

c o m p l e t e c h a r a c t e r i z a t i o n of t h e s e and r e l a t e d m a t e r i ­ als i s under a c t i v e i n v e s t i g a t i o n . N u c l e o p h i l i c R e a c t i o n s of (Silylamino)phosphines. The r e a c t i o n s o f ( s i l y l a m i n o ) p h o s p h i n e s w i t h simple a l d e h y d e s and k e t o n e s p r o c e e d v i a n u c l e o p h i l i c a t t a c k by p h o s p h o r u s f o l l o w e d by a [ 1 , 4 ] s i l y l m i g r a t i o n f r o m n i t r o g e n to oxygen t Ο). With a,3-unsaturate R

f

I 0 (Me Si) NPMe 3

I R-C-R

+

2

R-C-OSiMe CH C1 2

I Me SiN=PMe

2

1

>

3

3

2

0°C tion occurs hydrolysis,

producing s i l y l enol ethers which, y i e l d γ-carbonyl phosphine o x i d e s .

upon

0

I (Me Si) NPMe 3

2

+

2

CH "= CH

C

2

R C H C H = C. I OSiMe. Me SiN=PMe 2

X

H 0 2

J

3

>

2

o°c R

>

° g Κ I Me PCH CH CR 2

2

2

(Silylamino)phosphines also react with various h a l i d e s i n c l u d i n g e t h y l bromoacetate, a l l y l bromide, and c h l o r o f o r m â t e s . The i n i t i a l l y - f o r m e d p h o s p h o n i u m s a l t s e l i m i n a t e s i l y l h a l i d e s to a f f o r d f u n c t i o n a l i z e d p h o s p h i n i m i n e s M e S i N = P (R)Me2 w h e r e R = -CH2C (0) O E t , - C H 2 C H = C H 2 , and - C ( 0 ) 0 R . Two-coordinate (Silylamino)phosphines. Certain chlorο(silylamino)phosphines bearing a t r i m e t h y l s i l y l m e t h y l g r o u p c a n be d e h y d r o h a l o g e n a t e d t o y i e l d s t a b l e (methylene)phosphines. The v e r y low f i e l d (δ 309. 9) 31p s h i f t c o n f i r m s t h e t w o - c o o r d i n a t e n a t u r e of t h i s compound w h i l e t h e low f i e l d (δ 7.09) H s i g n a l shows i t t o be t h e P=CH r a t h e r t h a n t h e P=N isomer. Three modes o f r e a c t i v i t y o f t h i s ( m e t h y l e n e ) p h o s p h i n e h a v e been o b s e r v e d : a d d i t i o n t o t h e P=C b o n d , o x i d a t i v e 3

f

1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

242

PHOSPHORUS

a d d i t i o n at phosphorus, tion metal centers.

and c o m p l e x a t i o n w i t h

CI I (Me Si)2N-P-CH SiMe3 3

base >

2

(Me Si) N-P 3

2

-HC1

CHEMISTRY

transi-

-etc. From phosphorylated ketenes other phosphorylated cumulenes can be obtained,for example a l i è n e s , i s o c y a n a t e s , k e t e n i m i n e s 9

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

9

51.

KOLODYAZHNYI

ET AL.

Phosphorylated

HA

249

Ketenes

- R2P(0)CHR'-CO-A

A-OH.OR.SR.R^N RgPCO-CR^C-O C C HgPiO-CR'-C-O

RgPiO-CR'-CHg

R^P-CR^C-O -I Ph^P-N-R' L Ph P=CR »

RgPCO-CR'-CsN-R»»

3

HN-,

R2P(0)-CHR»-CON

3

— ^R2P(0)GHRAN=C=0 Phosphorylated ketenes add halogens to give halides of phosphorylated halogenoacetlc acids. HLgR2P(0)-CR»=C=0 RgPCO-GR'Hlg-CO-HLg Phosphorylated ketenes react with aromatic ortho hydroxy aldehydes to form coumarins by the Wittig Horner - type reaction.

•ο+x—cnr° — H

Nx^CHO

R P(0)-CHR-C0-0^\ 2

OHC

ONa R»

CHO X

NaOH

0

We have also developed convenient methods of prepara­ tion of the phosphorylated ketenimines. l i k e the phos­ phorylated ketenes the phosphorylated ketenimines are stable on storage and they readily react with variety of reagents having an active hydrogen atom,as shown i n t h . Scheme. _ ^ H

R P(0)-CPh°C'»NMe 2

R

'

(

a

I

H

»• 2P(0)-CPh=»C-HHMe XR» R

-RgPCO)-CHPh-CONHMe

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS

250

CHEMISTRY

Literature Cited

1. Kolodiazhnyi, Ο . I . ; Zh. Obsch.Khim. 1979, 49, 716. 2. Kolodiazhnyi, O.I.; Zh.Ubsch.Khim. 1980, 50 , 1485. 3. Kolodiazhnyi, O.I.; Kukhar. V.P.; Zh.Org.Khim. 1978, 14, 1339. 4. Kolodiazhnyi, O.I..; Yakovlev, V . I . ; Kukhar, V.P. Zh.Obsch. Khim. 1979,49,2458. 5. Kolodiazhnyi, O.I. Tetrahedron Letters, in press. 6. Kolodiazhnyi, O.I.; Yakovlev, V.I. Zh.Obsch.Khim. 1980, 50, 55. 7. Kolodiazhnyi, O.I..; Yakovlev, V . I . ; Kukhar, V.P. Zh. Obsch. Chim. 1980,50,1418. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

52 Preparation and Properties of N-(Hydroxycarbonlmethyl)aminomethyl Alkyl- and Arylphosphinic Acids and Derivatives LUDWIG MAIER Ciba-Geigy Limited, Agricultural Division, CH-4002 Basel, Switzerland

The reaction of alkyl- and aryldichlorophosphines (or phosphonous acids) with N-benzylglycin solution yields (N-benzyl-N-hydroxycarbonylmethyl-aminomethyl alkyl- and -arylphosphinic acids of structure 1 (R = alkyl, HOCH) or 2 (R = CC1 , CHC1, C H ), depending on the electronegativity of R: 2

3

[RPC1

2

6

5

H

t

Ί

H

+ 2 H 0 •+] R-P

0

o

Ζ

\

Ζ

î / R-P-CH N

C H

+

l

OH

C

H

2 6 5

C H

2

C 0

+ C,H CH NHCH C0 H

v

2

c

Λ

Ό

υ

Un

- C l

or

o

o

Ζ

D

Ζ

« / R-P-CH Ν

C H

+

H

-

o

Ζ

H

2 6 5

χ

C H

i

+ CH 0

o

2

C 0

2

H

(2)

Debenzylation with hydrogen in the presence of Pd/C as a catalyst in acetic acid or alcohol/water produces N-hydroxycarbonylmethy1aminomethyl)alkyl- and -arylphosphinic acids (3) ï /CH C H R-P-CH N + H 2 \„„ 2 OH CH C0 H 2

6

0

Λ

2

Λ

f R-P-CH NHCH C0 H ι 2 2 2

; ; 0

V

o

TT

2

O

o

+ C.H.CH. 6 5 3

o

H

(3) In the case of the t r i c h l o r o m e t h y l d e r i v a t i v e excess hydrogen must be avoided, otherwise d e c h l o r i n a t i o n occurs and (N-hydroxycarbonylmethyl-aminomethyl)-dichloromethylphosphinic a c i d (4)

J /CH C H CCI -P-CH N ° + 2 H, 3 OH I V CH H rC0 n H H 0

2

2

2

2

J 1

>

CHC1 -P-CH NHCH C0 H I 0

0

2

9

2

0

2

H

(4)

0097-6156/81/0171-0251$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

9

2

252

PHOSPHORUS

CHEMISTRY

is obtained. All phosphinic acid derivatives of structure 3 are obtained as crystalline, white solids of high decomposition points. Depending on the electronegativity of R in 3, the pro­ ducts crystallize either as semihydrochlorides or hydrochloride­ -free. The strong dependence of the P-chemical shift on the pH indicates that all derivatives possess the betaine structure. Thus 3 (R = CH ), dissolved in water, shows a 31p-hemical shift of 30 ppm; at pH 1 (adjusted with HC1) apparently a hydro­ chloride is formed with 31p 32.8 ppm, at pH 8 the monosodium salt ( P 35.6 ppm) and at pH 10 the disodium salt ( P 39.1 ppm) is produced. 31

3

c

31

31

An attempt to synthesize N-hydroxycarbonylmethy1-aminomethylphenylphosphinic acid (5) by o x i d a t i o n of bis(N-hydroxycarbony1methyl)-aminomethyl-phenylphosphini presence of c a t a l y s t s f a i l e d C

H

H/ 6 5 (HO CCH ) NCH Ρ +0 0H Z

X

cat.

1

H

«^6 5 HO CCH NHCH Ρ 0H (5)

1

1

Z

X

obtained. On the other hand, t h i s procedure was s u c c e s s f u l l y used i n the p r e p a r a t i o n of N-hydroxycarbonylmethyl-aminomethy1phosphonic acid [ 1 ] . The phosphinic a c i d s of s t r u c t u r e 3 g i v e c r y s t a l l i n e mono­ amine s a l t s , e.g. 0 » ο CH -P-CH NHCH C0 H · H ^ C ^ - i , m.p. 203-204 C (dec.) 3

2

?

2

OH and form monoesters when treated with a l c o h o l and hydrogen c h l o r i d e , e.g. 6 0 H ι R-P-CH NHCH C0 H + R OH o

(

o

Ζ

0 i 1 R-P-CH NHCH C0 R + H 0

HC1

i

o

o

ι

I I

OH

o

I

I

o

L

o

L

OH

(6) The d i e s t e r s (7) a r e obtained d i r e c t l y by h e a t i n g a mixture of O-alkylphosphonites and tris(N-ethoxycarbonylmethyl)hexahydrotriazine: 0 , »' 3 R-P v

T 2 Ν /"x. H


-

N

R 0 CCH- ^ -CH C0 R 2

2

2

2

2 3 R-P-CH-NHCH.CO.IT °

R (

?

)

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

52.

MAiER

Alkyl-

and Arylphosphinic Acids

and

253

Derivatives

However, i n t e r a c t i o n of 0-ethyl-2-chloroethylphosphonite and tris(N-ethoxycarbonylmethyl)hexahydrotriazine produces the l-ethoxycarbonylmethyl-l,3-azaphospholidine-3~ethoxy-3-oxide ( 8 ) : CH C0 R j2 2 o

0 H/H 3 C1CH CH P 2

2

+

N

O C

H

[ N s

2 5

o

Λ

0 /*^Inr Η

—s*» 3

I

2

N x

R0 CCH ^ ^ CH C0 R 2

2

5

2

2

(

g

)

Furthermore, cyanomethyIdichlorophosphine (b.p.^5 85-88°C, P 159.47 ppm) and 2-chloroethyIdichlorophosphine ( b . p . 98-102°, ^ P 182.8 ppm) when treated with b e n z y l g l y c i n e and formaldehyde in acetic acidic solutio

3 1

9 3

3

H0 CCH N-CH„P 2 N 2 o

o

v

\

w

9, R = CH C,H 2 6 5 11, R = H 0

C

10, R = CH C,H 2 65 0

Q

These on d e b e n z y l a t i o n y i e l d 11 (N-glycinomethyl-carboxymethylphosphinic a c i d ) and 12 (1,4,6-oxazaphosphocane-2-oxo-6-hydroxy6-oxide), r e s p e c t i v e l y . The s t r u c t u r e of the compounds has been confirmed by mass- and nmr-spectroscopic i n v e s t i g a t i o n s . Literature Cited

1. Monsanto Co., U.S. Patent 3 969 398 (1976) RECEIVED

June 3 0 , 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

53 Some Aspects of Aminoalkylphosphonic Acids Synthesis by the Reductive Amination Approach P. S A V I G N A C Equipe CNRS-SNPE, 2-8 Rue Henry Dunant, 94320 Thiais, France N. COLLIGNON I.N.S.C.I.R., B.P. 08, 76130 Mont-Saint-Aignan, France

The discovery by Horiguchi and Kandatsu in 1960 of 2-aminoethy1 phosphonic acid (ΑΕΡΑ) represent rence of a covalent C-P bond biologica materials (1). Severa laboratories attempted to elucidate the biosynthesis of the C-P bond. Horiguchi, who was studying the problem of ΑΕΡΑ induction, proposed two approaches (2) (Scheme 1). In the first, phosphonopyruvic acid (II) a substance produced by rearrangement of phosphoenolpyruvate (I) is readily decarboxylated to phosphonoacetaldehyde (III) and then via amination converted to ΑΕΡΑ. In the second, phosphonopyruvic acid (II) is at first transaminated to phosphonoalanine (IV) and then decarboxylated to ΑΕΡΑ. Recently Horiguchi has suggested that phosphonoalanine (IV) was deaminated in preference to decarboxylation (3). As seen in Scheme 1 a route similar to the biological pathway has now been explored by the inde­ pendent synthesis of each precur­ sors by chemical means. Work pre­ sented in this communication des­ cribes the production of synthetic 2-aminoethylphosphonic acids by the controlled reductive amination of 2-oxoalkylphosphonate diesters (Scheme 1) B r i e f l y we review the chemical improvements which we achieved i n the oxoalkylphosphonates f i e l d which represent the key com­ pounds . Phosphonic aldehydes are obtained i n adapting the Arbuzov procedure to $ or h a l o k e t a l s (4). A m o d i f i c a t i o n of the phosphon y l a t i o n c o n d i t i o n s (t°, stolchiometry) followed by removal of the p r o t e c t i n g group i n d i l u t e a c i d and then continuous e x t r a c t i o n allows synthesis of s u i t a b l y branched compounds on a large s c a l e (5). 0097-6156/81/017l-0255$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

256

PHOSPHORUS CHEMISTRY

1

R i BrCH (CH) CH(0R) 2

n

+

1

R ! * (RO) PCH (CH) CH(OR)

2

2

(RO)^P

2

I

n

1

H

+

2

R i ^ (RO) PCH (CH) CH0 2

2

n

0

Ο n-Buli

2

R -X η = 0,1 R

2

R

1

R

(R0) PCH(CH) CH(0R)2 It 0

2

R

1

» (RO) PCH(CH) CHO |l 0

2

2

n

n

Because of the Perkow r e a c t i o n the above route f o r the pro­ d u c t i o n of ketophosphonate By c o u p l i n g α-copperalkylphosphonate been able to produce i n one step ketophosphonate c o r r e c t l y funct i o n a l i z e d as w e l l as phosphonopyruvates i n good y i e l d and high p u r i t y (6). l R

i' (R0) PCH 2

n-Buli Ϋ Cul f » (R0) PCHLi » (R0) PCHCu

2

2

^ ™ ^ ™ f 0 0

2

Il

II

«

0

0

0

C

£ K

°Φν

1 R (R0) PCHCC00R 2

II

0 R = Me,Et

R

1

= Η,Me,Εt

R

2

= alkyl,

aryl...

Phosphonopyruvate systems were the f i r s t candidates submit­ ted to r e d u c t i v e amination. Because of the presence of the e s t e r group, the α-ketoester carbonyl i s l e s s r e a c t i v e than t r a d i t i o n a l oxoalkylphosphonates, and y i e l d s of i s o l a t e d amino-esters never exceeded 55 %. The r e a c t i o n i s run at ρΗ 7 i n ethanol and i t i s general f o r ammonia and primary amines. S t e r i c hindrance repre­ sents the second l i m i t i n g f a c t o r s i n c e α-substituted or thionophosphonopyruvates r e a c t s l u g g i s h l y ; thus secondary amines cannot be introduced. When the r e d u c t i v e amination process i s e f f e c t e d the e x c l u s i v e by-product i s the α-hydroxyester which a r i s e s by r e d u c t i o n of the carbonyl group (7-8). D1 3

I X = 0,S

R1

D1

I NaBH CN,EtOH (RO)pPCHCCOOR m

I

H NR3 2

R

3

= H, Me, E t

| (RO) PCHCHC00R 2

II

1^3

H+

HO | m. >PCHCHC00H

HQ/11

I

H R 3

25 - 70 %

The amino-esters were hydrolyzed i n aqueous EC1 to give phosphonoalanine as a l a r g e v a r i e t y of d e r i v a t i v e s .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

53.

SAViGNAC A N D COLLIGNON

Aminoalkylphosphonic Acids

257

Reductive amination was next c a r r i e d out w i t h the ketophosphonates. Our r e s u l t s i n d i c a t e that the s t e r i c hindrance around the carbonyl i s the l i m i t i n g f a c t o r . However the y i e l d s can be i n creased by i n c r e a s i n g the r e a c t i o n time without any side r e a c t i o n s lowering the p u r i t y of the products. Ammonia, primary and secondary amines can be introduced ; each one r e a c t s i n the enaminophosphonate form. Using ketophosphonate bearing f u n c t i o n a l groups we have observed e i t h e r a p a r t i c i p a t i o n of the f u n c t i o n a l group (halogen , ester or unsaturated group) to the r e a c t i o n or the complete conservation of the f u n c t i o n (aromatic group). The r e a c t i o n conduces a f t e r h y d r o l y s i s to a c i d s c o n t a i n i n g an asymétrie carbon. D1

D1

I NaBHjCN (R0) PCHCR —(R0) H » tWK HNRκR '

j

H+

HO

ο1 j

2

2

3

0

R

3

,

i+

0

0

h

= R = H, Me,

3k

m

ο

R

Et

NR R Q

55 - 80 %

The t h i r d type of compound studied were phosphonic aldehydes which are more r e a c t i v e . S t e r i c f a c t o r s are absent but we observe a d i f f e r e n c e i n behavior among phosphonicaldehydes according to the length of the carbon chain. Phosphonoacetaldehyde r e a c t s almost e x c l u s i v e l y i n the enaminophosphonate form which i s l e s s r e a c t i v e than the iminophosphonate form observed i n the case of homologous compounds. As f o r the aminating reagent we observe some d i f f e r e n ­ ces. Ammonia always leads to a mixture of aminophosphonate ( i ) and aminodiphosphonate ( i i ) while primary and secondary amines lead s p e c i f i c a l l y to monocondensed compounds ( i ) (9). R

1 U

I 3

^(R0) P(CH) CH NR R 2

n

Lf

2

— •

Il

ϋ 1

I NaBH CN (R0) P(CH) CH0 »

R

A

1

I

H+

Np(CH) CH NR R m 110 3

n

i4

2

3

2

R

n

I η = 1,2

3

HNR R

R

i[R0)2|(tH) CH ]M

4

n

2

^ | o > | ( t H ) C H ] NH n

2

12

The above route f o r the production of primary aminophosphonic acids was abandoned f o l l o w i n g t h e i r s u c c e s s f u l s y n t h e s i s , i n good y i e l d and high p u r i t y , by the s u c c e s s i v e d e b e n z y l a t i o n (H /Pd/C)~ h y d r o l y s i s (aqueous HC1) of benzylaminoalkylphosphonate d i e s t e r s (10). 2

D1

D1

pi

j H NCH 0 f HO f (R0) P(CH) CHO ^ (R0) P(CH) CH=NCH 0 — * ^ P ( C H ) CH NH 2

2

2

2

Il 0

n

η = 1,2

II 0

2

n

2

HO^II 0

N

47 - 90 %

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2

258

PHOSPHORUS

CHEMISTRY

In a d d i t i o n since the r e a c t i o n of 2-oxoethyl - phosphonate with amines showed a p r e f e r e n t i a l formation of an enaminophosphonate, we used that s t r u c t u r e f o r the production of s p e c i f i c a l l y nitrogen s u b s t i t u t e d compounds by the f o l l o w i n g sequence of reac­ tions (11). H NCH 0 2

2

(RO) PCH CHO 2

2

^ NaH (RO) PCH=CHNCH 0 « ^ 2

2

I

R

0

2

"

X

f (R0) PCH=CHNCH 0 2

2

0

H /Pd/C 2

HO ?

'

Me

>

E

t

'

P

r

35 - 55 %

5 2CH NHR2 2

H

A l l the aminophosphoni y i e l d and p u r i f i e d by th IRA 410, 0ΗΓ form).

acid

d

H+

PCH

0

0 obtained i

d

Literature Cited

1. Horiguchi, M ; Kandatsu, M. Agr. Chem. Soc. Japan. 1960,24,565 2. Horiguchi, M ; Kittredge, J.S ; Roberts, E. Biochim .Biophys Acta 1968,165,164 3. Horigane, A ; Horiguchi, M ; Matsumoto, Τ ; ibid. 1979,572,385 4. Razumov, A.I ; Liorber, B.G ; Moskva, V.V ; Sokolov, M.P Russ. Chem. Rev. 1973,42,538 5. Varlet, J.M ; Fabre, G ; Sauveur, F ; Collignon, Ν ; Savignac, Ρ Tetrahedron (in preparation) 6. Mathey, F ; Savignac, Ρ ; Tetrahedron 1978,34,649 7. Borch, R.F ; Bernstein, M.D ; Durst H.D.J. Am. Chem. Soc 1971, 93, 2897 8. Varlet, J.M ; Collignon, Ν ; Savignac, Ρ ; Can . J . Chem 1979, .57, 3216 9. Isbell, A.F ; Englert, L.F ; Rosemberg, H ; J. Org. Chem 1969, 34, 755 10. Szczepaniak, W ; Kuczynski, Κ ; Phosphorus and Sulfur 1979,7, 333 11. Nagata, W ; Hayase, Y ; J. Chem. Soc (c), 1969, 460 RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

54 Recent Results on Open-Chain and Cyclic Phosphanes and Organylphosphanes MARIANNE BAUDLER Institut für Anorganische Chemie der Universität Köln, Greinstrasse 6, D-5000 Köln 41, FRG

Compounds containin skeleto f cumulated P-P bond hav been rare until recently This means that they can easily be oxidized and have a strong tendency to disproportionate. Nevertheless, considerable progress has been achieved in this field lately. Thereby a significant analogy of phosphorus- to carbon-chemistry became apparent with respect to structural features. Phosphorus Hydrides Since 1965 we have found an unexpected number of binary phos­ phorus hydrogen compounds in addition to the well-known hydrides PH and P H (Table I). These phosphanes have been detected in the hydrolysis products of calcium phosphide or in the thermolysis products of P H (1,2) by mass spectroscopy. Only the compounds Ρ H , P H , Ρ H , and P H could be isolated in pure form so far, whereas the other phosphanes have been obtained only as mixtures. As the detailed structures are mostly unknown, a P-NMRspectro­ scopic investigation was initiated. Beginning with tetraphosphane(6), the structural situation of the open-chain phosphanes becomes more and more complex due to the existence of constitu­ tional and configurational isomers. The low temperature P{ H}3

2

4

2

3

5

4

6

5

4

5

7

3

13

NMR s p e c t r u m o f Ρ Η c o u l d b e s i m u l a t e d v e r y s a t i s f a c t o r i l y b y t h e 4 6 s u p e r p o s i t i o n o f two A A B B ' - s p i n s y s t e m s f o r t h e d,1- a n d mesoisomer o f n-P^H a n d o n e AB s p i n s y s t e m f o r i - P ^ H ^ w i t h a b r a n c h ­ ed P - s k e l e t o n (3). I n a s i m x l a r way t h e f o u r NMR s p e c t r o s c o p i c a l l y d i s t i n g u i s h a b l e i s o m e r s o f pentaphosphane(7) have been i d e n t i f i e d . The b r a n c h e d i - P ^ H ^ shows t h e h i g h e s t r e l a t i v e f r e q u e n c y . The c h e m i s t r y o f t h e h i g h e r h o m o l o g u e s o f PH^ was u n t i l t h e p r e s e n t a l m o s t unknown. We h a v e t h e r e f o r e i n v e s t i g a t e d f i r s t t h e m e t a l l a t i o n o f d i p h o s p h a n e (5). The r e a c t i o n o f P^H^ w i t h n - B u L i or L i P H y i e l d s the polyphosphide L i ^ P · 3 s o l v e n t s ^ a s t h e f i n a l product. A s i g n i f i c a n t feature o f the t r i c y c l i c P ion i s i t s f l u c t i o n a l behavior which i s analogous t o t h a t i n bu||valene, a s f o u n d b y s t u d y i n g t h e t e m p e r a t u r e d e p e n d e n c e o f t h e P-NMR s p e c 1

2

7

0097-6156/81/0171-0261$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

262

PHOSPHORUS

CHEMISTRY

to -J

56.

RiCHMAN E T AL.

Homologous

Cyclic

Phosphoramides

273

Two of the oxides, 5 and 6, shown i n the Table can exist i n only one structural form.

Both 5 and 6 show only one phosphorus NMR signal at +25.8 and +11.7 ppm, respectively, similar to the shift of hexamethylphosphoric triamide, δ +23.4. The higher f i e l d chemical s h i f t of 6 compared to 5 i s consistent with the effect of bond angle changes at phosphorus which for 5 and 6 are located at bridgehead p o s i ­ tions of fused 5,6- and 6,6-membered rings. The other members of the series of oxides shown i n the Table exhibit structural isomers and i n each case show two or more P NMR signals. The assignments of chemical shifts i n the Table to the various i s o ­ meric forms are analogous to the shifts of 5 and 6 and are consis­ tent with the expected effects of angle changes at phosphorus fused i n rings of different s i z e s . The chemical shifts change about 15 ppm to higher f i e l d on expansion from fused 5,5- to 5,6and 5,6- to 6,6-membered rings. This is comparable to the trends observed previously for analogous polycyclic compounds containing tetravalent and pentavalent phosphorus atoms. 5

6

31

4

7

The assignments for the 2,2,3,3 isomer, 7, are shown below.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

274

The s t a t i s t i c a l d i s t r i b u t i o n o f isomers la> b and c would be 1:2:1. The near absence o f isomer ^7a i n d i c a t e s unfavorable thermodynamic s t a b i l i t y f o r the phosphorus fused i n two f i v e membered r i n g s compared to 5,6- and 6,6-fusion. Greater s t a b i l i t y f o r the l a r g e r r i n g f u s i o n i s a l s o e x h i b i t e d f o r compounds were obtained i n a 85/15 r a t i o while the synthesis of 9_, using an aminodiol with a nor-ephedrine branch, leads to a s i n g l e diastereoisomer. S t a r t i n g w i t h the l i g a n d prepared y ^ t h + nor-ephedrine wg i s o l a t e d 9 i n pure enantiomeric form ( α = +86.8 c = 2.10 M i n benzene ) . Conformation : The s k e l e t o n of these molecules appears as a two-pitched r o o f , the lone p a i r s of phosphorus and n i t r o g e n being located on the r o o f . The study of the conformation of the f i v e membered r i n g s was performed i n the c l a s s i c a l way by d e t a i l e d a n a l y s i s of the proton NMR parameters. The conclusions are : the f i v e membered r i n g s have a blocked conformation. This i s to be expected as c y c l i s a t i o n s are accompanied by strong c o n s t r a i n t s . The most l i k e l y blocked c o n f o r ­ mation taken on by the r i n g s i s an envelope form, the carbon atoms l i n k e d to oxygen being at the end of the f o l d s . These f o l d s can be o r i e n t e d i n respect to the pseudoπ p o s i t i o n of the lone p a i r s of phosphorus and n i t r o g e n . The d e t a i l e d examination of the proton NMR parameters leads us to conclude that q u i t e g e n e r a l l y the phosphanes s t u d i e d have an endo-endo conformation J_2_

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

57.

BONNINGUE E T A L .

277

Bicyclophosphanes

O l i g o m e r i z a t i o n : The marked tendency of these bicyclophosphanes towards o l i g o m e r i z a t i o n i s an o b s t a c l e to t h e i r p u r i f i c a t i o n . In s p e c i f i c cases, 1__ and 10, t h i s d i f f i c u l t y became an advantage. I t appeared that the o l i g o m e r i z a t i o n was a step by step process and we were able to i s o l a t e pure dimers noted [_7]^ and [ΐθ1 p£ » Our r e s u l t s show the g e n e r a l i t y o f the macrocyclisaWion process™ considered as a set o f e q u i l i b r i a between n-mers, ( η = 1,2,3...) described f i r s t (8) and developed by J.B. Robert e t a l . ( 9 ) . Our examples are o r i g i n a l under s e v e r a l points : ( i ) the dimers are r e a d i l y a v a i l a b l e , ( i i ) we are not o b l i g e d t o s u l f u r i z e the t r i c o v a l e n t phosphorus atom i n order tçjj i s o l a t e them, ( i i i ) f Z l n i * f 1 θ] j , appear i n N.M.R. ( H and P) as a unique diastereoisomer, among ?he s i x which are p o s s i b l e . An X-Ray determination has con­ firmed t h i s statement f o r [ j _ o ] ^ » « I t also shows that the d i m e r i z a t i o n takes place e x c l u s i v e l cyclodecane c e n t r a l par conformation and the r e l a t i v e o r i e n t a t i o n of the two phosphorus lone p a i r s i s t r a n s . Chemical P r o p e r t i e s : The r e a c t i v i t y o f bicycloamidophosphites has been explored by means of Ρ N.M.R. spectroscopy, u s i n g mainly the racemic mixture 9 as a r e p r e s e n t a t i v e d e r i v a t i v e o f t h i s c l a s s o f compounds. As we have already mentioned these com­ pounds add e a s i l y X-H molecules to give the corresponding hydrido phosphoranes j6. With a l c o h o l s ROH ( R = Me, E t , n.Pr ) the r e a c ­ t i o n takes place immediately and the p o t e n t i a l tautomers 9a, 9b and 9c do not appear. With t-BuOH the a d d i t i o n i s slowed down and m

a n c

m

p

1

m

Ph Me >H

Ν

Ρ OR

Ν — Ρ OR

hT

9a

2*

9b

the formation of the phosphorane has been followed k i n e t i c a l l y . The r e a c t i o n i s o f second order and presents a s i g n i f i c a n t i s o t o p i c e f f e c t using t-BuOD. Several phenols have given s i m i l a r r e s u l t s , the o x i d a t i v e a d d i t i o n beeing a l s o s e n s i t i v e to s t e r i c hindrance. These r e s u l t s enable us to understand more complicated r e a c t i o n s as with p y r o c a t e c h o l . With benzoic açid, the a d d i t i o n compound 6 > ( X = C^-C-0- ) : δ Ρ = -43.3 J _ = 820 Hz p

Ph

u

Me

i s observed as an intermediate and the f i n a l product i s the eight membered r i n g JL3 which has been c h a r a c t e r i z e d , i s o l a t e d and analysed : δ

3 I

P = +5.7,

^

ρ

_ - 733 Hz. Η

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

278

PHOSPHORUS

CHEMISTRY

With amines, the v a r i e t y of r e s u l t s i s l a r g e r . There i s no r e a c t i o n w i t h p y r r o l e , diphenylamine o r N-methy1aniline, but with a n i l i n e , the e q u i l i b r i u m phosphane + amine -± aminophosphorane i s s h i f t e d to the r i g h t s i d e (>65%). With propylamine and methy1amine, only the phosphorane i s present. The o x i d a t i o n of occurs w i t h p y r i d i n e oxide, d i m e t h y l s u l f o x i ^ e and N^O,. The expected f i n a l product J_4 has been detected (6 Ρ = +18 ; i s o l a t e d and c h a r a c t e r i z e d . The d e t a i l e d o x i d a t i o n process i s not simple and intermediates a r e detected before the accomplishment o f the o x i d a t i o n . Compound _L4 a l s o c o l l a p s e s i n t o s e v e r a l t e t r a c o o r d i n a t e d phosphorus e n t i t i e s . Conclusion : As expected, the double c y c l i s a t i o n o f b i c y c l o phosphanes induces a strong r i n g c o n s t r a i n t . The marked tendency of these compounds to o l i g o m e r i z a t i o i s c e r t a i n l y favoured becaus d r i v i n g f o r c e o f the a d d i t i o great s t a b i l i t y o f the bicyç^çphosphorane s t r u c t u r e . Depending upon the nature o f X, the Ρ tautomer forms of the l a s t compounds could be observed o r n o t .

REFERENCES 1- D. Houalla, F.H. Osman, M. Sanchez and R. Wolf, Tetrahedron Letters 1977, 3041. 2- K. Sommer, W. Lauer and M. Becke-Goering, Z. Anorg. Chem. 1970, 379, 48. 3- C. Bonningue, D. Houalla, M. Sanchez, R. Wolf and F.H. Osman, J.C.S. Perkin II 1981, (1), 19. 4- C. Bonningue, Thèse de l'Université Paul Sabatier. Toulouse Juin 1980. 5- D. Grec, L.G. Hubert-Pfalzgraff, J.G. Riess and A. Grand, J . Amer. Chem. Soc. 1980, 102, (23), 7133. 6- D.B. Denney, D.Z. Denney, P.J. Hammond, Chialang Huang and Kuo-Shu Tseng, J . Amer. Chem. Soc. 1980, 102, (15), 5073. 7- D.B. Denney, D.Z. Denney, D.M. Gavrilovic, P.J. Hammond, Chialang Huang and Kuo-Shu Tseng, J . Amer. Chem. Soc. 1980, 102, (23), 7072. 8- J.P. Albrand, J.P. Dutasta and J.B. Robert, J . Amer. Chem. Soc. 1974, 96, 4584. 9- (a) J.B. Robert and H. Weichmann, J . org. Chem.1978, 43, (15), 3031. (b) J . Martin and J.B. Robert, Nouveau J . Chimie, 1980, 4, (8-9) 515. 10- J . Jaud, J . Galy, D. Houalla, C. Bonningue and R. Wolf, to be published. RECEIVED July 7,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

58 Reactions of 2,4-Bis(4-methoxyphenyl)-1,3,2,4dithiadiphosphetane 2,4-Disulfide SVEN-OLOV LAWESSON Department of Organic Chemistry, Chemical Institute, University of Aarhus, D K - 8 0 0 0 Aaarhus C, Denmark

The r e a c t i o n of anisole with high y i e l d s the title cially available)

PS

produces i n

In the s o l i d phase LR is i n the Ε - f o r m , but i n s o l u t i o n the Ρ NMR spectrum shows about 10 absorp­ tions showing that d i f f e r e n t species are present and that precautions should be exercised when considering mechanisms. We now want to report on LR as a t h i a t i o n reagent and i n synthesis of P - h e t e r o c y c l e s . It should be noted that LR also reacts with nucleophiles and i s a deoxygenation reagent. 31

LR i s superiour to most of the t h i a t i o n agents h i t h e r t o known as i t i s - e a s i l y prepared from inexpensive m a t e r i a l s - stable at room temperature and easy to handle - r e a c t i n g at r e l a t i v e l y low temperature (-20-140ºC) - forming a stable product a f t e r the>C=O->>C=St r a n s formation. It has thus been found that LR smoothly t r a n s forms - ketones i n t o thioketones - amides i n t o thioamides - lactams i n t o thiοlactams - N ' , N ' - d i s u b s t i t u t e d hydrazides into thiohydrazides - esters i n t o O - s u b s t i t u t e d t h i o e s t e r s - S-substituted t h i o e s t e r s into d i t h i o e s t e r s - lactones into thionolactones thiοlolactones into d i t h i o l a c t o n e s

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280

PHOSPHORUS

CHEMISTRY

pyrazolidinediones into pyrazoline-5-thione disul­ fides - enaminones i n t o enamino-thiones - peptides into thiopeptides ( s e e S c h e m e 1 , r e a c t i o n s 1 - 5 a n d Scheme 2 , r e a c t i o n 1 θ) -

Scheme 1.

I t i s a s s u m e d t h a t LR e x i s t s i n s o l u t i o n a s t h e d i m e r ( E a n d / o r Z ) o r a s monomer ( t r i c o o r d i n a t e d p e n tavalent species (2))

LR

^

p

2

S

CH 0-^Oy ^ —^ 3

S

2

CH 0-^h-P^^ ^— ^S 3

e

y

When r e a c t i n g LR w i t h d i f f e r e n t b i f u n c t i o n a l s u b ­ s t r a t e s (Schemes 1 and 2 : r e a c t i o n s 7 - 9 » 1 1 - 1 6 ) diffe­ rent types o f P-heterocycles are formed. Also d i s p i r o t r i t h i a p h o s p h e t a n e s a r e formed from cycloalkanones.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

58.

LAWESSON

Substituted

281

1,3,2,4-Dithiadiphosphetane

Scheme 2.

(9)

Ν — Ν

(16)

Ph P=S ι R

(15)

S 0 II "P-R l! ê

R S ι u Z-NH-CH-C-NH-CH-COOR

0 il R-C-NH-NHPh R 0 R' C=N-NHPh |Z-NH-CH-C-NH-CH-COOR

M

COOR* C=N^0H -

L

Cl

\

COOR

/

Ο

IS

R

S >-R

X.Y

=o,s

R'^H (11)

COOH NH,

N-C-R

" S "Co

C-NHR'

II

\

Ο

0

0 P-R (12)

(U)

N-R

Ο (13)

P-R H s

1. Thomson, I., Clausen, K . , Scheibye, S . , Lawesson, S . - Ο . Org. Synth. (submitted). 2 . Bertrand, G . , M a j o r a l , P . , Baceiredo, A. T e t r a ­ hedron L e t t e r s 1 9 8 0 , 5051. RECEIVED

June 30, 1981. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

59 Small Rings with Tervalent Phosphorus E K K E H A R D F L U C K and HORST RICHTER Institute of Inorganic Chemistry, University of Stuttgart, Pfaffenwaldring 55, D-7000 Stuttgart 80, F R G

3

3

In recent years diaza-λ ,λ -diphosphetidines (I) have found increasin

They can occur as cis and/or trans isomers (1). While R is always a dialkylamino, a bis(trimethylsilyl)amino group or a halogen atom,R' v a r i e s more. As to the compounds which are described i n li­ terature R' is very often a phenyl group (2), i n other cases a t - b u t y l (3) or t r i m e t h y l s i l y l (4) and in very few cases an a c y l group (5). We are able to synthesize the diazadiphosphetidine (II) i n which R' is a phosphoryl group. By reaction of amidophosphoric d i e t h y l ester with t r i s ( d i e t h y l amino) phosphane i n the absence of a solvent, II can be obtained i n 80% y i e l d according to eq. (1) and (2):

0097-6156/81/0171-0283$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

284

PHOSPHORUS CHEMISTRY

II forms c o l o r l e s s c r y s t a l s which are extremely s e n s i t i v e towards oxidation and h y d r o l y s i s . The che­ mical s h i f t of the r i n indicated, that the sumption was v e r i f i e d by X-ray s t r u c t u r a l analysis (molecular symmetry c ). i

If the reaction is c a r r i e d out i n the presence of a solvent such as toluene the intermediate product I I I does not s p l i t o f f diethylamine. By proton migration IV i s formed as the only product of r e a c t i o n :

1

The nmr coupling constants i n IV are J(PH) = 580 Hz, J(PP) = 46.7 Hz. Reaction of amidophosphoric diphenylester with tris(diethylamino)phosphane y i e l d s only 10% of the diazadiphosphetidine, even i n the absence of a solvent. The main product i s compound V. 2

By oxidation of II with mercury(II)-oxide the di­ aza-λ ,λ -diphosphetidine VI was obtained, c o l o r l e s s c r y s t a l s of m.p. 62 °C. The same product i s obtained when pure oxygen i s used f o r oxidation though it i s always accompanied by impurities of the corresponding diaza-λ ,λ -diphosphetidine VII. With elemental s u l f u r II can be oxidized to give mono- (VIII) and d i s u l f i d e (IX). Both form c o l o r l e s s c r y s t a l s having melting points of 56-57 °C and 135 °C, respectively. 3

5

5

5

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

59.

FLUCK AND

Small Rings

RICHTER

0=P(OC H ) 2

N

/ (C H ) N-P \ 9

q

1

b

\

9

1

N

5

2

2

VI

5

Tervalent

Phosphorus

0=P(OC H )

2

2

,0[S] p' / N(C H )

I 0=P(OC H )

with

5

(C H ) N 2

5

2

P

y /

[S]0

2

N

/

N

\

0[S]

N

/

N(C H ) 2

I 0=P(OC H )

2

2

[VIII]

2

P'

v

\

5

285

5

5

2

2

V I I [IX]

Reaction of phenylphosphonic d i a n i l i d e with t r i s (diethylamino)phosphane yields colorless crystals of compound X (m.p. 156-15 phenylsulfamide wit p o u n d X I , w h i c h i s t h e f i r s t member o f t h e c l a s s o f thiadiazaphosphetidines containing tervalent phos­ phorus. The c o l o r l e s s c r y s t a l s melt a t 94-95 ° C . With elemental sulfur the corresponding sulfide i s ob­ tained. Î6 5

2

X

0

I

/

\

/ P

N ( C

2

H

5>2

X

N

I

C H 6 5 C

In changed mixture

n

C

X

C H 6 5 C

C

XI

compound X t h e d i e t h y l a m i n o group c a n be e x ­ f o r c h l o r i n e when i t i s r e a c t e d w i t h P C l ^ . A o f i s o m e r s o f X l l a and X l l b was o b s e r v e d .

H

?6 5

|6

5

I C

H

6 5

Xlla

C

H

6 5

Xllb

In a s i m i l a r way t h e d i e t h y l a m i n o group i n t h e r e a c t i o n product o f Ν,Ν'-dimethylurea and t r i s ( d i ­ ethylamino) phosphane, compound X I I I (6), was r e a c t e d w i t h P C 1 ~ . The product,however, was compound X I V .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

286

0=C

P-N(C H ) 2

CH

5

2

+ 2 PC1

0=C

3

\

N-PC1 i

3

XIII

XIV +

PC1 [N(C H ) ] 2

2

5

2

Literature Cited 1.

2.

3. 4. 5.

6.

see e.g. Pohl, S. Z. Naturforsch. 1979, 34b, 256. Schwarz, W.; Hess, H.; Zeiss, W. Z. Naturforsch. 1978, 33b, 723. - Keat, R.; Keith, Α. Ν . ; Macphee, A.; Muir, K. W.; Thompson, D. G. J. Chem. Soc. Chem. Commun. 1978, 372. see e.g. Grimmel, H. W.; Guenther, Α . ; Morgan, J.F. J. Am. Chem. Soc. 1946, 68, 539. - Zeiss, W.; Weis, J. Z. Naturforsch. 1977, 32b, 485. - Fluck, E.; Wachtler, D. Liebigs Ann. Chem. 1979, 1125. Scherer, O. J.; Klusmann, P. Angew. Chem. 1969, 81, 743. Niecke, E.; F l i c k , W. J. Organometal. Chem. 1976, 104, C23. - Zeiss, W.; Feldt, C h . ; Weis, J.; Dunkel, G. Chem. Ber. 1978, 111, 1180. D e v i l l e r s , J.; Willson, M . ; Burgada, R. B u l l . Soc. Chim. France 1968, 4670. - Bowden, F. L.; Dronsf i e l d , A. T . ; Haszeldine, R. N . ; Taylor, D. R. J. Chem. Soc. Perkin I, 1973, 516. Bermann, M.; Van Wazer, J. R. J. Chem. Soc. Dalton 1973, 813.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

60 The Unexpected Formation of 1,2-Oxaphosphol-3ene 2-Oxides in the Reaction of Diacetone Alcohol with Phosphonous Dihalides K U R T M O E D R I T Z E R and R A Y M O N D E. M I L L E R Monsanto Agricultural Products Company, Research Department, 800 North Lindbergh Boulevard, St. Louis, MO 63166

In exploring various synthetic methods for the preparation of 1,2-oxaphospholene 2-oxide diacetone alcohol (4-hydroxy-4-methyl-2-pentanone and phenylphosphonous dichloride, which was reported (1) to pro­ ceed as shown i n eq (1) to give 2,3,3,5-tetramethyl-1,2-oxaphosphol-4-ene 2-oxide or the corresponding 2-phenyl derivative,

respectively. In the course of these studies we found, however, that the d i s t i l l e d product samples of the reaction of eq (1) dis­ played two P nmr signals. For R=CH (bp 120-144°/0.2 mm, 61% yield) the two signals (in the approximate intensity ratio 8:1) were at +77.0 and +61.8 ppm, respectively, with the chemical shifts measured versus 85% H P O and with downfield shifts being positive. For R=C H (bp 160°/0.1 mm, 80% yield) the two signals were at +65.9 and +52.3 ppm, respectively, also i n the approx­ imate intensity ratio of 8:1. By slow spinning band d i s t i l l a t i o n i n each case (R=CH , C H ) the two compounds corresponding to the two 31P nmr signals were separated with the major product i n both instances having the downfield P nmr chemical s h i f t (R=CH , δ P + 75.1, 36% yield; 6 5, δ · 58% y i e l d ) . These compounds were identified spectroscopically (1H and C nmr, MS, IR) and by microanalysis as the expected 1,2-oxaphosphol-4-ene derivatives of the reaction of eq (1). The minor product, having i n each instance the more upfield P nmr chemical s h i f t (R=CH , δ + 59.4, 10% yield); R=C H , δ P + 52.3, 5% yield), was identified spectroscopically ( H and C nmr, MS, IR) and by microanalysis as the isomeric 1,2-oxaphosphol-3-ene derivative of the structure shown below. 31

3

3

6

4

5

3

31

6

31

3

R = C

H

31P +

65

9,

13

31

31P

3

31

6

1

13

0097-6156/81/0171-0287$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

5

5

PHOSPHORUS C H E M I S T R Y

288

Key f e a t u r e s o f the proton nmr s p e c t r a o f l b and l i b are the f o l l o w i n g . The o l e f i n i c proton appears as doublet o f a p o o r l y r e ­ s o l v e d q u a r t e t , l b , δ 6.57, % = 38 H z ; l i b , δ 6.53, J = 38 Hz. The protons o f the two geminal methyl groups on the carbon next t o Ο i n the r i n g are not coupled to phosphorus, however, by v i r t u e of the c h i r a l i t y a t phosphorus appear as two s i n g l e t s , l b , δ 1.42 and 1.50; l i b , δ 1.48 and 1.57. The protons o f the methyl group attached to the o l e f i n i c carbon atom appear as a doublet o f doublets due proton, l b , δ 1.97, J 13, Hz. Further support f o r the s t r u c t u r e of l b and l i b i s d e r i v e d from C nmr s p e c t r a shown i n Table I , with the a s s i g n ­ ments confirmed by off-resonance d e c o u p l i n g . The i s o l a t i o n o f a s o l i d intermediate under c e r t a i n r e a c t i o n c o n d i t i o n s from the r e a c t i o n o f eq (1) f o r R=CH and i t s i d e n t i f i ­ c a t i o n as 3-chloro-2,3,5,5-tetramethy1-1,2-oxaphospholane 2-oxide, shown as compound D i n Scheme I , (mp 97°, δ P +65.7; % nmr, 3

Η

ρ

H

p

3

H

4

2

j

H

H

1 3

3 1

Table I .

1 3

1 J

3 1

C Nmr Chemical S h i f t s ( i n ppm) and C- P Coupling Constants (in parentheses i n H z ) a

2

. Y α// \ 5

c 6 C

lib

lb C-l C-2 C-3 C-4 C-5 C-6 C-7 a)

b)

129.31 148.46 87.20 14.71 28.77 27.71 15.84

Cl

(103.0) (18.4) (3.7) (11.5) (0.0) (2.9) (94.9)

148.80 (19.1) 87.71 (0.0) 11.66 (14.7) 29.06 (0.0) 27.54 (3.0) c

Spectra were obtained a t 25.05 MHz on a JOEL Spectrometer; peaks are r e f e r e n c e d versus TMS s h i f t s being p o s i t i v e . Only the u p f i e l d peak o f the doublet f o r C - l 127.38 ppm, the downfield peak o v e r l a p s w i t h carbons. Resonances f o r the aromatic carbon atoms not

\

W

C

6

R 64.34 (85.5) 51.65 (7.4) 85.13 (0.0) 29.15 (4.4) 31.93 (0.0) 25.55 (0.0) 10.69 (101.5) FX-100 FT NMR with downfield i s seen a t the aromatic

c

c)

shown here.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

MOEDRiTZER A N D M I L L E R

1,2-Oxaphosphol-3-ene

2-Oxides

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

289

290

PHOSPHORUS CHEMISTRY

geminal CH^ groups a t δ 1.53 and 1.55; CH on r i n g carbon atom next t o Ρ δ 1.81, d ( J = 14.9 Hz); C H on Ρ, 6 1.86, d ( J = 13 Hz); CH i s represented by an ABX (X=P) s p i n c o u p l i n g p a t t e r n with 6 2.54, 6 2.47, J = 15.1, J = 10.5 and J = 10.5 Hz; C nmr data i n Table I) g i v e s support t o a suggested mechanism f o r the unexpected formation o f the i s o m e r i c 1,2-oxaphosphol-3-ene 2-oxides as summarized i n Scheme I . In the mechanism o f Scheme I i t appears reasonable t o assume, i n agreement with e a r l i e r s t u d i e s (1) , t h a t s o l v o l y s i s i s the f i r s t step o f the r e a c t i o n o f eq (1). In a second step, i n analogy t o the w e l l documented (2) r e a c t i o n o f P - C 1 compounds with c a r bony 1 groups, A may c y c l i z e t o B_, with 13 having the c a p a b i l i t y o f r e a r r a n g i n g by two pathways, r e s u l t i n g i n £ and/or D (with D having been i s o l a t e d f o give the 4-isomer o r th 3

2

3

2

A

R

3

H p

3

n n

10

I][I

Literature Cited 1. Arbuzov, B . A.; Rizpolozhenskii, Ν. I.; V i z e l , Α. O.; Ivanovskaya, K. M.; Mukhametov, F. S.; Gol'dfarb, Ε. I. Izvest. Akad. Nauk SSSR, Ser. Khim. (Engl. Transl.), 1972, 1827. 2. F i l d , M.; Schmutzler, R.; Peake, S. C.; "Organic Phosphorus Compounds"; Eds. Kosolapoff, G. M.; Maier, L.; Wiley-Interscience, New York, N.Y.; 1972; Vol. 4, p 169.

RECEIVED June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

61 Dihydrophenophosphazines via the Interaction of Diarylamines and Phosphorus Trichloride: Applications and Limitations H A R O L D S. F R E E M A N and L E O N D . F R E E D M A N Department of Chemistry, North Carolina State University, Raleigh, NC 27650

In 1971 i t was shown (1) that the interaction of diphenylamine and phosphorus trichlorid of the reaction mixtur viously described phosphine oxide 1 but also the spirophosphonium chloride 2.

The mechanism of formation of the latter compound (a derivative of PV) from phosphorus trichloride has not been elucidated, but the following mechanism suggested (2) for the formation of 1 seems reasonable:

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In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

292

PHOSPHORUS CHEMISTRY

Studies (2,3) have also been reported of the reaction of phosphorus trichloride with diarylamines containing p-methyl or p-chloro substituents. In every case, the expected ring-substituted derivatives of 1 and 2 were obtained after the reaction mixture was treated with water. The interaction of N-phenyl-O-toluidine and phosphorus trichloride at 200°C also gave a reaction mixture from which the expected phosphine oxide was isolated (3). None of the corresponding spirophosphonium chloride, however, could be obtained. The failure to isolate this substance can not be explained simply by the presence of an ortho substituent in the diarylamine, since i t had been previously found that a 34% yield of a spirophosphonium chloride can be obtained via the interaction of N-phenyl-1-naphthylamineand phosphorus trichloride (2) No dihydrophenophosphazine derivative of di-O-tolylamine and phosphoru It was possible, however, to obtain a small yield of the expected phosphine oxide (isolated as the phosphinic acid) by converting di-O-tolylamine to the corresponding phosphoramidous dichloride, (O-MeC6H4)2NPCl2, dehydrohalogenating the latter substance, and treating the reaction mixture with water. The present paper is concerned with the reaction between phosphorus trichloride and the meta-substituted diarylamines listed in Table I. The TABLE I DIARYLAMINES STUDIED H

3a

R

i

-

3b

R

i

-

3c

R

i

-

3d

R

i

-

R

i

-

3e

3-CF

3

3,5-(CF ) 3

3,5-Me

2

3-Me 3-CF

3

2

R

2

R

2

R

2

R

2

R

2

= H = H = H = 3-CF

3

= 3-CF

3

s u b s t i t u e n t s i n c l u d e both the a c t i v a t i n g , ortho, p a r a - d i r e c t i n g methyl group and the d e a c t i v a t i n g , m e i a - d i r e c t i n g t r i f l u o r o methyl group. Each of the amines was heated with phosphorus t r i c h l o r i d e at 220-250°C f o r about 17 h, and the r e a c t i o n mixtures were then t r e a t e d with water. The f i r s t three amines (3a-3c) y i e l d e d modest amounts of phosphine oxides but no

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

61.

FREEMAN AND FREEDMAN

Dihydrophenophosphazines

293

spirophosphonium c h l o r i d e s , while the other two amines gave no organophosphorus compounds at a l l . A phosphine oxide was obtained from the f o u r t h amine (3d), however, v i a dehydrohalogenation o f the phosphoramidous d i c h l o r i d e a t 220°C. The l a s t amine (3e) could a l s o be converted to a phosphoramidous d i c h l o r i d e , but the l a t t e r substance could not be dehydrohalogenated to a dihydrophenophosphazine d e r i v a t i v e even a t 255°C. An H NMR study of the phosphine oxides obtained from amines 3a and 3d i n d i c a t e d that each oxide c o n s i s t s of a s i n g l e isomer. Of the two p o s s i b l e i s o m e r i c products from 3a, only 3-trifluoromethyl-5,10-dihydrophenophosphazine 10-oxide (4a) was a c t u a l l y i s o l a t e d . The % NMR spectrum o f t h i s substance i n deuterated DMSO showe two s i g n a l s assigned t about 13 Hz). Similarly, analysi spectru of the phosphine oxide obtained from amine 3d i n d i c a t e d that only 3-methy1-7-trifluoromethyl-5,10-dihydrophenophosphazine 10-oxide (4b) was present; no evidence f o r the formation of any o f the three other p o s s i b l e isomers was obtained. ±

4a

R = Η

4b

R = Me

S t e r i c f a c t o r s probably play a key r o l e i n determining the r e g i o s p e c i f i c i t y o f the r e a c t i o n s l e a d i n g to the phosphine oxides 4a and 4b. An intermediate i n v o l v e d i n both cases i s probably o f type 5, i n which r i n g c l o s u r e p r e f e r e n t i a l l y occurs para r a t h e r than ortho to the bulky CF3 group. The pre­ f e r e n t i a l formation o f 5b from the corresponding phosphor­ amidous d i c h l o r i d e i s undoubtedly a s s o c i a t e d with the f a c t that Η

5a

R = Η

5b

R = Me

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

294

PHOSPHORUS CHEMISTRY

the 6 - p o s i t i o n (para to the methyl group) i s l e s s hindered than the 2 - p o s i t i o n (which i s ortho to both the methyl group and the NHC H CF group). The r e s u l t s obtained i n t h i s i n v e s t i g a t i o n suggest that dihydrophenophosphazine s y n t h e s i s from a diarylamine r e q u i r e s that a t l e a s t one r i n g o f the amine must be free o f a metad i r e c t i n g group. I f t h i s requirement i s f u l f i l l e d , the PCI2 group bonded to the n i t r o g e n o f the phosphoramidous d i c h l o r i d e can migrate to an ortho p o s i t i o n of that r i n g , and c y c l o dehydrohalogenation w i l l subsequently occur. The r e g i o s p e c i f i c i t y noted i n the two cases where more than one i s o m e r i c product seemed p o s s i b l e i n d i c a t e s that s t e r i c f a c t o r s must be important i n determining both the s i t e to which the PCI2 group of the phosphoramidous d i c h l o r i d which r i n g c l o s u r e occurs 6

4

3

Literature Cited 1. 2. 3.

J e n k i n s , R.N.; Freedman, L.D.; Bordner, J . Chem. Commun. 1971, 1213. Jenkins, R.N.; Freedman, L.D. J . Org. Chem. 1975, 40, 766. B u t l e r , J.R.; Freeman, H.S.; Freedman, L.D. Phosphorus S u l f u r 1981, 9, 269.

RECEIVED

July 7,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

62 Contributions to the Chemistry of N-Phosphoryl Phosphazenes L. R I E S E L , E. H E R R M A N N , A . PFÜTZNER, J . STEINBACH, and B. T H O M A S Departments of Chemistry, Humboldt University of Berlin and Technical University Dresden, GDR

N-phosphorylated phosphazene quences. N-dialkoxyphosphory (R'O)2PO-N=P(OR)3, especially those with different alkyl groups are biologically active compounds. Tetraesters of imidodiphosphoric a c i d , (RO)2PO-NH-PO(OR)2, formally derived from the former by replacing one alkyl group by a hydroxyl group, are known as indeed good chelate ligands (1). Complex compounds with ligands of this kind are used for separating metal ions by extraction methods. Esters of N-phosphoryl phosphazenes are usually formed by the Staudinger reaction which requires the handling of the extremely toxic phosphoric acid ester azides (eq. 1). F o r developing new synthetic (R'O)2P(O)N + P ( O R ) 3

3

-->

(R'O) P(O)-N=P(OR) + 2

N2

3

(1)

approaches to obtain N-phosphoryl phosphazenes we thoroughly studied both the reaction of C l 3 P = N - P O C l with O-nucleophiles and reactions for P=N-P-bridge formation which avoid handling phosphoryl azides. 2

Solvolysis of C l 3 P = N - P O C l 2 . P2NOCl5 reacts with alcohols in the molar ratio 1:1, forming alkoxydichlorophosphazenes (eq. 2; n=l). Cl2OP-N=PCl3 + n R O H - - > C l 2 O P - N = P C l 3 - n ( O R ) n +

n

HCl

(2)

With excessive alcohol a further substitution occurs at the same phosphorus atom, though due to by-reactions to a considerably smaller extent. For instance in the reaction with ethanol (EtO)Cl P^N-POCU is formed in 97 % yield and (EtO) ClP=N-POCl in 75 % yield but (EtO) P=NP O C l only to an extent of less than 15 %, even when using a great excess of ethanoi. These by-reactions are alkylation reactions (eq. 3), phosphazene-phosphazane rearrangements (eq. 4) and olefin eliminations (eq. 5). In all cases imidodiphosphoryl compounds are formed. ?

2

2

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In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

298

PHOSPHORUS CHEMISTRY

(RC0X P=N-P(O)X

2

(RO)X P=N-P(0)X

2

(RO)X P=N-P(0)X

2

2

2

2

+ Nuc" ~

» Nuc-R +

[X P(0)~NHP(0)X ] " 2

2

fi»X P(0)-NR-P(0)X

R

2

X P(0)-NH-P(0)X 2

2

(3) (4)

2

+ olefin

(5)

X denotes C I o r O R . T h e e x c l u s i v e s u b s t i t u t i o n at the p h o s p h a z e n e s i d e of the m o l e c u ­ le as w e l l as these t h r e e types of b y - r e a c t i o n s c a n be u n d e r s t o o d by t a k i n g i n t o c o n s i d e r a t i o n the f o l l o w i n g m e s o m e r i c form of N - p h o s p h o r y l p h o s p h a z e n e s : ( R O ) X P - N = P ( - O ) X . T h e e l e c t r o p h i i i c n a t u r e of the p h o s p h a z e n e p h o s p h o r u s atom d e t e r m i n e s the s u b s t i t u t i o n o r d e r and e f ­ fects a s t r o n g tendency f o r f o r m i n g a d o u b l e bond between p h o s p h o r u s and o x y g e n c o n n e c t e d w i t p e r t i e s to the a l k y l g r o u p good a l k y l a t i o n agents f o r n u c l e o p h i l e s s u c h as H C 1 , R O and P h N M e f o r m i n g R C 1 , R 0 and P h N R M e , r e s p e c t i v e l y . In the a b s e n c e of e x t e r n a l n u c l e o p h i l e s s e l f - a l k y l a t i o n of the m o l e c u l e i s p o s s i b l e , i n w h i c h the e l e c t r o p h i i i c a l k y l g r o u p w i l l a t ­ tack both the p h o s p h o r y l o x y g e n atom and the n i t r o g e n a t o m . A s o n l y i n the l a t t e r c a s e a s u b s t a n c e without a l k y l a t i n g p r o p e r t i e s i s formed s e l f - a l k y l a t i o n f i n a l l y r e s u l t s i n the r e a r r a n g e m e n t of O - a l k y l into N - a l k y l compounds. N - a l k y l a t i o n takes place p a r t i c u l a r l y r e a d i l y in the c a s e of m o n o a l k o x y p h o s p h a z e n e s , ( R O ) C l P = N - P O C U , w i t h R = M e , E t and C H ^ C / T i - ( 2 ) . M o n o a l k o x y p h o s p h a z e n e s h a v i n g d i f f e r e n t a l k y l g r o u p s ( R i C H , i s o - C g H , C H , C - H , C g H ) form t h e ^ N - a l k y l r e a r r a n g e m e n t p r o d u c t s o n l y at rtigner Temperatures (about 75 C ) and to an e x t r e m e l y s m a l l extent (about 1 % ) . " P e n t a e s t e r s " c a n be r e a r ­ r a n g e d i n t o N - a l k y l d e r i v a t i v e s at about 1 5 0 ° C ( e q . 4; X = O R ; R = E t , B u , H e x ) . T h i s r e a r r a n g e m e n t i s c a t a l y s e d by a l k y l i o d i d e s . e

e

2

2

2

+

2

2

2

c

n

A f t e r a l l t h i s r e a c t i o n c a n a l s o be r e g a r d e d as a c h l o r i n e - o x y g e n e x c h a n g e . S u c h e x c h a n g e g e n e r a l l y seems to o c c u r i n r e a c t i o n s of N phosphoryl t r i c h l o r o p h o s p h a z e n e s with O - n u c l e o p h i l e s . T h i s is demon­ s t r a t e d by the r e a c t i o n s of Ρ Ν Ο Ο w i t h d i m e t h y l f o r m a m i d e and d i m e t h y l s u l f o x i d e ( e q . 6 , 7) as w e l l as by the fact that a l l attempts to synthesize N-dialkoxyphosphoryl trichlorophosphazenes, (RO)~P(0)-N= PC1 have f a i l e d so f a r . B o t h i n the r e a c t i o n of ( E t O ) P O N C 1 w i t h P C n ( e q . 8) and i n the r e a c t i o n of ( E t O ^ P ( O ) N H S i M e w i t h P C I ( e q . 9 i s o m e r i c diethoxyphosphazene ( E t O ) C l P = N - P O C l is obtained instead of t r i c h l o r o p h o s p h a z e n e as s h o u l d be e x p e c t e d . O n l y N - d i p h e n ?

ς

V

2

2

Cl P=N-POCl

2

+ Me NCHO

^|Me N=CClH]

Cl P=N-POCl

2

+ (CH ) SO

^

3

3

(EtO) P(0)NCl 2

2

3

2

+ PC1

(EtO) PONHSiMe 2

3

2

2

[ c ^ P O - N - P O C l J " (6)

C H ^ S - C H ^ l + (Cl PO) NH 2

^(EtO) ClP=N-POCl 2

3

+ PC1

+

5

_ f RC

(EtO) ClP=N-POCl 2

2

2

2

+ C l

2

+ Me SiCl 3

(7) (8) (9)

o x y p h o s p h o r y l t r i c h l o r o p h o s p h a z e n e , ( P h O ) P ( 0 ) - N = P C U , (3) and p r o ­ b a b l y compounds h a v i n g d i f f e r e n t a r y l g r o u p s seem to be s t a b l e . 2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

62.

RiESEL ET AL.

N-Phosphoryl

299

Phosphazenes

Due to the by-reactions (eq. 3 - 5 ) alcoholysis of CUP=N-POCl does not yield the desirable "pentaesters" (RO)^P=N-Pu(OR) . Depending on molar ratio, temperature and time the reaction mixtures contain mono-, di-and trialkoxyphosphazenes, tetrachloride and several esterchlorides of imidodiphosphoric acid. In the presence of a great excess of alcohol the final products are exclusively tetraesters of imidodiphosphoric acid, (RO) PO-NH-PO(OR) . Indeed these can be converted into "pentaesters" t>y reacting with diazoalkanes (eq. 10) (2), which, however, is not a convenient way for synthesizing "pentaesters" . 2

2

2

(RO) PO-NH-PO(OR) + R'N 2

2

(RO) P=N-PO(OR) + N

2

3

Using alcoholates instea trialkoxyphosphazenes, (RO)~P=N-POCl yields. However, this method? does not allo e s t e r s " with different alkyl groups.

2

(10)

2

to synthesize pure "penta

Formation of P=N-P-Bridges. A simple reliable synthesis of Nphosphorylated phosphazenes which avoid the handling of the dangerous phosphoryl azides consists in a direct reaction of d i - and t r i a l k y l phosphites and carbon tetrachloride with sodium azide in a single step procedure (eq. 11). The phosphoryl azides formed intermediately i n stantly react with the trialkylphosphites present. Therefore, their ( R O ) P + ( R O ) P ( 0 ) H + CC1 3

2

— (ROX^N-PCXOR'^

+ NaN^

4

+ CHC1 + NaCl

(11)

3

concentration is kept small all the time. In contrast to the classic Atherton-Todd reaction addition of amines is not necessary. In the absence of trialkylphosphite no reaction occurs; the formation of phosphoryl azides does not occur either. We used phosphites of aliphatic and aromatic alcohols and synthesized about 40 different "pentaesters" with yields up to 95 %. As by-products CI C-P(0)(OR) and small amounts of rearrangement products, (RO) Pîfo)-NR-P(0)COR ) » (P CK ?

2

Χ

/ /

NME

2

Ν I XI Ρ "^NME

V

2

(2) Further c r i s t a l l o g r a p h i e and b a s i c i t y data have been obtained for phosphazenylcyclophosphazenes. Both NPPh groups i n g.-N P CU (NPPh ) have been shown by X-ray crystallography t o have type I I conformations (_2). This i s i n l i n e with evidence from *J (PP) œupling constants and disproves the deduction made 3

3

3

3

2

t

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

64.

SHAW A N D NABI

Cyclophosphazenes

and Related

Compounds

309

e a r l i e r from b a s i c i t y d a t a . I t thus l e a v e s open t h e q u e s t i o n whether so f a r u n e x p l a i n e d d i f f e r e n c e s i n b a s i c i t y s h o u l d be a t t r i b u t e d t o d i f f e r e n t s i t e s o f p r o t o n a t i o n ( e x o v e r s u s endo) o r t o d i f f e r e n t conformations o f substituents c o n t r i b u t i n g d i f f e r e n t ­ l y t o t h e p K ' v a l u e s m e a s u r e d [ s e e (3) b e l o w ] . n g . - £ r a n s - N P F (NPMe ) h a s b e e n shown t o h a v e t w o o f i t s s u b ­ s t i t u e n t s i n t y p e I , t h e t h i r d i n t y p e I I c o n f o r m a t i o n (3) · N P M e may h a v e d i f f e r e n t s u b s t i t u e n t c o n s t a n t s i n d i f f é r a i t e n v i r o n m e n t s , but these are always equal t o o r greater than t h a t o f NPPh . (3) A g r e a t d e a l o f b a s i c i t y d a t a i s a v a i l a b l e o n s u b s t i t u t e d c h l o r o p h o s p h a z e n e s . None h a s h i t h e r t o b e e n p u b l i s h e d o n f l u o r o phosphazenes. A p r i o r i , o n e s u r m i s e s a g r e a t e r elecrt^con-^withdrawi n g i n d u c t i v e e f f e c t f o r f l u o r i n e , w h i c h c o u l d be compensated f o r by t h e g r e a t e r p o t e n t i a effect. D a t a i s new c o m p a r e fluoro-derivatives, e.g., a

3

3

3

3

3

3

3

PH

.PH

CI

PH

PH CL^ ^ N M E

^PH F

2

Ν M

E

2

N

/PH

X

X

NME

X

2

Ν

/

CI

ME N

/

^N^

2

B a s i c i t y v a l u e s f o r o t h e r s t r u c t u r a l l y r e l a t e d compounds a r e : n g . - N P X * ( N P P h ) X = C I o r F + 0 . 2 ; n g . - N P X * (NMe ) ( N P P h ) X = C I , - 4 . 8 ; X = F , - 4 . 2 ; n g . - N P X (NM3 )„ X = C l , - 1 . 4 ; Χ = F , +0.6. I t c a n b e s e e n t h a t , i n some c a s e s , t h e f l u o r o compounds h a v e a p p r o x i m a t e l y t h e same b a s i c i t y a s t h e i r d i l o r o a n a l o g u e s , w h i l s t i n o t h e r c a s e s , t h e y a r e m a r k e d l y more b a s i c . On t h e a s y e t l i m i t e d d a t a a v a i l a b l e , no s i g n i f i c a n t c o n c l u s i o n s c a n be drawn. R e l a t e d f l u o r o - a n d c h l o r o - c o t ç o m d s h a v e t h e same b a s i c ­ i t y , e x c e p t t h a t when N M e s u b s t i t u e n t s a r e p r e s e n t , t h e y seem t o i n c r e a s e t h e b a s i c i t y o f t h e f l u o r o - a n a l o g u e b y about 0 . 5 p K ' u n i t s p e r NMe g r o u p . (4) A c o n s i d e r a b l e amount o f b a s i c i t y d a t a h a s b e e n p u b l i s h e d o n cyclophosphazenes, i . e . , systems œ n t a i n i n g o n l y P - N - P segments. A s m a l l number o f m e a s u r e m e n t s h a v e b e e n p u b l i s h e d cm m i x e d P - N - S r i n g s y s t e m s , ( 4 ) , e . g . , (NPR ) (NSOR) a n d (NPR ) (NSOR) . I h e s e a n d o t h e r d a t a show t h a t p r o t o n a t i o n o f r i n g s e g m e n t s i s preferred i n the order P-N-P > P-N-S > S-N-S. The v a l u e s o f s u b s t i t u e n t constants on phosphorus and s u l p h u r appear t o be t h e same. 3

3

3

2

3

3

3

2

3

2

3

2

2

a

2

2

a

2

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

310

PHOSPHORUS CHEMISTRY

Sane b a s i c i t y d a t a on 1 , 3 , 5 - t r i a z i n e s , (NCR) , and mixed P-N-C systems, (NPR ) (NCR), i s now a v a i l a b l e . Our measurements i n d i c a t e t h a t i n t h e mixed r i n g systems p r o t o n a t i o n i s p r e f e r r e d a t P-N-C r a t h e r than a t P-N-P segments, i n l i n e w i t h n.m.r. s t u d ­ i e s by Schmidpeter and E b e l i n g (5). B a s i c i t y d a t a on t h i s mixed r i n g s y s t e n and on 1 , 3 , 5 - t r i a z i n e s has been e v a l u a t e d . α-Values o f s u b s t i t u e n t constants appear t o be s i m i l a r f o r phosphorus and carbon, b u t γ-values seem t o be h i g h e r f o r t h e l a t t e r than t h e former. Using t h e b a s i c i t y d a t a a v a i l a b l e , we can deduce t h a t t h e elœtron-withdrawing power o f t h e groupings d i s c u s s e d i s S0C1 > PC1 > CCI. Hence t h e probable o r d e r o f b a s i c i t i e s o f t h e p a r e n t c h l o r i d e s i s (with t e n t a t i v e calculated v a l u e s where a v a i l a b l e , i n b r a c k e t s ) : (NCC1) , ( -12.4) (NCC1) (NPC1 ) (NCC1)(NPC1 ) ( -13 t o -17); ( N P C 1 (NPC1 ) (NS0C1) ; (NS0C1 F i n a l l y , b a s i c i t y v a l u e s f o r two conpounds œ n t a i n i n g t h e As-N-As segments, N A s P h ( +6.0) and N^As^Phe ( +8.6) can new be compared w i t h t h e i r phosphorus analogues, N P P h ( +1.5) and N^P^Phe (+2.2). The much g r e a t e r b a s i c i t y o f t h e a r s e n i c analogues i s noteworthy. The b a s i c i t y o r d e r o f t h e segments As-N-As > P-N-P > C-N-C > S-N-S can now be t e n t a t i v e l y e s t a b l i s h e d f o r those conpounds where o n l y one h e t e r o element a p a r t frcm M t r o g e n i s p r e s e n t i n t h e r i n g system. Literature c i t e d 1. Shaw, Robert A. Z. Naturforsch. 1976, 31b, 641-667 2. Krishnaiah, M.; Ramamurthy, L.; Ramabrahman, P . ; Manohar, H. submitted for publication. 3. Bullen, G.J.; Tam, K.O. personal communication. Faucher, Jean-Paul; van de Grampel, Johan C.; Labarre, Jean-Francois; Nabi, Syed Nurun; de Ruiter, Barteld; Shaw, Robert A. J.Chem. Research, 1977, (S) 112-113; (M) 1257-1294. 5. Schmidpeter, Α . ; Ebeling, J. Chem. Ber. 1968, 101, 3883-3901. 3

2

2

2

3

2

2

2

3

3

6

3

3

6

RECEIVED July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

65 Phosphazene Rings and High Polymers Linked to Transition Metals or Biologically Active Organic Species H. R. ALLCOCK Department of Chemistry, The Pennsylvania State University, University Park, PA 16802

Macromolecules tha have been studied i n detai the vast array of known carbon-backbone polymers, macromolecules based on phosphorus have occupied only a small and very specialized niche. We have been systematically exploring the prospect that a broad new class of high polymers, the poly(organophosphazenes) (III), can be synthesized in which phosphorus rather than carbon plays a key role in the skeletal chain (1-3).

For most organic substituent groups, X, polymers of type III are hydrolytically stable and offer unusual combinations of physical and chemical properties not found in biological- or petrochemical-based macromolecules. Two key principles have played a pivotal role in our exploration and development in this f i e l d . F i r s t , unlike most macromolecules, nearly all poly(organophosphazenes) are prepared by a substitutive technique, i n which a broad range of different substituent groups are introduced via a reactive polymeric intermediate (II). Second, because substitution reactions play such an important role i n the chemistry of these 0097-6156/81/0171-0311$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

312

PHOSPHORUS

CHEMISTRY

p o l y m e r s , and b e c a u s e t h e r e a c t i o n s o f m a c r o m o l e c u l e s a r e u s u a l l y c o m p l e x , we h a v e made e x t e n s i v e u s e o f s p e c i e s s u c h a s I a s s m a l l m o l e c u l e models f o r t h e r e a c t i o n s o f I I . Thus, t h e r e a c t i o n s o f c y c l i c t r i m e r s and t e t r a m e r s have b e e n i n v e s t i g a t e d i n tandem w i t h t h e r e a c t i o n s o f t h e h i g h p o l y m e r s ( 4 ) . I n t h i s p a p e r we c o n s i d e r two s p e c i f i c c h a l l e n g e s . First, how m i g h t t r a n s i t i o n m e t a l s b e l i n k e d t o p h o s p h a z e n e h i g h polymers? Such s y s t e m s a r e o f i n t e r e s t a s i m m o b i l i z e d c a t a l y s t s or m a t e r i a l s w i t h unusual e l e c t r i c a l p r o p e r t i e s . S e c o n d , how c a n b i o a c t i v e a g e n t s be a t t a c h e d t o p o l y p h o s p h a z e n e s t o p r e p a r e , f o r example, t a r g e t e d , slow r e l e a s e chemotherapeutic agents? An i m p o r t a n t l i n k i n t h i s p r o c e s s w o u l d be t h e u s e o f a c a r r i e r polymer t h a t c o u l d biodegrade t o harmless s m a l l m o l e c u l e s . F i v e d i f f e r e n t approache linkage o f t r a n s i t i o n metal phosphazenes. The f i r s t t h r e e make u s e o f o r g a n i c s i d e g r o u p s as c o o r d i n a t i o n l i g a n d s , t h e f o u r t h u t i l i z e s t h e c o o r d i n a t i o n power o f t h e b a c k b o n e n i t r o g e n a t o m s , and t h e f i f t h i n v o l v e s t h e s y n t h e s i s o f d e r i v a t i v e s i n w h i c h t h e s i d e group i s i t s e l f an o r g a n o m e t a l l i c u n i t l i n k e d t o t h e s k e l e t o n through phosphorusmetal bonds. These p o s s i b i l i t i e s a r e i l l u s t r a t e d i n s t r u c t u r e s IV-VIII.

A

Ph

M

NH(CH ) C H N 2

Ν = Ρ 1 OR

3

3

2

N = Ρ -

Ph

! MR V

IV

CH — 9

C Ξ CH

NHR ι

I Ρ -

VI

3

I

Ν = Ρ -

R

M

NHR VII

M

I - Ν = Ρ [ M VIII

S p e c i e s IV were p r e p a r e d from p - b r o m o p h e n o x y - s u b s t i t u t e d p h o s p h a z e n e t r i m e r s and h i g h p o l y m e r s , b y m e t a l - h a l o g e n e x c h a n g e t o y i e l d t h e £-lithio-derivative, f o l l o w e d b y r e a c t i o n w i t h diphenylchlorophosphine. Both c y c l i c t r i m e r s and h i g h polymers c o n t a i n i n g t h e pendent phosphine r e a c t e d w i t h ^ O s C C O ) ^ ,

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

65.

Phosphazene

ALLCOCK

Rings and High

Polymers

313

MnCp(CO) , A u C l , C u l , o r R h ^ C l ^ C O ) ^ t o y i e l d the a p p r o p r i a t e p h o s p h a z e n e - t r a n s i t i o n m e t a l complex. The s k e l e t a l n i t r o g e n atoms d i d n o t i n t e r f e r e w i t h t h e p r o c e s s . On t h e o t h e r h a n d , i t was shown e a r l i e r t h a t P t C l r e s i d u e s a r e bound s t r o n g l y t o t h e s k e l e t a l n i t r o g e n atoms o f [ Ν Ρ ί Ο Η β ^ ^ , [ N P ( N H C H ) ] 4 , and [NP(NHCH ) ] (VII) (5). The l a t t e r compound i s a p r o s p e c t i v e polymer-bound antitumor agent. The p e n d e n t i m i d a z o l y l d e r i v a t i v e (V) c o o r d i n a t e d s t r o n g l y t o heme o r hemin i n aqueous m e d i a (6) t o y i e l d p r o d u c t s t h a t a r e o f i n t e r e s t b o t h a s hemep r o t e i n m o d e l s and a s r e d o x s y s t e m s . Our r e c e n t d i s c o v e r y o f a f a c i l e r o u t e t o the f o r m a t i o n o f p r o p y n y l phosphazenes v i a o r g a n o c o p p e r i n t e r m e d i a t e s (7) has a l l o w e d t h e s y n t h e s i s o f pi-coordination derivatives of structure VI. The c o m p l e x formed w i t h C02(CO)g i The l i n k a g e o f t r a n s i t i o a p h o s p h a z e n e h a s p r e s e n t e d an u n r e s o l v e d c h a l l e n g e f o r many years. We h a v e r e c e n t l y s u c c e e d e d i n t h e p r e p a r a t i o n o f i r o n and r u t h e n i u m p h o s p h a z e n e s by t h e r e a c t i o n shown b e l o w (8). 3

2

3

3

2

F

2

n

F

Cp —

Fe —

Fe Ρ

NaFeCp(CO) P F^

2

Ρ

v V

V

/

X

F

W

IX

X

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

Cp

314

PHOSPHORUS CHEMISTRY

An i m p o r t a n t f e a t u r e o f t h i s a p p r o a c h i s t h e i s o l a t i o n o f s p e c i e s IX (as a y e l l o w , c r y s t a l l i n e s o l i d ) a n d , f o l l o w i n g m i l d p h o t o l y s i s , t h e r e d , m e t a l - m e t a l bonded p r o d u c t , I X . X-Ray c r y s t a l s t r u c t u r e s h a v e been o b t a i n e d f o r b o t h compounds. The l i n k a g e o f s t e r o i d m o l e c u l e s t o b o t h c y c l i c and h i g h p o l y m e r i c p h o s p h a z e n e s h a s b e e n s t u d i e d (9). Steroids with h y d r o x y l groups a t t h e 3 - p o s i t i o n can be converted t o t h e i r sodium s a l t s by treatment w i t h sodium h y d r i d e . I f the A - r i n g i s a r o m a t i c , l i n k a g e o f t h e s t e r o i d t o t h e phosphazene s k e l e t o n o c c u r s i n a manner r e m i n i s c e n t o f t h e b e h a v i o r o f s i m p l e aryloxides. However, i f t h e Α-ring i s a l i c y c l i c , c o m p l e x r e a c t i o n s o c c u r , i n c l u d i n g d e h y d r a t i o n o f t h e Α-ring b y t h e phosphazene. Two t y p e s o f s i d e g r o u attached phosphazen r i n g o r chain induce h y d r o l y t i imidazole residues. Th decompos , a c i d , p h o s p h a t e , a n d ammonia ( 1 0 ) . Hexakis(imidazolyl)cyclot r i p h o s p h a z e n e h y d r o l y z e s r a p i d l y i n t h e pH r a n g e 6.5 t o 7.8 b y a mechanism t h a t i n v o l v e s a u t o c a t a l y s i s b y t h e f r e e i m i d a z o l e liberated. Thus, e i t h e r t y p e o f s i d e group c o u l d f a c i l i t a t e biodégradation o f c h e m o t h e r a p e u t i c c a r r i e r m a c r o m o l e c u l e s . A c k n o w l e dgmen t s The f o l l o w i n g c o w o r k e r s h a v e c o n t r i b u t e d t o t h i s w o r k : T. L . E v a n s , K. L a v i n , N. M. T o l l e f s o n , L . J . Wagner, P. P. G r e i g g e r , J . P. O ' B r i e n , R. W. A l l e n , J . L . Schmutz, T. J . F u l l e r , K. M a t s u m u r a , K. M. S m e l t z , D. P. Mack, P. J . H a r r i s , and R. A. N i s s a n . F i n a n c i a l s u p p o r t f r o m t h e Army R e s e a r c h O f f i c e , t h e O f f i c e o f Naval Research, and the N a t i o n a l I n s t i t u t e s of H e a l t h i s g r a t e f u l l y acknowledged.

References 1. Allcock, H. R., Kugel, R. L., Valan, K. J. Inorg. Chem. 1966, 5, 1709. 2. Allcock, H. R., Kugel, R. L. Inorg. Chem. 1966, 5, 1716. 3. Allcock, H. R. Makromol. Chem. 1981, Suppl. 4, 3. 4. Allcock, H. R. Accounts Chem. Res. 1979, 12, 351. 5. Allcock, H. R., Allen, R. W., O'Brien, J . P. J . Am. Chem. Soc. 1977, 99, 3984. 6. Allcock, H. R., Greigger, P. P., Gardner, J . Ε., Schmutz, J. L. J . Am. Chem. Soc. 1979, 101, 606. 7. Allcock, H. R., Harris, P. J., Nissan, R. A. J . Am. Chem. Soc. 1981, 103, 2256. 8. Allcock, H. R., Greigger, P. P., Wagner, L. J., Bernheim, M. Y. Inorg. Chem. 1981, 20, 716. 9. Allcock, H. R., Fuller, T. J . Macromolecules, 1980, 13, 1338. 10. Allcock, H. R., Fuller, T. J . J . Am. Chem. Soc. 1981, 103, 2250. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

66 Polymerization of Hexachlorocyclotriphosphazene JOHN W. FIELDHOUSE and DANIEL F. GRAVES The Firestone Tire and Rubber Company, Central Research Laboratories, 1200 Firestone Parkway, Akron, OH 44317

Hexachlorocyclotriphosphazene (or simply trimer) can be thermally polymerize 200-270ºC producing h y d r o l y t i c a l l y poly dichlorophosphazene (or simply chloropolymer)· A l l c o c k (1,2) obtained chloropolymer soluble in o r ganic solvents by l i m i t i n g the conversion of trimer to chloropolymer. This discovery permitted the chloropolymer to be converted to h y d r o l y t i c a l l y stable polyphosphazenes by chlorine s u b s t i t u t i o n with an approp r i a t e nucleophile. Polymerization c a t a l y s t s such as s u l f u r (3),water (4,5,6), oxygenated organics (7-10) and silica from the surface of glass (11,12) have been used to promote the polymerization. Many of these c a t a l y s t s promote the formation of crosslinked chloropolymer at conversions above 50 percent, thus rendering them unsuitable for r e a c t i o n with nucleophiles. We have discovered that boron h a l i d e s or boron halide•triarylphosphate complexes polymerize trimer at 160-250ºC to soluble chloropolymer i n y i e l d s up to 100 percent. The trimer used i n t h i s study was p u r i f i e d by sublimation at 130-140ºC and 20-30 mm Hg vacuum. Sublimation under these conditions allows entrapped hydrogen chloride to escape. Trimer (30g) and c a t a l y s t s were placed i n a 35 ml pyrex tube ( p r e v i o u s l y washed with 20% aqueous NaOH, water and then heated at 350ºC/24 hours) and sealed under vacuum p r i o r to polymerization. Using a boron t r i c h l o r i d e to trimer molar r a t i o of 1:15 almost 100% conversion to chloropolymer could be obtained i n 16 hours at 180 G or i n 2 hours at 250°C (D.S.V.=0.30 d l / g at 1.00% i n cyclohexane). At 200 G using a molar r a t i o of 1:1280 a higher molecular weight chloropolymer was obtained (D.S.V.=1.17 d l / g at 1.00% i n cyclohexane). Boron tribromide and ?

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© 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

316

PHOSPHORUS CHEMISTRY

phenylboron d i c h l o r i d e gave r e s u l t s comparable to boron t r i c h l o r i d e , although the former i s faster and the l a t t e r i s slower than boron t r i c h l o r i d e . Boron halides form complexes with phosphorus oxyhalides (13) and triarylphosphates (14,15)» Compar­ ed to boron t r i c h l o r i d e , boron trichloride*phosphorus oxychloride at comparable conditions reduced the rate of polymerization about two f o l d , whereas the molec­ u l a r weight, as measured by d i l u t e s o l u t i o n v i s c o s i t y remained unchanged. Use of boron trichloride·triphenyl phosphate ( r e c r y s t a l l i z e d from a 1:1 by weight carbon t e t r a c h l o r i d e s o l u t i o n ) 1 gave high molecular weight chloropolymer (2.5 d l / g , 1% i n chloroform) at a c a t a l y s t to trime mola r a t i f 1:5600 d lo molecular weight chloropolyme cyclohexane) at a c a t a l y s 1:38. A comparison of c a t a l y t i c a c t i v i t y o f the t r i phenyl phosphate complexes of boron t r i f l u o r i d e , b o r o n t r i c h l o r i d e and boron tribromide showed that compara­ ble rates of polymerization were obtained using the chloride or bromide complexes. The f l u o r i d e complex gave about h a l f the rate of the bromide or c h l o r i d e ; comparable molecular weights were obtained i n a l l three cases. The molecular weight of the chloropolymer made v i a 1 i s r e l a t i v e l y i n s e n s i t i v e to the time and temp­ erature of the polymerization. This i s shown i n Tables I and I I . Table I . Polymerization Of 30g Trimer Using 0.11 mmol 1 At 220 0 DSV % Con­ Hours v e r s i o n Ό

Table I I . Polymerization Of 30g Trimer Using 0.22 mmol 1

-

Hours

% G o n

_

T°C v e r s i o n

—

(7f )

90 160 30 0.60 28 0.92 64 180 64 0.52 53 0.97 16 220 80 0.45 0.93 55 7 250 89 0.63 67 0.95 83 0.90 Attempted homo- or co-polymerization of octachlorocyclotetraphosphazene (tetramer) with trimer at 220 G gave no conversion of tetramer i n t o chloro­ polymer. At a molar r a t i o of 1:1 trimer to tetramer, there was no change i n chloropolymer molecular weight, but a reduction i n the rate of polymerization (86% conversion o f 100% trimer vs. 20% conversion using 1:1 trimer-tetramer).

10.0 18.0 24.0 40.0

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

66.

FIELDHOUSE

A N D GRAVES

Hexachlowcyclotriphosphazene

317

Complex 1 i s reported (14) to be thermally stable at 200 C but decomposes rather thaa d i s s o c i a t e s at 300 C. This was confirmed i n our laboratory v i a thermogravimetric a n a l y s i s when only 10% weight loss occurred below 175 C hut a r a p i d loss occurred between 200-250°C. ^ F NMR (reference i s 85% HJPO^) was used to confirm that thermal rearrangement of 1 (-27·8ρρπι) occurred to produce 2 (-5·5ρρπΟ and 3 (1·8 ppm) i n a r a t i o of 1.74:1 r e s p e c t i v e l y . A mass spectrograph showed 2 and 3 t o be diphenyl chlorophosphate and phenyl dichlorophosphate r e s p e c t i v e l y , which were shown to not i n i t i a t e polymerization. The remaining fragments from t h i s rearrangement may be phenyl dichloroborinate 4 d diphenyl chloroboronat 5 shown i n Scheme I . Scheme I 0 Q Λ

n i

oon°n

( o) P 0:Bci ^^ a

5

=

CI

5

»/ h

0

,P.

n i

υ

0

ι

a

if >1

*

a

d

P i

0

1

*

CI

\

I

B-OFh +

,B PhO X

Cl

OPh

*(?) 5(?) An equilibrium mixture of 4 and 5 was prepared by the ligand exchange of boron t r i c h l o r i d e and t r i p h e n y l borate (16) and found t o be an e f f e c t i v e c a t a l y s t . T h i s suggests our e f f e c t i v e c a t a l y s t may be produced by the i n s i t u rearrangement o f 1 to give 4 and/or 5 which then i n i t i a t e s the polymerization. The Ρ NMR spectra of a polymerization o f a 1:1 molar r a t i o o f trimer and 1 i s shown i n Figure 1. A small amount o f 1 remains (-27*4ppm) along with unpolymerized trimer (19·77ρρπύ and tetramer (-6.7ppm). The sharp s i n g l e t at -18.3ppm represents i n t e r n a l -PClp- u n i t s . The sharp s i n g l e t at -4.87 represents diphenyl chlorophosphate 3· Based on model l i n e a r phosphorus compounds (17,18), the shoulder of peaks at -14 t o -18ppm may represent -PClp- u n i t s adjacent to a C1^P«N- group while the C1^P=N- group might be at 3»08ppm. A d d i t i o n a l studies"* are needed to con­ c l u s i v e l y elucidate the mechanism o f i n i t i a t i o n . The hydrolysis o f trimer produces hydrogen chloride and 2,2-dihydroxy-4,4,6,6-tetrachlorocyclotriphosphazeae 6 which may be present i n impure trimer. A Ρ NMR o f 6, prepared according t o Stokes (19), i s shown i n Figure 2 . Since 1 i s s e n s i t i v e to 7

0

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

318

(NPCI ) 2

3

+ l(PhO)

3

P=0-BCI

220°C^ 3

21 H R S

-18.3

308 19.77

1

Figure 1.

(NPCi ) 2

3

31

The Ρ NMR (CDCh) of the polymerization of l mol trimer with 1 mol boron trichloride Hripheny I phosphate after 21 h at 220° C.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

66.

FiELDHOUSE A N D GRAVES

CI CI ρ \f N N

π

1

CKp

11

π

+

EXCESS

P-CI

Figure 2.

H 0 2

Hexachlorocyclotriphosphazene

25°C

Η X

»

9,0H p

N ® N I Jws\ll X

X

n

i

2

31

The Ρ NMR (THF) of

2,2-dihydroxy-4,4,6,6-tetrachlorocyclotriphosphazene.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

319

PHOSPHORUS CHEMIST:

320

most p r o t i c materials, we expected 6 to hydrolyze 1. Reaction of 2 moles 1 with 1 mole of 6 gave a t o t a l conversion of 6 to trimer, along with by product t r i phenyl phosphate. A s i m i l a r r e a c t i o n occurred be­ tween boron t r i c h l o r i d e and 6, thus showing the great propensity f o r boron t r i c h l o r i d e to 'rechlorinate hydrolyzed cyclophosphazenes. 1

Acknowledgement « The authors wish to thank Dr. Tom Antkowiak f o r h i s guidance i n t h i s work and The Firestone T i r e and Rubber Company f o r permission to publish. L i t e r a t u r e Cited 1. A l l c o c k , H . R . ; Kugel R.L. J.Am. Chem Soc. 1965, 87, 4216-7 2. A l l c o c k , H . R . ; Kugel, R.L.; Valan, K.J.Inorg. Chem. 1966, 5, 1 7 0 9 - 1 5 . 3. MacCallum, J.R.; Tanner, J.J.Pol. S c i 1969, 7, 7 4 3 - 7 4 7 . 4. A l l c o c k , H . R . ; Gardner, J.E.; Smeltz, Κ.M. M a c r o molecules 1975, 8 (1), 36-42. 5 . Korsak, V.V.; Vinogradova, S . V . ; Tur, D . R . ; Kasarova, N . N . ; Komarova, L.I.; Gilman, L.M. A c t a . Polymerica 1979, 30 (5), 245-8. 6 . U . S. 4,137,330. 7. Konecny, J.O.; Douglas, C . M . J.Pol. S c i . 1959, 36, 195-203. 8. Konecny, J.O.; Douglas, C . M . ; Gray, M.J. J. Pol. Sci. 1960, 42, 383-90. 9. G i m b l e t t , F . G . R . Polymer 1960, 1, 418-24. 10. MacCallum, J.R.; Werninck, A . J.Pol. Sci.1967, A-1 5, 3061-70. 11. Gimblett, F . G . R . P l a s t . I n s t . Trans. 1960,28, 65-73. 12. Emsley, J.; Udy, P . B . Polymer 1972, 13, 593-4. 13. Peach, M . Ε . ; Waddington, T . C . J.Chem. Soc. 1962, 3450-3. 14. Frazer, M.J.; Gerrard, W.; P a t e l , J . K . J.Chem. Soc. 1960, 726-750. 15. A l l c o c k , H . R . ; L e v i n , M . ; Fieldhouse, J.W. A c t a . C r y s t a . 1981. 16. C o l c l o u g h , T . ; Gerrard, W.; Lappert, M . F . J. Chem. Soc. 1955, 907-11. 17. Fluck, Ε . Z . Anorg. Chem. 1962, 315, 181. 18. Becke-Goehring, M.; Fluck, E. Angew. Chem. ( I n t . E d . ) 1962, 1, 281. 19. Stokes, H.Ν. Amer. Chem. J.1985, 17, 275-290. RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

67 Alkenylfluorocyclotriphosphazenes CHRISTOPHER W. ALLEN, RANDALL P. BRIGHT, and KOLIKKARA RAMACHANDRAN Department of Chemistry, University of Vermont, Burlington,VT05405

The use of organometallic reagents such as organolithium Grignard and organocoppe with halocyclophosphazene number of organophosphazene derivatives (2). The vast majority of these compounds have been the aryl and alkyl derivatives. Recently, we have initiated an investigation of the synthesis, characterization and reactions of alkenylphosphazenes (3). Our interest in these materials is three-fold: comparison of the stereochemistry of substitution reactions with that observed for other organometallic reagents (2), elucidation of the electronic interaction between the phosphazene and unsaturated organic moieties (4), and synthetic transformations of the organofunction­ al exocyclic group (5). We have previously reported the preparation of propenyl phosphazenes via the reactions of propenyl lithium reagents with hexafluorocyclotriphosphazene, N3P3F6 (3). These materials under­ go a broad variety of reactions ranging from simple hydrogenation (2) to copolymerization with styrene (6). Given the potential

technological utility of these copolymers as flame retardant materials (6), we have now reinvestigated the reaction of 2­ -propenyl lithium with N3P3F6. In addition to the expected propenylphosphazene, we obtain an oily high-boiling by-product. The ratio of propenylphosphazene to by-product is strongly dependent on the source of lithium used to prepare the organolithium reagent. The average molecular weight of a typical by-product 0097-6156/81/0171-0321$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

322

i s a r o u n d 1000 a n d t h e mass s p e c t r u m o f a c a r e f u l l y f r a c t i o n a t e d m a t e r i a l shows o n l y o n e N^P^F^ u n i t . We p r o p o s e t h a t a n i o n i c a t t a c k b y the o r g a n o l i t h i u m r e a g e n t on the o l e f i n i c c e n t e r i n t h e propenylphosphazene i n i t i a t e s t h e f o r m a t i o n o f the observed b y products. ,3 I3 N P F C(CH )=CH + LiC(CH )=CH + N ^ ^ - C - C H ^ C ^ C ^ 3

3

5

3

2

3

2

Li Our e x p e r i e n c e w i t h p r o p e n y l p h o s p h a z e n e s s u g g e s t e d t h a t o n e c o u l d a v o i d some o f t h e c o m p l i c a t i o n s i n t h e s y n t h e s i s o f a l k e n y l phosphazenes by d e a l i n g w i t h alkenylphosphazenes c o n t a i n i n g e l e c t r o n donating f u n c t i o n s on t h e o l e f i n thus c o u n t e r a c t i n g t h e electron withdrawing e f f e c hypothesis by m e t a l a t i n and a l l o w i n g t h e οrgano-lithium r e a g e n t t o r e a c t w i t h N^^F^* U s i n g t h i s r e a c t i o n , we w e r e a b l e t o p r e p a r e b o t h t h e mono a n d disubstituted

derivatives,

NJ? F

C(0C H )=CH

3

2

5

2

and

3 3 4 [ ( ° 2 5 ) 2 J 2' V of t h e b y - p r o d u c t o b s e r v e d i n the case o f the p r o p e n y l l i t h i u m r e a c t i o n . S i m i l a r r e s u l t s were obtained s t a r t i n g with methylvinyl ether. Attempts t o achieve t r i s u b s t i t u t i o n l e d t o a complex s e r i e s o f r e a c t i o n s i n v o l v i n g

N

P

F

c

C

H

= C H

w

i

t

N P F . + nLiC(0R)=CH Q

Q

J J ο

h

o

o

ζ

R=C H ,CH ; 2

5

3

u

t

a n

-> N P F . 0

0

J J ο—η

[C(0R)=CH ] O

ζ η

n=l,2

such p r o c e s s e s as c l e a v a g e o f the e t h o x y group from the e t h o x y vinylphosphazene. The d i s u b s t i t u t e d m a t e r i a l was shown t o h a v e the geminal c o n f i g u r a t i o n ( 2 , 2 - N J P ^ [C(0C H ) = C H J ) by % , C , 19 and ^ P nmr s p e c t r o s c o p y . The m o n o s u b s t i t u t e a m a t e r i a l s show l o n g - r a n g e f l u o r i n e c o u p l i n g w i t h e x o c y c l i c group. These i n t e r ­ a c t i o n s a r e n o t o b s e r v e d i n t h e d i s u b s t i t u t e d d e r i v a t i v e s . The 31p a n d F nmr s p e c t r a c l e a r l y show, b y t h e phosphorus-fluorine c o u p l i n g p a t t e r n s , t h e p r e s e n c e o f E P F a n d EPR^ c e n t e r s a n d t h e absence o f EPFR c e n t e r s thus c o n f i r m i n g the g e m i n a l n a t u r e o f t h e disubstituted materials. The c h e m i c a l s t u d i e s d i s c u s s e d above s t r o n g l y s u p p o r t o u r h y p o t h e s i s t h a t the p o l a r i t y o f the o r g a n i c f u n c t i o n i n a l k e n y l ­ phosphazenes can be s i g n i f i c a n t l y a l t e r e d by the n a t u r e o f t h e o l e f i n s u b s t i t u e n t s . We s o u g h t a l t e r n a t i v e methods t o e v a l u a t e t h e s e e f f e c t s a n d f o u n d t h a t 1 3 c nmr s p e c t r o s c o p y i s a v e r y u s e f u l t o o l i n t h i s regard. G e n e r a l l y , theβ carbon chemical s h i f t i n substituted olefins i s s e n s i t i v e to electronic effects at the α p o s i t i o n ( 7 ) . Thus on g o i n g f r o m e t h y l v i n y l e t h e r t o N J F C ( 0 C J )=CH„, t h e β c a r b o n atom e x p e r i e n c e s a 15 ppm downf i e l d s h i f t and the p r o p e n y l d e r i v a t i v e , N P F C ( C H ~ ) = C H , ppm d o w n f i e l d f r o m t h e e t h o x y v i n y l d e r i v a t i v e . S i m i l a r o b s e r v a ­ t i o n s h o l d f o r mixed p h e n y l / a l k o x y v i n y l and dimethy1amino/alkoxy1

2

3

2

F

3

2

I

3

3

5

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

S

3

2

67.

ALLEN

ET AL.

323

Alkenylfluorocyclotriphosphazenes

v i n y l fluorophosphazenes. T h i s l a t e r o b s e r v a t i o n c l e a r l y shows t h e l a r g e d i f f e r e n c e i n c h a r g e d i s t r i b u t i o n i n t h e s e two o l e f i n s . E x a m i n a t i o n o f t h e 31p d a t a a l s o h a s u n c o v e r e d some i n t e r e s t i n g t r e n d s , f o r e x a m p l e , t h e r e i s a s i g n i f i c a n t d i f f e r e n c e i n 31p d a t a c h e m i c a l s h i f t s when a n e t h o x y v i n y l g r o u p i s r e p l a c e d b y a p h e n y l g r o u p (Δ6 = 6 ppm) . The e f f e c t o f t h e v a r i o u s v i n y l s u b s t i t u e n t s on t h e 31p s h i f t s i s a l s o s i g n i f i c a n t . Having demonstrated t h a t t h e ethoxyvinylphosphazene can be c o n v e r t e d t o t h e d i s u b s t i t u t e d d e r i v a t i v e , we d e c i d e d t o e x p l o r e a v a r i e t y o f reactions i n v o l v i n g the ethoxyvinylphosphazene. S i n c e much o f o u r i n t e r e s t i n a l k e n y l p h o s p h a z e n e s i s r e l a t e d t o t h e i r i n c o r p o r a t i o n i n t o t r a d i t i o n a l v i n y l p o l y m e r s Ç5,6), we were p l e a s e d t o observe f a c i l e c o p o l y m e r i z a t i o n o f 3 3 5 ^ 2 5^ 2 substituent derivatives N

P

F

C

O C

H

= C H

w

i

t

h

s t

OC H 2

N„P F_C(0C H ,)=CH Q

o

J J3

{

Ζ 3

o

Ζ

+ C.H_CH=CH

03

»

0

Ζ

[(CHCH ) 0

j

C H 6

5

(CCH ) ] 0

Z x j Z y n P N F

5

3

3

5

N P F C(OC H )=CH leads t o the geminally substituted material 2 , 2 - N P F f C H ) c f O C H ) = C H ; t h e same p r o d u c t i s o b t a i n e d f r o m the reaction o r ethoxyvinyl l i t h i u m w i t h phenylpentafluoroeyclot r i p h o s p h a z e n e . However, t h e r e a c t i o n o f two m o l e c u l e s o f p h e n y l l i t h i u m w i t h N P F ^ i s known t o f o l l o w a p r e d o m i n a n t l y n o n - g e m i n a l pathway ( 8 ) . 3

3

5

2

3

3

5

2

6

2

3

5

2

3

Ο N P F C(OC H )=CH 3

3

5

2

5

L i —

2

2,2-N P F (C H )C(OC H )=CH 3

N P F C H 3

3

5

6

LiC(OC H )=CH

5

2

5

3

4

6

5

2

5

2

I n a n o t h e r s e r i e s o f e x p e r i m e n t s , we f o u n d t h a t t h e r e a c t i o n o f NJP JBVC(OC H,.) =CH w i t h d i m e t h y l a m i n e l e a d s t o t h e n o n - g e m i n a l i s o m e r s , 2 , [ N ( C H ) ] C ( O C H ) = C H ; t h e same p r o d u c t i s o b t a i n e d from t h e r e a c t i o n o f e t h o x y v i n y l l i t h i u m w i t h dimethy1aminopentafluorocyclotriphosphazene. 2

2

3

2

N P F C(OC H )=CH 3

3

5

2

5

2

v 2

5

2

(CH ) NH 3^2 Q

0

H

f2 5 2,4-N P F N(CH ) C=CH 3

N P F N(CH ) 3

3

5

3

2

LiC(OC H )=CH 2

5

3

4

3

2

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2

2

PHOSPHORUS CHEMISTRY

324

The s t r u c t u r e s o f a l l t h e m i x e d s u b s t i t u e n t d e r i v a t i v e s w e r e u n ­ ambiguously e s t a b l i s h e d by 31 and l ^ F nmr s p e c t r o s c o p y . The o b s e r v a t i o n o f t h e v a r i a t i o n o f t h e s t e r e o c h e m i c a l c o u r s e of thereaction o f ethoxyvinyl l i t h i u m with various monosubstituted p e n t a f l u o r o c y c l o t r i p h o s p h a z e n e s w i t h the n a t u r e o f t h e phospha­ zene s u b s t i t u e n t c l e a r l y demonstrates t h a t t h e r e i s a d i r e c t i v e e f f e c t based on t h e r i n g s u b s t i t u e n t which i s o p e r a t i v e i n these reactions. These f i n d i n g s a r e a t v a r i a n c e w i t h c u r r e n t t h i n k i n g which s t r e s s e s t h e c o n t r o l o f t h e incoming reagent on t h e s t e r e o ­ c h e m i s t r y o f t h e s u b s t i t u t i o n r e a c t i o n ( 9 ) . We p r o p o s e t h e f o l l o w i n g model f o r c a s e s where s u b s t i t u e n t c o n t r o l o f d i r e c t i v e e f f e c t s occurs. We h a v p r e v i o u s l exocycli release i n organofluorophosphazene The n e t r e s u l t o f t h i s e f f e c g nitroge p a i r e l e c t r o n d e n s i t y i s p r e f e r e n t i a l l y t r a n s f e r r e d t o t h e =PF^ c e n t e r , t h u s l e a v i n g t h e EPFR c e n t e r a s t h e s i t e o f n u c l e o p h i l i c attack. When a π d o n a t i n g s u b s t i t u e n t , s u c h a s dime t h y l a m i n e , i s on t h e r i n g , e l e c t r o n r e l e a s e i s i n t o t h e p h o s p h o r u s atom s y s t e m at t h e s u b s t i t u t e d phosphorus c e n t e r . T h i s mechanism reduces t h e f o r m a l p o s i t i v e c h a r g e a t t h e s u b s t i t u t e d p h o s p h o r u s atom a n d h e n c e l e a v e s t h e ξΤΈ^ c e n t e r a s t h e s i t e o f s u b s t i t u t i o n . Acknowledgement T h i s w o r k was s u p p o r t e d , i n p a r t , b y t h e O f f i c e o f N a v a l Research. P

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9.

Allcock, H.R.; Harris, P . J . J. Am. Chem. Soc. 1979, 101, 62219. Allen, C.W. Ind. Eng. Chem. Prod. Res. Dev. 1981, 20, 77-79. Dupont, J . G . ; Allen, C.W. Inorg. Chem. 1978, 17, 3093-6. Allen, C.W.; Green, J.C. Inorg. Chem. 1980, 19, 1719-22. Allen, C.W.; Dupont, J.G. Ind. Eng. Chem. Prod. Res. Dev. 1979, 18, 80-1. Dupont, J . G . ; Allen, C.W. Macromolecules 1979, 12, 169-72. Strothers, J.B. "Carbon-13 NMR Spectroscopy"; Academic Press: New York, N.Y., 1972; p. 184. Allen, C.W.; Moeller, T. Inorg. Chem. 1978, 7, 2177-83. Shaw, R.A. Z. Naturforsch. 1976, 31b, 641-67.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

68 The Reactions of Halophosphazenes with Organometallic Reagents PAUL J. HARRIS Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg,VA24061 HARRY R. ALLCOCK Department of Chemistry, Pennsylvania State University, University Park,PA16802

The interactions of cyclic halophosphazenes with organo­ metallic reagents are som stood reactions in Mai was thought that the initial products formed during these reactions were acyclic or "ring opened" species.3,4 However, we have undertaken a detailed investigation of the reactions of both Grignard reagents and organocopper reagents with hexachlorocyclotriphosphazene (I) and find that the products from these reactions contain intact phosphazene rings. The results of these studies are presented in this paper. The reactions of hexachlorocyclotriphosphazene (I) with a variety of Grignard reagents (RMgCl where R = Me, Et, n-Pr, n-Bu, i-Pr, t-Bu, Ph) were investigated. It was found that these reactions did not lead to initial clevage of the phosphazene ring, but led exclusively to the formation of two well defined types of products, both of which contained intact phosphazene rings as shown in Scheme I. These products were either mono-or di-substituted phos­ phazene trimers of type II and III,5,8 or compounds IV in which two cyclic phosphazene rings were linked together through a direct P-P bond. The ratios of the two types of products formed in the different reactions studied were found to be markedly dependent on both the reaction temperature and the Grignard reagent employed. Thus, while methyl- or phenyl-magnesium chlo­ ride led almost exclusively to formation of the respective dimer (IV, R * Me, Ph), indépendant of reaction temperature, _i-propyl magnesium chloride gave the mono-substituted compound (II, R » i-Pr) as the only product. Reactions involving n-butyl magnesium chloride were found to be extremely temperature dependent; at -10°C dimer formation (IV, R - n-Bu) was preferred, while at reflux temperatures (~66°C) the mono-and di-alkyl products pre­ dominated (II and III, R » n-Bu). More detailed studies of the reactions indicated that two competing mechanisms were in operation. Compounds of type II and subsequently III resulted from a simple nucleophilic attack by 0097-6156/81/0171-0325$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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68.

HARRIS

AND

ALLCOCK

Reactions

of

Halophosphazenes

327

the G r i g n a r d r e a g e n t a t p h o s p h o r u s , f o l l o w e d by e l i m i n a t i o n o f a c h l o r i d e i o n . Compounds o f t y p e IV w e r e f o u n d t o r e s u l t f r o m a m e t a l - h a l o g e n e x c h a n g e t y p e r e a c t i o n . The a l k y l c h l o r i d e g e n e r a t e d by t h i s r e a c t i o n b e t w e e n t h e G r i g n a r d r e a g e n t and t h e p h o s p h a z e n e was d e t e c t e d i n some c a s e s . The i n i t i a l r e a c t i o n p r o d u c t , a m e t a l l o p h o s p h a z e n e , was t o o r e a c t i v e t o i s o l a t e and a t t a c k e d a n o t h e r m o l e c u l e o f [NPC1213 t o g e n e r a t e t h e b i c y c l i c compound I V . Thus i t a p p e a r s t h a t t h e more n u c l e o p h i l i c G r i g n a r d r e a ­ g e n t s , o r h i g h e r r e a c t i o n temperatures, f a v o r the f o r m a t i o n of compounds I I a n d I I I , w h i l e w e a k e r n u c l e o p h i l e s u n d e r g o t h e m e t a l - h a l o g e n exchange r e a c t i o n , a r e a c t i o n t h a t i s a l s o p r e ­ f e r r e d a t low t e m p e r a t u r e s . An i n v e s t i g a t i o n i n t with hexachlorocyclotriphosphazen The o r g a n o c o p p e r r e a g e n t was g e n e r a t e d i n s i t u by t h e r e a c t i o n b e t w e e n a G r i g n a r d r e a g e n t and t h e c o m p l e x [ n - B u 3 P C u I ] 4 , w h i c h was u s e d as a s o l u b l e f o r m o f copper!I]· T h e s e r e a c t i o n s were f o u n d t o p r o c e e d e x c l u s i v e l y by t h e m e t a l - h a l o g e n e x c h a n g e pathway.2 I n t h e s e c a s e s h o w e v e r , t h e c o p p e r was a b l e t o s t a b i l i z e t h e r e d u c e d p h o s p h a z e n e r i n g and t h u s d i m e r s o f t y p e IV w e r e n o t o b s e r v e d . The i n i t i a l p r o d u c t s formed f r o m t h e s e r e a c t i o n s were f o u n d t o be m e t a l l o p h o s p h a z e n e s o f t y p e V. These i n t e r m e d i a t e s h a v e p r o v e d t o be e x t r e m e l y u s e f u l i n t h e s y n t h e s i s of a v a r i e t y o f p h o s p h a z e n e compounds a s shown i n Scheme I I . Thus r e a c t i o n w i t h a l k y l h a l i d e s s u c h a s a l l y l b r o m i d e o r p r o p a r g y l b r o m i d e a l l o w f o r t h e i n t r o d u c t i o n o f o l e f iniçZ.»^ o r a c e t y l e n i c ^ s i d e groups onto the phosphazene r i n g V I , w h i l e a l c o h o l l e a d s t o the f o r m a t i o n of hydrido-phosphazene complexes^.*? V I I . The h y d r o g e n i n t h e s e compounds c a n be r e ­ placed w i t h h a l o g e n ! t o y i e l d the f i r s t s e r i e s of iodop h o s p h a z e n e compounds V I I I . Thus, from the s e r i e s of r e a c t i o n s p r e s e n t e d i n t h i s paper i t a p p e a r s t h a t a m a j o r r e a c t i o n pathway f o r c h l o r o cyclophosphazenes with c e r t a i n o r g a n o m e t a l l i c reagents, i n v o l v e s a m e t a l - h a l o g e n e x c h a n g e p r o c e s s . S u b s e q u e n t c h e m i s t r y however a p p e a r s t o be e x t r e m e l y d e p e n d e n t on t h e m e t a l I n v o l v e d i n t h e organometallic reagent.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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68.

HARRIS A N D A L L C O C K

Reactions

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329

Acknowledgement We t h a n k t h e O f f i c e o f N a v a l R e s e a r c h f o r t h e s u p p o r t o f t h i s work.

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

DuPont, J.G.; Allen, C. W. Inorg. Chem. 1978, 17, 3093. Ranganathan, T. N.; Todd, S. M.; Paddock, N. L. Inorg. Chem. 1973, 12, 316. Biddlestone, M.; Shaw, R. A. J.Chem. Soc. (A), 1971, 2715. Biddlestone, M.; Shaw, R. A. Phosphorus, 1973, 3, 95. Allcock, H. R.; Harris, P. J.Inorg. Chem. in Press. Harris, P. J.; Allcock J.Am. Chem Soc 1968 100 6512. Harris, P. J.; Allcock, H. R. J.Chem. Soc. Chem. Comm. 1979, 714. Allcock, H. R.; Harris, P. J., Connolly, M. S. Inorg. Chem. 1981, 20, 11. Allcock, H. R.; Harris, P. J.J.Am. Chem. Soc. 1979, 101, 6221. Allcock, H. R., Harris, P. J., Nissan, R. A. J.Am. Chem. Soc. in Press.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

69 1,2-Bis(dichlorophosphino)alkanes Ε. H. UHING and A. D. F. TOY Eastern Research Center, Stauffer Chemical Company, Dobbs Ferry,NY10522

This paper presents a new method for preparing 1,2-bis(dichlorophosphino)alkane hydrocarbons with PCl3 under autogenous pressure1. The basic reaction with ethylene is shown in eq 1.

A prior method for making 1 involved the reaction of 1,2-bis(diphenylphosphino)ethane with PCl3 at 280°C using AlCl3 as a catalyst2. To show that eq 1 could be feasible we hypothesized the reaction occurring via eq 2 and 3. The addition of PCl3 across

a double bond using uv or other free radical initiators to form 2-chloroalkylphosphonous dichlorides is well known3. The thermal initiation of the reaction shown in eq 2 has not been reported. When excess PCl3 and ethylene (eq 2) are reacted at 200-250°C under pressure, our study showed only trace amounts of 2 being formed. At 250°C, with an excess of ethylene, a black solid formed. We believe the low yield of 2 might be due to an un­ favorable equilibrium or decomposition reaction. Trapping of 2 by some further reaction as shown in eq 3 could allow eq 2 to proceed. The reaction of alkyl chlorides with PCl3 and elemental phosphorus at 200-300°C to yield alkylphosphonous dichlorides has been reported4. Therefore, i f 2 reacts like an alkyl chloride then eq 3 could form 1. One of the proposed mechanisms for the uv initiated addition of PCl3 to isobutene involves a cyclic or bridged free radical 0097-6156/81/0171-0333$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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i n t e r m e d i a t e to account f o r the absence of c r o s s - t r a n s f e r prod­ u c t s ^ . A n a l o g o u s l y , the f o r m a t i o n of a t r a n s i t o r y c y c l i c a d d i ­ t i o n c o m p l e x b e t w e e n P C l ^ and e t h y l e n e a s shown i n Scheme I c o u l d a l s o be an a l t e r n a t e r e a c t i o n pathway f o r t h e f o r m a t i o n o f 1. Scheme I CH =CH 2

+

2

PC1

C H — CKL \ Ζ0

3

'

PCI

3 +

CH -ÇH

Ρ,

ζ

2

PCI

Cl 4 4_ + P C 1

•

3

1

A c y c l i c p h o s p h i r a n e r e l a t e d t o 4 has b e e n r e p o r t e d - . The p r a c t i c a l s c o p e o f o u r new method f o r p r e p a r i n g 1 , 2 - b i s ( d i c h l o r o p h o s p h i n o ) a l k a n e s u s i n g the r a t i o of alkene to elemental p h o s p h o r u s shown i n eq 1 and a 50-150% e x c e s s o f PC1~ a t 200-250 -C f o r 4-6 h o u r s u n d e r a u t o g e n o u s p r e s s u r e i s shown i n T a b l e I . Table I

Y i e l d s of C1 PCH CH(R)PC1 2

1-Alkene Used ethylene propylene 1-butene 1-pentene 1-octene

2

R H CH„ CH^CH (cL)^CH (CH )^CH 2

3

2

(1) (5) (6) (7_) (8)

% Yield 70 66 47 41 20

T a b l e I shows a s h a r p r e d u c t i o n i n y i e l d s a s t h e m o l e c u l a r w e i g h t of t h e 1 - a l k e n e i n c r e a s e s . F o r a l k e n e s a b o v e 1 - p r o p e n e , I was added a s a c a t a l y s t e v e n t h o u g h i t s b e n e f i c i a l e f f e c t was n o t c l e a r l y e s t a b l i s h e d . A l l t h e above r e a c t i o n s w e r e r u n i n a 316 S t a i n l e s s S t e e l a u t o c l a v e r a t e d a t 5000 p s i g . A t y p i c a l c h a r g e f o r m a k i n g 1 i n a 300 mL a u t o c l a v e i s 1.0m P C 1 0.45m e t h y l e n e and 0.3 gram-atom o f w h i t e p h o s p h o r u s . The maximum p r e s s u r e g e n e r a t e d a t 200°C i s 2000 p s i g . A l l p r o d u c t s w e r e i s o l a t e d by vacuum d i s t i l l a t i o n . I n T a b l e I I we show t h e 31p-NMR o f t h e s e b i s compounds. The o b v i o u s p o i n t o f i n t e r e s t f o r t h e 3Ip-NMR s p e c t r a shown i n T a b l e I I i s t h a t t h e 1^ and .5 b o t h a r e s i n g l e t s a t a b o u t t h e same frequency. S i n c e ,5 i s n o t a s y m m e t r i c a l m o l e c u l e , we r a n t h e 2

3 >

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

69.

UHiNG A N D T O Y

1,2-Bis(dichlorophosphino)alkanes

335

J1

T a b l e I I P-NMR S p e c t r a o f Compounds i n T a b l e I Compound

6 (+ppm f r o m HJP0, )

1

Jp-p(Hz)

190.6 190.7 194.8(d);191.4(d) 194.5(d);191.6(d) 194.5(d);191.3(d)

5

6 I 8

10 10 10

13C-NMR s p e c t r a t o be s u r e t h a t a 1 , 3 - b i s p r o d u c t d i d n o t f o r m . The 13C-NMR s p e c t r a o f 1_ a n d 5_ a r e shown i n T a b l e I I I . Compound 1_ h a s t h e s p e c t r u m o f a s y m m e t r i c a l 1 , 2 - b i molecule

Table I I I

I3

Compound

C-NMR S p e c t r a o f 1 a n d 5 6(4- ppm f r o m

(CH^^Si) ^Jc-p

1 .5

3 6 . 1 ( d o f d) 4 5 . 5 ( d o f d) 4 0 . 5 ( d o f d) 16.0(t)

50 53 50

2

Jc-p

^ J c - p (Hz)

10 13 11 13.5

The l^c-NMR s p e c t r u m o f 5^ shows t h e p r e s e n c e o f a m e t h y l g r o u p t h a t i s c o u p l e d t o two m a g n e t i c a l l y e q u i v a l e n t p h o s p h o r u s atoms. To c o n f i r m t h a t 5^ h a s t h e e x p e c t e d 1 , 2 - b i s s t r u c t u r e , we h y d r o l y z e d and o x i d i z e d i t t o t h e b i s - p h o s p h o n i c a c i d . The P - N M R s p e c t r a o f t h i s a c i d shows two d o u b l e t s c o n s i s t e n t f o r a 1 , 2 - b i s structure. The P-NMR s p e c t r a r e p o r t e d f o r t h e 1 , 3 - b i s (phosphonic a c i d ) propane i s a s i n g l e t ? . S e v e r a l i n t e r n a l o l e f i n s were a l s o t r i e d i n t h e r e a c t i o n shown i n eq 1. When t h e r e a c t i o n o f b o t h c i s - o r t r a n s - 2 - b u t e n e w e r e r u n a t 230°C, t h e y gave a l o w ( 1 0 % ) y i e l d o f t h e 2 , 3 - b i s ( d i c h l o r o p h o s p h i n o ) b u t a n e a s e v i d e n c e d b y a s i n g l e 31P_NMR p e a k a t 193.6 ppm a n d a s y m m e t r i c a l l^c-NMR s p e c t r a . When t h e r e a c t i o n t e m p e r a t u r e i s r a i s e d t o 250°C, b o t h c i s - a n d t r a n s - 2 - b u t e n e y i e l d a compound w h i c h h a s t h e same 31p a n d 13c-NMR s p e c t r a a s 6^ i n ­ d i c a t i n g a 1,2-bis(dichlorophosphino)butane product. Along with t h i s r a t h e r complex isomer p r o d u c t change, t h e r e i s an i n c r e a s e i n t h e amount o f b u t y l p h o s p h o n o u s d i c h l o r i d e f o r m e d . A b r a n c h e d a l k e n e , i s o b u t y l e n e , gave a 2 3 % y i e l d o f 1 , 2 - b i s ( d i c h l o r o p h o s p h i n o ) i s o b u t a n e a t a r e a c t i o n t e m p e r a t u r e o f 210°C a l o n g w i t h a t r a c e o f t e r t - b u t y l p h o s p h o n o u s d i c h l o r i d e a n d two isobutenylphosphonous d i c h l o r i d e s . Cyclohexene f a i l e d t o produce 31

J1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

336

PHOSPHORUS CHEMISTRY

even a t r a c e o f b i s p r o d u c t u n d e r a v a r i e t y o f r e a c t i o n c o n d i ­ tions. The o n l y p r o d u c t i s o l a t e d was c y c l o h e x y l p h o s p h o n o u s d i c h l o r i d e which i s one o f the p r o d u c t s p r e v i o u s l y r e p o r t e d f o r t h e t h e r m a l a d d i t i o n o f PC1« t o c y c l o h e x e n e Z . S i n c e t h e 1 , 2 - b i s ( d i c h l o r o p h o s p h i n o ) a l k a n e s made b y t h i s new process a r e r e a c t i v e i n t e r m e d i a t e s they have a v a r i e t y o f poten­ t i a l uses. Compound 1 h a s b e e n c o n v e r t e d t o t h e 1 , 2 - b i s ( d i ­ me t h o x y p h o s p h i n o ) e t h a n e a n d u s e d f o r m a k i n g m e t a l c a r b o n y l complexes.?. T h e r e a l s o i s a r e p o r t o n t h e c o n v e r s i o n t o 1 , 2 - b i s (dimethylphosphino)ethane and 1,2-bis(diethylphosphino)ethane^.. The t e t r a - s o d i u m s a l t o f e t h y l e n e d i p h o s p h i n e t e t r a a c e t i c a c i d h a s b e e n made u s i n g i n t e r m e d i a t e The r e a c t i o n s w i t h p h e n o l s and c y c l i c a l i p h a t i c a l c o h o l s a l s o h a v e b e e n r e p o r t e d — .

LITERATURE CITED 1.

Toy, A.D.F.; Uhing, E.H. (to Stauffer Chemical Co.) U.S. 3,976,690 (1976). 2. Sommer, Κ. Ζ. Anorg. Allg. Chem. 1970, 376, 37. 3. Fild, M.; Schmutzler, R. "Organic Phosphorus Compounds"; Kosolapoff, G. M.: Maier, L. Ed.; Wiley-Interscience, NY, 1972, Vol. 4; Chapter 8. 4. Bliznyuk, N.K.; Kvasha, Z.N.; Kolomiets, A.F. Zh. Obshch. Khim. 1967, 37, 890. 5. Little, J. R.; Hartman, P.F. J. Am. Chem. Soc. 1966, 88, 96. 6. Wagner, R. I.; Freeman, L. D.; Goldwhite, H . , Rowsell, D. G. J. Am. Chem. Soc. 1967, 89, 1102. 7. Wunder, K.; Drawe, H.; Henglein, A. Z. Naturforschg. 1964, 19b, 999. 8. King, R. B.; Rhee, W. M. Inorg. Chem. 1978, 17, 2961. 9. Burt, R. J.; Chatt, J.; Hussain, W.; Leigh, G. J. J. Organomet. Chem. 1979, 182, 203. 10. Podlahova, J.; Podlaha, J. Collect. Czech. Chem. Commun. 1980, 45, 2049. 11. Uhing, Ε. H. (to Stauffer Chem. Co.) U.S. 4,263,230 (1981). RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

70 Products of Peracid Oxidation of S-Alkyl Phosphorothiolate Pesticides YOFFI SEGALL1 and JOHN E. CASIDA Pesticide Chemistry and Toxicology Laboratory, Department of Entomological Sciences, University of California, Berkeley,CA94720

Biooxidation is an essential activation process for some organothiophosphorus neurotoxicant acid (MCPBA) has been use without identifying the products derived from phosphorothiolates (2,3). We observed that S-alkyl phosphorothiolates react with MCPBA to form a new and unexpected class of phosphinyloxysulfonates via a novel rearrangement process (Eq. 1).

Peracid oxidation of S-alkyl phosphorothiolates (1) appears to proceed by initial formation of S-oxides (2) which undergo spontaneous and very rapid rearrangement, via phosphoranoxide intermediates, to the corresponding sulfenate esters (3) that are 1Current address: Israel Institute for Biological Research, Ness-Ziona, P.O.B. 19, Israel.

0097-615 6/81/0171-03 37$05.00/ 0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

338

further oxidized to the oxysulfinate (4) and oxysulfonate esters (5) (Eq. 1). With equimolar MCPBA very l i t t l e starting material undergoes reaction because most of the oxidant is used up in con­ version of 3 and 4 to 5. As a result the most extensively oxidiz­ ed product (5) is strongly favored. These generalizations are based on studies with four S-alkyl phosphorothiolate pesticides (6a, 7a, 7b, 8) and related compounds as follows:

The oxidation rate with excess peracid decreases in the order ϋ Jjk 7J> >> 6a; the first three compounds react readily below -30°C whereas 6a requires > 10°C for significant reaction in 24 hr. The nitrogen free electrons of 7ji and 7b may facilitate their oxidation by increasing the polarizability of the sulfur. >

>

Profenofos (6a) and its derivatives were selected for detailed examination. Sulfonate ester 6b is obtained pure in 86% yield on reacting 6a with five equivalents of MCPBA in ethanol-free chloro­ form at 25 C for 8 hr followed by rapidly extracting the solution with aqueous NaHS0 and NaHC03 at 0°C. Similar treatment at 25°C for 5 min results in complete hydrolysis of 6b to J>£ and propylsulfonic acid. NMR studies (Table I) suggest conversion of the phosphorothiolate to a phosphate. Thus, on going from 6ji to 6b there is a significant high field shift in the ^Ip NMR signals and downfield shifts in the and -^C signals of the α-methylene bonded to sulfur. In addition, neither the proton nor the carbon of the ^-methylene in 6b is coupled with the phosphorus. Three minor phosphorus-containing products formed on oxidation of 6a are: the acid 6c (δ P -6.82 ppm in CDC1 ); the 3-chlorobenzoyl U

3

3 l

3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

70.

SEGALL

AND

S-AlkyI Phosphorothiolate

CASiDA

TABLE I .

Pesticides

339

NMR S p e c t r a l D a t a f o r 6 a a n d 6b (CDC1 > 3

C h e m i c a l s h i f t s d e n o t e d a s f o l l o w s : "^H f o r d i a s t e r e o t o p i c p r o t o n s o f t h e m e t h y l e n e d i r e c t l y bonded t o s u l f u r ( d o w n f i e l d o f TMS); 13c f o r c a r b o n d i r e c t l y bonded t o s u l f u r (TMS); l p a r e n e g a t i v e when u p f i e l d o f 1% t r i m e t h y l p h o s p h a t e i n C,D, (6 P = 0 ) . 3

3

1

6b

6a δ ppm

Nucleus

2.91 13

c

33.44

31

p

+22.91

δ ppm

^31p_nucleus

^31p~nucleus none

3.49

9.3 Hz

-

-21.77

31 e s t e r 6e (δ Ρ - 1 6 . ^ J ) ; t h e d i a s t e r e o m e r i c p y r o p h o s p h a t e 6^ (two l i n e s centered a t δ Ρ - 2 2 . 7 4 , Δδ 0.03 ppm). Comparable o x i d a ­ t i o n o f £ (δ P +31.28 i n a c e t o n e , r e f e r e n c e d t o 1% t r i m e t h y l p h o s p h a t e i n CDCI3) y i e l d s t h e a n a l o g o u s d i e t h y l p h o s p h o r i c a c i d (δ P + 1 . 8 0 ) , d i e t h y l 3 - c h l o r o b e n z o y l o x y p h o s p h a t e (δ P -10.30) and t e t r a e t h y l p y r o p h o s p h a t e (one l i n e a t δ ^ P - 1 0 . 7 8 ) . M i x e d a n h y d r i d e 6b i s a s u l f o n y l a t i n g r a t h e r t h a n a p h o s p h o r y l a t i n g a g e n t . Thus, h y d r o l y s i s w i t h H 0 g i v e s a c i d 6c and p r o p y l s u l f o n i c a c i d i n w h i c h t h e 0 isotope i s incorporated o n l y i n t h e s u l f o n i c a c i d ( E q . 2 ) . Compound 61) r e a c t s w i t h e i t h e r a l c o h o l s (methanol, e t h a n o l , sec-butanol) o r L - c y s t e i n e t o y i e l d a c i d 6 c and w i t h t r i e t h y l a m i n e t o g i v e t h e a n i o n o f 6c, p r o b a b l y v i a p r o p y l s u l f e n e (4) ( E q . 2 ) . 3

3

1

1

3 1

3

1 8

2

1

C

2 5°v H

/?

u

Y

ArO^

H

\ s 0

2

C

3

H

ι · 2 0 Λ

ArO^

7

6b

\)H 6c

Eq. 2

-(C H ) N 2

5

3

-(C H ) NH 2

5

3

HOS0 C H 2

3

7

)H O 2

v y

+

Ρ

9

ArO

0-S0 -CHCH CH 2

2

3

ArO

0 S=CHCH CH 2

2

3

0"

Phosphoramidothiolates 7a a n d 7b w i t h MCPBA y i e l d t h e r m a l l y u n s t a b l e p r o d u c t s i n c o n t r a s t t o t h e more s t a b l e 6b o b t a i n e d on o x i d a t i o n o f 6a. N e u t r a l aqueous h y d r o l y s i s o f t h e r e a c t i o n p r o d ­ u c t s o f Ta t h e n d e r i v a t i z a t i o n w i t h d i a z o m e t h a n e y i e l d s many

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

340

PHOSPHORUS

CHEMISTRY

compounds, i n c l u d i n g 10 a n d JUL i d e n t i f i e d b y MS a n d NMR. These products i n d i c a t e involvement o f both t h e -SCH3 a n d -NH2 g r o u p s i n t h e o x i d a t i o n and d e c o m p o s i t i o n p r o c e s s e s . Phosphorotrithiol a t e 8 (6 P +66.40 ppm i n CDCI3) r e a c t s a l m o s t i n s t a n t l y w i t h MCPBA (3-4 e q u i v a l e n t s ) a t -30°C t o g i v e r e a r r a n g e d p r o d u c t s (δ P +0.50, -7.60 a n d -17.00) t h a t do n o t c o n t a i n a n y d i r e c t P-S bond a s t h e i r p r o t o n c o u p l e d and d e c o u p l e d ^ P NMR s i g n a l s are i d e n t i c a l t o each o t h e r . 3 1

3 1

3

The b i o l o g i c a l p r o p e r t i e s o f a p h o s p h o r o t h i o l a t e S^-oxide p r e s u m a b l y depend i n p a r t on t h e r e l a t i v e r a t e a t w h i c h i t r e a c t s as a p h o s p h o r y l a t i n g a g e n t a s opposed t o t h e r a t e i t r e a r r a n g e s to t h e p h o s p h i n y l o x y s u l f e n a t e ( E q . 3 ) . A s i m p l e e x p e r i m e n t . . , phosphorothiolate A

mfojo] oct,vot,on

·*·

[phosphorothiolottl L

S-ox.d.

hydrolate(t)

J

.

,

.

hydrolai.L)

deactivation

phosphinyloxysulfenote

Eq. 3

M0 2

hydrolysis products

i l l u s t r a t e s t h i s p o i n t . On o x i d a t i o n o f j>a i n e t h a n o l t h e o n l y p h o s p h o r u s p r o d u c t i s o l a t e d i s t h e d i e t h y l e s t e r 6d u n d o u b t e d l y obtained from p h o s p h o r y l a t i o n o f e t h a n o l by the S-oxide i n t e r ­ m e d i a t e ; p h o s p h o r o t h i o l a t e 6a by i t s e l f does n o t r e a c t w i t h e t h a ­ n o l a n d p h o s p h i n y l o x y s u l f o n a t e 6b g i v e s t h e a c i d 6 c . T h u s , i f the S-oxide a c t i v a t i o n p r o d u c t i s formed on m i x e d - f u n c t i o n o x i d a s e (mfo) a c t i v a t i o n w i t h i n t h e c e l l i t may i m m e d i a t e l y phosphorylate s e n s i t i v e s i t e s such as h y d r o l a s e s i n c l u d i n g a c e t y l c h o l i n e s t e r a s e . However, when t h e S - o x i d e i s f o r m e d i n a n e n v i r o n m e n t where r e ­ arrangement occurs f a s t e r than p h o s p h o r y l a t i o n t h e o v e r a l l r e s u l t i s the d e a c t i v a t i o n process o f h y d r o l y s i s . T h i s h y p o t h e s i s war­ r a n t s c a r e f u l c o n s i d e r a t i o n i n e v a l u a t i n g t h e t o x i c o l o g y and metabolism o f S_-alkyl phosphorothiolate p e s t i c i d e s . Acknowledgment S u p p o r t e d i n p a r t b y G r a n t 5 P01 ES00049 f r o m t h e N a t i o n a l Institutes of Health.

Literature Cited 1. 2. 3. 4.

Eto, M. "Organophosphorus Pesticides: Organic and Biological Chemistry," CRC Press, Cleveland, 1974. Bellet, E. M.; Casida, J . E. J . Agric. Food Chem. 1974, 22, 207. Eto, M.; Okabe, S.; Ozoe, Y.; Maekawa, K. Pestic. Biochem. Physiol. 1977, 7, 367. Michalski, J.; Radziejewski, C.; Skrzypczyński, Z. J . Chem. Soc. Chem. Comm. 1976, 762.

RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

71 Research on Organophosphorus Insecticides, Synthesis of O-Alkyl O-Substituted Phenyl Alkylphosphonothioates W U K I U N - H O U O , SUN Y U N G - M I N , and WANG S I N G - M I N Department o f Chemistry, F u d a n University, Shanghai, C h i n a

In order to obtai for agriculture in China prepare organo-phosphorus compounds. After screening for the efficiency of insecticides, we found that o-l,3,-dichlorophenyl o-alkyl ethylphosphonothioates showed high activities against a wide variety of insects as an efficient contact insecticide. We have synthesized fifteen compounds of the homologs by the following reactions:

For the last step of the preparation we used method 4A and 4B, and found that method 4B is better. For the synthesis of the alkyldichlorothiophosphine, we also used the aluminum chloride complex method: 0097-6156/81/0171-0341$05.00/0 ©

1981

American

Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

342

PHOSPHORUS CHEMISTRY

The molecular structural formulas, boiling points, melting points and the yields are listed in Table I. Table I

C H 2

y

5

RO

^OR

1

S t r u c t u r a l Formulas R CH

h

R

£

2

£

2

n-C H

y

5

n-C H

7

3

3

Λ/ C

7

H

2 5

C H

A*

8

C H

9

n-C H

10

CH

11

C H

12

n-C H

13

CH

14

C H

1 5

n-C H

2

6

7

2

3

?

3

7

4B 61.3 4A 80.0

o,£-Cl C H

3

bp 152-153°/0.8

4A 56.9

6

2

6

£

-ClC H

4

bp 128°/0.1

4A 78.6

£

-ClC H

4

bp 124-125°/0.6

4A 62.5

6

6

£-t-BuC H

4

bp 130-131°/0.3

4B 66.1

£-t-BuC H

4

bp 134.5°/0.7

4B 78.2

£-t-BuC H

4

bp 135-136°/0.2

4B 77.2

6

o,o, -Cl C H

2

mp 49°

4B 92.3

o,o,£,Cl C H

2

mp 43°

4B 90.0

o,o,£,Cl C H

2

mp 48°

4B 77.1

3

6

3

6

6

ci c

6

mp 66-67°

4A 58.6

ci c

6

mp 79°

4A 58.8

mp 64-65°

4A 44.3

5

5

bp 118-119°/0.9 bp 130-131°/0.5

5

3

4B 70.4

3

2

3

5

bp 128-129°/0.9

o, ,Cl C H

£

3

3

4

6

5

3

,

-ClC H

6

6

3

2

2

£

5

4

j6

°C/mmHg

o, -Cl C H

3

C H

f

C 1

5 6 C

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

71.

KIUN-Houo E T A L .

TABLE I I .

1 2 1 2 1 2 1 2 1 2 1 2 1 2 1

46

34

36

37

34

45

37

33

38

43

47

52

34

30

41 35 36 30 30 25 32

38

28

40

12

1 38 2 1 37 2 1 25

28 28 35 32 12

13

ζ 1

2 3 4 5 6 7 8

33

-

42

_

32 31 31 31 42 33

Ζ

9

1 ο Ζ

10 11

-

0

_

1 1

— 33 _ 30

-36

-

42

35

44

43

34

41

71

60

59

21

Melanogaster Mortality % (17 h o u r s ) (3) (2) 100 100 _ 100

-

100 100 100 100 100 100

100

100 100

100

100

55.0

100

100 100 100 100 34.2

-31 -24 _

343

100 100 100 100 100 73.3 62.5

100

43

100 -

100

-

22

42

100

100

33

38

(1)

28

-

9 Ζ

15

(4)

22 _

9 Ζ

14

Insecticides

T o x i c i t y Test f o r Drosophila

Numbers o f insects f o r test (2) (3) (1)

Sample Number 1

Organophosphorus

100

-

100 73.5

100 100

(4)

-

100

- 3.3 100 14.3 83.9

-25.0 -

100

-81.8 -

7.9

0

0

0

0

0

0

0

0

100

100

85.7

-40.9 -

Δ.

Standard Sample 1 Rogor

-

3.4

-

N o t e s Α. (1) = 100 ppm (2) « 10 ppm (3) = 1 ppm (4) = 0.1 ppm Β. The t e s t s o l u t i o n made o f 1 0 % a b s o l u t e a l c o h o l i c i n s e c t i c i d e , was d i l u t e d g r a d u a l l y w i t h w a t e r . C. D e t e r m i n a t i o n 1by method1 o f a g a r - a g a r p o i s o n d i e t . *Rogor i s ; 0 , 0 - d i m e t h y l - S -- ( N - m e t h y l c a r b o m o y l met h y l ) d i t h i o p h o s phate.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

344

PHOSPHORUS

Table I I I . Sample Number 1 3 6 10 Rogor *Notes:

R e s u l t s f o r Second

Screening Test

M o r t a l i t y o f I n s e c t s %* Tetranychus Agrotis Myzus Urticae Ipsilon Persicae

Emulsion Concentration 47.1% 50.4% 48.9% 18.9% 25.0%

10.0 50.0 0 18.8

55.1 80.0 65.7 78.3 99.4

77.8 77.8 70.0 0

100 oThe e m u l s i o n c o n c e n t r a t i o n i np r a c t i c e was d i l u t e d w i t h 2000 v o l u m e s o f s o l u t i o n .

Table IV.

Insecticide Emulsion Concentran.

Test f o r F i r s F i r s t I n s t a Lava Quantity of Insecticide Jin/Mou*

No. 1 (47.1%) No. 3 (50.4%) No. 5 (48.1%) No. 10 (18.9%) Suraithion (50 % Sample) *Notes:

CHEMISTRY

1 1 1 3 ^

( O u t d o o r s :i n P o t ) .

No. o f Rice Plants

No. (Df I n s e c t s Dead Mortality P e r ]Pot H e a r t % %

58 49 26 28

60 60 60 60

1.7 2.0 30.7 32.1

100.0 98.7 95.5 89.5

45

60

0

100.0

J i n ; C h i n e s e m e a s u r e o f w e i g h t , 1 J i n = 500 gm. Mou; C h i n e s e m e a s u r e o f a r e a , 1 Mou = 6.67 a c r e s

Literature Cited

1. Hoffman, F.W.; Moore, T.R. J. Am. Chem. Soc. 1958, 80, 1151. 2. Fukuto, T.R. J. Am. Chem. Soc. 1959, 81, 372. 3. Schegk, E.; Schrader, G. Ger. 1, 078, 124, Chem. Abstr. 1963, 58, 1492. RECEIVED

June 30,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

72 Introduction of Phosphorus into the Polyethyleneterephthalate Molecule G . B O R I S O V , K. TROEV, a n d

A.

GROZEVA

Central L a b o r a t o r y for Polymers, Bulgarian A c a d e m y o f Sciences, Sofia 1113, Bulgaria

The introduction of phosphorus into the polyethyleneterephtha­ late molecule is expecte ance to combustion but polycondensation stages as well as the side reactions taking place during its synthesis. The influence of various phosphorus-containing modifiers, i.e. diethyl phosphite (I), the sodium salt of diethyl phosphite (II) and the disodium salt of 1,2-dicarbomethoxyethylphosphonic acid (III), on the transesterification, polycondensation and side re­ actions were examined.

Dimethyl terephthalate was transesterified with ethylene glycol in the presence of the modifiers taken at different concentrations. The alcohol distillate (Table 1) obtained from conducting the pro­ cess with diethyl phosphite as modifier revealed the increased pre­ sence of water, acetaldehyde and acetal as compared with the alco­ hol distillate from the transesterification of dimethyl terephtha­ late with ethylene glycol (1,2). These observations were in support of the conclusion that diethyl phosphite is unsuitable as a modi­ fier for polyethyleneterephthalate. Table

I,

Y i e l d s o f by-products Modifier

Dy—prouuces,

J/o

Water 2-methyldioxolane Acetaldehyd Acetal

Sodium s a l t Disodium 1,2-diof d i e t h y l carbomethoxyethylphosphite phosphonate Phosphorus c o n t e n t , % 0.0 0.6 0..8 0.5 1.0 1.5 0.5 1.0 1.5 1.02 3.60 4..80 2.50 3.84 4.30 2.37 3.42 3.85

Diethylphosphite

0.13 0.15 0,,16 0.04 0.04 0.04 0.02 t r a c e s " 0.01 0.12 0..13 t r a c e s " " " 0.02 t r a c e s . II II II II II 0.08 0.11 0..15 t r a c e s 0097-6156/81/0171-0345$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

346

PHOSPHORUS CHEMISTRY

The s t u d i e s c a r r i e d o u t o n t h e a l c o h o l d i s t i l l a t e o b t a i n e d from the c o - t r a n s e s t e r i f i c a t i o n o f d i m e t h y l t e r e p h t h a l a t e w i t h e t h y l e n e g l y c o l i n t h e presence o f t h e sodium s a l t o f d i e t h y l p h o s p h i t e o r the di-sodium s a l t o f 1,2-dicarbomethoxyethylphosphonic a c i d i n v a r i o u s c o n c e n t r a t i o n s showed ( T a b l e I ) t h a t t h e s i d e r e a c t i o n s were m a r k e d l y s u p p r e s s e d . The h y d r o x y 1 v a l u e , m e t h o x y c a r b o n y l g r o u p c o n t e n t , a c i d v a l u e , m e l t i n g p o i n t , c o n t e n t o f d i e t h y l e n e g l y c o l and o f t h e o b t a i n e d p r e - c o n d e n s a t e s were d e t e r m i n e d i n o r d e r t o o b t a i n more d e t a i l e d i n f o r m a t i o n on t h e t r a n s e s t e r i f i c a t i o n s t a g e i n t h e p r e s e n c e o f t h e sodium s a l t o f d i e t h y l p h o s p h i t e o r d i - s o d i u m s a l t o f 1 , 2 - d i carbomethoxyethylphosphonic a c i d . The r e s u l t s o b t a i n e d ( T a b l e I I ) i n d i c a t e t h a t t h e p r e c o n d e n s a t e s m o d i f i e d w i t h sodiu sin of following structur VCO(CH ) )-(0-P-(CH )iOC-(

o r c

2

2

2

7 - C 0 ( C H ) - ) -0 2

2

x

0 —^ 0 ONa 0 0 With the di-sodium s a l t o f 1,2-dicarbomethoxyethylphosphonic a r e s i n o f t h e f o l l o w i n g s t r u c t u r e (4) was o b t a i n e d

acid

c

-0-(C- / / v v - - ° ( C H ) - ) (o-C-CH - CH - C-) 0 il \ — / H I» , H m 0 —' 0 0 Ρ-0 0 NaO^ 0Na The d i e t h y l e n e g l y c o l a n d c a r b o x y l g r o u p c o n t e n t s o f t h e r e s i n and i t s d i s p e r s i t y were u s e d a s a measure o f t h e d e g r e e o f s i d e reactions taking place a t the polycondensation stage. W i t h t h e sodium s a l t o f d i e t h y l p h o s p h i t e as m o d i f i e r t h e d i e ­ t h y l e n e g l y c o l c o n t e n t i s w i t h i n 0.13 t o 2.6% a g a i n s t 1.5 t o 2.0% for the un-modified r e s i n . 2

2

2

n

v

V

T a b l e I I . A n a l y s e s o f pre-condensates m o d i f i e d w i t h sodium s a l t o f d i e t h y l phosphite or disodium 1,2-dicarbomethoxyethylphosphonate Modifier

eristics

Sodium s a l t o f Disodium 1,2-dicarbomethd i e t h y l phosphite xyethylphosphonate Phosphorus Content, %

0.0 0.5 1.0 1.5 0.4 0.7 1.2 1.5 1.9 OH value,mgKOH/g 440 436 268 310 378 403 186 398 379 CH 0,% 2.0 2.5 3.2 4.4 7.0 9.9 1.7 2.6 3.3 Acid value, mgKOH/g 0.8 2.1 3.2 2.1 3.2 3.0 3.0 2.2 3.1 DEG, % 1.4 1.1 0.2 1.2 1.5 1.2 0.8 0.3 1.4 M e l t i n g point,°C 160 146 132 167 155 155 123 165 116 The c a r b o x y l g r o u p s c o n t e n t i s i n c r e a s e d . The d i f f e r e n t i a l d i s ­ t r i b u t i o n c u r v e ( F i g . l ) i n d i c a t e s a good p o l y d i s p e r s i t y c o m p a r a b l e w i t h t h e one e x h i b i t e d by t h e u n - m o d i f i e d o n e . 3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

72.

BORisov E T A L .

Table I I I .

Characterist

l

C

Phosphorus

in

347

Polyethyleneterephthalate

C h a r a c t e r i s t i c s o f p o l y e t h y l e n e t e r e p h t h a l a t e modi­ f i e d w i t h sodium s a l t o f d i e t h y l p h o s p h i t e o r d i s o dium 1,2-dicarbomethoxyethylphosphonate Modifier Sodium s a l t o f Disodium 1,2-dicarbomethoxyd i e t h y l phosphite ethylphosphonate Phosphorus c o n t e n t , %

S

0.0 0.32 0.80 1.05 1.47 0.45 0.8 1.35 1.62 η 1.33 1.23 1.42 1.18 1.28 1.34 1.33 1.32 1.28 M e l t i n g point,°C 259 259 243 252 248 259 258 258 255 COOH.IO mgeq/g 67 99 120 117 132 44 40 38 34 DEG,% 1.4 0.13 2.5 2.6 2.5 0.48 0.55 0.5 0.70 DEG-diethylene g l y c o l ; η relativ viscosity 6

With the di-sodium s a l a c i d a s m o d i f i e r t h e d i e t h y l e n e g l y c o l c o n t e n t and t h e c a r b o x y l group c o n t e n t i s v e r y l o w (Table I I I ) . These r e s u l t s i n d i c a t e t h a t t h e u s e d m o d i f i e r h a s a l s o t h e r m o s t a b i l i z i n g p r o p e r t i e s . The i n t e g r a l and d i f f e r e n t i a l c u r v e s ( F i g . 2 ) o f m o l e c u l a r mass d i s ­ t r i b u t i o n show t h a t t h e p o l y d i s p e r s i t y o f m o d i f i e d r e s i n i s com­ parable t o that o f the un-modified. The t h e r m o g r a v i r a e t r i c c u r v e s o b t a i n e d i n d i c a t e t h a t t h e m o d i f i ­ ed a n d u n - m o d i f i e d r e s i n s b e g i n t o decompose a t 300°C. The c o m b u s t i o n t e s t s o f r e s i n m o d i f i e d w i t h t h e s o d i u m s a l t o f d i e t h y l p h o s p h i t e samples i n d i c a t e ( T a b l e IV) t h a t w i t h t h e i n ­ c r e a s e i n t h e p h o s p h o r u s c o n t e n t t h e s a m p l e s c e a s e t o b u r n and t h e o v e r a l l time o f combustion l e n g t h e n s . Table I V . Data from Combustion T e s t s W e i g h t Oxygen Time r e q u i r e d Duration of Modifier Index of f o r complete combustion combustion,sec. residue, P, % after igni­ % tion,sec . Without 5.2 modifier 19 181 181 0. 0 Diethyl phosphite sodium

0. 32 0. 80 1. 05 1. 47 0. 45

Disodium 1,2-dicarbornethoxy- 0. 80 e t h y l p h o s - 1. 35 1. 62 phonate

extinguished 11 11 II

II

11 11 II

188 220 265 275 202

8.0 21.0 30.0 29.9 25.0

19.8 21.6 21.8 22.4 21.4

229 227 240

50.0 52.0 50.0

22.8 23.6 24.0

The r e s i d u e a f t e r c o m b u s t i o n i n c r e a s e s c o n s i d e r a b l y f r o m 5.2% f o r t h e u n - m o d i f i e d r e s i n t o 3 0 % f o r t h e one c o n t a i n i n g 1.05% of phosphorus. The o x y g e n i n d e x c h a n g e s f r o m 19 f o r t h e u n - m o d i ­ f i e d r e s i n t o 22.4 f o r .the one c o n t a i n i n g 1.47% o f p h o s p h o r u s .

American L.iemicst Society library 1155 isth St. H. w.

In Phosphorus Chemistry; Quin, L., et al.; Washington, D. C. Society: 20036Washington, DC, 1981. ACS Symposium Series; American Chemical

348

PHOSPHORUS CHEMISTRY

Figure 1. Molecular mass distribution curves from phosphorus-containing poly­ ethyleneterephthalate sample with 0.74% phosphorus modified with sodium salt of diethyl phosphite. Key; 1, integral curve; 2, differential curve; and 5, integral curve of phosphorus distribution.

0

10 20 30 40

50 ,-3 M .10 v

w

7A

1

2.2 100

zo

90

1.8

80

1.6

70

Figure 2. Molecular mass distribution curves from phosphorus-containing poly­ ethyleneterephthalate sample with Ο.8ΟΦ0 phosphorus modified with disodium salt of 1,2-dicarbomethoxyethylphosphonic acid. Key; 1, integral curve; and 2, differ­ ential curve.

60

1,2

50

1.0

i.0

0,8

30

0.6

20

OA

10

0.2

0

18

26

34 M . 10" v

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

72.

BORisov E T A L .

Phosphorus

in Polyethyleneîerephthalate

349

The s a m p l e s m o d i f i e d w i t h t h e d i - s o d i u m s a l t o f 1 , 2 - d i c a r b o m e t h o x y e t h y l p h o s p h o n i c a c i d showed ( T a b l e I V ) t h e w e i g h t o f r e s i d u e r e a c h i n g 52%. LITERATURE CITED

1. Troev, K.; Grozeva, At.; Journal 1979, 15, 437. 2. Troev, K.; Grozeva, At.; Journal 1981, 17, 27. 3. Troev, K.; Grozeva, At.; Journal 1979, 15, 1143. 4. Troev, K.; Grozeva, At.; Journal 1981, 17, 31. RECEIVED

July 7,

Borisov, G. European Polymer Borisov, G. European Polymer Borisov, G. European Polymer Borisov, G. European Polymer

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

73 Selected Novel Trivalent Organophosphorus Processing Stabilizers for Polyolefins J. D. S P I V A C K , A. P A T E L , and L. P. S T E I N H U E B E L CIBA-GEIGY Corporation, Ardsley, N Y 10502

Processing stabilizers are a special class of antioxidants used to inhibit polymer degradatio to polymerization such etc. These steps are carried out at relatively high temperatures (220-320°) in the presence of some oxygen. Attempts to counteract degradation by the use of 2,6-di-tert.butyl-4-methylphenol (BHT) and various organophosphorus compounds, such as tris-nonyl-phenylphosphite (7) and 3,9-dioctadecoxy-2,4, 8,10,3,9-tetraoxadiphospha(5,5)-spiroundecane (8), have been only partially successful. BHT is volatile at high temperatures and contributes to discoloration during processing. 7 and 8 undergo hydrolysis even during ambient storage conditions leading to ex­ trusion and spinning problems, corrosion of equipment and contami­ nation of extrudate with hydrolysis and corrosion products, etc. A generally accepted (l) mechanism for the oxidation of polyole­ fins in the presence of antioxidants of the hydrogen donor type, AH, involves the conversion to hydroperoxides of polymer radicals, R·, and polymer peroxy radicals, R00·, formed during the initia­ tion and propagation steps. Propagation is promoted by homolysis of ROOH to RO· and ·OΗ. Chain transfer will take place to only an insignificant degree if A· is a stable free radical. Equations 1 and 3 below show how trivalent phosphorus compounds can inhibit oxidation by converting hydroperoxides to non-radical products. Equation (2) illustrates how the phosphorus derivatives may also act as chain transfer agents with peroxy radicals.

R00H

+ R

f

00R

S i m i l a r l y w i t h R0* and R* 0097-6156/81/0171-0351$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

(1)

352

PHOSPHORUS CHEMISTRY

R00-

+

PR

+

PR"

M

->

3

M

[R00PR ] 3

However

->

RO-

+

0=PR"

3

->

ROH

+

0"PR"

3

(2)

RO

ROOH

PR'S

3

(3)

HO I t i s t h u s a p p a r e n t t h a t h y d r o g e n d o n o r s AH and h y d r o p e r o x i d e decomposers, such as P R " , c a n a c t s y n e r g i s t i c a l l y t o i n h i b i t r a d i c a l i n i t i a t e d polymer c h a i n o x i d a t i o n s . 3

The f o l l o w i n g s i x h i n d e r e d p h o s p h o n i t e and p h o s p h i t e e s t e r s w e r e s t u d i e d as p r o c e s s i n g s t a b i l i z e r s and compared w i t h 1_ and 8. (A)

0,0*-Biphenylene

P h o s p h o n i t e s and P h o s p h i t e s ι. *

= (O

P-R 2, R = CH 03

(B)

Unsymmetrical

3)

(ref.

4)

(ref.

4)

(ref.

4)

(ref.

4)

Pi-Hindered Phenylphosphonites

jL

(c)

(ref.

4,

R = (CH ) C — 3

3

Symmetrical Pi-Hindered Phenylphosphonites "

5,

-η

R = CH

—

3

6, R = ( C H ) C — 3

—• 2

CqH 19

o>°

7

-P

n-C

1 8

H

3 7

0-P

x

0-CH

CH -0 P-0-n-C H ^c' 0-CH CH -0 2

2

X

1 8

/

X

2

7

3

3 7

/

2

8

Oxidation during processing of polypropylene i s p r i n c i p a l l y a c c o m p a n i e d b y c h a i n s c i s s i o n made e v i d e n t b y a r e d u c t i o n i n m e l t viscosity. The o x i d a t i o n d u r i n g p r o c e s s i n g o f p o l y e t h y l e n e o n t h e o t h e r hand i s accompanied m a i n l y by c r o s s l i n k i n g . The f o l l o w i n g two t e s t s a r e , t h e r e f o r e , u s e d :

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

73.

SPIVACK E T A L .

Organophosphorus

Processing

353

Stabilizers

(1)

P o l y p r o p y l e n e - M e l t f l o w r a t e a f t e r t h e f i r s t , t h i r d and f i f t h e x t r u s i o n , a t 500°F t o d e t e r m i n e t h e d e g r e e o f c h a i n s c i s s i o n ( 5 ) . Y . I . index i s a l s o determined ( 6 ) .

(2)

H i g h D e n s i t y P o l y e t h y l e n e - [ B o t h r e g u l a r and h i g h m o l e ­ c u l a r w e i g h t (HMW)]. The t i m e t o i n c r e a s e i n t o r q u e a t 220°C. b y t h e B r a b e n d e r P l a s t i c o r d e r was d e t e r m i n e d a s a measure o f c r o s s l i n k i n g . Y e l l o w n e s s I n d e x a f t e r t h e B r a b e n d e r t e s t a t 220°C. and a f t e r t h e f i r s t e x t r u s i o n a t 260°C. were a l s o p e r f o r m e d .

M o i s t u r e - P i c k u p and H y d r o l y s i s The m o i s t u r e ρickup and h y d r o l y s i s t e s t s were c a r r i e d o u t a t room t e m p e r a t u r e and 8 0 $ R.H shown i n t h e f o l l o w i n g t a b l e M o i s t u r e P i c k u p and H y d r o l y s i s a t Room T e m p e r a t u r e , 8 0 $ R.H. Time - 1200 Hours Compound

Notes:

Water P i c k u p $

Hydrolysis $

Notes

I

0.5

ca.

0

(2)

2

0.1

ca.

0

(2)

3

0.1

ca.

0

(2)

4

0.5

ca.

0

(2)

5

0.0

0

(2)

6

0.0

0

(2)

ι

18.9 ( 1 )

ca.

100

Π,3)

8

34.0 ( 1 )

ca.

100

(1,3)

( l ) a t 400 h r s . (2)

L i t t l e o r no change b y TLC a n d I R b e f o r e and a f t e r e x p o s u r e ,

(3)

TLC shows d i s a p p e a r a n c e o f s t a r t i n g compounds. IR shows s t r o n g h y d r o x y 1 band a f t e r e x p o s u r e .

Summary o f P r o c e s s i n g C h a r a c t e r i s t i c s p h o r u s Compounds Polypropylene A t 500°F

(Profax 6801, Hercules

o f S e l e c t e d Organophos­ Inc.) M u l t i p l e E x t r u s i o n

(260°C)

On t h e b a s i s o f m e l t f l o w r a t e measurements a f t e r 1, 3 a n d 5 e x t r u s i o n s , compounds JL, 2 and 3 when u s e d a l o n e a t 0.1$ i n t h e p o l y p r o p y l e n e b a s e r e s i n p r o v i d e s u p e r i o r s t a b i l i z a t i o n t o BHT, ]_ a n d 18, U n d e r t h e s e c o n d i t i o n s compound 2 p r o v i d e s t h e l o w e s t Y e l l o w n e s s I n d e x ( Y . I . ) c o l o r o v e r o t h e r compounds e v a l u a t e d .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

354

PHOSPHORUS

CHEMISTRY

Under t h e same t e s t c o n d i t i o n s on t h e b a s i s o f m e l t f l o w r a t e , compounds 1 2, 3 and 4 p r o v i d e s i g n i f i c a n t l y b e t t e r p e r f o r m a n c e t h a n BHT, 1_ and «8 when u s e d i n c o n j u n c t i o n w i t h p h e n o l i c AO-1 (neopentanetetrayl-tetrakis[3,5-di-tert.-butyl]-4-hydroxyhydrocinnamate). Compounds 2 3 and 4 a l s o d e v e l o p l e s s c o l o r t h a n BHT and 8. Compounds 6 and 7_ d e v e l o p t h e most c o l o r i n the p r e s ­ ence o f AO-1, 9

9

At 550°F (288°C.) A l l s i x c a n d i d a t e compounds p r o v i d e b e t t e r p r o c e s s s t a b i l i t y t h a n BHT when e v a l u a t e d a l o n e a f t e r 5 e x t r u s i o n s . I n c o n j u n c t i o n w i t h p h e n o l i c A0-1, a l l s i x compounds e x h i b i t s u p e r i o r s y n e r g i s m and p r o v i d e b e t t e r p r o c e s s s t a b i l i t y and c o l o r t h a n (7_) and (8) d u r i n g multiple extrusion. High D e n s i t y P o l y e t h y l e n at 260 C. U

When u s e d i n HDPΕ as c o l o r i m p r o v e r s f o r p h e n o l i c A0-1, compounds 1., 2 and 3 p r o v i d e s i g n i f i c a n t l y i m p r o v e d c o l o r t h a n o b t a i n a b l e w i t h TNPP w h i l e b e i n g e q u i v a l e n t i n r e s i s t a n c e t o d i s c o l o r a t i o n to ( 7 ) . High M o l e c u l a r Weight - High D e n s i t y P o l y e t h y l e n e

(Lupolen-BASF)

E m p l o y i n g t h e B r a b e n d e r p l a s t i c o r d e r a t 220°C, 50 R.P.M. w i t h t h e ram open compounds l 2,2 * A prevent c r o s s l i n k i n g about t h r e e t i m e s l o n g e r t h a n BHT and A0-1 a l o n e . a n (

9

Conclusions A number o f o r t h o h i n d e r e d a l k y l - s u b s t i t u t e d p h e n y l p h o s p h i t e s and p h o s p h o n i t e s were f o u n d t o be e f f e c t i v e p r o c e s s s t a b i l i z e r s f o r p o l y p r o p y l e n e and h i g h d e n s i t y p o l y e t h y l e n e c o m b i n i n g more e f f e c t i v e s t a b i l i z a t i o n a c t i v i t y a t h i g h t e m p e r a t u r e s w i t h good s t o r a g e s t a b i l i t y a t r e l a t i v e l y e l e v a t e d h u m i d i t y and a m b i e n t t e m p e r a t u r e , as w e l l as r e s i s t a n c e t o d i s c o l o r a t i o n . REFERENCES CITED

(1) (2) (3) (4) (5) (6)

For Example, Chapter 12, J. A. Howard in Free Radicals Vol. II, Jay K. Kochi, Ed., John Wiley, N.Y. (1973). J. D. Spivack, U.S. 4,143,028 (March 6, 1979). J. D. Spivack, U.S. 4,196,117 (April 1, 1980). J. D. Spivack, U.S. 4,233,207 (November 11, 1980). ASTM Method 1238 Condition L. ASTM Method D1925-63T.

RECEIVED

June 30,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

74 Oligomeric Phosphorus Esters with Flame Retardant Utility E D W A R D D. WEIL, RALPH B. F E A R I N G , and F R E D J A F F E Stauffer Chemical Company, Eastern Research Center, Dobbs Ferry, N Y 10522

The term oligomer refers to a polymer-like material having only a few repeating units. The oligomeric phosphorus esters which are the subject of the present paper are generally viscous liquids having an average of two or more phosphate and/or phosphonate ester units per molecule. Pioneering work on phosphorus ester oligomers has been done by Monsanto in the U.S. (1), by Hoechst in Germany (2), and in the Soviet Union. These "studies involved synthesis and flame retardant applications. The polycondensation of 2-chloroethyl phosphates as a route to oligomeric phosphorus esters (Equa­ tion 1) was first reported by Korshak et al. (3). This Russian publication describes the polycondensation of tris(2-chloro­ ethyl) phosphate at 240-280° under non-catalytic conditions. An acidic dark product was obtained. Besides the desired transalky lation, side reactions yielding acetaldehyde, vinyl chloride, phosphorus acids, and pyrophosphates were described by other Soviet researchers (4). Such a multitude of concurrent re­ actions is undesirable if this process is to be controllable and useful for flame retardant manufacture. P o l y c o n d e n s a t i o n o f 2 - C h l o r o a l k y l Phosphates and Phosphonates Each s t e p o f t h e p o l y c o n d e n s a t i o n can be d e s c r i b e d b y t h e following general reaction: (1)

#

2RR'P(0)0CH CH C1—RR P(0)OCH CH OP(0)RR 2

2

2

#

2

+ ClCI^CÏ^Cl

Polycondensation r e a c t i o n s o f 2 - c h l o r o a l k y l phosphates o r phosphonates t o o b t a i n products having a c o n t r o l l a b l e degree o f c o n d e n s a t i o n a n d l o w a c i d o r l a t e n t a c i d c o n t e n t s w e r e accom­ p l i s h e d i n o u r l a b o r a t o r y u s i n g c a t a l y s t s such as quaternary ammonium s a l t s , a m i n e s , a m i d e s , s o d i u m c a r b o n a t e , o r l i t h i u m c h l o r i d e (5) . R e d u c t i o n o f t h e t e m p e r a t u r e d i m i n i s h e d t h e 0097-6156/81/0171-0355$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

356

PHOSPHORUS CHEMISTRY

u n d e s i r a b l e s i d e r e a c t i o n s . Further e f f o r t was necessary to e l i m i n a t e l a t e n t a c i d products i f the products were to be u s e f u l i n , f o r example, urethane foams. T r e a t i n g the crude product w i t h ethylene oxide a f f o r d e d a means f o r c o n v e r t i n g phosphorus a c i d groups to hydroxyethyl e s t e r s . Anhydride groups could a l s o be removed by r e a c t i o n with epoxides. P a r t i c u l a r l y p e r s i s t e n t , how­ ever, were five-membered c y c l i c phosphate e s t e r groups, which i n the case of the polycondensation product o f t r i s ( 2 - c h l o r o e t h y 1 ) phosphate can occur as chain ends or as small molecules. These five-membered phosphate s t r u c t u r e s show a l a r g e Ρ shift (17-18 ppm) downfield from the a c y c l i c phosphates. Five-membered of h y d r o l y s i s corresponding c y c l i c esters used as flame

c y c l i c phosphate and phosphonate e s t e r s have r a t e s orders o a c y c l i c ester are u n d e s i r a b l e components i f the oligomers are retardants.

The presence o f these c y c l i c e s t e r s i n the crude polycondensation r e a c t i o n product was found to be unavoidable ; indeed some e v i ­ dence was developed that the polycondensation a t l e a s t i n p a r t proceeds v i a these c y c l i c e s t e r s . Considerable e f f o r t was ex­ pended to f i n d means f o r e l i m i n a t i n g these c y c l i c five-membered e s t e r s from our polycondensation products. The c y c l i c e s t e r s can be e l i m i n a t e d by e i t h e r inducing them to polymerize by use of Lewis a c i d c a t a l y s t s such as stannous octoate, o r by subjec­ t i n g them to r i n g opening by means of an a l c o h o l or water ( 7 ) . Copolycondensation A f u r t h e r v a r i a t i o n on the t rans a I k y l a t i on r e a c t i o n described above i s the cocondensation of d i f f e r e n t phosphorus e s t e r s ( 8 ) ; as shown i n the f o l l o w i n g equation: q RP(0CH CH C1) 2

2

2

q + CH P(OCH ) 3

3

2

2 C H

3

Γ ç ο ι >» |-0^-OCH CH -o|-OCH CH

C 1

2

2

2

2

One embodiment o f t h i s general r e a c t i o n l e d to a product which was commercially produced f o r s e v e r a l years by S t a u f f e r as F y r o l 76 (9), a copolycondensation product o f dimethyl methylphosphonate with b i s ( 2 - c h l o r o e t h y l ) vinylphosphonate. The features o f F y r o l 76 were high phosphorus content (20%), water s o l u b i l i t y , and a b i l i t y to be polymerized by means of a r a d i c a l i n i t i a t o r to a c r o s s l i n k e d polymer. A r e l a t e d polycondensation product was developed from t r i s ( 2 - c h l o r o e t h y l ) phosphate and d i ­ methyl methylphosphonate. By c o n t r o l of the reagents and proce­ dure used f o r n e u t r a l i z a t i o n , these o l i g o m e r i c products were produced with primary a l c o h o l f u n c t i o n a l groups (7) .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

74.

WEIL

ET AL.

Oligomeric

Phosphorus

Esters

357

Oligomers V i a Metaphosphate(Phosphonate) Intermediates The d i s s o l u t i o n of P^O^ i n a phosphate or phosphonate e s t e r b r i n g s about a r e o r g a n i z a t i o n r e a c t i o n i n which a metaphosphate or metaphosphonate/phosphate i s formed (10). In the r e a c t i o n of 4°10 y ! methylphosphonate, the i n i t i a l l y - f o r m e d pro­ duct mixture at 60-110° undergoes a s t r u c t u r a l r e o r g a n i z a t i o n when the mixture i s h e l d a t r e a c t i o n temperature. An i n c r e a s e i n 0,0-dimethylphosphoric anhydride end groups ( $ - 1 1 . 4 , -11.6, -11.9) and Ρ-methyl(meta)phosphonic "middle" groups ($14.2, center of unresolved t r i p l e t and/or doublet of doublets) takes p l a c e at the expense of a decrease i n 0,P-dimethylphosphonic anhydride end groups (doublet at £ 25.7) and 0-methyl (meta)phosphoric anhydride middl and/or doublet of doublet p h o r i c anhydride (é-43) disappears e a r l y i n the h e a t i n g process. P

w

i

t

n

d i m e t n

The intermediate metaphosphate/phosphonate can then be made to r e a c t with ethylene oxide to e f f e c t the i n s e r t i o n of ethyleneoxy u n i t s i n t o the P-O-P l i n k a g e s . I f a l i m i t e d amount of water or an a l c o h o l i s added to the meta intermediate, the r e s u l t a n t oligomer can be produced with a c o n t r o l l e d hydroxy1 f u n c t i o n a l i t y (11, 12). An example of a f u n c t i o n a l oligomer made t h i s way i s the f o l l o w i n g : H-fOCH CH OP« -h0CH CH 0P — r 0 C H C H 0 H *2~"2 2 2 CH. CH„0 3 JxL ""3 2

o

2

n

O

o

v

There i s some evidence that the r e a c t i o n of ethylene oxide with the metaphosphonate/phosphate may a c t u a r y form some c y c l i c f i v e membered e s t e r s i n i t i a l l y , as shown by r s i g n a l s a t 18.4, 17.4 (phosphates) and 49 (phosphonate) which then are converted to a c y c l i c e s t e r s . In another example of t h i s route to o l i g o m e r i c phosphorus e s t e r s , P^O^Q i s reacted with t r i s ( 1 , 3 - d i c h l o r o i s o p r o p y l ) phosphate to prepare a metaphosphate which i s ethoxylated with ethylene oxide to produce a s u b s t a n t i a l l y hydroxy-free phosphate oligomer (12). A p p l i c a t i o n s as Flame Retardants S e v e r a l commercial products have r e s u l t e d from our phosphorus oligomer r e s e a r c h . F y r o l 99, a 2 - c h l o r o e t h y l ethylene phosphate oligomer, has been s u c c e s s f u l l y used as a flame r e t a r d a n t a d d i t i v e i n rebonded urethane foam, i n thermoset r e s i n s , i n intumescent c o a t i n g s , adhesives, paper a i r f i l t e r s (13), and r e l a t e d uses. T h i s product i s l e s s v o l a t i l e and has a h i g h e r flame r e tardant e f f i c a c y than the parent compound t r i s ( 2 - c h l o r o e t h y l ) phosphate. A r e l a t e d product was developed e s p e c i a l l y f o r use i n f l e x i b l e polyurethane foams. A vinylphosphonate/methylphospho-

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

358

n a t e o l i g o m e r whose c h e m i s t r y was d e s c r i b e d above ( F y r o l 76) was found e f f e c t i v e f o r meeting t h e F e d e r a l f l a m m a b i l i t y standard f o r c h i l d r e n ' s c o t t o n sleepwear ( 1 4 ) . A r e l a t e d methylphosphate/phosphonate oligomer has primary a l c o h o l e n d g r o u p s , a n d c a n c o r e a c t w i t h amino r e s i n s t o f o r m a w a t e r - r e s i s t a n t f l a m e r e t a r d a n t r e s i n f i n i s h on p a p e r o r o n t e x t i l e s u b s t r a t e s . The a p p l i c a t i o n o f t h i s o l i g o m e r w i t h a c o r e a c t a n t me t h y l o l m e 1 a m i n e o n c o t t o n u p h o l s t e r y f a b r i c c a n e n a b l e f u r n i t u r e c o v e r e d w i t h t h i s f a b r i c t o p a s s t h e Consumer Product S a f e t y Commission's proposed c i g a r e t t e i g n i t i o n t e s t . LITERATURE CITED

1. Birum, G. H. (to Monsant 3,042,701 (1962). 2. Wortmann, J., Dany, F. J., and Kandler, J. (to Hoechst A.-G.), U.S. Pat. 3,850,859 (1974). 3. Korshak, V. V., Gribova, I. Α., and Shitikov, V. Κ., Proc. Acad. Sci. USSR, Div. Chem. Sci., 196-201 (1958). 4. Kafengauz, I. M., Samigulin, F. Κ., Kafengauz, A. P., Polyakova, Τ. A., Tsarfin, Ya. A., and Gefter, E. L . , Soviet Plastics, 73-75 (Apr. 1967). 5. Weil, Ε. D. (to Stauffer Chemical Co.), U.S. Pats. 3,896,187 (1975), 4,005,034 (1977), and 4,013,814 (1977). 6. Westheimer, F. H., Acc. Chem. Res. 1, 70-77 (1968). 7. Weil, E. D. (to Stauffer Chemical Co.), U.S. Pat. 3,891,727 (1975); Shim, K. S. and Walsh, Ε. Ν. (to Stauffer Chemical Co.), 3,959,414 (1976), 3,959,416 (1976); Walsh, Ε. N. (to Stauffer Chemical Co.), 4,012,463 (1977). 8. Weil, E. D. (to Stauffer Chemical Co.), U.S. Pats. 4,086,303 (1978), 4,152,371 (1979), 4,202,842 (1980), 4,225,522 (1980). 9. Weil, E. D. (to Stauffer Chemical Co.), U.S. Pats. 3,822,327 (1974), 3,855,359 (1974), 4,017,257 (1977), 4,067,927 (1978). 10. Schep, R. A., Coetzee, J. H. J., and Norval, S., J. S. Afr. Chem. Inst. 27, 63-69 (1974); Inorg. Chem. 12, 2711-13 (1973). 11. Fearing, R. B. (to Stauffer Chemical Co.), U.S. Pat. 4,199,534 (1980). 12. Hardy, T. A. and Jaffe, F. (to Stauffer Chemical Co.), S. Afr. Pat. 79/1120 (Mar. 26, 1980). 13. Weil, E. D., Leitner, G. J., and Kearnan, J. Ε., "Phosphorus Flame Retardants for Resin-Treated Paper", in Proc. TAPPI Paper Synthetics Conf., Orlando, FL, Sept. 27, 1978. 14. Eisenberg, B. J. and Weil, E. D., Textile Chemist and Colorist 6 (8), 180-2 (1974); Bruce, J., Am. Dyestuffs Rep. 62 (10), 68-70 (1973). RECEIVED

June 30,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

75 Crystalline Calcium Polyphosphate Fibers E. J. G R I F F I T H Monsanto Company, St. Louis, M O 63166

Asbestos

Two molecular type Chrysotile is a magnesium silicate built upon a layered structure of silicate rings and Mg(0H) . The layered structure causes the sheets to roll into cylinders approximately 200Å in diameter. Amphibole asbestos may contain a variety of cations but is built upon a double chain silicate structure. The chrysotile asbestos is always found as an asbestiform crystal while the amphiboles may be either acicular or asbestiform. The diseases attributed to asbestos are a result of the fiber morphology and stability of the fibers rather than any specific chemical reactions between the asbestos and a host organism. It is probable that any refractory substance of similar morphology should stimulate similar diseases. Ingleman and Malgren (1) first demonstrated that long chain polyphosphates were enzymatically degraded by Aspergillius Niger in a manner similar to the enzymatic hydrolytic degradation of adenosine triphosphate in energy transfers of biological systems. Phosphatase chemistry has been the subject of numerous research efforts and the concepts are well established. The utility of asbestos is a result of a number of extraordi­ nary properties exhibited by the minerals. They are nonflammable, temperature resistant fibers composed of fibrals about 200Å in diameter, exhibit tensile strengths up to 1·10 psi, and moduli as great as 25·10 psi. The fibers are particularly resistant to attack by biological organisms and corrosive environments. 2

6

6

Phosphate F i b e r s The c h e m i s t r i e s o f p h o s p h a t e s a n d s i l i c a t e s a r e s i m i l a r , b u t the morphology o f t h e c r y s t a l s o f t h e s p a r i n g l y s o l u b l e phosphates a r e u n s u i t e d f o r f i b e r a p p l i c a t i o n s . Amorphous p h o s p h a t e g l a s s e s c a n b e e a s i l y s p u n i n t o f i b e r s i n a p r o c e s s s i m i l a r t o t h e manu­ facture offiberglass. U n f o r t u n a t e l y , amorphous p h o s p h a t e s l a c k b o t h s t r e n g t h and h y d r o l y t i c s t a b i l i t y . 0097-6156/81/0171-0361$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

362

C a l c i u m p o l y p h o s p h a t e s o f a metaphosphate c o m p o s i t i o n [ C a ( P 0 ) 2 ] h a v e p r o p e r t i e s and m o l e c u l a r s t r u c t u r e s w h i c h s h o u l d y i e l d a s u b s t a n c e w h i c h i s r e f r a c t o r y i n most e n v i r o n m e n t s b u t i s r a p i d l y d e g r a d e d i n s y s t e m s c o n t a i n i n g a c t i v e enzymes. None o f t h e known s y s t e m s o f c a l c i u m p h o s p h a t e s y i e l d f i b r o u s c r y s t a l s , a l t h o u g h v e r y s h o r t a c i c u l a r c r y s t a l s have been grown.(2) When c a l c i u m p o l y p h o s p h a t e s a r e grown f r o m a s o d i u m o r p o t a s ­ sium u l t r a p h o s p h a t e m e l t , a f i b r o u s c r y s t a l w i t h d i a m e t e r s as low a s 3μ and l e n g t h s as l o n g as 3cm w e r e g r o w n . The u l t r a p h o s p h a t e m a t r i x s e r v e s two f u n c t i o n s : 1) i t i s a g r o w i n g medium w h i c h a l l o w s t h e g r o w t h o f l o n g , v e r y s l e n d e r c r y s t a l s ; and 2) i t c o n ­ t r o l s t h e r e l e a s e o f CaO t o t h e c r y s t a l l i z i n g p o l y p h o s p h a t e a n i o n s p e r m i t t i n g t h e p o l y p h o s p h a t e c h a i n s t o grow t o v e r y h i g h m o l e c u l a r weights. When c r y s t a l l i z a t i o be e x t r a c t e d f r o m t h e u l t r a p h o s p h a t y g syste w i t h hot water. 3

Phase

n

Chemistry

The w a l l s f o r t h r e e o f t h e s i d e s o f t h e t h r e e - d i m e n s i o n a l t r i a n g u l a r phase d i a g r a m have been p u b l i s h e d , b u t the i n t e r n a l d e t a i l s o f t h e d i a g r a m a r e b u t p o o r l y u n d e r s t o o d . I t can be s t a t e d t h a t f i b r o u s c a l c i u m p o l y p h o s p h a t e s c a n be g r o w n t h r o u g h o u t t h e u l t r a p h o s p h a t e d i a g r a m d o m i n a t e d by [ C a ( P 0 ) ] c r y s t a l s . An a p p r o x i m a t e p h a s e d i a g r a m i s shown i n F i g u r e 1. 3

2

n

Property of Fibers The c a l c i u m p o l y p h o s p h a t e f i b e r s a r e v e r y v e r y s l o w l y d i s ­ s o l v e d i n w a t e r . E v e n i n b o i l i n g 0.1N HC1 t h e f i b e r s a r e r e s i s ­ t a n t t o d e g r a d a t i o n , b u t t h e f i b e r s a r e n o t as r e s i s t a n t t o b o i l ­ i n g 0.1N NaOH s o l u t i o n s . See F i g u r e 2. The f i b e r s a r e h i g h l y c r y s t a l l i n e and s i n g l e c r y s t a l t e n s i l e s t r e n g t h measurements r a n g e f r o m 2 · 1 0 p s i t o 1·10 p s i , while the modulus o f e l a s t i c i t y ranges from 10·10 p s i to 26·10 p s i . These v a l u e s are comparable to the p u b l i s h e d v a l u e s f o r c h r y s o t i l e asbestos. C h r y s o t i l e a s b e s t o s i s decomposed a t t e m p e r a t u r e s b e l o w 500°C. C a l c i u m p o l y p h o s p h a t e f i b e r s do n o t m e l t a t t e m p e r a t u r e s b e l o w 970°C, b u t t h e β-phase p h o s p h a t e i s c o n v e r t e d t o α-phase p h o s p h a t e a t 940°C. 6

6

6

6

Animal Studies A l l a n i m a l s t u d i e s made w i t h c a l c i u m p h o s p h a t e f i b e r s h a v e shown t h a t t h e f i b e r s a r e d e g r a d e d by t h e enzymes i n l i v i n g s y s ­ tems . To d a t e , t h e p h o s p h a t e s h a v e been t e s t e d as i m p l a n t s i n t h e p l e u r a l o r p e r i t o n e a l c a v i t i e s of r a t s . As was t o be e x p e c t e d

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

75.

GRIFFITH

Crystalline

Calcium

Polyphosphate

p o 2

363

Fibers

5

Figure L A schematic phase diagram for CaO- Na 0- P 0 system based on published diagrams. [Published diagrams: Na 0-P 0^, CaO-P 0 , (4); and Na 0-CaO-P 0 , (5).] 2

2

2

2

2

2

5

2

5

5

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

75.

GRIFFITH

Crystalline

Calcium

Polyphosphate

Fibers

365

w i t h i m p l a n t s o f p h o s p h a t e s , t h e f i b e r s and t h e i r d e g r a d a t i o n p r o ­ d u c t s a r e n u t r i e n t s f o r a l l b i o l o g i c a l s y s t e m s and no a d v e r s e r e ­ s u l t s have been o b t a i n e d . Conclusion I t i s concluded that calcium polyphosphate f i b e r s a r e v i a b l e c a n d i d a t e s a s s a f e r e p l a c e m e n t s f o r a s b e s t o s i n many o f i t s a p p l i ­ c a t i o n s , p a r t i c u l a r l y i n t h o s e a p p l i c a t i o n s where human e x p o s u r e i s considered hazardous. Literature Cited

1.

Ingelman, B.; Malgren H Acta Chem Scand 1947 1 422; 1948, 2, 365; 3, 157 2. Abe, Y. Nature 1979, , 3. Morey, G. N. and Ingerson, E. Am. J. Sci., 1944, 242, 4 4 H i l l , M. L., Foust, G. T., and Reynolds, D. S. Am. J. Sci. 1944, 242, 547. 5. Gremier, J. C., Martin, C., and Durif, A. Bull. Soc. Fr. Mineral. Cristallogr. 1970, 93, 52. R E C E I V E D June 30,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

76 Fluorination of Phosphoapatites Possible Alterations of Their Structure G. M O N T E L , G. BONEL, J. C. H E U G H E B A E R T , M. V I G N O L E S , and M. H A M A D Laboratoire de Physico-Chimie des Solides et des Hautes Températures, INP, E R A N° 263, CNRS, 38, Rue des 36 Ponts. 31400 Toulouse, France G. B A C Q U E T Laboratoire de Physique des Solides, L A CNRS, Université Paul Sabatier, 118, Route de Narbonne. 31062 Toulouse Cédex, France

As soon as chemists become interested in natural apatites, the problem with fluorin the fluorine must be removed necessary to fluorinate calcium phosphates in the mineral part of calcified tissues. Obviously, in industry and medecine it is neces sary to know the mechanism of phosphate fluorination as well as the structure and the properties of products obtained. The structure of fluorapatite Ca (PO ) F was described in the 30's owing to the existence of well-defined single crystals. It is crystallized in the hexagonal system (space group Ρ 6 / ) and it is characterized by the presence of channels, crossing the crystal from one end to the other. The fluoride ions (two for each unit-cell) are localized along the axis of the channel. The methods of synthesis of fluorapatite have been widely dis cussed (1). It is for example possible to obtain fluorapatite by substituting the hydroxyl ion for the fluoride ion, either in aqueous solution at room temperature, or through a solid state re­ action at 800°C. It can also be prepared by the action of β-tricalcium phosphate on calcium fluoride at about 800°C. Its solubi­ lity and thermal stability have already been established. While much is known about fluorapatite, many questions still exist con­ cerning the mechanism of their formation, their composition and the structure of some of them. Two of these problems are dealt with here. First, we discuss the formation mechanism of fluorapa­ tite by a solid state reaction between calcium fluoride and apatitic tricalcium phosphate. Then we present the preparation and the structure of a carbonated apatite rich in fluoride ions. 10

4 6

2

3 m

Mechanism of formation of fluorapatite from apatitic tricalcium phosphate and calcium fluoride in the solid state. We s t u d i e d ( 2 ) t h e mechanism o f f o r m a t i o n o f f l u o r a p a t i t e f r o m a p a t i t i c t r i c a l c i u m p h o s p h a t e and c a l c i u m f l u o r i d e i n t h e s o l i d s t a t e . O v e r a l l , t h e c h e m i c a l r e a c t i o n may be w r i t t e n : Ca (HP0 )(P0 ) (OH) + CaF 9

4

4

5

2

^

C a

( P 1 0

)

F

H

°4 6 2 * 2°

0097-6156/81/0171-O367$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

368

PHOSPHORUS CHEMISTRY

As t h e r e a c t i o n o c c u r s e n t i r e l y i n t h e a p a t i t i c p h a s e , i t c a n be n e i t h e r a n e x c h a n g e r e a c t i o n , n o r a n a d d i t i o n r e a c t i o n . Our o b s e r ­ v a t i o n s o n t h i s r e a c t i o n p o i n t o u t t h a t t h e mechanism i s v e r y com­ p l e x . The f o l l o w i n g r e a c t i o n s o c c u r s u c c e s s i v e l y w i t h o v e r l a p p i n g temperature : ^_ (a) From 110 t o 550°C, t h e d e h y d r a t i o n o f HPO^ ions of a p a t i t e i s o b s e r v e d g i v i n g r i s e t o ?2®7^~ i o n s i n s o l i d s o l u t i o n i n apatite. (b) From 400 t o 760°C, an e x c h a n g e r e a c t i o n b e t w e e n t h e OH ions o f a p a t i t e and t h e F~ i o n s o f c a l c i u m f l u o r i d e o c c u r s . T h i s phenomenon l e a d s t o a n i n c r e a s e i n t h e c r i s t a l l i n i t y , w i t h o u t any v a r i a t i o n i n t h e v a l u e o f t h e u n i t - c e l l p a r a m e t e r a_. ( c ) From a b o u t 600°C t o 900°C, t h e r e m a i n i n g c a l c i u m f l u o r i d e a d d s to w i t h t h e f l u o r i n a t e by a d e c r e a s e o f t h calcium d e f i c i e n t f l u o r a p a t i t e i s then observed. (d) From 600 t o 1000°C, t h e P 0 " * i o n s i n t h e a p a t i t e l a t t i c e r e a c t w i t h t h e c a l c i u m o x i d e p r e v i o u s l y formed d u r i n g the ex­ change r e a c t i o n , l e a d i n g t o t h e f l u o r a p a t i t e . However, f r o m 200° t o 500°C, a s m a l l q u a n t i t y o f ?2°7 ions react w i t h t h e f l u o r i d e i o n s p r o d u c i n g an u n i d e n t i f i e d f l u o r i n a t e d phos­ p h a t e s p e c i e s . The f l u o r a p a t i t e o b t a i n e d by t h i s m e t h o d , t h o u g h very c l o s e to the i d e a l f l u o r a p a t i t e , i s not e x a c t l y stoichiome­ tric. 4

2

7

A p a t i t e s w i t h l a r g e amounts o f f l u o r i d e i o n s : t h e B - t y p e c a r b o n a ­ ted f l u o r a p a t i t e . LEHR and Mc CLELLAN (3) d e m o n s t r a t e d numerous n a t u r a l a p a t i ­ t e s and a c o r r e l a t i o n b e t w e e n t h e amount o f f l u o r i d e i o n s and t h a t o f t h e c a r b o n a t e i o n s . T h i s l e d them t o p r o p o s e t h a t Ρ 0 ^ ~ i o n s c a n be r e p l a c e d by € 0 3 ^ " i o n s a s s o c i a t e d w i t h F~ i o n s . S u c h a h y p o t h e s i s c o u l d e x p l a i n t h e a b n o r m a l l y h i g h amount o f f l u o r i d e i n some FRANCOLITES. However t h i s t y p e o f s u b s t i t u t i o n was n o t p r o v e d by t h e a u t h o r s . We s t u d i e d some s y n t h e t i c a p a t i t e s where f l u o r i d e and c a r b o n a t e i o n s were s i m u l t a n e o u s l y i n t r o d u c e d . Samples o f B - t y p e c a r b o n a t e d f l u o r a p a t i t e ( 0 0 3 ^ " s u b s t i t u t i n g PO4 ) were o b t a i n e d a s a powder f r o m a n a q u e o u s medium r i c h i n f l u o r i d e i o n s and a l s o a n aqueous medium p o o r i n f l u o r i d e i o n s . C h e m i c a l a n a l y s i s o f t h e p r o d u c t s p r e p a r e d i n t h e medium r i c h i n f l u o r i d e i o n s showed t h e p r e s e n c e o f more t h a n two f l u o r i d e i o n s p e r u n i t c e l l ( T a b l e I ) and a c o r r e l a t i o n b e t w e e n t h e amounts o f c a r b o n a t e and f l u o r i d e i o n s . _ , Sample

1

2

:

3

:

4

:

5

:

6

9,74

9,72

9,78

9,72

9,84

9,87

ca ;_ nPO/ 4 nC0 "

4,03

4,20

4,75

4,87

5,30

5,54

1,97

1 ,80

1 ,25

1,13

0,70

0,46

η -

3,46

3,30

2,60

2,59

2,36

2,20

n

2

0

3

ρ

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

76.

MONTEL ET A L .

Fluorination

of

369

Phosphoapatites

T h e s e r e s u l t s a g r e e w i t h t h e h y p o t h e s i s o f LEHR a n d Me CLELLAN ^_ t h a t c a r b o n a t e i o n s a s s o c i a t e d w i t h F i o n s s u b s t i t u t e s f o r PO^ Such a p a t i t e s m i g h t h a v e t h e f o r m u l a : Ca

(PO,). ( C O F ) F_ 10 4 6-x 3 χ 2

i r i

Q

However a l a c k o f c a l c i u m i s o b s e r v e d a n d t h e c o r r e l a t i o n b e t w e e n the amounts o f f l u o r i d e i o n s a n d c a r b o n a t e i o n s i s n o t r i g o r o u s . T h i s i s due t o t h e e x i s t e n c e o f a second type o f s u b s t i t u t i o n as o r i g i n a l l y p r o p o s e d b y LABARTHE ( 4 - 5 ) . A c c o r d i n g t o t h i s a u t h o r , the s u b s t i t u t i o n o f a P O ^ i o n s b y a CO^" i o n i s a c c o m p a n i e d b y the f o r m a t i o n o f v a c a n c i e s i n a n o x y g e n s i t e and a l s o i n t h e C a ^ and F~ s i t e s o f t h e c h a n n e l w h i c h a r e t h e c l o s e s t t o t h e m i s s i n g o x y g e n . The B - t y p e c a r b o n a t e formula :

10-x+u

x-u

(PO,), (C0 ,D ) (C0_F) F 4 6-x 3' x - u 3 u 2-x+u Q

Q x-u

Both types o f charge compensation are c o n s i d e r e d p r e s e n t i n each c a s e , b u t t h e v a l u e o f u i s l o w when t h e a p a t i t e s a r e p r e p a r e d i n an aqueous medium p o o r i n F " ( i n w h i c h t h e s e c o n d t y p e o f l a t t i c e s u b s t i t u t i o n i s dominant) ( T a b l e I I ) and h i g h e r f o r t h e a p a t i t e s p r e p a r e d i n a n aqueous medium r i c h i n F~ i o n s ( i n w h i c h t h e f i r s t type o f s u b s t i t u t i o n dominates) (Table I ) Table I I Sample n

Ca

2 +

3

"PO. " n

2

co, -

V

3

1

2

9,61

9,46

4,90

5,05

5,65

1, 10

0,95

0,35

2,36

1 ,87

1 ,87

9,76

The X-band E.S.R. r e s u l t s (6) o b t a i n e d w i t h t h e c a r b o n a t e d a p a t i t e s s u p p o r t t h e p r o p o s e d m o d e l . I n d e e d , i n X - i r r a d i a t e d sam­ p l e s we have o b s e r v e d t h e r e s o n a n c e o f a d e f e c t i n w h i c h a n e l e c ­ t r o n i s t r a p p e d b y a n o x y g e n v a c a n c y . The number o f s u c h d e f e c t s i s g r e a t e r i n t h e compounds p r e p a r e d f r o m a n aqueous medium p o o r i n F i o n s t h a n i n t h e a p a t i t e s p r e p a r e d f r o m a n aqueous medium r i c h i n f l u o r i d e i o n s . Moreover t h e r e e x i s t s a c l o s e c o r r e l a t i o n b e t w e e n t h e s p e c t r a l i n t e n s i t y and t h e number o f o x y g e n v a c a n c i e s c a l c u l a t e d f r o m t h e m o d e l we p r o p o s e . The p r o p e r t i e s o f t h i s m a t e r i a l s w i l l l e a d t o a b e t t e r i n s i g h t i n t o phosphates o f b i o l o g i c a l i n t e r e s t .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

+

370

PHOSPHORUS CHEMISTRY

Literature cited

1. WALLAEYS R. Ann. Chim., Paris, 12ème série, 1952, 7, 808-848. 2. HAMAD M. Thèse, Institut National Polytechnique de Toulouse, 1980. 3. LEHR J.R. ; Me CLELLAN G.H. Colloque International sur les Phosphates Minéraux Solides. Toulouse 16-20 mai 1967. 2, 29-44. 4. LABARTHE J.C. Thèse, Université Paul Sabatier, Toulouse, 1972. 5. LABARTHE J.C. ; BONEL G. ; MONTEL G. Ann. Chim., Paris, 1973, 8, 289- 301. 6. BACQUET G. ; VO QUANG TRUONG ; BONEL G. ; VIGNOLES M. J. Solid State Chem., 1980, 33, 189-195. RECEIVED

June 30, 1981

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

77 Photo- and Thermo-Coloring of Reduced Phosphate Glasses Y. A B E and R. E B I S A W A Nagoya Institute of Technology, Inorganic Materials, Showa-ku, Nagoya 466 Japan D. E. CLARK and L. L. H E N C H University of Florida, Gainesville, F L 32611

Various reduced phosphat glasse g phenomenon In the as-cast glasses which were made with a higher cooling rate from the melts, phosphorus may be atomically dispersed or it may form very fine particles; this leads to transparent and colorless glasses when the glasses contain no coloring agents such as tran­ sition metal ions. However, phosphorus associates into colloidal red phosphorus (~50 nm) to give a reddish color to the glasses, when the glasses are subjected to a heat-treatment at moderately high temperatures (e.g., 400°-600°C) (1-3). This phenomenon is known as "striking." The colored glasses are bleached to be almost transparent and colorless again, when they are subjected to a heat-treatment above 600°C and subsequent quenching. These bleached glasses are referred to as PTC-RP glasses (3), since they were found to be Photo-and Thermo-Colorizable Reduced Phosphate glasses. They are easily red-colored either by sun­ light (2) or UV light at room temperature or by heating above 200°C 03). Thermo-coloring of reduced glasses having composition of 3Κ 0·12Β20 ·69Ρ20 and 6K 0·22A1 0 ·72P 0 , both of which have glass transition temperature >600°C have been reported (3). In the present paper, only a simple composition, as an example of PTC-RP glass, is discussed. The dependence of sensi­ tivity on the irradiation light wavelength is described in this paper. 2

3

5

2

2

3

2

5

Sample P r e p a r a t i o n The f o l l o w i n g t h r e e k i n d s o f g l a s s e s w e r e p r e p a r e d . (a) G l a s s r e d u c e d b y s i l i c o n (CP-RS): A mixture o f di-hydrogen c a l c i u m p h o s p h a t e , C a ( H P O ^ ) · Η 0 a n d m e t a l l i c s i l i c o n powder w e r e m e l t e d i n a n a l u m i n a c r u c i b l e a t 1200°-1250°C f o r 1 h o u r a n d poured on a c o l d g r a p h i t e p l a t e . The s i l i c o n was 0.15 m o l e p e r mole o f P 0 . (Formula: CaO»P 0 *0.15Si0 ) (b) G l a s s r e d u c e d b y ammonium s a l t (CP-RN): A m i x t u r e o f 2

2

5

2

2

2

5

2

0097-6156/81/0171-0371$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

372

PHOSPHORUS CHEMISTRY

C a ( H P 0 ) H 0 , CaCOo, and N H H P O , w e r e u s e d as raw m a t e r i a l s . 20% o f P 0 o f t h e g l a s s was s u p p l i e d by u s i n g N H ^ P O ^ . Glasses w e r e p r e p a r e d i n a s i m i l a r way t o C P - R S . (Formula: CaO Ρ 0 ) ( c ) G l a s s n o t r e d u c e d ( C P - O S ) : G l a s s e s w e r e p r e p a r e d i n t h e same way as CP-RS e x c e p t t h a t S i O ? was s u b s t i t u t e d f o r S i i n t h e b a t c h . (Formula: CaO P 0 0 . 1 5 S i O ) A l l t h e g l a s s e s w e r e a n n e a l e d and a l l r e a g e n t s w e r e o f r e a g e n t grade. 2

4

2

2

4

2

2

5

2

2

Striking

5

5

2

( C o l o r i n g by C o l l o i d

Formation)

Reduced p h o s p h a t e g l a s s e s o f w h i c h a s - c a s t g l a s s e s a r e t r a n s ­ p a r e n t and c o l o r l e s s become t i n g e d w i t h r e d t o y e l l o w d e p e n d i n g on t h e r e h e a t i n g t i m e and t e m p e r a t u r e T h i s " s t r i k i n g phenomenon" i s due t o t h e f o r m a t i o n o f The s p e c i m e n s o f CP-R u n d e r a r e d u c i n g c o n d i t i o n , e x h i b i t s t r i k i n g phenomenon b u t CP-OS does n o t . An example o f t h e o p t i c a l t r a n s m i s s i o n c u r v e s o f CP-RN g l a s s s p e c i m e n h e a t e d a t 580°C i s g i v e n i n F i g u r e 1, w h i c h shows s i m i l a r c h a n g e s t o t h a t f o r CP-RS p r e v i o u s l y r e p o r t e d ( 2 ) , n a m e l y , t h a t t h e a b s o r p t i o n edge a t s h o r t e r w a v e l e n g t h s i d e s s h i f t s t o l o n g e r wavelength w i t h i n c r e a s i n g time of r e h e a t i n g . Thus, the s p e c i m e n s become t i n g e d w i t h r e d . The c o l o r i n g i s s a t u r a t e d f o r 30-50 h o u r s a t 5 8 0 ° C . Photo-Coloring

(Photochromism)

The b l e a c h e d s p e c i m e n s (PTC-RP g l a s s e s ) w e r e p r e p a r e d by h e a t i n g the s a t u r a t e d - r e d c o l o r e d specimens a t ^600°C f o r s e v e r a l m i n u t e s and s u b s e q u e n t q u e n c h i n g . F i g u r e 2 g i v e s an example o f t h e t r a n s m i s s i o n c u r v e s i n c o l o r i n g o f t h e b l e a c h e d CP-RN g l a s s s p e c i m e n e x p o s e d t o s o l a r r a y s . The b l e a c h e d s p e c i m e n o f CP-RS (2) e x h i b i t e d t r e n d s s i m i l a r t o t h a t o f CP-RN. F i g u r e 3 shows t h e d e p e n d e n c e o f c o l o r i n g s e n s i t i v i t y b l e a c h e d CP-RS g l a s s on t h e w a v e l e n g t h o f t h e i r r a d i a t i n g l i g h t , w h e r e Ae4Q i n t h e o r d i n a t e gives a parameter of c o l o r i n g s e n s i t i v i t y . This parameter i s the d i f f e r e n c e b e t w e e n t h e p h o t o n e n e r g y (ev) c o r r e s p o n d i n g t o wave­ l e n g t h a t 40% o f t h e t r a n s m i s s i o n c u r v e o f a b l e a c h e d g l a s s b e f o r e and a f t e r t h e i r r a d i a t i o n . As i s shown, i t was f o u n d t o be most s e n s i t i v e l y c o l o r e d by i r r a d i a t i n g w i t h l i g h t o f ^350 nm b u t i t i s n o t c o l o r e d by a w a v e l e n g t h l o n g e r t h a n ^500 nm. As an e x a m p l e o f change i n c o l o r i n g o f a PTC-RP s p e c i m e n o f CP-RS g l a s s by t h e i r r a d i a t i o n w i t h a g i v e n w a v e l e n g t h (253.7 nm), a p l o t o f λ^. i s u s e d as a measure o f t h e a b s o r p t i o n e d g e , i n d i c a t i n g a w a v e l e n g t h c o r r e s p o n d i n g t o h a l f o f t h e maximum t r a n s m i s s i o n of the spectrum (approximately a wavelength at a transmission of 40%). τ

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

ABE E T AL.

Reduced

Phosphate

Glasses

373

100

U

200

Figure 2.

/ / Κ /(

ι

ι

ι

400 600 Wavelength ( nm)

ι

800

Transmission curves of a bleached CP-RN glass exposed to solar rays (photo-coloring; I mm thick specimen).

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

374

PHOSPHORUS CHEMISTRY

Time Figure 4.

Coloring

(h)

of a bleached CP-RS specimen by irradiation 750 μ W cm- , i mm thick specimen).

light (253.7 nm,

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

77.

ABE ET AL.

Reduced

Phosphate

375

Glasses

Thermo-Coloring (Thermochromism) As p r e v i o u s l y r e p o r t e d o n some g l a s s e s o f d i f f e r e n t c o m p o s i ­ t i o n ( 3 ) , PTC-RP g l a s s i s c o l o r e d a l s o b y h e a t i n g above 200°C. F o r c o n v e n i e n c e , we d e f i n e a c o l o r i n g p a r a m t e r α i n e q . [1]. α

where,

-

(λ,

i s λ

\ X^ X^

-λ, ) / (λ,

# i

# g

4

%

-λ, .)

[1]

a f t e r h e a t i n g f o r time τ,

is

before heating

is

o

(initial

specimen),

An a p p a r e n t a c t i v a t i o n e n e r g y f o r t h e thermo-coloring was e s t i ­ mated t o b e ^35 K c a l / m o l , a c c o r d i n g t o t h e method d e s c r i b e d p r e v i o u s l y ( 3 ) . T h i s v a l u e i s a l m o s t t h e same a s t h a t o f t h e o t h e r g l a s s e s r e p o r t e d b y Abe e t a l . ( 3 ) . Determination Glasses

of Elemental

P h o s p h o r u s Formed i n t h e R e d u c e d

The p e r m a n g a n o m e t r i c method d e v e l o p e d b y V e n u g o p a l a n (4) was m o d i f i e d i n o u r l a b o r a t o r i e s . I t was f o u n d t h a t t h e r e d u c e d g l a s s c o n t a i n e d M).2 w t % o f e l e m e n t a l p h o s p h o r u s . M e c h a n i s m o f C o l o r i n g and

Bleaching

The c o l o r i n g and b l e a c h i n g phenomena a r e c a u s e d b y c h a n g e s i n m o l e c u l a r c o n f i g u r a t i o n of c o l l o i d a l phosphorus formed i n t h e g l a s s e s . The P^ m o l e c u l e ( l i q u i d o r w h i t e p h o s p h o r u s ) i s c o l o r ­ less. I t polymerizes t h e r m a l l y or photochemically to the • · *-P

I Ρ-· · · c o n f i g u r a t i o n w h i c h g i v e s a r e d d i s h c o l o r ; i t Ρ

d i s s o c i a t e s i n t o P^ m o l e c u l e

a g a i n when

melted.

Literature Cited:

1. A. Naruse, Y. Abe, J . Ceram. Soc. Japan, 1965, 73, 253-58. 2. Y. Abe, R. Ebisawa, A. Naruse, J . Am. Ceram. Soc., 1976, 59 453-54. 3. Y. Abe, K. Kawashima, S. Suzuki, J . Am. Ceram. Soc., 64, 20609 (1981). 4. M. Venugopalan, K. U. Matha, Z. Anal. Chem., 1956, 151, 26268. M. Venugopalan, K. J . George, Bull. Chem. Soc. Japan, 1957, 30, 51-53. RECEIVED

June 30, 1981. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

78 A Gel Chromatographic Study on the Interactions of Long-Chain Polyphosphate Anions with Magnesium Ions T O H R U M I Y A J I M A , T O S H I M I T S U O N A K A , and S H I G E R U O H A S H I Department of Chemistry, Faculty of Science, Kyushu, University 33, Hakozaki, Higashiku, Fukuoka, 812 Japan

In spite of much information available for the interactions of various metal ions wit tively l i t t l e informatio tion of long-chain polyphosphate ion. This may be due to the fact that the conventional methods useful for the study of the complex formation of a relatively small ligand are not always applicable to the polyanion complex formation system. Since a gel chromato­ graphic method based on the same principle as the equilibrium dia­ lysis method has been proved to be applicable in the field of inorganic complex chemistry (1), this method has been applied to the study of the binding of long-chain polyphosphate ions to mag­ nesium ion. A long-chain polyphosphate ion is composed mainly of middle PO -units and two end PO -units. A middle and an end unit have a formal charge of minus one and two, respectively. Therefore, the affinity of an end unit for a metal ion is much greater than that of a middle unit. When the chain length of polyphosphate is suf­ ficiently long, the contribution of end units to the metal binding is small enough to be neglected. The complexation ability of middle units in a long-chain polyphosphate is expected to be dif­ ferent from that of middle units in a cyclic phosphate. 3

3

T h i s w o r k was u n d e r t a k e n i n o r d e r t o e v a l u a t e t h e b i n d i n g o f m i d d l e u n i t s o f l o n g - c h a i n p o l y p h o s p h a t e t o magnesium i o n f r o m a v i e w p o i n t o f t h e mass a c t i o n l a w . A sample s o l u t i o n c o n t a i n i n g m e t a l i o n , M , h i g h - m o l e c u l a r w e i g h t l i g a n d , L and t h e i r complexes i s a p p l i e d t o a g e l column conditioned w i t h an eluent containing M o f a s p e c i f i e d concentra­ t i o n , [ M ] Q , a n d i s e l u t e d w i t h t h e same e l u e n t . The i n i t i a l f r e e m e t a l c o n c e n t r a t i o n i n t h e sample s o l u t i o n u s u a l l y d i f f e r s from [M]Q. D u r i n g t h e e l u t i o n , h o w e v e r , t h e s a m p l e l i g a n d zone ( z o n e a ) i s e q u i l i b r a t e d w i t h t h e m e t a l s o l u t i o n o f [M]Q t o r e a c h a s t e a d y s t a t e , i n w h i c h a f r e e m e t a l c o n c e n t r a t i o n i n zone a , [ M ] , i s e q u a l t o [M]Q . I n zone α t h e d i s t r i b u t i o n o f t h e c h e m i c a l s p e c i e s i s c h a r a c t e r i z e d b y t h e f r e e m e t a l c o n c e n t r a t i o n , [M]Q. The r a t i o o f t h e amount o f bound m e t a l t o t h e t o t a l amount o f t h e l i g a n d , n , can u s u a l l y be e x p r e s s e d a s t h e f o l l o w i n g f o r m a t i o n f u n c t i o n . A

0097-6156/81/0171-0377$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

378

PHOSPHORUS

f ¥

M

]

CHEMISTRY

o (1)

1 +

^[MjJ

where

i s t h e o v e r a l l s t a b i l i t y c o n s t a n t o f an M^L c o m p l e x . I n t h i s work a m i x t u r e of l o n g - c h a i n polyphosphates having v a r i o u s d e g r e e s o f p o l y m e r i z a t i o n was u s e d as t h e l i g a n d . There­ f o r e , η d e f i n e d i n e q n ( l ) c a n n o t be c a l c u l a t e d . I n s t e a d o f n, t h e a v e r a g e number o f bound magnesium p e r one PO3 u n i t , m, was c a l c u ­ lated. A v a l u e o f m c a n be o b t a i n e d by d i v i d i n g t h e amount o f bound magnesium, % g t b PO i n zone a . A P e r k i n Elme p h o t o m e t e r was u s e d as a magnesiu ( 2 ) N

Ms

(2)

I t has b e e n p o i n t e d o u t t h a t t h e h i g h and v a r i a b l e e l e c t r i c f i e l d a t t h e s u r f a c e o f a c h a r g e d p o l y m e r makes t h e q u a n t i t a t i v e d e s c r i p t i o n o f i t s e q u i l i b r i a v e r y complecated ( 3 ) . I n t h i s work t h e f o l l o w i n g a s s u m p t i o n s w e r e made i n o r d e r t o c a l c u l a t e t h e s t a ­ b i l i t y c o n s t a n t s o f t h e c o m p l e x e s o f m i d d l e PO3 u n i t s w i t h mag­ nesium i o n . 1) C o n c e n t r a t i o n s a r e u s e d i n p l a c e o f a c t i v i t i e s . 2) A s e t o f a d j a c e n t PO3 u n i t s , t h e number o f w h i c h i s n*, b i n d s one magnesium i o n t o f o r m a o n e - t o - o n e c o m p l e x , Mg(P0 ) . J n x

M g

+

( P 0

3 n*

W

)

° 3 K *

( 3 )

3) The b i n d i n g a b i l i t y o f e a c h magnesium i o n t o one s i t e i s n o t a f f e c t e d by t h e c o m p l e x f o r m a t i o n a t o t h e r s i t e s o f t h e same c h a i n . The amount o f bound magnesium, N , c o r r e s p o n d s t o t h e peak a r e a o f zone a. S i n c e t h e amount o f t o t a l l i g a n d c a n be o b t a i n e d by d i v i d i n g Np by n*, t h e amount o f f r e e l i g a n d i n zone α i s (Np/n* - N ) . The s t a b i l i t y c o n s t a n t o f t h e c o m p l e x c a n be d e f i n e d as f o r lows. Mg β (η*) = (4) [Mg] (N /n* N ) M

Mg

0

p

U s i n g e q n ( 2 ) , e q n ( 4 ) c a n be e x p r e s s e d

M g

as

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

78.

MiYAJiMA

Interactions

E T AL.

β. (η*) 1

=

Γ

of Polyphosphate

379

Anions

m -, , . =r [ M g J ( l / n * - m) Μ

(5)

Ί /

0

m

a

v

With an appropriate n* value, a constant value of β·^(η*) be obtained w i t h i n a s p e c i f i c [Mg]g range. The p a i r o f n* and β-^(η*) which accounts f o r the experimental p l o t s i n d i c a t e s that n* PO3 u n i t s b i n d one magnesium i o n t o form a s p e c i f i c complex i n the [ M g ] range. In order to estimate proper n* and (3-j.(n*) values which s a t i s ­ fy the experimental data, a curve f i t t i n g method was employed. Q

6 (n*)[Mg] 1

m

=

1

( )

1

m values were obtained f o r v a r i o u s [Mg]Q values i n 0.1 M t e t r a methylammonium c h l o r i d e s o l u t i o n a t 25°C. The c a l c u l a t e d curves f o r n* = 3 through 7 were examined. When n* i s assumed to be 4, 5 and 6, the c a l c u l a t e d curves showed a good f i t f o r the experimental p l o t s , even though they are not s a t i s f a c t o r y i n the whole [Mg]g range. Since the c a l c u l a t e d curve f o r n* = 3 o r 7 g r e a t l y deviates from the p l o t s , the formation o f M g ( P 0 3 > * 3 or M g ( P 0 3 > * type complexes i n t h i s [Mg]g range can be excluded. The s t a b i l i t y con­ s t a n t s (β-j^n*)) thus obtained are l i s t e d i n Table 1. I t i s note­ worthy that the formation o f M g ( P 0 3 ) * _ ^ type complex was c l e a r l y observed when [Mg]g was between 10~5 and 10~4 mol dm~3. In order to compare the complexation a b i l i t y o f middle P O o u n i t s o f long-chain polyphosphate with those o f r e l a t i v e l y small polyphosphates, s t a b i l i t y constants of the magnesium complexes o f diphosphate, t r i p h o s p h a t e , tetraphosphate, tetrametaphosphate, and hexametaphosphate were evaluated by the g e l chromatographic method under the same experimental c o n d i t i o n s . The s t a b i l i t y constants of magnesium complexes w i t h l i n e a r phosphates (β-^(ηΐ)) and those with c y c l i c phosphates (g-^(nc)) are a l s o t a b u l a t e d i n Table 1. By comparing the s t a b i l i t y constants o f l i n e a r phosphate complexes one another, i t can be concluded that the a d d i t i o n o f another PO3 u n i t to a l i g a n d does not n e c e s s a r i l y c o n t r i b u t e to the b i n d i n g of the f i r s t magnesium i o n , when the degree o f p o l y m e r i z a t i o n o f the l i g a n d i s more than 3. I t i s worthwhile to compare β^ίη*) w i t h g-^(nc), because a c y c l i c phosphate i o n i s composed of only middle POo u n i t s . By comparison o f β-^4*) with β ( 4 ο ) and β - ^ ό * ) with PjAOc), i t can be concluded that β^ίη*) i s always g r e a t e r than βj, (nc) . T h i s i n d i c a t e s that the complexation a b i l i t y o f middle PO3 u n i t s of a long-chain polyphosphate i o n i s g r e a t e r than that of the corresponding c y c l i c phosphate i o n . T h i s may be a t t r i b ­ uted to the f l e x i b i l i t y o f long-chain polyphosphate i o n . I t can be seen that the d i f f e r e n c e between β·^(η*) and β-^(ηο) decreases with an i n c r e a s e In n. The f l e x i b i l i t y o f c y c l i c phosphate i o n may i n c r e a s e with n. n

=

n

n

χ

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

= 7

380

PHOSPHORUS

Table

n,

n

1.

S t a b i l i t y c o n s t a n t s o f magnesium c o m p l e x e s for d i f f e r e n t types o f phosphates.

logif^inl)/

K

CHEMISTRY

3

mol-^dm )

b

)

b

l o g ^ n c ) /

)

log(B (n*)/ 1

3

mol^dm )

3

mol'^-dm )

-

2

5.57

-

3

6.53

1.80

4

6.53

3.40

5.60

5

-

-

6.03

6

-

5.50

6.22

a) b) c)

c

-

)

t h e number o f PO3 u n i t s w h i c h c o n s t i t u t e s t h e l i g a n d . I = 0.1, S u p p o r t i n g e l e c t r o l y t e ; ( C H ) N C 1 , Temp.; 25°C . obtained with i o n - s e l e c t i v e electrode ( 4 ) . 3

4

Literature Cited

1. 2. 3. 4.

Miyajima, T; Ohashi, S. Bull. Chem. Soc. Jpn., 1978, 51, 2543. Yoza, N; Ohashi, S. Anal. Lett., 1973, 6, 595. Marinsky, J . A. Coord. Chem. 1976, 19, 125. Kalliney, S. Υ., "Topics in Phosphorus Chemistry", Vol. 7, Griffith E. J. and Grayson Μ., Eds., Interscience, New York, 1967, p 294.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

79 Phosphaalkenes, R C=PR', and Phosphaalkynes, 2

RC≡P H . W. ΚROTO and J . F. N I X O N School of Molecular Sciences, University of Sussex, Brighton, Sussex, England

The chemistry of trivalent phosphorus compounds in which phosphorus is one or two coordinate is rapidly developing. These systems contain sp or sp π-bonds between Ρ and othe believed that bond formation involving ρπ-ρπ overlap was unfavourable. Subsequently certain -P=C systems resulted from the use of charged (1, 2, 3) and or delocalized systems (4) but it is only in the past few years that successful syntheses of phospha-alkenes, RC=PR', and phospha-alkynes, RC≡p, have been reported. These novel compounds are the subject of this paper. 2

Pyrolysis techniques developed by Kroto et al. to produce sulphur and selenium doubly bonded species in a low pressure flow system where the lifetimes are of the order of seconds, enabled species such as HCS (5), FCS (6), CHCHS (7), CHCHSe (8), CHCCS (9) and HBS (10) to be identified by microwave and/or P.E. spectroscopy. 2

2

3

3

2

An extension of this approach led to the study of some simple molecules in which trivalent phosphorus is bonded to carbon by a double or a triple bond. These spectroscopic experiments have not only yielded conclusive identification but a wealth of molecular information such as geometric and electronic structural data. More importantly, the >C=P- and -C≡P moieties could be considered as viable functional groups with interesting and well defined chemical properties. In 1961 Gier (11) reported the s y n t h e s i s o f HCEp v i a a carbon arc discharge o f P H 3 . The compound which polymerised above -120 was long regarded as a chemical c u r i o s i t y b u t i n 1968 Kroto, Nixon e t a l . (12) reported the f a c i l e synthesis o f FC=P by dehydrofluorination of C F 3 P H 2 . CF3PH2

• CF =PH 2

• FC=P

NMR, microwave and He(I) p h o t o - e l e c t r o n s p e c t r o s c o p i c s t u d i e s on "this compound have been reported (12, 1_3) . 0097-615 6/81/0171-03 8 3$05.00/ 0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

384

PHOSPHORUS

A whole new c l a s s o f compounds o f the type RC=P now some o f which are l i s t e d below (14-22). HCEP

FCEP

NCCEP e.g.

PhCEP

RCH PC1 R CF PH 2

2

•

CNN

HCP

â

3

R

f

3

2

• RCEP c

E

exists,

CH CEP

CH =CHCEP

2

2

f

CF3CΞP

CHEMISTRY

CHECCEP

p

_

* NCC=P

Very r e c e n t l y (February 1981) a s i g n i f i c a n t advance has been made with the syntheses o f Me3SiC (22) and the s t a b l e l i q u i novel route shown below. • R3S1—Ρ

(R Si) P 3

3

y

OS1R3

¥ tBuCΞp

Our r e c e n t syntheses o f CH =CH-C=p and HC^c-C=p u s i n g the HX e l i m i n a t i o n approach has i n d i c a t e d t h a t many more RC=P compounds w i l l be soon a v a i l a b l e . Our s t r u c t u r a l data i n d i c a t e t h a t the C=p bond l e n g t h 1.545 8 i s r e l a t i v e l y i n s e n s i t i v e t o the nature of the R s u b s t i t u e n t , whereas other p r o p e r t i e s , e.g. NMR parameters and I.P. data, are s i g n i f i c a n t l y a f f e c t e d by R. 2

The P-C d i s t a n c e s i n simple phosphines, phospha-alkenes and phospha-alkynes are summarised i n F i g u r e 1 and the r e s u l t s c o n t r a s t e d with C-C, C=C and C=C bond lengths when a simple r e l a t i o n s h i p i s seen to e x i s t . A d d i t i o n a l l y the data f o r the phosphabenzene systems shows e x c e l l e n t agreement with e x p e c t a t i o n . Compounds o f the type R C=PX were f i r s t p o s t u l a t e d by Haszeldine and coworkers (24-27) as r e a c t i o n intermediates i n the r e a c t i o n o f c e r t a i n perfluoroaLkyl phosphines with bases. These s p e c i e s were f i r s t i s o l a t e d and c h a r a c t e r i s e d by s p e c t r o s c o p i c techniques by Kroto and Nixon and coworkers ( 2 8 ) . Microwave and/ or NMR data on CH =PH, CH =PC1 and CF =PH were obtained on samples generated by the p y r o l y s i s o f s u i t a b l e p r e c u r s o r s , but subsequently a v a r i e t y o f a l t e r n a t i v e s y n t h e t i c r o u t e s have been developed to o b t a i n the f o l l o w i n g phospha-alkene molecules (28-34): 2

2

2

2

CH =PH, CH =PC1, CH =PBr, CH =PF, 2

2

2

2

CF =PH, CF =PCF , PhRC=PCl, e t c . 2

2

3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

KROTO A N D NIXON

Phosphaalkenes

and Phosphaalkynes

385

— ι — 1.5

1.6 r C-P

Figure L

- (°A)

vs. r _ . Gives covalent radius of Ρ; Sp , 1.07 °A; Sp , 1.00; Sp, 0.94. 3

Plot of r _ c

1.8

1.7

P

c

c

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

2

PHOSPHORUS CHEMISTRY

386 ,

,,

R SiCR R PX 3

CF PH 3

• R S i X + CR'R'^PX

2

3

* CF =PH

2

2

Thermal s t a b i l i z a t i o n o f phospha-alkenes can be i n f l u e n c e d by the attachment o f a heteroatom t o the P=C bond as evidenced by the elegant work o f Becker ( 3 5 - 4 0 , 4 3 ) , Appel ( 4 1 ) and Issleib ( 4 2 ) .

e.g.

RP(SiMe ) 3

^OSiMe • R-P=C^ tBu

+ tBuCOCl

2

^Cl PhP(SiMe ) 3

2

R

3

R

1

+

In 1978 B i c k e l h a u p t e t al_. ( 4 4 ) r e p o r t e d the f i r s t s t a b l e phospha-alkene with carbon s u b s t i t u e n t s o n l y . u s i n g the f o l l o w i n g s y n t h e t i c approach. RPC1

2

— • RPClCHPh

• RP=CPh

2

(R - m e s i t y l )

2

(L) Kroto, Nixon e t a l . have r e p o r t e d s e v e r a l examples o f complexes o f the phospha-alkene, L, RP=CPh (R = m e s i t y l ) ( 4 5 ) . In p r i n c i p l e phospha-alkenes can coordinate t o t r a n s i t i o n metals i n any o f the three modes shown but so f a r evidence only f o r type (a) has been obtained. 2

C — R

C— R

/ /

C— R

/ A R*— Ρ s v

R*— Ρ \ M

f

R — Ρ 4 M

*M

(a)

(b)

A ν M

(c)

Complexes obtained a r e : cis-M(CO) i*L (M = Cr,Mo,W) ? M(C0) 5 L (M = W); R h C l ( P P h ) L ; RhCl(CO)L ; R h ( C H ) L ; P t X L (X = Cl,I,Me)j P t C l ( P E t ) L . The l a t t e r i s the s u b j e c t o f an X-ray s t r u c t u r a l a n a l y s i s ( 4 6 ) . These r e s u l t s a r e important i n r e l a t i o n t o other r e c e n t developments i n t h e c o o r d i n a t i o n 2

3

2

2

2

9

7

2

2

2

3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

79.

KROTO A N D NIXON

Figure 2.

Phosphaalkenes

Structure

and

Phosphaalkynes

of cis-PtC 1 (Ρ Et 3)(P(mes)=CPh2). 2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

387

388

PHOSPHORUS

CHEMISTRY

chemistry o f RPNR' and RPO (47) where phosphorus i s the coordinating s i t e . Of p a r t i c u l a r i n t e r e s t i s the r e c e n t l y determined s t r u c t u r e o f the complex c i s - P t C l 2 ( P E t ) (P(mes) = CPÏ12) shown i n F i g u r e 2. The p r e v i o u s l y p o s t u l a t e d (46) mode o f c o o r d i n a t i o n o f the phospha-alkene t o the metal atom u s i n g the lone p a i r on phosphorus has now been confirmed. The phosphorus-carbon double bond i s 1.668 8 i n e x c e l l e n t agreement with our p r e v i o u s l y p u b l i s h e d data from microwave spectroscopy on simpler uncoordinated phospha-alkenes ( i t should be noted t h a t the s t r u c t u r e o f f r e e Ρ(mes)=CPh i s not known). The angles subtended a t phosphorus namely 2 P C o 2 ( C O ) ] and [{(Me Si)2CH}2PCo(CO)2] » r e s p e c t i v e l y . I t i s not p o s s i b l e to r e c o r d Ε and * C {J-H} NMR s p e c t r a f o r I I I ; h o w e v e r , t h e P {^-H} NMR s p e c t r u m c o n s i s t s o f a b r o a d s i n g l e t a t 4420 ppm. The m a g n e t i c moment o f I I I i s 1.82 U a t 300K. The p a t t e r n o f CO s t r e t c h i n g f r e q u e n c i e s ( 2 0 7 0 , 2035, 2010, 1990, and 1975 c m " l ) i s v e r y s i m i l a r t o t h a t o f p h o s p h i n e and p h o s p h i t e c o m p l e x e s o f com­ p o s i t i o n R PCo2(CO)y ( 8 ) , thus s u g g e s t i n g a comparable s t r u c t u r e for I I I . The ESR s p e c t r u m o f I I I i n t o l u e n e c o n s i s t s o f a 1 5 l i n e p a t t e r n , i n d i c a t i n g d e l o c a l i z a t i o n of the unpaired e l e c t r o n f r o m t h e p h o s p h i n y l r a d i c a l o n t o t h e C02(CO)7 m o i e t y ( 5 9 c o , I = 7/2, n a t u r a l abundance 1 0 0 % ) . 3

2

7

+

3

+

3

λ

3

3 1

B

3

P e n t a m e t h y l c y c l o p e n t a d i e n y l - S u b s t i t u t e d Phosphenium Ions S i n c e t h e h e a v i e r g r o u p 4A e l e m e n t s c a n engage i n p e n t a h a p t o b o n d i n g w i t h c y c l o p e n t a d i e n y l and p e n t a m e t h y l c y c l o p e n t a d i e n y l g r o u p s , we w e r e prompted t o i n v e s t i g a t e t h e b o n d i n g i n i s o e l e c t r o n i c compounds f e a t u r i n g P+ and A s . T r e a t m e n t o f ( M e 5 C ) P C l 2 (9) w i t h M e S i N M e 2 a f f o r d s ( M e 5 C 5 ) ( M e N ) P C l ( I V ) w h i c h was c h a r a c t e r i z e d by e l e m e n t a l a n a l y ­ s i s , mass s p e c t r o s c o p y ( p a r e n t peak, m/e 2 4 5 ) , and NMR: ^H M e N ( d , δ 2.58, J = 11.3 H z ) , M e C ( b r s , δ 1 . 9 ) ; C {^-H} Me N ( d , δ 41.51, J = 17.5 H z ) , C5MÇ5 ( b r , δ 1 3 8 . 6 ) ; P {1H} ( s , 144.8 ppm). The Me5C5 r i n g o f I V i s bonded i n t h e monohapto +

5

3

2

1 3

2

P

N

C

H

P

N

C

5

5

3 1

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

80.

BAXTER ET AL.

Dicoordinated

Phosphorus

Radicals

and

Cations

393

manner, s i n c e on c o o l i n g t o -40°C t h e 200 MHz 1H NMR s p e c t r u m o f the p e n t a m e t h y l c y c l o p e n t a d i e n y l methyl protons e x h i b i t s t h r e e resonances: Me ( d , 3 H , δ 1.37, J C H · H z ) , Me ( d , 6H, δ 1.77, JpccCHb · >> c ( s , 6H, δ 1 . 8 3 ) . Treatment o f IV w i t h a s t o i c h i o m e t r i c q u a n t i t y of AI2CI5 i n CH2CI2 s o l u t i o n a t -78°C, f o l l o w e d by w a r m i n g t o room t e m p e r a t u r e a f f o r d s a red-brown s o l u t i o n . The p r e s e n c e o f t h e A l C l ^ anion as t h e s o l e a l u m i n u m - c o n t a i n i n g s p e c i e s was e v i d e n c e d by t h e p r e s e n c e o f a s h a r p s i n g l e t (w^ - 9 Hz, δ = 103 ppm) (10) i n t h e 27A1 NMR, t h u s i n d i c a t i n g t h e f o r m a t i o n o f t h e p h o s p h e n i u m i o n , [ ( M e C ) ( M e N ) P ] + ( V ) . *H M e N ( d , 6 H , δ 3.12, J = 7.8 H z ) , C M e s ( d , 15H, δ 2.14, J C C H = 2.6 H z ) ; 13c {1H} Me2N ( d , δ 4 3 . 0 4 , P N C = 12*9 H z ) , CsMes ( s , δ 1 0 . 7 6 ) , C^Mes ( d , δ 130.4, J = 11.8 H z ) . Several piece spectroscopi evidenc c o n c l u s i o n t h e Me5C5 r i n manner. F i r s t , t h e 1H an spectr r i n g and Me c a r b o n s o f t h e Me5C5 m o i e t y a r e e q u i v a l e n t ; m o r e o v e r , t h e e q u i v a l e n c e o f t h e m e t h y l g r o u p s p e r s i s t s t o -100°C and -80°C i n 1H and 13c NMR e x p e r i m e n t s , r e s p e c t i v e l y . S e c o n d , t h e 31p c h e m i c a l s h i f t o f V (111.0 ppm) i s 33.8 ppm u p f i e l d ( i . e . s h i e l d e d ) compared t o t h a t o f t h e p h o s p h o r u s ( I I I ) c h l o r i d e p r e ­ c u r s o r , IV. I n a l l cases r e p o r t e d t o d a t e , phosphenium i o n f o r ­ mation v i a h a l i d e i o n a b s t r a c t i o n from p r e c u r s o r p h o s p h o r u s ( I I I ) h a l i d e s has b e e n a c c o m p a n i e d by a d o w n f i e l d 3 1 NMR c h e m i c a l s h i f t i n e x c e s s o f 100 ppm. (11-14) The u p f i e l d s h i f t i s a t t r i ­ b u t e d t o m u l t i h a p t o b o n d i n g b e t w e e n P and t h e Me5C5 l i g a n d . S u p p o r t f o r t h i s s u g g e s t i o n i s p r o v i d e d by t h e f a c t t h a t -100 ppm u p f i e l d 11β NMR c h e m i c a l s h i f t s h a v e b e e n o b s e r v e d (15) when p e n t a h a p t o b o r o n c a t i o n s , [ n ^ - M e 5 C 5 ) B X ] a r e f o r m e d v i a X~ a b s t r a c t i o n f r o m t h e c o r r e s p o n d i n g monohapto b o r o n d i h a l i d e s , (nl-Me C )BX . The f o r e g o i n g NMR o b s e r v a t i o n s on V a r e c o n s i s t e n t w i t h a s t a t i c p e n t a h a p t o s t r u c t u r e , o r w i t h t r i - and d i h a p t o s t r u c t u r e s w i t h l o w b a r r i e r s t o m i g r a t i o n . MNDO c a l c u l a t i o n s (16,17) on [(Me5C5)(Me2N)P] r e v e a l the f o l l o w i n g : ( i ) t h e g l o b a l minimum i s t h e d i h a p t o s t r u c t u r e , ( i i ) t h e p e n t a - and t r i h a p t o s t r u c t u r e s do n o t c o r r e s p o n d t o m i n i m a , and ( i i i ) t h e b a r r i e r t o c i r c u m a n n u l a r m i g r a t i o n o f t h e Me2NP m o i e t y i n t h e d i h a p t o s t r u c t u r e i s v e r y l o w (

/ C.H 65

P=C

\

/ P(C,H_)SiMe 6 5 3

C

A

Β

\

C(C,H )OSiMe c:

5

Q

3

PC.H 65

C

J

6

\ /

C.H 65

0

Q

C

A

S i n c e t h e r i n g was f o r m e y sily migration, c o n f i g u r a t i o n w i t h r e s p e c t t o t h e P=C d o u b l e bond d i d n o t c h a n g e . T h i s a s s u m p t i o n i s s u p p o r t e d by t h e ^ l p nmr d a t a d e s c r i b e d i n t h e next s e c t i o n . T r a n s f o r m a t i o n o f a n o t h e r compound was done by t r e a t m e n t w i t h more i o s c y a n i d e d i c h l o r i d e , g i v i n g 1 , 3 , 4 , 6 - t e t r a p h o s p h a - 1 , 5 hexadiene. C,H

C

Ό

3

2

N(C,H )SiMe ,

0

c

0

C,H

3

J

0

\=C

+C H^NCC1 6

4

A

0

y

3

\

2

P(C.H .)SiMe - 2 C l S i M e 6 5 3 3 Β E

N(C.H )SiMe

C

0

c

Q

3

J

/ PC.H. J PC.H

Q

Α

6

β

5

7

C

/

6

5

P=C C H 6

N 5

N(C H )SiMe 6

5

3

The x - r a y s t r u c t u r e o f t h e meso-form o f t h e p r o d u c t (3) i n d i c a t e s an E-E c o n f i g u r a t i o n . A g a i n we presume t h e same o r i e n t a t i o n i n t h e s t a r t i n g m a t e r i a l on t h e b a s i s o f 31p nmr s h i f t c o m p a r i s o n . NMR

Investigations

Two p a r t i c u l a r s t r u c t u r e s and t h e s t a r t i n g compounds i n d i ­ cate a stronger 3 1 s h i f t f o r the A phosphorus t o lower f i e l d i n c a s e o f an Ε c o n f i g u r a t i o n . The J ( A B ) c o u p l i n g i s n o t d i a g ­ n o s t i c o f an Ε o r Ζ s t r u c t u r e . P n

3 1

P 6 (A) P δ (B) J(AB) iHÔSiCH J(PH) 3 1

5

m

r

Ζ Ε (Z) J ϋ Ζ ppm +112.7 +155.3 +258.0 ppm + 72.3 - 38.6 - 12.3 Hz 22.1 160.0 24.6 ppm +0.3 0.0 - 0.4 Hz 0.9 , 0.3 0.0 P ( 8 5 % H3PO4), H (TMS), f r e q u e n c y s c a l e 3 1

(Ε) 3 +213.8 - 39.0 78.9

1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

81.

APPEL

ET AL.

Ε/Ζ

3 1

Dicoordinated

ΡδΑ

3 1

Phosphorus

ΡδΒ

J(AB)

397

Compounds

^-Ηδ SiMe

5

J(PH)

structure predicted

1 1

10% 90%

+192.0 +153.0

-90.0 -65.0

23.5 29.5

E Z

2 1 JLâ 2ç 2Â Je M

2% 98%

+276.5 +231.0 +232.0 +222.0 +223.3 +241.5 +235.5

-30.0 -11. + 3.0 +15.8 +47.5 +39.6

30.0

E

5.9 0.0 6.5 13.0

Z Z Z Z

2b

+252.1 +255.0

+106.0 +61.0

g

+164.0

-37.0

73.0

?

4 4e. AI Az AS Ak Ah M _4d

+213.8 +221.9 +200.9 +220.4 +203.6 +228.8 +142.4 +139.8 +143.0 +157.4 +135.6 +141.1 +137.0

-39.0 -39.0 -39.9 -34.4 -40.0 -38.8 -41.0 -40.9 -40.6 -40.2 -40.7 -41.4 -39.3

78.9 77.7 82.5 77.8 80.8 70.0 36.8 39.1 36.6 71.9 41.5 62.0 35.9

E E E E E E Z Z Z Z Z Z Z

+243.7 +180.3 +155.3

-30.3 -41.2 -38.6

81.0 204.0 160.0

70% 30%

Ah ±X

_5a 3â 5b

50% 50%

δ ppm, J Hz,

J

i

374/422 (t°) 11.5

? ?

-0.2

0.0

-0.13 +0.19 +0.21 +0.12 +0.06

0.0 2.4 2.2 2.5 2.0

1

P ( 8 5 % H P 0 ) , H (TMS) 3

4

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

E Z Z

398

PHOSPHORUS

Low T e m p e r a t u r e

CHEMISTRY

Spectra

31 On l o w e r i n g t h e t e m p e r a t u r e we o b s e r v e d i n t h e Ρ nmr s p e c ­ t r a o f ^ a a n a d d i t i o n a l s p l i t t i n g o f t h e s i g n a l s , g i v i n g two p a i r s o f d o u b l e t s s h o w i n g t e m p e r a t u r e d e p e n d e n t i n t e n s i t i e s due t o i n v e r s i o n and o r r o t a t i o n h i n d r a n c e . F u r t h e r m o r e we d e t e c t e d a t -80°C two new p a i r s o f d o u b l e t s i n t h e P-SiMe3 r e g i o n o f t h e s p e c t r u m , g i v i n g f o r t h e f i r s t t i m e e v i d e n c e o f a p h o s p h a g u a n i d i n e , t h e s i l a t a u t o m e r o f 4a R N = C ( P ( R ) SiMe3)2· The r e v e r s i b l e l o w t e m p e r a t u r e p a t t e r n i s o f t h e p r e ­ d i c t e d t y p e f o r a m i x t u r e o f t h e two d/1 d i a s t e r e o m e r i c p a i r s o f compounds. f

R e s u l t s and D i s c u s s i o W i t h r e s p e c t t o t h e two s t r u c t u r e s known so f a r , t h e more p o s i t i v e 31p nmr s h i f t p o i n t e d t o w a r d s an Ε c o n f i g u r a t i o n . T h i s seemed t o be s u p p o r t e d by a s e r i e s o f compounds p r e p a r e d w i t h d i f f e r e n t l y s u b s t i t u t e d i s o c y a n i d e d i c h l o r i d e s , s h o w i n g t h e more s p a c e r e q u i r i n g g r o u p s t o move o p p o s i t e t o t h e s u b s t i t u e n t on the methylene phosphorus. Moreover, because o f easy c i s - m i g r a t i o n , o n l y t h e Ζ compounds seemed t o be c a p a b l e o f f o r m i n g diastereomeric m o d i f i c a t i o n s of the silatantomer. To be on t h e s a f e s i d e , we added a t h i r d s t r u c t u r e d e t e r m i ­ n a t i o n a f t e r being s u c c e s s f u l i n growing c r y s t a l s o f 4a. T h i s was c o m p l e t e d s h o r t l y b e f o r e we l e f t f o r t h e c o n f e r e n c e and i t t u r n e d o u t t o be a Ε s t r u c t u r e i n s t e a d o f t h e p r e d i c t e d Ζ c o n ­ figuration. The d e t e r m i n a t i o n was r e d o n e u s i n g a d i f f e r e n t c r y s t a l and i n a d d i t i o n a 31 nmr o f t h e s o l i d compound was k i n d ­ l y r u n by D r . F o r s t e r ( B r u k e r Company). The s t r u c t u r e was c o n ­ f i r m e d , t h e ^ I p nmr s p e c t r a i n s o l u t i o n and i n t h e s o l i d p h a s e showed n e a r l y t h e same s h i f t s o f c l o s e i n s p e c t i o n o f t h e t h r e e c r y s t a l s t r u c t u r e s showed t h e n i t r o g e n t o be p l a n a r , b u t o n l y two s t r u c t u r e s show t h e n i t r o g e n and i t s l i g a n d s t o be c o p l a n a r w i t h the methylene phosphorus, thus o p t i m i z i n g o r b i t a l i n t e r a c t i o n s . P

3

S t r u c t u r e C o p l a n a r i t y ^ P δ(A) ppm 4a

Ε

yes

+132.8

6

Ζ

yes

+115.7

7 EE no +258.0 I t i s t h e r e f o r e not the proposed Ε o r Ζ c o n f i g u r a t i o n which g o v e r n s t h e s t r o n g s h i f t d i f f e r e n c e s s e e n i n t h e ^ P nmr s p e c t r a , but r a t h e r t h e p o s s i b l e i n t e r a c t i o n o f t h e Π-system w i t h o t h e r suitable orbitals. 3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

81.

APPEL ET AL,

Dicoordinated

Phosphorus

Compounds

399

Si(CH 3 3 ι ;

31

Ρη.ι P=C H

5

C

6

Cl P(C H )Si(CH , 6

5

room temperature

J. J

Figure L

-80C

Ή NMR spectra of 4a.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

3

3

400

PHOSPHORUS CHEMISTRY

Literature Cited

1. Appel, R.; Barth, V. Angew. Chem. 1979, 91, 497, Angew. Chem. Int. Ed. Engl. 1979, 18, 469. 2. Appel, R.; Laubach, B. Tetrahedron Lett. 1980, 2497. 3. Appel, R.; Barth, V.; Knoll, F.; Ruppert, I. Angew. Chem. 1979, 91, 936, Angew. Chem. Int. Ed. Engl. 1979, 18, 873. 4. Becker, G.; Mundt, O. Z. Anorg. Allg. Chem. 1980, 462, 130. 5. Becker, G.; Mundt, O. Z. Anorg. Allg. Chem. 1978, 443, 53. RECEIVED

July 7,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

82 Synthesis and Properties of Phosphaalkenes T. A . V A N DER KNAAP, T. C. K L E B A C H , F. VISSER, R . LOURENS, and F. B I C K E L H A U P T Vakgroep Organische Chemie, Vrije Universiteit, De Boelelaan 1083, 1081HVAmsterdam, The Netherlands

Three years ago, i t wa show that phosphaalkene (1) which are not substituted at th their thermal s t a b i l i t y y can be obtained by base-induced elimination of HC1 from 2 (1). The predominant role of steric hindrance was obvious from the i n ­

1

fluence of the groups R on s t a b i l i t y : 1 with R = mesityl (= Mes) or 2,6-dimethylphenyl resulted in stable, isolable compounds, while those with R = 2-methylphenyl or phenyl were too unstable for iso­ lation. For this reason i t was expected that trimesitylphosphaethene (1b) would be a particularly stable phosphaalkene. However, in this case the amount of the steric hindrance is apparently so large as to prevent the formation of 1b. Even 2b (R =R =R =mesityl) could not be obtained in the usual way by treatment of 3 with HC1; i n ­ stead, the interesting phosphonium salt 4 ( p-NMR: δ=31.9 ppm, JpH = 574 Hz) was formed, providing, as a spin-off, insight into the mechanism of transformations of the type R2PX + HY -> R PY. The primary product 4, in this case is presumably for steric reasons prevented from further reaction via phosphoranes such as 5 to form 2a. 1

1

2

3

31

1

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

402

However, 2b c o u l d be s y n t h e s i z e d by r e a c t i n g 6^ w i t h d i m e s i t y l m e t h y l p o t a s s i u m ; e l i m i n a t i o n o f H C l c o u l d n o t be a c h i e v e d u n d e r a v a r i e t y o f c o n d i t i o n s , p r o b a b l y due t o t h e i n a c c e s s i b i l i t y o f t h e p r o t o n i n 2b f o r b a s e . MesPCl

+ KCHMes

2

—HCl * » MesP=CMes

» 2b

2

6

2

lb

S i m i l a r l y , a t t e m p t e d e l i m i n a t i o n o f H C l f r o m 1^ t o f u r n i s h 8^ was unsuccessful. Cl P-CHMes 2

ClP=CMes

2

7

2

—^—>

lb

8

With r e s p e c t t o the s t r u c t u r e of phosphaalkenes, c o n s i d e r a b l e p r o g r e s s has b e e n a c h i e v e d by t h e X - r a y c r y s t a l s t r u c t u r e d e t e r m i ­ n a t i o n o f Ja (2) and o f i t s C r ( C 0 ) c o m p l e x 2 (3) . B o t h t h e s t r u c ­ t u r a l d a t a and t h e c l o s e s i m i l a r i t y o f s p e c t r a l d a t a c o n f i r m t h a t La as s u c h and as a l i g a n d i n £ has e s s e n t i a l l y t h e same s t r u c t u r e of a p l a n a r , n o n - d e l o c a l i z e d phosphaethene (Table 1). 5

Table 11. S e l e c t e d

s p e c t r a l and

3

.—Z^ ,C(C6H ) CH Λ . r 5

HH Com­ pound

31 la

233.06

2

I'

N X

13

p

l a : X = lone p a i r

0

3

NMR: P=C (6 i n ppm) c

La and j j i .

s t r u c t u r a l data of

X=Cr(C0)

5

Bond d i s t a n c e s (in pm)

bond angle ( i n °)

P=C

C=P-C

P-C

193.37 J =43.5Hz

170

184

190.94 J =32.3Hz

168

182

P-Cr

108.7

P C

237.3

236

109.8

P C

The P=C bond l e n g t h s o f 170 and 168 pm, r e s p e c t i v e l y , a r e c l e a r ­ l y s h o r t e r than those of d e l o c a l i z e d systems which t y p i c a l l y range f r o m 172 t o 176 pm. I n v i e w o f t h e w e l l - k n o w n t e n d e n c y o f t r i c o o r d i n a t e p h o s p h i n e s t o w a r d s s m a l l bond a n g l e s , i t i s n o t s u r p r i s i n g t o f i n d t h e C=P-C bond a n g l e i n l a (108.70°)to be more a c u t e t h a n e x p e c t e d f o r p u r e s p 2 - h y b r i d i z a t i o n , w h i l e i n t h e f i r s t row a n a l o g o f Uif N - m e s i t y l b e n z o p h e n o n e - i m i n e , t h e C=N-C a n g l e i s 120.8° 0 4 ) . The s t r u c t u r a l d a t a o f j a i m p l y a r e l a t i v e l y h i g h s - c h a r a c t e r i n

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

VAN D E R K N A A P

82.

ET A L .

Phosphaalkenes:

Synthesis and Properties

403

the lone p a i r a t phosphorus, i n t e r m e d i a t e between those i n t e r t i a ­ r y phosphines and_X3-phosphorins. I nline with this interpretation t h e I R - s p e c t r u m (vco=1955 cm"1) and t h e s t r u c t u r a l d a t a o f (CrC t r a n s 1 8 7 pm, C - O t r a n s 113 pm) show l a t o be a l i g a n d o f i n t e r m e ­ d i a t e b a s i c i t y and π-acceptor s t r e n g t h . F i n a l l y , a p r o g r a m was i n i t i a t e d t o i n v e s t i g a t e t h e c h e m i c a l r e a c t i v i t y o f JLa. E a r l i e r e x p e r i m e n t s h a d shown (J_) t h a t t h e p o l a ­ r i t y o f t h e P=C bond i n p o l a r r e a c t i o n s i s r e v e r s e d a s compared t o t h a t o f t h e N=C bond i n i m i n e s ; t h i s i s f u r t h e r e x e m p l i f i e d b y t h e following reactions : :

la

HCl

2a

»

^excess HCl 5 + C H ^ C ^ ) ^

0 )

i^/Mes^-cHC^H ) OH ' H

C

2°2. H

0

Mes-P-CH(C,H )„ OH

H

3 CH 0Na

Mes-P-CH(C,H,.) 3

3

0

C

H

'·) EtOH, 2·) 0

0 Mes-P-CH(C,H.) OEt

1.) n - B u L i 2·) D 0

Mes-P-CD(C,H,) _ è

6

2

6

2

n

0 )

9

1

3

5

5

9

2

9

2

u

R e m a r k a b l e a r e t h e r e a c t i o n s w i t h O 2 , S g , and B r 2 , i n w h i c h f o r m a l l y t h e P=C bond o f l a i s c l e a v e d : la.

^

polymer

+

0=C(C H )

^

polymer

+

S=C(C H )

5£l^MesPBr2

+

6

5

6

5

2

2

Br C(C H ) 2

6

5

2

R e a c t i o n s w i t h d i e n e s and c a r b o n y l compounds d i d e i t h e r n o t o c c u r b e l o w 150°C ( e . g . 2 , 3 - d i m e t h y l b u t a d i e n e , c y c l o p e n t a d i e n e , t e t r a c h l o r o - a - p y r o n ; a c e t a l d e h y d e ) , o r were a c c o m p a n i e d b y decom­ p o s i t i o n (2,3-dicarbomethoxybutadiene, hexachlorocyclopentadiene, 1 , 3 - d i p h e n y l i s o b e n z o f u r a n ; a c r o l e i n ) . However, 1 , 3 - d i p o l e s r e a c ­ ted r e a d i l y t o give w e l l - d e f i n e d a d d i t i o n products :

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

404

PHOSPHORUS CHEMISTRY

/r-° C6H5 V

la

Mes-cJ-0

250C, r a p i d

M e S

C

" ^P^C H 6

5

Mes ,N~C H Mes-P. \-C H 6

ΤΈι*

6

t H 6

la

+

*~

C.H_N Ό J

5

11 5

5

80 0

J

N=N \CS2 24h 12

Mes

1H20»0

2

p 13 Mes-f-CH(C H ) ,C H NHC6H5 6

5

2

6

IS

+

«*Η > ™ 5

2

300c,

2

24h

>

S

5

C H5 6

Mes The s t r u c t u r e a s s i g n m e n t s o f 10 (δ-^Ρ: 9.3 ppm; δ 1 C: 98.8 ppm i J p c = 30 H z ) , P-Ç-0; 160.6 p p m ^ J p c = 45 H z ) , P-C=N) and J i (δ 31P: 47.36 ppm; 6 1 3 c : 47.75 ppm ( l j p = 14.7 H z ) ; 64.06 ppm ( 2 j = 20.5 Hz) f o l l o w f r o m t h e s p e c t r a l d a t a . I n t h e r e a c t i o n b e t w e e n La and p h e n y l a z i d e , t h e s t r o n g s o l v e n t dependence o f b o t h t h e r a t e and t h e p r o d u c t f o r m a t i o n i s r e m a r k a b l e . I n C^E^ ( a s i n C D C I 3 ) , the r e a c t i o n i s f a s t , a f f o r d i n g t h e i m i n o - y l i d JM a s t h e s o l e p r o d u c t (631p: 18.8 ppm; 6 1 3 c : 68.32 ppm ( l j = 166?5 H z ) ; 68.26 ppm ( 1 J = 166.5 H z ) ; c a . 1:1 m i x t u r e o f c i s / t r a n s i s o m e r s ) . I n C S 2 , t h e r e ­ a c t i o n i s s l o w ; b e s i d e s 8% Π , t h e m a j o r p r o d u c t i s t h e c y c l o a d d u c t \2 (631p: 140.8 ppm; o ^ C : 6Î.1 ppm ( 1 J c = 49 H z ) ) ; t h e s t r u c t u r e o f \2 i s f u r t h e r c o n f i r m e d b y i t s c o n v e r s i o n t o Γ3. Once f o r m e d , Π[ i s n o t c o n v e r t e d t o \2.; t h u s , b o t h compounds a r e o b v i o u s l y formed by d i f f e r e n t mechanisms. 3

1

C

P

P C

C

P C

P

Literature Cited

1. Klebach, Th.C.; Lourens, R.; Bickelhaupt, F.; J. Am. Chem. Soc. 1978, 100, 4886. 2. Stam, C.H.; personal communication. 3. Klebach, Th.C.; Lourens, R.; Bickelhaupt, F.; Stam, C.H.; Van Herk, Α.; J. Organometal. Chem. 1981, 210, 211. 4. Bokkers, G.; Kroon, J.; Spek, A.L.; Acta Cryst. Β 1979, 35, 2351. RECEIVED

July 7,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

83 Routes to Dicoordinated Phosphorus Compounds K. ISSLEIB, H. O E H M E , H .

SCHMIDT,

and G . - R .

VOLLMER

Department of Chemistry, M a r t i n - L u t h e r - U n i v e r s i t y , Weinbergweg 16, 4022 Halle Saale, FRG

Derivatives of trivalent phosphorus of coordination number two are available from stabl elimination of small stabl

scheme where XY may be hydrogen halide, water, alcohol, alkoxysilane, chlorosilane, ether and elemental hydrogen. Examples of the application of this concept are the various p o s s i b i l i t i e s of formation of 1,3-benzazaphospholes, 1,3-benzthiaphospholes, carbosilylated phosphaalkenes, dialkylaminoalkylidene-phosphines and other compounds of that type. 1,3-Benzazaphospholes These compounds (1) are synthesized from primary o-aminophenylphosphine and various cyclization reagents, from secondary o-aminophenylphosphines under elimination of an ether and by o x i ­ dation or thermal treatment of 1,3-benzazaphospholenes (Scheme 1). In these cyclizations the NH-benzazaphospholes are formed exclu­ sively. This underlines the C=P double bond system in these special cases to be favored over the C=N bond. A PH isomer was never observed.

0097-6156/81/0171-0405$05.00/0 ©

1981

American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

406

PHOSPHORUS

CHEMISTRY

1,3-Benzthiaphosphates o-Mercaptophenylphosphine i s i n d i f f e r e n t towards i m i d o e s t e r hydrochlorides o rortho esters. By u s e o f Ν,Ν-dimethyl c a r b o x y l i c a c i d amide a c e t a l s , h o w e v e r , 1 , 3 - b e n z t h i a p h o s p h o l e s (2) c o u l d be prepared. The 2 - p h e n y l d e r i v a t i v e i s made more c o n v e n i e n t l y b y h e a t i n g a m i x t u r e o f t h e p h o s p h i n e and b e n z a l d e h y d e t o 1 2 0 ° C T h i s r e a c t i o n i s a f u r t h e r example o f a n a r o m a t i z a t i o n t h r o u g h e l i m i n a t i o n o f m o l e c u l a r h y d r o g e n (Scheme 2 ) . Scheme 2.

_

2

RC(0Me) NMe

J ! ^

f Y

PhC(0)H

VlR

R:H,CH C H 3 l

6

5

1 , 3 - b e n z a z a p h o s p h o l e s and 1 , 3 - b e n z t h i a p h o s p h o l e s a s w e l l a s the 2 - t - b u t y l - l , 3 - b e n z o x a p h o s p h o l e (3) a r e phosphorus a r o m a t i c s of e x t r a o r d i n a r y s t a b i l i t y . T h e i r s t r u c t u r e s have been proved b a s e d o n t h e i r nmr, u v and mass s p e c t r a ( e . g . , P s h i f t s a t +70 t o +80 ppm, C s h i f t s (C-2) a t +159 t o 214 ppm). The r e a c t i v i t y o f t h e compounds i s r a t h e r l i m i t e d . F o r e x a m p l e , b e n z a z a p h o s p h o l e s a r e n o t a t t a c k e d by d i l u t e aqueous a c i d s and b a s e s , o x y g e n , s u l f u r o r a l k y l h a l i d e s . The c o o r d i n a t ­ i n g a b i l i t i e s , m e t a l a t i o n and i n t e r a c t i o n o f t h e s o formed a m b i d e n t a n i o n w i t h a c y l h a l i d e s i s d e m o n s t r a t e d i n Scheme 3 ( 4 ) . 3 1

1 3

Scheme 3.

CH

3

LiNEtjj

H

PCl

2

CH3-C=0 Carbosilylated

Phospha-Alkenes

C o n t i n u e d r e s e a r c h o n N - s i l y l - p h o s p h a - a m i d i n e s and N , N - b i s s i l y l a t e d phosphaguanidines (5) l e d u s t o c a r b o s i l y l a t e d phos­ p h a a l k e n e s . The v a r i o u s r o u t e s t o t r i m e t h y l s i l y l m e t h y l - c h l o r o p h o s p h i n e s and t h e i r c o n v e r s i o n i n t o c a r b o s i l y l a t e d p h o s p h a ­ a l k e n e s i s g i v e n i n Scheme 4 ( 6 ) . I n t e r a c t i o n o f t h e s e p r o d u c t s w i t h h y d r o g e n c h l o r i d e l e a d s t o S i C H - P R C l and S i - C H - P R C 1 , r e ­ spectively. By H C l a b s t r a c t i o n f r o m t h e s e p r o d u c t s , t h e p a r e n t 2

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

83.

ISSLEIB ET A L .

Routes to Dicoordinated

Phosphorus

Compounds

407

p h o s p h a a l k e n e c a n be r e g e n e r a t e d b u t m o n o - c a r b o s i l y l a t e d p h o s ­ p h a a l k e n e s c a n a l s o be p r o d u c e d . When R i s CH2-S1 a s a c o n s e ­ quence o f e l i m i n a t i o n o f e i t h e r H C l o r t r i m e t h y l c h l o r o s i l a n e , d i f f e r e n t phosphorus d e r i v a t i v e s a r e o b t a i n e d . A noteworthy c h a r a c t e r i s t i c o f c a r b o s i l y l a t e d p h o s p h a - a l k e n e s a r e t h e i r P-nmr s i g n a l s w h i c h a p p e a r a t e x t r e m e l y l o w f i e l d s (+376 t o +438 ppm). Scheme 4.

(MeaSiJjC-P^

(Me Si) C-Li 3

© 2

'

P

S i )

3

3

C - P C l

2

S0,C=PCl

~-Me SiCl

2

H

- ^ ( M e

I

4

Si) C=P-R • HCl - H C l C

3

3

I

' c i

~i&

•HCl I

W e ^ C H I - i \

3

Dialkylamino Alkylidene

Me SiCsP 3

Me SiCH MgCl 2

Me Si-CH=PR

Phosphines

3

In the s y n t h e s i s o f s p e c i a l l y s u b s t i t u t e d methylene d i p h o s p h i n e s , made f r o m s e c o n d a r y p h o s p h i n e s a n d c a r b o n y l d e r i v a t i v e s (7 ) , a c a r b e n i u m i o n a d j a c e n t t o t r i v a l e n t p h o s p h o r u s a s t h e t r a n s i t i o n s t a t e has been d i s c u s s e d . The t r a n s f e r o f t h i s r e a c ­ t i o n p r i n c i p l e t o p r i m a r y p h o s p h i n e s a n d s u i t a b l e c a r b o n y l com­ pound r e v e a l e d a f u r t h e r pathway t o d e r i v a t i v e s o f d i c o o r d i n a t e d phosphorus ( 8 ) . Aromatic phosphines r e a c t w i t h c a r b o x y l i c a c i d amide a c e t a l s u n d e r e l i m i n a t i o n o f a l c o h o l g i v i n g d i a l k y l a m i n o a l k y l i d e n e p h o s p h i n e s (Scheme 5 ) . A m o d i f i c a t i o n o f t h e s y n t h e s i s

NMe, Ar-P=C(

N M e

Ar:Ph

#

SwP-c%>

Mesityl

Ri H CH3,NMe ... a

2

of ϋ p a s s i n g through the i d e n t i c a l u n i s o l a t e d intermediates, i s t h e i n t e r a c t i o n o f a l k a l i m e t a l p h o s p h i d e s (MPHR) w i t h d i a l k y l ­ amino a l k o x y c a r b e n i u m f l u o r o b o r a t e s (Scheme 6 ) . The a p p l i c a t i o n o f f u r t h e r s u i t a b l e c a r b e n i u m s a l t s o f f e r s a wide f i e l d o f s y n t h e t i c r o u t e s t o d e r i v a t i v e s o f d i c o o r d i n a t e d phosphorus. Scheme 6.

ArPC

-NoBF

H

Να

R-C(0R*)NMe ]BF
2

--> Cl(Me)PN(Me)C(:O)Ν(Me)Ρ(Me)Cl

+ 2

Me3SiCl

(1)

Attempted oxidative addition of 1 at 3 which was expected to produce a Ν,Ν'-dimethylurea-bridged diphosphorane, led to an un­ usual reaction and product 5 with simultaneous elimination of one 0097-6156/81/0171-0425$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

426

PHOSPHORUS

phosphorus as MePCL^ (eq.

3) Me^

2 1

+

3

6

0

»

^

^0

! I JP—Ν

3d ( C F

CHEMISTRY

+

MeFCl

(3)

0 z

3>2f^

(CF ) 3

I ;

2

δ ρ -32.9

The r e a c t i o n m y proceed by o x i d a t i v e a d d i t i o n o f 2 e q u i v a l e n t s o f 1 a t a A P atom o f 3, producing a monophosphorane intermediate i n which a t t a c k a t the λ ^ Ρ atari by the n i t r o g e n atari γ t o P , f o l ­ lowed by n u c l e o p h i l i c a t t a c 3

Me

/ C

x

x

^Me

Ν Me. I >P~C1-IP

3 + 2 1 —

—·*

MePCl-

+

5

(4)

1

o. /° c

(CF ) 3

2

A l t e r n a t i v e l y , o x i d a t i v e a d d i t i o n o f 1 may occur a t a λ Ρ atari o f 1,3-dimethyl-2-methyl-1,3,2A -prosphadiazetidin-4-one, § resulting frcm t h e t h e r m o l y s i s o f 3 i n a c c o r d w i t h e q . (5) f o r which we have o b t a i n e d 31p n . m . r . evidence, 3

0 3

-£±+

Me-N \

N-Me

+

MePCl-

^ §

(5)

κ ι Me ρ

T h i s l a t t e r p o s s i b i l i t y , however, i s thought t o be l e s s l i k e l y , i n view o f observations on the r e a c t i o n o f 3 w i t h two e q u i v a l e n t s o f TOB, I which o c c u r s snoothly a t temperatures as low as 0 ° C , producing the n o v e l spirophosphorane 6, c l o s e l y analogous t o | .

g ;

δ ρ -24.4

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

87.

WEFERLiNG A N D S C H M U T Z L E R

Dimethylurea-Bridged

Phosphorus

427

The formation o f | i s noteworthy a l s o , i n as much as i n the r e a c t ­ i o n s o f Ρ (III) compounds w i t h HFA, c a r t o n - c a r b o n condensation o f the l a t t e r w i t h formation o f t h e 1 , 3 , 2 λ dioxaphospholane system i s normally observed J*. Formation o f the 1 , 4 , 3 λ ^ dioxaphospholane r i n g system as i n | has r a r e l y been r e p o r t e d ; furthermore, products o f t h i s type a r e known t o undergo decomposition i n t o the s t a r t i n g compounds _r ' 1 £ o r , i n the presence o f hydrogen on the carbon atari a t o A ^ - P , t o rearrange d i r e c t l y i n t o 1,2A^-oxaphosphetanes _ 1 1 Ή · We have observed by and P n . m . r . t h a t | i s unchanged over the e n t i r e temperature r e g i o n i n v e s t i g a t e d (roan temperature t o 1 6 Q ° C ) . The s t r u c t u r e o f | has been e s t a b l i s h e d by a s i n g l e c r y s t a l X - r a y d i f f r a c t i o n study (W.S. S h e l d r i c k ) ; the geometry a t phos­ phorus i s r e l a t i v e l y c l o s e t o t r i g o n a l - b i p y r a m i d a l . 5

3 1

Reaction o f | w i t h f o u a complicated mixture o d i t i o n o f 1 a t both A P atoms o f | w i t h r e t e n t i o n o f the P-P bond was found. When TOB was employed, however, a c l e a n r e a c t i o n i n a c c o r d w i t h eqn . (6) was observed. 3

Λ

3 2

aO »

1

»

+

M e - P ^

(6)

-8.5 5

3

A s t a b l e intermediate λ Ρ Α bonded œ m p o u n d , § i s formed when 2 and 4 a r e allowed t o r e a c t i n an exact 1:1 molar r a t i o i n e t h e r between -40 t o 0 ° C . E l i m i n a t i o n o f methylphosphinidene, MeP (un­ dergoing o x i d a t i v e a d d i t i o n w i t h | ) a p p a r e n t l y i s p r e f e r r e d t o r e a c t i o n o f | w i t h f u r t h e r g t o g i v e a λ Ρ Λ Ρ bonded diphosphorane. The A % atari i n | does, however, e x h i b i t r e a c t i o n s t y p i c a l o f P ( I I I ) , w i t h r e t e n t i o n o f the P-P bond, such as shown below 5

5

Fe(C0)

5

-16.5

4

+54.9

δ(λ Ρ) δ(λ Ρ) 1

J(PP)

232

3

5

δ(Α /λ Ρ)

+3.5

5

δ(λ Ρ) 4

δ(Α Ρ) 1

J(PP)

-8.4 108.4 46

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

4

PHOSPHORUS CHEMISTRY

428

S i n g l e c r y s t a l X - r a y d i f f r a c t i o n s t u d i e s o f both | and 1Q (J.W. G i l j e ; D. Schomburg; W.S. S h e l d r i c k ) have confirmed t h a t the P-P bond i n these compounds has remained i n t a c t . Both com­ pounds represent a n o v e l s t r u c t u r a l f e a t u r e , λ %>λ^Ρ, i n phosphorus c h e m i s t r y . Compound 1Q, i n a d d i t i o n , i s noteworthy as i t œ m b i n e s both a n o n m e t a l l i c and a m e t a l l i c f i v e - c o o r d i n a t e c e n t e r i n the same molecule.

Literature cited 1. L. Maier, in "Organic Phosphorus Compounds" (eds. G.M. Kosolapoff and L. Maier); Wiley-Interscience, New York, London, Sydney, Toronto 1972; Vol. 1, pp. 1, 289. I.F. Lutsenko and M.V. Proskurnina, Uspekh. Khim., 47, 1648 (1978). 2. A.H. Cowley (Editor) -Phosphorus Bonds; Dowden, Hutchinson + Ross, Inc., Stroudsburg, Pa., 1973. 3. H.W. Roesky, K. Ambrosius, and W.S. Sheldrick, Chem. Ber., 1979, 112, 1365. 4. H.W. Roesky, K. Ambrosius, M. Banek, and W.S. Sheldrick, Chem. Ber., 1980, 113, 1847. 5. J . E . Richman and R.R. Holmes, J . Am. Chem. Soc., 1980, 102, 3955. 6. R.E. Dunmur and R. Schmutzler, J. Chem. Soc. (A), 1971, 1289; R.K. Harris, J.R. Woplin, R.E. Dunmur, M. Murray, and R. Schmutzler, Ber. Bunsenges. Phys. Chem., 1972, 76, 44; O. Schlak, R. Schmutzler, R.K. Harris, E.M. McVicker, and M.I.M. Wazeer, Phosphorus and Sulfur, in press. 7. P N.m.r. shifts (ext. 85% H3PO4 ref.) to high field are given with a negative sign. 8. E.g. F. Ramirez, C.P. Smith, J . F . Pilot, and A.S. Gulati, J . Org. Chem., 1968, 33, 3387. 9. V.N. Volkovitskii, I . L . Knunyants, and E.G. Bykhovskaya, Zh. Vses. Khim. Obshch., 1973, 18, 112 (C.A. 78, 148035w (1973)). 10. R.K. Oram and S. Trippett, J. Chem. Soc. Perkin I, 1973, 1300. 11. F. Ramirez, C.P. Smith, and J . F . Pilot, J . Am. Chem. Soc., 1968, 90, 6726. 12. J.A. Gibson, G.V. Röschenthaler, K. Sauerbrey, and R. Schmutzler, Chem. Ber., 1977, 110, 3214. 31

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

88 A Stable Monocyclic Triarylalkoxyhydridophosphorane A 10-P-5 Species with an A p i c a l P-H B o n d 1

MICHAEL R. ROSS and J. C. MARTIN Roger Adams Laboratory, University of Illinois, Urbana,IL61801

Spectroscopic data presented i earlie t (1) interpreted in terms o gonal bipyramidal (TBP) monocycli triarylhydrido phosphorane (1b). We have an X-ray crystallographic solution of the structure of apical hydridophosphorane 1a as well as the structure of its diaryldialkoxy spirobicyclic analogue, 2. Table I lists important bond lengths and angles for the two species, and, for comparison, the phosphatrane of Verkade (2), 3, and equatorial hydridophosphorane 9. Phosphorane 1a has a1JPHvalue (269 Hz in CDCl3) and an infrared P-H stretching frequency (2100 cm-1, CHCl3) that are sig­ nificantly smaller than the corresponding values for 2 (1JPH = 733 Hz, νP-H = 2430 cm-1) (1) and other equatorial hydridophosphoranes (3). These observations are reconciled with an apical P-H disposition for 1a in solution on the basis of a correlation between 1JPH and ligand electronegativity (Equation 1). This was developed using data for a large number of hydridophosphoranes 1JPH = 306 [σI(equatorial) + 0.505σI(apical)] + 595

(1)

which could, with some assurance, be assigned TBP structures with equatorial P-H bonds. Apical hydridophosphoranes 1a, 1b, and 3 (3, 4) a l l have 1JP-H values much lower than Equation 1 predicts. The apical P-H bond length of 1.35(3) Åfor 1a is, within experimental error, the same as that reported for the equatorial P-H bond of 2, 1.32(3) Å, and for the apical P-H bond of 3, 1.349(71) Å (2). A l l are shorter than the sum of phosphorus and hydrogen covalent radii, 1.40 Å (4), and considerably shorter than P-H bond lengths in a variety of hydridophosphines and in the PH + cation, 1.41-1.45 Â (5). The two apical P-0 bonds for £ (average value = 1.745 Â are in the usual range of bond lengths for such species (6). The P-0 bond for TJj (1.825(3) Â is longer. 4

7

Current Address: Monomer Process Research Department, Rohm and Haas Company, Research Laboratories, Spring House, PA 19477 0097-6156/81/0171-0429$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

430

Table I .

Bond L e n g t h s (Â) and A n g l e s (Deg) i n H y d r i d o p h o s p h o r a n e s

Bond L e n g t h , Angle

a b c Làb& Zed Z.ac Ζ ad Z de Z.ae Ice

Compound la

a

2

a

3

9

b

C

1.825(3) 1.35(3) 1.825(3) 176(1) 112.7(1) 90.7(1)

1.743(2) 1.748(3) 1.32(1) 178.47(3) 114.5(11) 86.1(11)

1.986(5) 1.35(7) 1.577(3) 172.2(48) 120.0(1) 87.6(1)

1.721(2) 1.701(3) 1.36(3) 177.4(1) 115(1) 91(1)

123.6(2 85.5(1) 123.7(2)

88.48(14) 117.9(11)

87.6(1) 120.0(1)

92.6(1) 121(1)

Reported h e r e i n . R e f e r e n c e (_3). R e f e r e n c e ( 1 0 ) . The 0-P-H angle f o r ^ i s bent toward the t-Bu a r y l group; the N-P-H angle f o r ^ i s bent toward one e q u a t o r i a l oxygen; ^ and ^ have 0-P-P angles bent away from the e q u a t o r i a l hydrogen. The p h o s p h o r u s atom l i e s 0.036 Â b e l o w t h e e q u a t o r i a l p l a n e o f toward the a p i c a l hydrogen. T h i s r e p r e s e n t s a s m a l l d i s p l a c e m e n t a l o n g t h e pathway f r o m t h e i d e a l TBP t o w a r d ^, w i t h P-0 bond l e n g t h e n i n g and P-H bond s h o r t e n i n g . Addition of trifluoromethanesulfonic ( t r i f l i e ) acid to a CDCI3 s o l u t i o n o f ^ Q^) gives alkoxyhydridophosphonium s a l t ^ (^). H e l l w i n k e l ' s (7) b i c y c l i c p h o s p h o r a n e £ b e h a v e s i n an a n a l o g o u s manner. An i n c r e a s e o f a b o u t 300 Hz i n t h e v a l u e o f "SlPH upon f o r m a t i o n o f ^ , J j f r o m i s consistent with a smaller d e g r e e o f p h o s p h o r u s s - o r b i t a l c h a r a c t e r i n t h e a p i c a l P-H bond o f t h e p h o s p h o r a n e (p/2 h y b r i d i z a t i o n ) t h a n i n t h e s p ^ p h o s p h o n i u m P-H bond ( 8 ) . The c o n v e r s i o n o f ^ t o ^ c a u s e s o n l y t h e s m a l l change (17 Hz) i n "**Jp_ e x p e c t e d f o r a s m a l l e r change i n s - o r b i t a l character (ca. sp^ to s p ^ ) . I n o u r p r e l i m i n a r y c o m m u n i c a t i o n (jl) we r e p o r t e d a pKa o f 11.7±0.1 f o r l b . U t i l i z i n g t h e same P NMR t e c h n i q u e we f i n d pKa = 10.3±0.2 f o r W h i l e the s t r u c t u r e of the conjugate base o f 2, p h o s p h o r a n i d e ^ can be u n a m b i g u o u s l y a s s i g n e d ( s e e c h e m i c a l s h i f t models and ^ ) ( 1 1 ) t h e same s t r u c t u r a l a s s e s s m e n t i s not as s a t i s f y i n g f o r the conjugate base of ^ (or ^ ) . Phosphine d e r i v a t i v e s (12) have 31p NMR c h e m i c a l s h i f t s s i m i l a r to those seen f o r the conjugate bases of ^ (-9.92 ppm) and ^ (-11.1 ppm). Weak P-0 b o n d i n g w o u l d n o t , h o w e v e r , be e x p e c t e d (13) t o l e a d t o a s i g n i f i c a n t u p f i e l d ^ l p s h i f t i f t h e bond i s a s u f f i c i e n t l y weak one. E s t i m a t e s o f pKa v a l u e s f o r t h e e q u i l i b ­ r i u m b e t w e e n o p e n - c h a i n t a u t o m e r o f ^ and i t s c o n j u g a t e o p e n - c h a i n base c a n be u s e d w i t h t h e measured pKa v a l u e f o r ^ and t h e H

3 1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

88.

Ross

AND MARTIN

Monocyclic

C F

F

Ο

3^

C F

^ 3^ 3 O"

Ph-

3 OH

CF S0 -

Η ί α , X =^-Bu, δ »b, X = Η, δ

3 1

3 1

p + 10.2 ^Jpjj = 569 Hz)

P + 11.7 ^Jpjj = 560 Hz)

CFo CFo 3 -OH

F

^ 3^

C F

3

6H ^CF SO ' 2

CF3SO3Η

3

C F

f

CF C F 3

δ

3 1

3

-Ph

P h - ^ |I

jj"**Ph

Ρ

C F

3

Η

431

Triarylalkoxyhydridophosphorane

Ρ + 2.75 ^Jpjj = 730 Hz)

δ

3 1

3

S

3 °3

3

1

P + 38.5 ( J

p H

= 716 Hz)

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

CH N-T|b

C

3

Ρ

-25.9 X

OCÎ

Ό Ρ: " L i

+

Ph-

13 X

, δ

3 1

P + 113

X δ

, X = CFg, Y

3 1

Ρ

H,

=:

-18.5 , X = CFg, Y — CHg, -17.9 -35.0 or

, X = CHg, Y = H,

OC -Χ

Ph-

P:

I

Ph δ X = -C(CH ) OCH Ph, 3

2

2

3 1

Ρ

X = -C(CH ) OH, 2

-11.1

X = -CH OH,

-16.0

3

2

X = -C0 H, X = -OCH ,

«·

P:

Ph^^l Ph

-5.0

2

b

-13.5

3

X = -HC(CH K>H, X = -CF , 3

0

O"

+21.9

-17.0 -10.9

21 (δ 31P O

A

-

9.92

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

ppm)

88.

ROSS A N D

MARTIN

Monocyclic

Triarylalkoxyhydridophosphorane

433

e x p e r i m e n t a l lower l i m i t f o r t h e f r e e energy d i f f e r e n c e between ^ and i t s u n o b s e r v e d o p e n - c h a i n i s o m e r t o d e t e r m i n e t h a t t h e l o w e r l i m i t t o t h e energy d i f f e r e n c e between t h e t r u e c o n j u g a t e base o f (either o r ^Uj) a n d t a u t o m e r fyfo i s z e r o . There i s t h e r e o r e no d i r e c t e v i d e n c e r e q u i r i n g t h a t we p o s t u l a t e e n e r g e t i c a l l y s i g n i f i c a n t P-0 b o n d i n g i n On t h e o t h e r h a n d , s i n c e we have o n l y a lower l i m i t f o r t h e energy d i f f e r e n c e between ^ and i t s o p e n - c h a i n i s o m e r , we c a n n o t r u l e o u t some P-0 b o n d i n g i n ^J.. F u r t h e r w o r k w i l l b e r e q u i r e d t o remove t h i s a m b i g u i t y . T h i s r e s e a r c h was s u p p o r t e d i n p a r t b y a g r a n t the N a t i o n a l Cancer I n s t i t u t e .

Literatur 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

13.

(CA13963) f r o m

Cited

Ross, M. R.; Martin, J . C. J . Am. Chem. Soc. 1981, 103, 1234. Milbrath, D. S.; Verkade, J . G. J . Am. Chem. Soc. 1977, 99, 6607. Clardy, J . C.; Milbrath, D. S.; Springer, J . P.; Verkade, J . G. J . Am. Chem. Soc. 1976, 98, 623. Brazier, J . F.; Houalla, D.; Loenig, M.; Wolf, R. Top. Phos­ phorus Chem. 1976, 8, 99. Pauling, L. "The Nature of the Chemical Bond"; Cornell Uni­ versity Press: Ithaca, N.Y., 1973; p 224-228. Corbridge, D. E. C. Top. Phosphorus Chem. 1966, 3, 91. Holmes, R. R.; Deiters, J . A. J . Am. Chem. Soc. 1977, 99, 3318. Hellwinkel, D.; Krapp, W. Chem. Ber. 1978, 111, 13. Hoffmann, R.; Howell, J . M.; Muetterties, E. L. J . Am. Chem. Soc. 1972, 94, 3047. Musher, J . I. Angew. Chem., Int. Ed. Engl. 1969, 8, 54. Clark, T. E . ; Day, R. O.; Holmes, R. R. Inorg. Chem. 1979, 18, 1653. Granoth, I.; Martin, J . C. J . Am. Chem. Soc. 1979, 101, 4623. Granoth, I.; Martin, J . C. J . Am. Chem. Soc. 1981, 103, in press (compound 14); Landvatter, E . ; Rauchfuss, T. B.; Wrobluski, D. A., private communication (compounds 16, 19); Granoth, I.; Alkabets, R.; Shirin, E . ; private communication (compound 15); Wrobluski, D. A.; Rauchfuss, T. B. Inorg. Synth., submitted (compound 17); McEwen, W. E . ; Shiau, W.-I.; Yeh, Y . - I . ; Schulz, D. N.; Pagilagan, R. Α.; Levy, J . B.; Symmes, C. J r . ; Nelson, G. O.; Granoth, I. J . Am. Chem. Soc. 1975, 97, 1787 (compound 18); Miller, G. R.; Yankowsky, A. W.; Grim, O. S. J . Chem. Phys. 1969, 51, 3185 (compound 20). Granoth, I.; Martin, J . C. J . Am. Chem. Soc., in press.

RECEIVED

July 1, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

89 Monocyclic Phosphoranide and Phosphoranoxide Anions P ( V ) Oxyphosphorane C a r b a n i o n — P ( I V ) Ylide A l k o x i d e Tautomerism ITSHAK GRANOTH, RIVKA ALKABETS, EZRA SHIRIN, YAIR MARGALIT and PETER BELL Israel Institute for Biological Research, Ness-Ziona 70450, Israel

Pentacoordinate hydroxyphosphorane likel intermediate or transition states in phosphorus (1). Recently, stable hydroxyphosphoranes (2, 3) and their conjugate bases - metal phosphoranoxides (4, 5) have been isolated. Spectroscopic evidence (4 - 7) for equilibria between Ρ(IV) compounds and hydroxyphosphoranes have been reported. Ob­ servation (8) and isolation (9) of Ρ(IV) TBP phosphoranide species have also been announced. A l l these phosphoranes are stabilized by several features dominated by their spirobicyclic nature. Monocyclic Phosphoranide Anion. The intramolecular oxida­ tive addition of hydroxyalkyl phosphites, which gives P-H phos­ phoranes, is well known (10). Some P-H phosphoranes are so stable that the open-chain P(III) tautomers cannot be detected spectroscopically or even by attempted H2O2 oxidation (8). Thus, it is surprising to find no evidence for an equilibrium between phosphine alcohol 1 and its closed-ring tautomer phosphorane 2. Phosphine 1 is quaternized by alkyl halides giving phosphonium halides such as 3. These in turn are converted to alkoxyphosphoranes, such as 4, by NaH (Scheme I). Phosphine 1 shows the expected P NMR δP-11.1 (THF), typi­ cal (11) of ortho substituted triphenylphosphine. Addition of LiAlH4 to this solution gives molecular hydrogen and two signals in the P NMR spectrum at -11.1 and -30.3. This observation sug­ gests that deprotonation of jL leads to a relatively slow equili­ brium of phosphine alkoxide _5 (major component) and phosphoranide This mixture and alkyl halides give phosphoranes such as 4_. The instability of phosphorane 2_ is surprising because accommodates four features which are known to stabilize hypervalent compounds (12). The central phosphorus atom in the TBP 2_ bears two highly apicophilic and three poorly apicophilic ligands (2). The phosphorus atom is contained in a five-membered ring linking an apical oxygen to an equatorial aromatic ring carbon (12). The gem-dimethyl conformational effect favors a closed ring structure. The increased stability of phosphoranide 6·, com3l

3 1

0097-6156/81/0171-0435$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

436

PHOSPHORUS CHEMISTRY

Scheme I

4,

δΡ-60.7

6_,

δΡ-30.3

p a r e d w i t h i t s c o n j u g a t e a c i d _2, i s a n a l o g o u s t o t h e e n h a n c e d s t a ­ b i l i t y o f r e p o r t e d p h o s p h o r a n o x i d e a n i o n s (3_4_» 5) . T h i s may r e ­ s u l t from t h e i n c r e a s e d e l e c t r o n e g a t i v i t y d i f f e r e n c e between a p i ­ c a l and e q u a t o r i a l l i g a n d s i n t h e s e TBP b a s e s , compared w i t h t h e i r respective conjugate acids. P h o s p h o r a n e - Y l i d e T a u t o m e r i s m . The l a b i l i t y o f α p r o t o n s i n a l k y l p h o s p h o r a n e s i s n o t known. D e u t e r i u m e x c h a n g e o f t h e b e n z y l p r o t o n s i s n o t o b s e r v e d , e v e n i n t h e p r e s e n c e o f NaOD i n D2OCD3SOCD3. D e p r o t o n a t i o n o f 4_ i n THF b y C H g L i a t room t e m p e r a t u r e is fast. T h i s r e d s o l u t i o n i s shown b y v a r i a b l e t e m p e r a t u r e 31p NMR t o c o n t a i n a n e q u i l i b r i u m m i x t u r e o f p h o s p h o r a n e 7_ and y l i d e 8_ (Scheme I I ) . T h i s m i x t u r e a n d CH3I g i v e p h s o p h o r a n e j ) . s

Scheme I I

9,

6P-54.9

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

89.

GRANOTH E TAL.

Phosphoranide

and Phosphoranoxide

J

Anions

437

±

Monocyclic Phosphoranoxide Anion. The P NMR c h e m i c a l s h i f t v a l u e and l i n e w i d t h o f 10 i s s o l v e n t and pH s e n s i t i v e , s u g g e s t i n g t h e e q u i l i b r i a shown i n Scheme I I I . The s t r u c t u r e o f 11 i s c o n f i r m e d b y p r e p a r a t i o n and c h a r a c t e r i z a t i o n o f t h e a n a l o ­ gous s t a b l e BF4"" s a l t . D e p r o t o n a t i o n o f 1Ό b y NaH i n THF i s much f a s t e r than t h a t o f i t s para isomer. This deprotonation i s f o l ­ lowed b y b r o a d e n i n g , g r a d u a l u p f i e l d s h i f t and r e s h a r p e n i n g o f the P NMR s i g n a l f r o m 38.5 t o -31.0 ppm. The l a t t e r , somewhat b r o a d l i n e i s c o n s i s t e n t w i t h s t r u c t u r e 14 i n e q u i l i b r i u m w i t h a s m a l l c o n c e n t r a t i o n o f 13. 3 1

Scheme I I I

The e q u i l i b r a t i n g 14 and 13^ r e a c t s u r p r i s i n g l y f a s t with CH3I, g i v i n g ether L5 as the s o l e product. The para isomer o f 13 does not r e a c t with CH3I i n THF a t room temperature during 24 hours. The e x t r a o r d i n a r y r a p i d formation of 15, presumably from 13, may r e s u l t from the increased r e a c t i v i t y of 13 enabled by i n t r a m o l e c u l a r s o l v a t i o n of the metal by the phosphine oxide oxygen. A l t e r n a t i v e mechanisms, such as a methoxyphosphorane intermediate, cannot be r u l e d out a t t h i s stage.

Literature Cited 1. Westheimer, F.H. Acc. Chem. Res. 1968, 1, 70. 2. Segall, Y . ; Granoth I. J . Am. Chem. Soc. 1978, 100, 5130. 3. Granoth, I.; Martin, J.C. J . Am. Chem. Soc. 1979, 101, 4618. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

438

4. 5. 6. 7. 8. 9. 10. 11. 12.

PHOSPHORUS

CHEMISTRY

Granoth, I.; Martin, J.C. J . Am. Chem. Soc. 1978, 100,5229. Munoz, Α.; Garrigues, B; Koenig, M. J.C.S. Chem. Comm. 1978, 219. Gallagher, M.; Munoz, Α.; Gence, G.; Koenig, M. J.C.S. Chem. Comm. 1976, 321. Ramirez, F . ; Nowakowsky, M; Marecek, J . F . J . Am. Chem.Soc. 1977, 99, 4515. Granoth, I.; Martin, J.C. J . Am. Chem. Soc. 1979, 101, 4623. Garrigues, B.; Koenig, M.; Munoz, A. Tetrahedron Lett. 1979, 4205. Burgada, R. Bull. Soc. Chim. France 1975, 407. Grim, S.O.; Yankowsky, A.W. Phosphorus and Sulfur 1977, 3, 191. Martin, J . C . ; Perozzi 3155.

RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

90 Selectivity in Reactions of Tricyclic Phosphatranes D. V A N A K E N , I. I. M E R K E L B A C H , J . H . H . H A M E R L I N C K , H. M . BUCK

P. S C H I P P E R , and

Eindhoven University of Technology, Department of Organic Chemistry, The Netherlands

Five-coordinated phosphoru compound know t adopt th trigonal bipyramidal (TBP positions are preferre y g groups, electron-donating groups are situated in equatorial positions (1). In addition, the apical bonds are longer and weaker than the equatorial bonds originating apical entry and departure of groups (phosphorylation) (2). Little attention has been paid to reactions in which external nucleophiles discriminate between pseudo­ -equatorial and pseudo-apical carbon atoms in a TBP configuration. The observation of such selective reactions is hampered by the occurrence of pseudo-rotation which brings about ligand exchange in the TBP (3). In order to obtain a definite answer with respect to equatorial vs. apical reactivity for nucleophiles we have syn­ thesized the rigid tricyclic phosphatranes 1-4 in which a transannular Ν -> Ρ bond brings phosphorus in a TBP configuration. Previously the characterization of the related compound 5 was published by Verkade et al. (4a). +

[RXP(OCH CH )3N] BF ~ 1 R = Me; X = 0 2 R = Et; X = 0 3 R = Me; X « S 4 R = Et; X = S 2

2

4

[HP(OCHCH)3N] BF " 5 2

2

4

The molecular constraint which precludes ligand exchange unambi­ guously ensures that the tricyclic compounds undergo nucleophilic attack exclusively at the pseudo-equatorial carbon atom, irrespective of the nature of the carbon atom situated in the apical ligand of the TBP. The compounds 1-4 were obtained by alkylation of the chalcogen atom of the corresponding bicyclic (thio)phosphate, 6 and 7, with trialkyloxonium tetrafluoroborate at -78 °C (5). X « P(OCH CH ) N 6 X=0 7 X= S 2

2 3

0097-6156/81/0171-0439505.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

440

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A l l experimental evidence i n d i c a t e s t h a t the s t r u c t u r e of the 0(S) a l k y l a t e d compounds i s a t r i c y c l i c c a g e ( 4 b ) . I n s o l u t i o n NMR c o n ­ f i r m s t h e p r e s e n c e o f a Ν -> Ρ bond ( 4 b ) . To v e r i f y t h e g e o m e t r y , t h e s t r u c t u r e o f 4 was d e t e r m i n e d c r y s t a l l o g r a p h i c a l l y . The c o n ­ f i g u r a t i o n o f p h o s p h o r u s i s i n d e e d TBP w i t h O-P-0 a n g l e s n e a r 120 , 0-P-N a n g l e s o f 85-87°, and 0-P-S a n g l e s o f 94-95°. The S-P-N a n g l e i s 178°. The N-P bond l e n g t h i s 2.05 I w h i c h i s o n l y s l i g h t l y l o n g e r t h a n t h e c o r r e s p o n d i n g d i s t a n c e ο f 1.99 8 f o u n d i n 5 ( 4 a ) . W i t h aqueous OH"", compounds 1-4 r e a c t e x c l u s i v e l y a t t h e p s e u d o e q u a t o r i a l c a r b o n atom l e a d i n g t o t h e m o n o c y c l i c p r o d u c t s 8-11. RXP(:0)(OCH CH )2NCH2CH OH 8 R = Me; X = 0 9 R = Et; X 10 R » Me; X 11 R = Et; X = S 2

2

2

I n a l l p r o d u c t s t h e 31p c o u p l i n g s show t h a t t h e bond o f t h e exoc y c l i c g r o u p l i n k e d t o p h o s p h o r u s i s p r e s e r v e d i n 8, J ( P 0 C H 3 ) » 11 Hz and i n 10, J(PSCH3) = 16 Hz. I n o u r o p i n i o n , t h e preference for pseudo-equatorial n u c l e o p h i l i c a t t a c k i s an i n t r i n s i c p r o p e r t y o f t h e e l e c t r o n i c c o n f i g u r a t i o n o f t h e TBP. The dp π bond (Ρ = 0 ) , w h i c h i s f o r m e d i n t h e r e a c t i o n i s a l r e a d y d e v e l o p e d t o some e x t e n t f o r t h e e q u a t o r i a l o x y g e n atoms i n t h e TBP o w i n g t o b a c k d o n a t i o n ( 1 ) . As a r e s u l t , some e l e c t r o n d e n s i t y i s t r a n s f e r r e d from the p s e u d o - e q u a t o r i a l c a r b o n atoms t o p h o s p h o r u s , r e n d e r i n g them more a c c e p t a b l e f o r n u c l e o p h i l i c a t t a c k . S i n c e f i v e c o o r d i n a t i o n i s v e r y w i d e - s p r e a d f o r g r o u p I V and V e l e m e n t s as w e l l as f o r t r a n s i t i o n m e t a l s , o u r model f o r pseudo-equatorial a t t a c k of n u c l e o p h i l e s might have a g e n e r a l i z e d f e a t u r e . I n a d d i t i o n , we w i l l p r e s e n t t h e m e c h a n i s t i c a s p e c t s c o n c e r n i n g t h e e l e c t r o n - e n t r y on f o u r - c o o r d i n a t e d p h o s p h o r u s compounds. T h e r e a r e i n d i c a t i o n s p r o m o t i n g t h e c o n c e p t t h a t a TBP i s i n v o l v e d w i t h t h e odd e l e c t r o n i n an e q u a t o r i a l p o s i t i o n . T h i s p r e s u m p t i o n i s b a s e d on t h e t e m p e r a t u r e - d e p e n d e n t ESR s p e c t r a o f t h e r a d i c a l s d e r i v e d f r o m 5. X - i r r a d i a t i o n o f a s i n g l e c r y s t a l o f 5 a t l i q u i d n i t r o g e n t e m p e r a t u r e (77 K) y i e l d s t h e s p e c t r u m o f r a d i c a l 13 e x c l u s i v e l y w i t h ap// = 1120 G, a p i = 930 G, w h i l e , ^ N s p l i t t i n g i s n o t r e s o l v e d . From t h e s e v a l u e s one c a l c u l a t e s a p - 993 G, i n d i c a t i n g t h e p h o s p h o r u s 3s s p i n d e n s i t y i s 0.27, w h i l e t h e a n i s o ­ t r o p i c c o n t r i b u t i o n p l a c e s 0.61 o f t h e s p i n d e n s i t y i n i t s 3p o r b i t a l , g i v i n g a t o t a l s p i n d e n s i t y o f 0.88 on p h o s p h o r u s . R o t a t i o n on t h e c r y s t a l l o g r a p h i c c - a x i s shows two o r i e n t a t i o n s w i t h an a n g l e b e t w e e n t h e i r ap//components o f 70°. R a i s i n g t h e t e m p e r a t u r e , t h e s e s i g n a l s d i s a p p e a r i r r e v e r s i b l y a t 193 K, and t h o s e o f 12 become a p p a r e n t ( 6 ) . A g a i n on r o t a t i o n two o r i e n t a t i o n s a r e p r e s e n t w h i c h a r e p e r p e n d i c u l a r . The a n i s o t r o p i c p h o s p h o r u s c o u p l i n g c o n s t a n t s ap// = 888 G, a p i = 753 G, i n d i c a t e a s p i n d e n s i t y o f 0.21 i n t h e p h o s p h o r u s 3s o r b i t a l and 0.43 i n i t s 3p o r b i t a l . An a d d i t i o n a l h y p e r f i n e c o u p l i n g i s o b s e r v e d due t o l ^ N , a = 22 G, w h i c h v a l u e i s n e a r l y i s o t r o p i c , i n d i c a t i n g a s p i n l s o

N

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

90.

VAN AKEN E T A L .

Reactions

X - ray

of

Tricyclic

Phosphatranes

Δ 193 Κ

77 Κ

5a

13

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

441

442

PHOSPHORUS

CHEMISTRY

d e n s i t y o f 0.05 i n t h e 2s o r b i t a l o f n i t r o g e n . I n t h e p l a n e p e r p e n d i c u l a r t o t h e c r y s t a l mounting a x i s ( c - a x i s ) the d i r e c t i o n s o f ap // o f 12 a n d 13 d i f f e r 35° o r t h e c o m p l e m e n t a r y a n g l e o f 55° w h i c h c a n n o t be a s s i g n e d u n i q u e l y , due t o t h e p r e s e n c e o f two o r i e n t a t i o n s f o r b o t h r a d i c a l s i n t h e u n i t c e l l ( 4 a ) . The i r r e ­ v e r s i b l e a r r a n g e m e n t o f 13 t o 12 a t h i g h e r t e m p e r a t u r e s e x h i b i t s t h e l a t t e r s p e c i e s a s t h e r m o d y n a m i c a l l y more s t a b l e . T h i s may be c o n c e i v a b l e on t h e b a s i s o f r e l e a s e o f r i n g s t r a i n by t h e f i v e membered r i n g i n s t r u c t u r e 13 w h i c h s p a n s two e q u a t o r i a l p o s i t i o n s . However, t h e d r i v i n g f o r c e f o r t h e i n t e r m e d i a t e f o r m a t i o n o f s t r u c t u r e 13 i s l e s s o b v i o u s . I t s g e o m e t r y c a n o n l y b e f o r m e d p r i o r t o P-H bond s c i s s i o n 5 -*· 5 a s i n c e a t t h e r a d i c a l s t a g e o n l y t h e r e v e r s e r e a c t i o n was o b s e r v e d . A p p a r e n t l y , d u r i n g X - i r r a d i a t i o n 5 a b s o r b s e n e r g y i n a p h o t o c h e m i c a l way t o p r o d u c e 5 a i n t h e excited state. Subsequently with retention of configuratio may be u n d e r s t o o d o n t h e b a s i s o f b a l a n c i n g e l e c t r o n i c e n e r g y v e r s u s s t r a i n e n e r g y . A p p a r e n t l y , s t r u c t u r e 5a w i t h t h e h y d r o g e n i n an e q u a t o r i a l p o s i t i o n i s e l e c t r o n i c a l l y favoured over 5 w i t h hydrogen i n an a p i c a l p o s i t i o n . I n c o n t r a s t , t h e s t r a i n energy i n 5a i s e n h a n c e d w i t h r e s p e c t t o t h a t o f 5. The l a t t e r f a c t o r may be l e s s i m p o r t a n t f o r 5a i n t h e e x c i t e d s t a t e , s i n c e i n t h e e x c i t e d s t a t e t h e bond l e n g t h s a r e i n c r e a s e d . T h e r e f o r e , i n t h i s p a r t i c u l a r s i t u a t i o n t h e e l e c t r o n i c f a c t o r h a s become d o m i n a n t . I n t h i s way t h e i r r e v e r s i b l e r e t r o - a r r a n g e m e n t o f 13 t o 12 i s a l s o c o n s i s t e n t . These experiments s t r o n g l y suggest t h a t t h e i n i t i a l s t a t e f o r t h e capture o f an e l e c t r o n by a f o u r - c o o r d i n a t e d phos­ p h o r u s may l e a d t o a TBP c o n f i g u r a t i o n v i a a n e q u a t o r i a l e n t r y o f the e l e c t r o n . The a u t h o r s t h a n k D r . J . C . S c h o o n e , U n i v e r s i t y o f U t r e c h t , The Netherlands, f o r c o l l e c t i n g the X-ray data. T h i s w o r k was s u p p o r t e d b y t h e N e t h e r l a n d s F o u n d a t i o n f o r C h e m i c a l R e s e a r c h (SON) w i t h f i n a n c i a l a i d f r o m t h e N e t h e r l a n d s O r g a n i z a t i o n f o r t h e Advancement o f P u r e R e s e a r c h (ZWO).

Literature Cited 1. Muetterties, E . L . ; Schunn, R.A. Quart. Rev. Chem. Soc. 1966, 20, 245. For a review, see: Luckenbach, R. "Dynamic Stereo­ chemistry of Penta-coordinated Phosphorus and Related Elements"; Thieme, G., Stuttgart, 1973. 2. Marquarding, D.; Ramirez, F . ; Ugi, I.; Gillespie, P. Angew. Chem. 1973, 85, 99. 3. Ugi, I.; Ramirez, F. Chem. Brit. 1972, 8, 198; Musher, J . I . J. Chem. Educ. 1974, 51, 94. 4. a. Clardy, J . C . ; Milbrath, D.S.; Springer, J . P . ; Verkade, J.G. J. Am. Chem. Soc. 1976, 98, 623. b. Milbrath, D.S.; Verkade, J.G. ibid. 1977, 99, 6607. 5. Murray, M.; Schmutzler, R.; Gründemann, E . ; Teichmann, H. J. Chem. Soc. (B) 1971, 1714. 6. Hamerlinck, J.H.H.; Schipper, P.; Buck, H.M. J. Am. Chem. Soc. 1980, 102, 5679. RECEIVED

June 30, 1981. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

91 The Perfluoropinacolyl Group: A Stabilizing Substituent for Unusual Phosphites and Phosphoranes GERD-VOLKER RÖSCHENTHALER, and RAINER BOHLEN Fachbereich 3 der Universität, 28 Bremen 33, FRG WERNER STORZER Lehrstuhl Β für Anorganische Chemie der Technischen Universität, 33 Braunschweig, FRG

The perfluoropinacolyl moietyOC(CF3)2C(CF3)2Ostabilizes higher valence states of main group elements (1) because of its high group electronegativity and bidentate character. The inves­ tigations of Ramirez, Trippett, and Knunyants show that pentacovalent phosphorus compounds containing this grouping are readi­ ly obtained by oxidative cyclisation reacting phosphorus(III) compounds with hexafluoroacetone. We were successful in synthe­ sizing fluorophosphoranes in a similar manner (2, 3):

Two fluorines attached to phosphorus instead of the perfluoro­ pinacolyl moiety would cause rapid decomposition. These findings prompted us to try the synthesis of phosphites, cyclic and bicyclic phosphoranes by a step by step procedure using dilithium perfluoropinacolate 1 and phosphorus halogenides as starting materials:

0097-6156/81/0171-0443$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

444

The chlorophosphite 3 is a precursor f o r s e v e r a l s u b s t i ­ tution r e a c t i o n s y i e l d i n g s u r p r i s i n g l y s t a b l e phosphorus(III) compounds (Scheme 1):

Scheme 1 The phosphites 3 and 4 are o x i d i z e d by c h l o r i n e and bromine to f u r n i s h s t a b l e covalent phosphoranes. No Arbuzov r e a c t i o n was observed. The trichlorophosphorane 5 can be reacted w i t h 1 again to form a spirophosphorane 7 which is hydrolyzed without r i n g cleavage to g i v e an extremely s t a b l e hydroxyphosphorane or a phosphoraneoxide a n i o n :

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

91.

ROSCHENTHALER

E TAL.

The Perfluoropinacolyl

445

Group

Aminophosphites are t r a n s f e r r e d t o aminospirophosphoranes v i a a s i m i l a r r e a c t i o n route: 1 C F) 3'2

ClR

2

N

\ ~>(CF ) Q

Cl •R N-P| 2

3

!

0

(CF

2

9 X c F3J' 2

_

-2LiCI

0y ^ X

{C

3 2

1CF )

/Ci )2

[/O

2

\ Q

>(CF )

0

3

1CF )

]

32

3

2

2

A n i t r o g e n - b r i d g e d d i p h o s p h o r a n e i s o b t a i n e d by r e a c t i n g t h e p h o s p h i t e p r e c u r s o r w i t h c h l o r i n e The d i p h o s p h o r a n e decomposes s l o w l y t o form 5 and a

|. Me

Cl Cl I/CICI\I ,0-P. .P-0 ^ I ^ N ^ I >(CF )

ci,

(CF )2< ;/ V/ 3)2 0

3

(CF ^ 3

XN

CF

HF ) 3

3

(Cr ) 3

Me

32 ;

2

2

r

O

X

p

/

(CF ) 3

2

2

Me I Cl i NN> i / • Ο­ ΙΟ F,) 3'2 X

i

y i ^ N (CFo) 3'2 Cl 1 Me 7

3

V

0-i(CF ) 3

2

3

2

A v e r y i n t e r e s t i n g c h e m i s t r y d e v e l o p s from t h e aminop h o s p h i t e J3 h a v i n g a H^N g r o u p bonded t o p h o s p h o r u s , t h e f i r s t s t a b l e species o f that type, which i s synthesized by r e a c t i n g 3^ w i t h l i t h i u m a m i d e . Compound e a s i l y adds h y d r o g e n f l u o r i d e to form a aminofluorohydridophosphorane. C h l o r i n e y i e l d s a d i c h l o r o p h o s p h o r a n e _9 w h i c h decomposes upon h e a t i n g t o g i v e a c y c l i c p h o s p h a z e n e . S u b s t i t u t i o n o f t h e two c h l o r i n e s i n compound 9_ b y t h e p e r f l u o r o p i n a c o l y l g r o u p i n g y i e l d s a a m i n o s p i r o s y s t e m . Two r e m a r k a b l e compounds a r e f o u n d d u r i n g t h e r e a c t i o n o f 8^ w i t h ammonium p e r f l u o r o p i n a c o l a t e a n d h e x a f l u o r o a c e t o n e . I n t h e f i r s t case a hydridospirophosphorane, i n t h e l a t t e r a phosphorane c o n t a i n i n g a f o u r a n d f i v e membered r i n g c a n be i s o l a t e d ( S c h e m e 2).

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS

446

CHEMISTRY

Scheme 2 Deutsche Forschungsgemeinschaft i s thanked f o r f i n a n c i a l support, Professor Schmutzler f o r access t o research f a c i l i t i e s , and D a i k i n Company, O s a k a , J a p a n f o r t h e g e n e r o u s g i f t o f h e x a fluoroacetone.

1. 2. 3.

Allen, M.; Janzen, A. F . ; Willis, C. J . Can. J . Chem. 1968, 46, 3671. Gibson, J . Α.; Röschenthaler, G.-V.; Schmutzler, R. J . Chem. Soc. Dalton Trans. 1975, 918. Röschenthaler, G.-V.; Gibson, J . Α.; Schmutzler, R. Chem. Ber. 1977, 110, 611.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

92 Tartaric Acid in Phosphorus Chemistry: Phosphor Emetics and Oligomers A. MUNOZ, L. LAMANDÉ, M. KOENIG, and R. WOLF E R A N° 926 Associée au CNRS, Laboratoire des Hétérocyeles du Phosphore et de Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse, France

l'Azote,

The complex of tartaric acid and antimony (emetic) was des­ cribed three centuries ago Nevertheless th structur f thi compound has been elucidate diffraction (1). In fact, emetic presents a binuclear cyclic structure. Many authors mentioned similar complex with transition metals (vanadium (2), chromium (3)) or metalloids (arsenic (4), bismuth (5)). Emetic with phosphorus was not mentioned. Neverthe­ less, tartaric acid or alkyl tartrates has been utilized in phos­ phorus chemistry : tartaric acid reacts with trialkyl phosphites giving heterocyclic phosphites (6). Starting from alkyl tartra­ tes, we prepared spirophosphoranes with a P-H bond and sixcoordinated compounds (7). With unprotected tartaric acid, many possibilities appear : condensation as a diol, as a di(α-hydroxyacid), or even as a β-hydroxyacid. In fact, natural tartaric acid (R,R) reacts easily at room temperature with phosphorus trichloride. The main products of the reaction are spirophosphoranes with a P-H bond formed from the α-hydroxyacid linkage (scheme (A)).

We isolated two kinds of compounds : - After six hours (or less) of condensation, we obtained a white powder, soluble in THF, whose nmr spectrum and elemental analysis are consistent with the oligomer 1a. - When condensation time is higher than six hours, we isola­ ted a white powder insoluble in THF, whose spectrum, elemental analysis and molecular weight are consistent with the cyclic dimer 2a. 0097-6156/81/0171-0447S05.00/0 SOCIETY LIBRARY

1151 16th S i N. if. WwWAflton, 0. C. 20038

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

448

PHOSPHORUS

HO-CO

Co-Ox, ? /O-CO

CO-OH

-O-CO

CO-O

-O-CH

~" -CH-O"

CHEMISTRY

f

v

x

,Ο,ΙΤΗΤ

,2 THF HO-CH

•CH-σ

O-CH n—CH-OH

la

λ

/

: 2 ^ 6

N

2a

S t a r t i n g w i t h t h e s e compounds, we s y n t h e t i s e d t h e c o r r e s p o n ­ d i n g o l i g o m e r o r d i m e r h y d r o x y p h o s p h o r a n e s and a d d u c t s w i t h a n h e x a c o o r d i n a t e d p h o s p h o r u s atom, a c c o r d i n g t o r e a c t i o n s (B) and (C). OH...DMF -SMe -O-CO CO-0, ι -O-CO CO-Ov -1 ,CH„ ~DMF ι ι ΝΑΊ -O-CH; — C H - C T ^ 2

1,2a

η NEt

η NEt,

3

(B) -O-CO ι I l-O-CH

(C) HNEt' CO-0, /

J

>/Α,

I CH-O /\ x

V i n

-O-CO

0~" HNEt CO-Ov 1 Λ

1 -O-CH

I X CH-(T

3 : η = 2

1 x

1,2b' #

f o r oligomers terminal omitted.

groups

On t h e o t h e r h a n d , c o n d e n s e d s p i r o p h o s p h o r a n e s la_ a n d 2 a a r e d e p r o t o n a t e d , u n d e r m i l d c o n d i t i o n s , by t r i e t h y 1 a m i n e , g i v i n g a n e q u i l i b r i u m b e t w e e n p h o s p h o r a n i d e and p h o s p h i t e a n i o n s , q u i t e s i m i l a r t o t h a t observed p r e v i o u s l y w i t h monomolecular phosphora­ nes (scheme (D)) ( 8 ) . u

HNEt.

Ν

-O-CO -O-CO

CO-0

-O-CH

CH-0 1,2a

ι

1

+ η

CO-0

NEt. -O-CH-

JH-O

χ

X

(D) -O-CO

CO-0

HNEt.

-O-CH

(L-0- -PI

J

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

92.

MUNOZ E T A L .

Tartaric

Acid

in Phosphorus

Chemistry

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

449

450

PHOSPHORUS CHEMISTRY

Figure 2.

Dimers 2a and 2b.

Figure 3.

Hexaeoordinated

adduct 3.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

92.

MUNOZ ET AL.

Tartaric

Acid

in

Phosphorus

Chemistry

451

A n a l y s i s o f nmr s p e c t r a a l l o w e d us t o d e t e r m i n e t h e a b s o l u t e c o n f i g u r a t i o n o f t h e p h o s p h o r u s atom o f p e n t a c o - o r d i n a t e d com­ pounds l a , 2a and l b , 2b. P r o t o n s P-0-CH-CH-O-P and e x o c y c l i c s u b s t i t u e n t s P-H and P-0 Χ (X = H...DMF, HNEt^j) a r e i n a c i s p o s i t i o n . The more l i k e l y s t r u c t u r e o f o l i g o m e r s l a and Lb i s a s e q u e n c e o f TBP drawn up as h e l i x ( f i g . 1 ) , w h i l e d i m e r s 2ja and 2b s h o u l d p r e ­ s e n t an e m e t i c s t r u c t u r e w i t h a p e n t a c o - o r d i n a t e d p h o s p h o r u s atom ( f i g . 2 ) . A l l t h e s e compounds m a n i f e s t s t r o n g o p t i c a l a c t i v i t y . These r e s u l t s complete t h e c h e m i s t r y o f t h e t a r t a r i c a c i d through elements o f p e r i o d i c c l a s s i f i c a t i o n . I f adducts between p h o s p h o r u s and t a r t a r i c a c i d have b e e n l a s t l y d i s c o v e r e d , t h e y o f f e r , i n r e t u r n , a l a r g e r c o - o r d i n a t i o n v a r i e t y than emetics which e x h i b i t e x c l u s i v e l to n o t i c e that r e a l phosphoru i s r a t h e r u n s t a b l e i n c o n t r a s t w i t h t h e a r s e n i c o r a n t i m o n y homo l o g u e s , w h i l e p e n t a c o - o r d i n a t e d o r s i x c o - o r d i n a t e d compounds, w h i c h a r e s t a b l e , a r e unknown f o r t h e s e m e t a l l o i d s . Concerning phosphorus c h e m i s t r y , t h e s y n t h e s i s o f condensed compounds, o p t i c a l l y a c t i v e , w i t h p e n t a c o - o r d i n a t e d p h o s p h o r u s a d o p t i n g hélicoïdal o r m a c r o c y c l i c s t r u c t u r e s , r e p r e s e n t s , i n o u r o p i n i o n , s i g n i f i c a n t p r o g r e s s . T h u s , h y d r o x y p h o s p h o r a n e s l b , 2b a r e tautomers o f hydroxyphosphoric e s t e r s , s i m i l a r t o p h o s p h o r i c e s t e r s o f n a t u r a l p o l y h y d r o x y l a t e d compounds.

LITERATURE CITED

1. KIOSSE, G.A. ; GOLOVASTIKOV, N.I.; BELOV, N.V. Soviet. Phys. Doklady. 1964, 9, 198. 2. ORTEGA, R.B.; CAMPANA, C.F.; TAPSCOTT, R.E. Acta Cryst. 1980, Β 36, 1786, and references there in. 3. KAIZAKI, S.; HIDAKA, J.; SHIMURAI, Y. Bull. Soc. Chim. Jap. 1967, 40, 2207 4. SCHLESSINGER, G.; Inorg. Synth. 1970, 12, 267, and references there in. 5. ROSENHEIM, A.; VOGELSANG, W. Z. Anorg. Chem. 1906, 48, 205 6. SAMITOV, YU.YU.; MUSINA, A.A.; GURARII, L . I . ; MUKMENEV, E.T.; ARBUSOV, B.A. Bull. Acad. Sci. USSR 1975, 24, 1407, and refe­ rences there in. 7. KOENIG, M.; MUNOZ, A.; GARRIGUES, Β.; WOLF, R. Phosphorus and Sulfur 1979, 6, 435 8. GARRIGUES, Β.; KOENIG, M.; MUNOZ, A. Tetrahedron Letters 1979, 4205 RECEIVED

July 7,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

93 Nucleophilic Substitution at Pentacoordinated Phosphorus Addition-Elimination Mechanism A. SKOWROŃSKA, J. STANEK-GWARA, and M. NOWAKOWSKI Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, 90-362 Łódź, Boczna 5, Poland

There is a growing realization that hexacoordinate phosphorus species may play an importan (1-8). The intriguing proble coordinate compounds are involved as intermediates in the substitution at pentacoordinate phosphorus atom s t i l l remains unresolved. Recently we undertook the study of nucleophilic displacement in chlorophosphoranes containing one or two catechol bidentate ligands with trimethylsilyl azide or tetraalkylammonium azide (9). We found that this process proceeds via individually distinct hexacoordinate species. The present investigation was undertaken in an effort to generalize the above findings. Low temperature 31p NMR spectroscopy has been used for the detection and identification of hexa­ coordinate compounds and for the elucidation of subsequent reactions. Reaction between hexafluoroisopropoxyspirophosphorane 1 and 1,2 mole of phenol in the presence of triethylamine in methylene chloride solution at -80°C led to the hexacoordinate adduct 2 accompanied by some phenoxyspirophosphorane 4 and traces of compounds 5. After warming of the reaction mixture to -70°C the amounts of 2 and 4 increased to 76% and 20% respectively. At -40°C the hexacoordi nate adduct _3 appeared and the amount of _4 decreased in favour of 5. At room temperature the spect rum i ndi ca ted hexacoordi nate adducts 3 and 6» as mai η products . The f ul 1 pi cture of the above reaction i s presented in Scheme I . The chemi cal shi fts related to 85% phosphori c aci d of compounds 2, A> Σ> k ' hi ghf i el d range of -1 Ok ppm to -109 ppm whi ch must be associated with hexacoordi nate phosphorus derivatives. The st ruct ure of hexacoo rd i nate an ions _2 and J> i s in addi t ion supported by the doublet due to the spli tt i ng of phosphorus by the methi ne proton of Rf = CH(CF3) 2 group. There i s no i ndi cation for formati on of a hexacoordi nate structure contai ni ng two ORf groups when an excess of phenol i s present. Among two pa i rs of hexacoordi nate i someri c structures _2, _3 and j>, _6, the 2 and j> seems to be ki net i ca 11 y and _3, 6^ thermodynami cal ly control led. a

r

e

n

t

n

e

0097-6156/81/0171-045 3$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

454

PHOSPHORUS

Scheme

δ:

- 1 0 2 . 9 ppm t

6:

OR^ ^

I

- 1 0 4 . 5 ppm t

0R + PhOH + E t , Ν 3

,

f

1

- 2 8 . 8 ppm d

c

PhO~

6:

d^

χ

=

e

Ρ

l ppm

R

-106 ppm d

^sJ^OPh

+

1

l δ:

- 1 0 6 . 5 ppm

δ:

- 1 0 8 . 5 ppm

• GOO®

X f

δ:

OPh

i δ : -30.4

n

2

-104 ppm d

OPh

R

ι

/ ,

1 δ:

CHEMISTRY

( C F ) CH 3

2

M = Et^ΝΗ On t h e b a s i s o f t h e work o f R a m i r e z (10) , T r i p p e t t (11) and D i l l o n (12) t h e more s t a b l e h e x a c o o r d i n a t e i s o m e r s a r e o f c i ss t r u c t u r e and c o n s e q u e n t l y we a s s i g n e d t h e s t r u c t u r e s o f 2_, j> as t r a n s and t h o s e o f 3, 6^ as c i s . T h e e l imi n a t i o n s t e p (c) 1 e a d i ng t o t h e p h o s p h o r a n e ¥ a l s o i n v o l v e s t h e 1 e s s s t a b l e i s o m e r 2. The r a t e o f e l i m i n a t i o n seems i n t h i s c a s e t o be h i g h e r t h a n t h a t o f i s o m e r i s a t i o n o f 2 ( r e a c t i o n b) i n t o t h e more s t a b l e h e x a c o o r d i n a t e a n i o n Ji ( b ) . The l a t t e r d o e s n o t u n d e r g o e l i m i n a t i o n t o J* u n d e r e x p e r i m e n t a l c o n d i t i o n s e m p l o y e d . T h e s e o b s e r v a t i o n s i n d i c a t e t h a t n u c l e o p h i 1 i c di s p l a c e m e n t a t p e n t a c o o r d i n a t e p h o s p h o r u s i n ]_ i m p l i e s a t r a n s - r e l a t i o n s h i ρ o f n u c l e o p h i 1 e t o

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

SKOWRONSKA

93.

ET AL.

Nucleophilic

455

Substitution

l e a v i n g group a n d , t h e r e f o r e , s h o u l d ρ roceed w i t h c o n f i g u r a t i o n a t the phosphorus atom.

in vers ion o f

A s s o c i a t i v e n u c l e o p h i 1 i c d i s p l a c e m e n t a t Ρ ( 5 ) has been o b s e r v e d in o t h e r r e a c t i o n s o f the phosphorane and n u c l e o p h i l e s d e s c r i bed i n Scheme I I . Scheme

A [ ;pr

II

A +

Β

^ =

Β 1

»it

/Ν

Β 12

1,9,J_0, A = R 0 ; f

3 1

P

NMR c h e m i c a l -108.5;

21

4,6,JM , A = PhO; Β = N shifts,

6 ppm: 6 - 1 0 8 . 1 ;

13

3

9 - 1 0 2 . 2 d ; J_0 - 1 0 7 . 9 d ;

_ 1 2 - 2 7 ; J_3 - 1 1 3 .

T r e a t m e n t o f s p i r o p h o s p h o r a n e J_ wi t h 1.1 e q u i v . o f t e t r a a l k y l ammoni urn a z i de i n CH2CI2 s o l u t i o n a t - 9 5 ° C g a v e t h e Ρ ( 6 ) t r a n s a d d u c t 9 a s a m a j ο r p r o d u c t (47%) , a c c o m p a n i e d by c i s - a d d u c t s J_0 ( 1 4 % ) , J_3 (10%) and u n c h a n g e d s p i r o p h o s p h o r a n e U A t - 2 0 ° C t h e amount o f J_0 i n c r e a s e d t o 8 2 % wi t h p a r a l l e i d e c r e a s e o f a d d u c t !9 (4%) a n d 1 d i s a p p e a r e d .

T h e 3"1p NMR s p e c t r u m o f a s o l ut i o n o f s p i r o p h o s p h o r a n e 4_ i n CH2CI2 , t r e a t e d a t - 9 5 ° wi t h t e t r a a l k y l a m m o n i urn a z i d e showed t h e p r e s e n c e o f P ( 6 ) c i s - a d d u c t s _M_ (55%) , J _ 3 (12%) , t r a c e s o f s p i r o ­ p h o s p h o r a n e J 2 . ( 4 % ) and u n c h a n g e d s p i r o p h o s p h o r a n e k. A t - 3 0 ° C t h e s p e c t r u m showed s i g n a l s due t o _Π ( 4 7 % ) , J_3 (25%) and 6 (23%) . Format i on o f h e x a c o o r d i n a t e an i o n 1 3 ρ r o v i de i n d i r e c t p r o o f f o r t h e e l i mi n a t i o n p r o c e s s c g i v i n g t h e p h o s p h o r a n e 12.

F u r t h e r s t u d i e s on phosphorane 1,4,15 brought o u t addi t i o n a l s i gn i f i c a n t î n f o r m a t i o n . T h e r e a c t i o n s o f j4 w i t h pheno 1 a n d 1 5 wi t h d i e t h y l p h o s p h o r i c a c i d i n t h e p r e s e n c e o f t r i e t h y l a m i n e i n C H C l 2 s o l u t i o n g i v e t h e o c t a e d r a l Ρ (6) a d d u c t s o f t r a n s c o n f i g u ­ r a t i o n s j>, _16. A d d u c t s _ 5 , J 6 , t h e on l y p r o d u c t s a t - 1 0 0 ° C , g r a d u a l l y r e a r r a n g e i n t o c i s - i somers 6^, YJ_ b e i n g t h e on l y s p e c i es a t - 5 0 ° C . When p o t a s s i urn h e x a f 1 u o r o i s o p r o p a n o l a t e was a l l o w e d t o r e a c t wi t h t h e p h o s p h o r a n e 1 i n t h e p r e s e n c e o f 18-crown e t h e r 2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

456

PHOSPHORUS CHEMISTRY

a t - 8 0 ° C , t h e f i r s t formed t r a n s - a d d u c t ]_ s l o w l y i s o m e r i s e s a t room t e m p e r a t u r e i n t o a d d u c t 8·. The * T NMR c h e m i c a l s h i f t s o f _5, 6^ a n d _7, S a r e v e r y c l o s e t o t h o s e o b s e r v e d i n t h e e x p e r i m e n t d e s c r i bed i n Scheme I. Scheme

Ρ

+A

III

^

4,

^

P^

A

l A J l

trans-5,7j6

cis-6,8j7

I, 5 , 6 , A = P h O ; 1 , 7 , 8 , P NMR c h e m i c a l s h i f t s , 6 p p m : 5 - 1 0 6 . 5 ; 6 - 1 0 8 . 5 ; 7. - 1 0 2 . 6 t , Jp. 16.1 t 0 , 4 8 H z ; 8 - 1 0 5 . 5 t , J - 1 7 . 0 9 t 0 , 4 8 H z ; Jj6 - 1 2 . 8 d , - 1 0 6 . 2 t , Jp-o-p 29 ± 2 . 4 4 H z ; 17 -13-75 d , - 1 1 4 . 7 t , J - o - P 22 + 2 . 4 4 H z . 3 1

H

P

H

P

F u r t h e r work i s r e q u i r e d t o g e n e r a l i s e

t h e above f i n d i n g s .

Literature Cited: 1. Trippett Stuart, Ed.; Organophosphorus Chemistry (Specialist Periodical Report); The Chemical Society, London, vol. 4-10, 1973-79, ch. 2. 2. Ramirez F., Tasaka Κ., Desai N.B., Smith C.P., J.Am.Chem.Soc., 1968, 90, 751. 3. Ramirez F . , Ugi I., Marquarding D., Angew.Chem. Int. Ed. Engl., 1973, 13, 91. 4. Kluger R., Covitz F . , Dennis Ε., Williams L.D., Westheimer F.H. J.Am.Chem.Soc., 1964, 91, 6066. 5. Archie W.C. J r . , Westheimer F.H., J.Am.Chem.Soc., 1973, 95, 5955. 6. Ramirez F . , Marecek J . F . , Tetrahedron Lett., 1977, 967. 7. Aksnes G., Eide A . I . , Phosphorus 1974, 4, 209. 8. Aksnes G., Khall F.Y., Majewski P . J . , Phosphorus and Sulfur 1977, 3, 157. 9. Skowrońska Α., Pakulski M., Michalski J., J.Am.Chem.Soc., 1979, 101, 1979. 10. Sarma R., Ramirez F., McKeever Β., Marecek J.F., Prasad V.A.V., Phosphorus and Sulfur, 1979, 5, 323. 11. Font Friede J.J.H.M., Trippett S., J.C.S.Chem.Comm., 1980, 157. 12. Dillon K.B., Platt A.W.G., Waddington T . C . , J.C.S. Chem.Comm., 1979, 889. RECEIVED

July 2, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

94 Metal Chelates of Aminoalkylphosphonic Acids Stabilities, Properties, and Reactions ARTHUR E. M A R T E L L Department of Chemistry, Texas A&M University, College Station, TX 77843

Stabilities Alkylphosphonate group ate hardness that may replac carboxylat group g agents such as nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), and diethylenetriaminepentaacetic acid (DTPA). The corresponding ligands nitrilotrimethylenephosphonic acid (NTP), 1, ethylenediaminetetraraethylenephosphonic acid (EDTP), 2, and diethylenetriaminepentamethylenephosphonic acid (DTPP), 3, form metal chelates that are generally more stable than those of the analogous aminopolycarboxylates. The stability constant data in Table I (1) for representative alkaline earth and transition metal chelates of these ligands show mixed effects. The alkaline earth NTP chelates are more stable than those of NTA, while the reverse is the case for EDTP and EDTA. For both NTP and EDTP, the transition metal chelates are considerably more stable than Table I Comparison of Stabilities of Metal Chelates of Aminopolyacetate and Aminopolymethyleneph osphonate Ligands* Log K+f Metal Ion Mg Ca

NTP 7.2

NTA

2+

7.5

2+

2+

Co Ni

2 +

6.39

EDTP 8.43 9.36

EDTA 8.83 10.61

14.4

10.38

17.11

16.26

5.47

11.1

11.50

16.38

18.52

Cu

2+

17.4

12.94

23.21

18.70

Zn

2+

16.4

10.66

18.76

16.44

* t = 25.0°C,

μ = 0.10 (KNO3);

+

HEDTP

HEDTA

5.62

8.2

16.29

17.5

-(n-2)]/[ 2+][L-n] Log K = [ML M

f

where HnL represents the ligand. 0097-6156/81/0171-0459$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

460

PHOSPHORUS

CHEMISTRY

those of the aminopolycarboxylate analogs, except for Ni(II), which shows a curious and thus far unexplained reversal. The metal chelates of hydroxyethylethylenediaminetriacetic acid (HEDTA) seem to be more stable than those of hydroxyethylethylenediaminetrimethylenephosphonic acid (HEDTP), 4, but the lack of data for the latter precludes a more complete comparison for these ligands. For metal ions of higher charge, the phosphonates are clearly superior to the corresponding aminoacetates (2). An ex­ ample of this effect may be found in the comparison of the stabil­ ities of the Fe(III) chelates of N,N -bis(o-hydroxybenzy^-NjN'ethylenediaminedimethylphosphonic acid (HBEDP0), 5, and the corresponding diacetic acid ligand N,N -bis(o-hydroxybenzyl)-N,N ethylenediaminediacetic acid (HBED) 6 Although th latte specifically designed t iron(III), the iron(III) ligan 4-5 orders of magnitude more stable. Although only qualitative evidence is generally available for the chelates of aminopolyalkylphosphonic acids of tripositive and tetrapositive metal ions, it appears that in such complexes phosphonate donor groups are increasingly more effective, relative to carboxylate donor groups, as the charge of the metal ions increase. The difference in stabilities of the metal chelates of ligands 1-6 and the corres­ ponding ligands containing aminoacetate functions are both enthalpic and entropie in origin (_2» 3>). The higher charge of the phosphonate group leads to increased mutual coulombic repulsion when more than one phosphonate donor is coordinated to a metal ion, an effect that is increasingly compensated for as the charge of the central metal ion increases. A related effect involves hydration energy of the free ligands that is lost on formation of the metal chelates, which is compensated for by the energy of co­ ordinate bond formation, which increases with the charge of the metal ion. The entropy effects resulting from the release of solvated water molecules from both the anion and cation favor metal chelate formation. This effect increases rapidly with the charge of the central metal ion. f

f

f

Insolubility of Protonated Chelates The usefulness of aminophosphonic acids as sequestering agents for highly charged metal ions is somewhat impaired by the strong tendencies of the metal chelates of these ligands to form highly protonted species that tend to precipitate in neutral or weakly acid solution. Thus metal chelates of the ligand EDTP in which the four phosphonate groups are coordinated to a metal ion, have four negative oxygen donors that are not coordinated to the metal. These chelates readily combine with hydrogen ions, forming protonated chelates of the type MH L(8-n-m)~ where m is the charge of the metal ion and η may vary from 1-4. The reduction of ionic charge and intermolecular hydrogen bonding resulting from n

?

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

MARTELL

94.

Metal

Chelates

of Amino alkyl phosphoric

461

Acids

e x t e n s i v e p r o t o n a t i o n tends t o induce p r e c i p i t a t i o n o f the m e t a l chelates. Thus t h e i r o n ( I I I ) c h e l a t e o f EDTP i s i n s o l u b l e i n t h e w e a k l y a c i d t o n e u t r a l pH r a n g e , w h i l e a t h i g h e r pH t h e c h e l a t e s p e c i e s become more s o l u b l e a s t h e r e s u l t o f p r o t o n n e u t r a l i z a t i o n and i n c r e a s e d n e g a t i v e c h a r g e o f t h e c o m p l e x . Thermal D e g r a d a t i o n i n S o l u t i o n Another problem encountered i n the i n d u s t r i a l a p p l i c a t i o n s o f aminopolymethylenephosphonic a c i d c h e l a t i n g agents i s t h e i r hydro­ l y t i c i n s t a b i l i t y a t h i g h t e m p e r a t u r e i n aqueous s o l u t i o n . I t has b e e n f o u n d ( 4 ) , f o r e x a m p l e , t h a t NTP decomposes a b o u t 100 t i m e s more r a p i d l y t h a n NTA a t t e m p e r a t u r e s above 200°C i n aqueous s o l u ­ tion. NMR e v i d e n c e i n d i c a t e aminomethylphosphonic a c i d 10, a s i n d i c a t e d b y t h e f o l l o w i n g r e a c t i o n scheme. T h i s type of h y d r o l y t i c i n s t a b i l i t y i s much d i f f e r e n t f r o m t h e d e c o m p o s i t i o n r o u t e o f NTA, w h i c h h a s b e e n f o u n d t o o c c u r t h r o u g h a d e c a r b o x y l a ­ t i o n p r o c e s s . The h i g h b a s i c i t y o f t h e NTP a n i o n w o u l d b e e x p e c t e d t o i n c r e a s e t h e t e n d e n c y t o w a r d h y d r o l y s i s by i n c r e a s i n g the p o p u l a t i o n o f p r o t o n a t e d s p e c i e s s u c h a s 7 a t h i g h pH.

0

° \ H

^ N t v

>—CH ~

II

0

-

^N—H

CH —Ρ—0 V L-

.P—CH

0

"(r

9

9

8

+

HOH

0 H0CH -P _ ^ 0

+

2

CH —Ρ—0 N L / 9

H 0 0 Η 0 Mκ " Κ ιl. P-CH -N - C H - P - 0 N

+

^

° \ H

2

2

i

Q

Î ~

ο

0

P—CH —NH 0

2

"o/

2

0

+

CH —P—0 0

\

κ

V

0'

11

Polyphosphates a s Ligands I t i s i n t e r e s t i n g t o n o t e t h a t condensed phosphate l i g a n d s s u c h a s t r i p o l y p h o s p h a t e ( T P P ) , ATP, a n d ADP c o n t a i n n e g a t i v e donor oxygens t h a t a r e h a r d e r bases than those o f t h e phosphonates, and h a v e c h a r a c t e r i s t i c a l l y d i f f e r e n t m e t a l i o n a f f i n i t i e s . The s t a b i l i t i e s o f the a l k a l i n e earth chelates o f these ligands are

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

462

PHOSPHORUS

CHEMISTRY

a c c o r d i n g l y h i g h e r r e l a t i v e t o those o f the t r a n s i t i o n metal ions than t h e r e l a t i v e s t a b i l i t i e s o f t h e phosphonates d e s c r i b e d i n T a b l e I . F o r example t h e s t a b i l i t y c o n s t a n t s o f t h e M g ( I I ) and C a ( I I ) c h e l a t e s o f TPP a r e 1 0 · and 1 0 * , r e s p e c t i v e l y , w h i l e those o f C o ( I I ) and N i ( I I ) a r e o n l y 1 0 * and 1 0 · , r e s p e c t i v e ­ ly. S i m i l a r l y , t h e s t a b i l i t y c o n s t a n t s o f t h e M g ( I I ) and C a ( I I ) c h e l a t e s o f ATP a r e 1 0 * · and 1 0 · , w h i l e t h o s e o f C o ( I I ) a n d N i ( I I ) a r e o n l y 10 and 1 0 * , r e s p e c t i v e l y . The r e l a t i v e s t a b i l i t i e s o f t h e M g ( I I ) and C a ( I I ) c h e l a t e s o f t h e s e l i g a n d s i s M g ^ > C a , which i s a r e v e r s a l of the order observed f o r the c o r r e s p o n d i n g c h e l a t e s o f t h e a m i n o p o l y c a r b o x y l a t e and a m i n o p o l y phosphonate l i g a n d s . 5

6 7

5

6

1

k

63

0 6

3

5

9 l +

2 0

6

7 5

7 7

0 2

z

Pyridoxal-Catalyzed

Dephosphonylatio

Because o f t h e i r w i d e s p r e a d o c c u r r e n c e biologica systems the p h o s p h o n a t e a n a l o g s o f n a t u r a l amino a c i d s s u c h a s aminom e t h y l p h o s p h o n i c a c i d ( A P ) , 2 - a m i n o e t h y l p h o s p h o n i c a c i d (ΑΕΡ), and 2-amino-3-phosphonopropionic a c i d (APP), t h e i r r e a c t i o n s a r e of i n t e r e s t a s models f o r b i o l o g i c a l p r o c e s s e s . These aminophosphoni c a c i d s form m e t a l c h e l a t e s h a v i n g s t r u c t u r e s analogous t o those of t h e c o r r e s p o n d i n g a m i n o c a r b o x y l i c a c i d s . They a l s o f o r m S c h i f f bases (7) w h i c h i n t h e form o f t h e i r d i p o l a r i o n s , o r i n t h e form o f t h e i r m e t a l c h e l a t e s , a r e more s t a b l e (7) t h a n t h o s e formed by the a n a l o g o u s a m i n o c a r b o x y l i c a c i d s ( g l y c i n e , β-alanine, and aspartic acids, respectively). The m e t a l c h e l a t e s o f t h e S c h i f f base o f APP have been f o u n d t o u n d e r g o an i n t e r e s t i n g a n d n o v e l dephosphonylation r e a c t i o n ( 8 ) , which required a p r i o r transamina­ t i o n step. The p r o d u c t s o f t h e r e a c t i o n a r e a l a n i n e a n d i n o r g a n i c phosphate, w h i l e the p y r i d o x a l i s regenerated, thus p r o v i d i n g the basis f o r a c a t a l y t i c process.

Literature Cited 1. 2. 3. 4. 5. 6. 7. 8.

Martell, Α. Ε.; Smith, R. M. "Critical Stability Constants", Vol.1, Plenum Press, New York, 1974. Martell, Α. Ε. Pure & Appld. Chem., 1978, 50, 813. Pitt, C. G.; Martell, A. E."Inorganic Chemistry in Biology and Medicine"; American Chemical Society, Washington, D.C., 1980 pp.279-312. Martell, Α. Ε.; Motekaitis, R. J.; Fried, A. R.; Wilson, J. S.; MacMillan, D. T. Can. J . Chem., 1975, 53, 3471. Smith, R. M.; Martell, Α. Ε. "Critical Stability Constants", Vol.4, Plenum Press, New York, 1976, p.63. Smith, R. M.; Martell, A. E. "Critical Stability Constants", Vol.2, Plenum Press, New York, 1975. Langohr, M.; Martell, A. E. J . Inorg. Nucl. Chem., 1978, 40, 149. Martell, Α. Ε.; Langohr, M. J.C.S. Chem. Commun., 1977, 342.

RECEIVED

June 30, 1981. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

95 3

Transition VIB Metal π-Complexes of λ and λ -Phosphorins and Some of Their Reactions 5

K. DIMROTH Fachbereich Chemie, Philipps-Universität, Hans-Meerwein-Strasse, D-3550 Marburg, FRG

3

In spite of the aromaticit f λ -phosphorins 1 (1) th che mistry of 1 is quite differen λ -phosphorin1a(3) i dies. Therefore Märkl and we have investigated the chemical reac­ tions of 2,4,6-trisubstituted λ -phosphorins such as 1b (4) and 1c. Two reasons are mainly responsible for the different chemical properties of pyridines and λ -phosphorins: i) The two coordinate nitrogen is more electronegative than the two coordinate phospho­ rus; i i ) In all λ -phosphorins phosphorus is the reactive moiety which partakes therefore in chemical reactions. Reason i) is the cause that phosphorins are electron rich aromatic heterocycles. This is proven by physical methods, e.g. by PE-spectra (5,6) and by reactions with M(CO) (M=Cr, Mo, W) which give rise to η π M(CO) complexes 2 (7), whereas in phenyl substituted pyridines the phenyl substituents are complexed (8). Point i i ) can be i l l u ­ strated by the reaction with nucleophiles. Whereas pyridines add the nucleophile to C-2 of the ring, λ -phosphorins add nucleophi­ les (Me", Ph", OMe") to the phosphorus atom, producing x^-phosphorin anions 3 which, by addition of electrophiles (Me , Et ) to the phosphorus atom, afford x -phosphorins 4 (9). C NMR spectroscopy clearly shows that x -phosphorins 4, containing also a planar he­ terocyclic ring (10), are phosphorus ylids with a delocalized ne­ gative charge in tïïe pentadienyl part of the ring (|1,12)^ The pyridine nitrogen atom easily adds hard (H , "Cïï ) and soft (Cr(CO)s, HgAc ) acids. In contrast x -phosphorins add soft acids only, giving P-complexes (V3>11)- Complexes of the type x phosphorin P+Hg(Ac) are important intermediates for the synthesis of 1,1-dialkoxy- and many other x -phosphorins (e.g. 4b) in the presence of nucleophiles (ROH, ArOH, RNH) in a redox process yielding Hg (15). Another important reaction of the x -phosphorins is the addition of two radicals (*NPh , -OR, ·01) to the phospho­ rus atom ( 16 Y7). The 1,1-substituents, especially in the 1,1-dichloro-x -gïïosphorins 4c, can be easily exchanged for many nucleophiles (Me , OR", SR",~T~, etc.). This leads to a large number of X -phosphorins 4 with varying 1,1-substituents at phosphorus. The remainder of the phosphorin ring is unaltered (17,2). 3

3

3

3

6

6

6

3

3

5

1 3

5

3

3

2

3

2

5

2

3

2

9

5

5

0097-6156/81/0171-0463$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

CHEMISTRY

95.

DIMROTH

Metal

^-Complexes

of

Phosphorins

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

465

466

PHOSPHORUS CHEMISTRY

B o a t - l i k e η π C r ( C 0 ) complexes 5 (18) are formed 0 9 , 2 0 ) by t r e a t i n g 2 , 4 , 6 - s u b s t i t u t e d X -phospïïorTns with C r ( C 0 ) . C NMR spectroscopy confirms a phosphorus y l i d s t r u c t u r e , and the C P c o u p l i n g constants o f the 1,1-substituents allow a determinat i o n o f t h e i r exo/endo c o n f i g u r a t i o n in agreement with X-ray anal y s i s (21), the l a r g e r s u b s t i t u e n t always being i n exo p o s i t i o n . x -Phospïïorin CrTCÔ) "complexes 5 and 1_ a l s o can b e " s y n t h e s i z e d _ from x -phosphorin C r ( C 0 ) complexes 2. Nucleophiles such as Me", E t " , P h " , 0 C H " , add to the exo p o s i t i o n a t t h e phosphorus atom g i v i n g anions 6 which add e l ê c t r o p h i l e s (Me , Et ) to the endo p o s i t i o n producing the same o r s t e r e o i s o m e r i c x -phosphorin C r ( C 0 ) complexes 5 or 7 (22,23). M i l d o x i d a t i o n of the x -phosphorin C r ( C 0 ) complexes aTTows regeneration of the x -phosphorins 4. The y l i d c h a r a c t e r o plexes again i s evident when one or both groups on phosphorus are CHR as one can a b s t r a c t a proton g i v i n g a c a r b a n i o n . Reaction with e l e c t r o p h i l e s ( e . g . D , CH , and RCHO) causes s i d e chain a d d i t i o n . No W i t t i g o l e f i n a t i o n i s found with aldehydes. Instead a 1(2*-hydroxy) product 9^ i s formed which can be dehydrated to the X -phosphorin d e r i v a t i v e 10. 5

6

3

5

1 T

6

1 3

3ÎL

5

3

3

3

3

+

5

5

3

5

3

2

3

5

Literature cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

Ashe III, A. J. J. Acc. Chem. Res. 1978, 11, 153. Dimroth, K. Top. Curr. Chem. 1973, 38, 1. Ashe III, A. J. J. Am. Chem. Soc. 1 9 7 1 , 93, 3293. Märkl, G. Angew. Chem. Engl. 1966, 5, 846. Oehling, H.; Schäfer, W.; Schweig, A. Angew. Chem. Engl. 1971, 10, 656. Batich, C.; Heilbronner, E . ; Hornung, V.; Ashe III, J. A.; Clark, D. T.; Cobley, U. T.; Kilcast, D.; Scalan, I. J. Am. Chem. Soc. 1973, 95, 928. Deberitz, J.; Nöth, H. Chem. Ber. 1970, 103, 2541. Deberitz, J.; Nöth, H. J. Organomet. Chem. 1973, 61, 271. Märkl, G.; Lieb, F . ; Merz, A. Angew. Chem. Engl. 1967, 6, 87. Thewalt, U. Angew. Chem. Engl. 1969, 8, 769. Bundgaard, T.; Jakobsen, H. J.; Dimroth, K.; Pohl, H. H. Tetrahedron Lett. 1974, 3179. Dimroth, K.; Berger, S.; Kaletsch, H. Phosphorus and Sulfur 1981 in press. Deberitz, J.; Nöth, H. Chem. Ber. 1973, 106, 2222. Kanter, H.; Dimroth, K. Tetrahedron Lett. 1975, 541. Dimroth, K.; Städe, W. Angew. Chem. Engl. 1968, 7, 881. Dimroth, K.; Hettche, A.; Kanter, H.; Städe, W. Tetrahedron Lett. 1972, 835. Kanter, H.; Mach, W.; Dimroth, K. Chem. Ber. 1977, 110, 395. Debaerdemaeker, T. Acta Crystallogr., Sect. Β 1979, 35, 1686. Lückoff, M.; Dimroth, Κ. Angew. Chem. Engl. 1976, 15, 503.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

95.

DIMROTH

Metal

π-Complexes

of

Phosphorins

467

20. Dimroth, K.; Lückoff, M.; Kaletsch, H. Phosphorus and Sulfur 1981 in press. 21. Dimroth, K.; Berger, S.; Kaletsch, H. Phosphorus and Sulfur 1981 in press. 22. Dimroth, K.; Kaletsch, H. Polish J . Chem. 1981, 6 in press. 23. Dimroth, K.; Kaletsch, H. Angew. Chem. 1981 in press. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

96 Synthesis of Transition Metal Phosphoranides Conversion o f Bicyclic Phosphoranes into Phosphoranides and Phosphane A d d u c t s with Transition M e t a l Derivatives J. G. RIESS, F. JEANNEAUX, P. VIERLING, and J. WACHTER1 Laboratoire de Chimie Minérale Moléculaire (ERA 473), Université de Nice, 06034 Nice, France A. GRAND Laboratoire de Chimie, Département de Recherches Fondamentales, Centre d'Etudes Nucléaires de Grenoble 85X, 3804

Phosphoranide anions 1 - i.e. species based on pentacoordinated phosphorus having a lone pair as one of its five substituents were proposed by Wittig and Maercker as early as 1967, to act as intermediates or transition states in nucleophilic substitutions at tricoordinated phosphorus (1). Shortly afterwards in 1969, Hellwinkel brought indirect evidence for the formation of phospho­ ranide 3 in equilibrium with the carbanion 4, since the action of a base on phosphorane 2 gave, after acidic treatment, a mixture of 5 and 6 in proportions that depend on the experimental conditions (2).

1Currentaddress: Universität Regensburg, Fachbereich Chemie, 8400 Regensburg, Universitätsstrasse 31, FRG

0097-6156/81/0171-0469$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

470

PHOSPHORUS CHEMISTRY

Similarly, Savignac et al obtained the alkylated compound 8 when treating phosphorane 7 with NaH, NaNH2 or BuLi/R2NH, then with MeI, which strongly suggests a phosphoranide intermediate (3).

On the other hand, evidence against an intermediate hypervalent tetracoordinated phosphorus anion in nucleophilic substitutions at phosphorus in tertiary phosphines was put forward by Kyba: the fact that the substitution reaction 3 occurs with complete inver­ sion of configuration a it proceeds without eve passage through such an intermediate unlikely (4).

It was only in 1978 that the first direct observation of a phosphoranide lithium salt was made by Granoth and Martin (_5) . By allowing the phosphonium trifluoromethane sulfonates ^ to react with L1AIH4 they obtained new compounds which were characte­ rized by NMR (631 ρ = -35 ppm) and assigned structure Π . Further evidence was gained by protonation, which afforded phosphoranes ^2; the latter reaction could be reversed under the action of L1AIH4 :

More recently, Munoz et al assigned a signal at +78.4 ppm to the presence of phosphoranide anion 14 in a dynamic equilibrium mixture 5, obtained by treating 13 with triethylamine or pyridine (6) :

Transition metal compounds having a phosphoranide Izgand remained unknown. The approach we chose to accede to this new class of compounds was to provoke the intramolecular addition of an ionic fifth substituent on the phosphorus atom of a phosphane previously coordinated to the transition metal. The anionic site was created by abstraction of a proton from a secondary amine. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

96.

RiESS

ET AL.

Transition

Metal

Phosphoranides

471

was o b t a i n e d i n 66% y i e l d a s y e l l o w c r y s t a l s b y a l l o w i n g L i M e t o r e a c t w i t h t h e c a t i o n i c a d d u c t 15 i n a t h f / e t h e r s o l u t i o n ( 3 : 1 ) a t -20°C. I n f r a ­ r e d m o n i t o r i n g o f t h e r e a c t i o n showed t h a t t h e v ( C 0 ) v i b r a t i o n s o f ^ a t 1850 and 1978 cm"1 h a d c o m p l e t e l y d i s a p p e a r e d a f t e r 30 mn, w h i l e two new a b s o r p t i o n s h a d d e v e l o p e d a t 1855 a n d 1945 cm""*. The e v o l u t i o n o f methane was a s c e r t a i n e d b y I R . I t a p p e a r s i n d e f i ­ n i t e l y s t a b l e a t room t e m p e r a t u r e a n d m e l t s ( w i t h decomp) a t 1 4 5 Î . Ph

15

17

Compound 16 e x h i b i t s a s i n g l e r e s o n a n c e i n t h e 3 l p { 1 H } N M R s p e c t r u m a t 4 3 ? ? ppm, w h i c h i s a n u n u s u a l l o c a t i o n when compared t o t h e 185-200 ppm r a n g e u s u a l l y f o u n d f o r M o - P ( I I I ) a d d u c t s (_7) . The 1H s p e c t r u m shows a s i n g l e s h a r p s i g n a l f o r t h e C5H5 p r o t o n s at

5.32 ppm i n

CDCI3.

The most p r o m i n e n t f e a t u r e s o f t h e m o l e c u l e a s e s t a b l i s h e d b y X - r a y d i f f r a c t i o n a r e : t h e 5 - c o n n e c t e d c h a r a c t e r o f t h e metat-bound p h o s p h o r u s a t o m , i.e. t h e p r e s e n c e o f t h e o r i g i n a l p h o s p h o r a n i d e l i g a n d ; t h e s h o r t e s t M o ( I I ) - P bond r e p o r t e d s o f a r (2.38Â), 0.070.14A s h o r t e r t h a n t h o s e f o u n d i n c o m p l e x e s h a v i n g t h e Cp-Mo(II)PR^ p a t t e r n ; t h e p r e s e n c e o f t h e h i t h e r t o unknown ^ ^ ^ c y c l e (Mo-N: 2.23A) w h i c h i s a l l t h e more r e m a r k a b l e i n v i e w o f the low b a s i c i t y e x p e c t e d f r o m a P-bond n i t r o g e n atom; one o f t h e l o n g e s t P-N bonds known (1.91 A ) . A l s o v e r y u n u s u a l i s t h e l o c a t i o n o f t h e o x y g e n atoms i n t h e e q u a t o r i a l s i t e s a n d o f t h e p h e n y l group i n a n a p i c a l s i t e o f the a l m o s t p e r f e c t b i p y r a m i d a l arrangement o f t h e s u b s t i t u e n t s on phosphorus. S i m i l a r b e h a v i o r was o b s e r v e d w i t h t h e t u n g s t e n a n a l o g o f ,JJj, g i v i n g i n 9 0 % y i e l d a n o r a n g e - y e l l o w c r y s t a l l i n e compound (δ31ρ = 26.4 ppm; J p - y = 232 Hz) whose s p e c t r a l a n d a n a l y t i c a l d a t a a r e c o n ­ s i s t e n t w i t h the f o r m u l a t i o n . Upon h e a t i n g a t 60°C f o r 4 h , p h o s p h o r a n i d e converts into t h e i s o m e r i c s t a b l e compound 17 w h i c h a l s o c o n t a i n s a b i p y r a m i d a l p h o s p h o r a n i d e l i g a n d . B u t i n Yjf t h e two a d d i t i o n a l e l e c t r o n s needed by t h e m e t a l t o c o m p l e t e i t s 1 8 - e l e c t r o n v a l e n c e s h e l l a r e p r o v i d e d by a n o x y g e n i n s t e a d o f t h e n i t r o g e n a t o m , t h u s g i v i n g t h e new ^ 0 cycle. P h o s p h o r a n i d e 17 shows a s i n g l e t a t 23.8 ppm i n t h e ^ l p NMR. The p r o m i n e n t f e a t u r e s o f i t s c r y s t a l s t r u c t u r e ( 9 ) a r e : a s i n 16 a v e r y s h o r t P-Mo b o n d (2.37Â); a v e r y l o n g P-O(Mo) b o n d ( 1 . 8 9 3 X 3 ^ compared t o t h e o t h e r P-0 b o n d (1.653Â); and t h e f a c t t h a t t h e o x y ­ gen atoms r e c o v e r t h e i r u s u a l more f a v o r a b l e a p i c a l p o s i t i o n s , w h i c h may b e t h e d r i v i n g f o r c e o f t h i s c o n v e r s i o n . Q

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472

When compound Π3, t h e i r o n a n a l o g o f V^, was t r e a t e d u n d e r s i m i l a r conditions with LiMe, i t d i d noty i e l d a phosphoranide, but e x h i b i t e d a n o t h e r o r i g i n a l b e h a v i o r : i t underwent t h e a b s t r a c ­ t i o n o f a p r o t o n , b u t a l s o t h e c l e a v a g e o f t h e Fe-N b o n d , w i t h f o r m a t i o n o f a P-N bond ( w h i c h c o n v e r t s t h e b i d e n t a t e c y c l i c l i g a n d i n t o a m o n o d e n t a t e , t h r o u g h Ρ, b i c y c l i c o n e ) , a n d t h e m i g r a t i o n o f the p h e n y l group f r o m p h o s p h o r u s t o i r o n , t o y i e l d compound 19!

1 The s t r u c t u r e o f 19 was e s t a b l i s h e d b y X - r a y c r y s t a l l o g r a p h y . I t shows a s h o r t F e - C ( p h e n y l ) σ-bond (2.04Â) when compared t o t h a t f o u n d i n (n5-Cp)Fe(CO)(PPh )(η -C6H5) (2.14Â) ( J O ) and t h e s h o r t e s t P-Fe bond o b s e r v e d s o f a r (2.105Â) w h i c h may a r i s e f r o m a h i g h π-accepting c a p a b i l i t y a n d / o r a s m a l l c o n e - a n g l e o f t h e c o n s t r a i ­ ned b i c y c l i c l i g a n d ( 1 1 ) . T h a t t h e s e t r a n s f o r m a t i o n s c a n be r e v e r s e d u n d e r t h e a c t i o n o f a n a c i d i s e v e n more s u r p r i s i n g , a n d seems t o have no p r e c e d e n t i n t h e l i t e r a t u r e . T h i s new b e h a v i o r p r o b a b l y e n t a i l s t h e a s s i s ­ t a n c e o f t h e N-H g r o u p . I t i s t h e a c t i o n o f a n a c i d o r o f a b a s e on t h a t group t h a t t r i g g e r s t h e r e d i s t r i b u t i o n o f bonds a b o u t p h o s p h o r u s and i r o n , p r o b a b l y i n a s y n c h r o n o u s p a i r o f 1,2 s h i f t s a t t h e P-Fe b o n d , t h a t i s p e r h a p s u n i q u e l y a t t r i b u t a b l e t o t h e t r a n s a n n u l a r r e l a t i o n s h i p o f Ν and Ρ i n t h i s f l e x i b l e 1 i g a n d . 1

3

Literature Cited 1 Wittig, G.; Maercker, A. Organometal. Chem. 1967, 8, 91. 2 Hellwinkel, D. Chem. Ber. 1969, 102, 528. 3 Savignac, P.; Richard, Β.; Leroux, Y . , Burgada, R. J . Organome­ tallic Chem. 1975, 93, 331. 4 Kyba, Ε.Ρ. J . Am. Chem. Soc. 1979, 98, 4805. 5 Granoth, I.; Martin, J.C. J . Am. Chem. Soc. 1978, 100, 7434; 1979, 101, 4623. 6 Garrigues, Β.; Koenig, M.; Munoz, A. Tetrahedron Lett. 1979 p.4205. 7 Wachter, J.; Jeanneaux, F.; Riess, J.G. Inorg. Chem. 1980, 19, 2169. 8 Reisner, M.G.; Bernal, I.; Brunner, H . ; Doppelberger, J . J. Chem. Soc. Dalton Trans. 1979, 1664. 9 Wachter, J.; Mentzen, B.F.; Riess, J.G. Angew. Chem. 1981, 93, 299. 10 Semion, V.A.; Struchkov, Yu.T. Zh. Struckt. Khim. 1969 p. 88. 11 Grec, D.; Hubert-Pfalzgraf, L . G . ; Riess, J . G . ; Grand, A. J. Am. Chem. Soc. 1980, 102, 7133. RECEIVED

July 1, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

97 Secondary Phosphino Macrocyclic Ligands EVAN P. KYBA and HEINZ H. HEUMÜLLER Department of Chemistry, The University of Texas at Austin, Austin,TX78712

The use of secondary phosphines as ligands for transition metals has led to some interesting complexes (2,3). Our interest in unusual macrocyclic ligand systems led us to the synthesis of the first macrocycles (VI, VII, Scheme 1) which contain secondary­ -phosphino ligating sites. In order to prepare these macrocycles it was necessary to synthesize the previously unknown o-bis(phosphino)benzene (IV). Lithium aluminum hydride reduction of the o-bis(phosphonate) III gave IV in 50% yield ( P NMR, δ-123.8 ppm, JPH = 207 Hz). The phosphonate III could be obtained in modest yields by the photo­ -activated nucleophilic aromatic substitution by sodium diethylphosphite on o-chloroiodobenzene in liquid ammonia solution (4). Recently we have developed a more general approach to mole­ cules exemplified by III. Thus the Diels-Alder cycloaddition of alkyne II and α-pyrone, followed by aromatization by loss of car­ bon dioxide, led to the isolation of III (72%) (5). Alkyne II was obtained in high yields, in two steps from dichloroacetylene and triethylphosphite via Arbuzov-type reactions (5). Since the intermediate chloroalkyne phosphonate I was isolable (90%), phos­ phorus nucleophiles other than triethylphosphite could be used to give unsymmetrical alkyne diphosphoryl species. We have demon­ strated this approach by the reaction of I with Ph2POEt and PhP(OEt) (5). Treatment of II in THF with two equivalents of n-butyllithium generated V, which gave VI and VII upon high dilution reactions (6) in THF with bis(3-methanesulfonyloxypropyl)sulfide and bis(3chloropropyl)methylamine, respectively in yields of about 80%. Both macrocycles were highly air sensitive, colorless, distillable viscous oils, and both were isolated as a mixture of two 3 1

2

0097-6156/81/0171-0473$05.00/0 © 1981 American Chemical Society

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In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

KYBA AND HEUMULLER

97.

Secondary Phosphino

Maerocyclic

Ligands

475

i s o m e r s . Thus V I i n CeV& e x h i b i t e d two s i n g l e t s i n t h e p r o t o n d e c o u p l e d *P NMR s p e c t r u m a t δ -58.1 a n d -64.0 ppm i n a n a r e a r a t i o o f 62:38, a n d s i m i l a r l y , V I I i n CeD6 g a v e s i n g l e t s a t - 5 5 . 1 and -61.5 ppm ( a r e a r a t i o 6 9 : 3 1 ) . The m a j o r i s o m e r s o f V I a n d V I I show no f l u x i o n a l i t y a t t e m p e r a t u r e s a s l o w a s -90°C i n t o l u e n e s o l u t i o n a s o b s e r v e d b y P NMR s p e c t r o s c o p y . I n c o n t r a s t , t h e m i n o r i s o m e r s e x h i b i t e d c o a l e s c e n c e t e m p e r a t u r e s a t c a . -60°C, a n d w i t h f u r t h e r c o o l i n g , two p e a k s a r o s e ( l o w t e m p e r a t u r e l i m i t i n g ¥ NMR a b s o r p t i o n s a t 6 -70.2 a n d -60.0 ppm) f o r V I a n d t h r e e p e a k s a t δ - 7 4 . 1 , - 5 4 . 6 , a n d -44.5 ppm f o r V I I . Treatment o f a benzene s o l u t i o n o f V I w i t h an excess o f n i c k ­ el c h l o r i d e i n methanol r e s u l t e d i n the p r e c i p i t a t i o n o f a y e l l o w powder. T h i s was r e c r y s t a l l i z e d f r o m m e t h a n o l t o g i v e a i r - s t a b l e y e l l o w - o r a n g e c r y s t a l s (60%) w i t h t h s t o i c h i o m e t r (VI) NiCl2· 3MeOH ( b y c o m b u s t i o n a n a l y s i s ) was t r e a t e d w i t h e x c e s aqueou cyanid presenc C6D6 a t room t e m p e r a t u r e f o r 10 m i n V I was r e g e n e r a t e d , b u t now t h e ¥ NMR a b s o r p t i o n s a t δ -58.1 a n d -64.0 ppm w e r e i n a n a r e a r a t i o o f 95:5. S i m i l a r treatment of V I I w i t h n i c k e l c h l o r i d e l e d to a dark o i l y p r e c i p i t a t e which r e q u i r e d c o n s i d e r a b l e manipula­ tion to partially purify i t . Treatment w i t h sodium c y a n i d e a s above l e d t o t h e r e g e n e r a t i o n o f V I I a l s o e n r i c h e d i n t h e major isomer (85:15). E x a m i n a t i o n o f D r e i d i n g and C o r e y - P a u l i n g - K o l t u n g m o l e c u l a r models r e v e a l s t h a t t h e t r a n s - l i g a n d (b) cannot c h e l a t e a m e t a l i o n w i t h o u t s e v e r e s t e r i c i n t e r a c t i o n s w h i l e t h e c i s - ( a ) c a n do so e a s i l y . The f a c t t h a t t h e n i c k e l ( I I ) c o m p l e x a t i o n - c y a n i d e décomplexâtion s e q u e n c e l e a d s t o e n r i c h m e n t o f t h e m a j o r i s o m e r s of V I and V I I l e a d s us t o p o s t u l a t e t h a t the major isomers a r e t h e c i s - ( a ) s p e c i e s . We h a v e e q u i l i b r a t e d V i a a n d V I b t h e r m a l l y t o a r a t i o o f 58:42; t h u s t h e m a c r o c y c l i z a t i o n g i v e s a n o n - e q u i l ­ i b r i u m m i x t u r e f a v o r i n g t h e c i s i s o m e r , a n a l o g o u s t o P P h a n d AsMe m a c r o c y c l i z a t i o n s t h a t we h a v e d e s c r i b e d r e c e n t l y (1,7_, 8) . 3

3 X

3

3

Acknowledgement. We a r e most g r a t e f u l t o t h e A i r F o r c e O f f i c e o f S c i e n t i f i c R e s e a r c h (AFOSR-79-0090) a n d t h e R o b e r t A. W e l c h F o u n d a t i o n ( F 573) f o r g e n e r o u s s u p p o r t o f t h i s work.

Literature Cited. 1.

2.

For the previous paper in the series, Phosphino-macrocycles, see Kyba, E.P.; Davis, R.E.; Hudson, C.W.; John, A.M.; Brown, S.B.; McPhaul, M.J.; Liu, L.-L.; Glover, A.C. J . Am. Chem. Soc. 1981, 103, 0000. Stelter, O. in "Topics in Phosphorus Chemistry", Volume 9, Griffith, E . J . and Grayson, Μ., Editors, Wiley Interscience, New York, 1972, p. 433.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

476

3. 4. 5. 6. 7. 8.

Booth, G. in "Organic Phosphorus Compounds", Volume 1, Kosolapoff, G.M. and Maier, L . , Editors, Wiley Interscience, New York, 1972, p. 433. Bard, R.R.; Bunnett, J . F . ; Traber, R.P. J . Org. Chem. 1979, 44, 4918. Kyba, E.P.; Rines, S.P.; Owens, P.O.; Chou, S.-S.P.; Tetra­ hedron Lett. 1981, 22, 1875. Kyba, E.P.; Chou, S.-S.P. J . Org. Chem. 1981, 46, 860. Kyba, E.P.; John, A.M.; Brown, S.B.; Hudson, C.W.; McPhaul, M.J.; Harding, A.; Larsen, K.; Niedzwiecki, S.; Davis, R.E. J . Am. Chem. Soc. 1980, 102, 139. Kyba, E.P.; Chou, S.-S.P. J . Am. Chem. Soc. 1980, 102, 7012.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

98 Dicoordinated and Tricoordinated Acyclic Phosphazenes as Complex Ligands O. J. SCHERER, H. JUNGMANN, and R. KONRAD University of Kaiserslautern, Paul-Ehrlich-Strasse, 6750 Kaiserslautern, FRG

Starting with the phospha(III)azen

RR'N-P=NR R=(CH ) C

R'=(CH ) Si, and Pt(COD) 3

3

three phospha(III)azene ligands can be synthesized in high yield.

R=(CH ) C, R'=(CH ) Si 3 3

3

3

A

DNMR studies show that at ambient temperature the (CH ) Si-groups 3

3

of A are dynamic. This intramolecular 1.3-exchange can be stopped at about - 20° C. PtL (A) is a very useful starting material for the synthesis of 3

a variety of new platinum(O) complexes containing phospha(III)azenes as ligands (see scheme).

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PHOSPHORUS CHEMISTRY

According to reaction (a) mixed substituted platinum(O)Complexes of the hitherto unknown type PtL2L' and PtLL'2 (where L and L' are phosphorus ligands) can be isolated and characterized by nmr spectroscopy. Instead of Ph3P other R3P derivatives and Ph3As can be used. Complex D is very labile. IR data give evi­ dence for a σ-coordination of theCS2ligands. With the double ylide RR'N-P(S)=NR (reaction (c) ) the four-membered chelate complex Ε with pentavalent phosphorus of coordination number four is formed. Compound F is an example of the well character­ ized alkyne complexes (here with the phospha(III)azene ligand L). All platinum phospha(III)azene complexes (A + F ) show dynamic behaviour for L. As described for A the 1.3 - (CH^Si-group exchange within the ligand L can be stopped at low temperature (ca. - 20 to - 30° C) for Β -> F . It is interesting to note that for Ε even at - 80° C the (CH ) Si-group exchange of the R'-group 3

3

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

98.

SCHERER E T A L .

Acyclic

Phosphazenes

i s f a s t on the nmr time s c a l e . A l l (III)

as Complex

compounds with two phospha-

azene ligands L at about - 6 0 ° C show hindered

around the Pt-L

1

j^P

Ν

i

"cis"

Pt

1

—

isomers.

I 1

/P

?ti

— Ν 1

rotation

bond with formation of " c i s " and " t r a n s " \ pt

ι

479

Ligands

PC Ν —

t

ι

"trans"

With Β as s t a r t i n g materia done in the same way with formation of (Ph P)Pt(CS )2> 3

2

L ( P h P ) P t ( C P h ) and L(Ph P)PtSp (=NR)(NRR )(L=RR*N-P=NR 3

2

R=(CH ) C, 3

3

2

>

3

l

S

R'=(CH ) Si). 3

3

Compound C with RR'N-P(S)=NR forms G,

Ph P Q

\

3

^

/

/

P

P h

3

Pt

\

R»-N ^ p t R a

complex with a d e r i v a t i v e 2 ΓΠ a c i d as η - l i g a n d Contrary to the free

of monomeric metathiophosphoric

l i g a n d RR*N-P(S)=NR, the (CH )u Si-group 3

of G can be hydrolyzed with formation o f (Ph P) PtSP(=NR)(NHR) 3

2

( R = ( C H ) C ) ; a platinum complex with the unknown RHNP(S)=NR 3

3

as a side-on coordinated l i g a n d .

[1] O. J . Scherer and H. Jungmann, Angew. Chem. 91, 1020 (1979), Intern. Edit. 18, 953 (1979). RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

99 Metal Complexes of Amino(cyclophosphazenes) V. CHANDRASEKHAR and S. S. KRISHNAMURTHY Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore560 012, India M. WOODS Department of Chemistry, Birkbeck College, University of London, Malet Street, London WC1E 7HX, England

Metal complexes of cyclophosphazenes have aroused considerable i n t e r e s medical points of v i e w ( 1 ) cyclo phosphazenes to metal ions occurs i n d i f f e r e n t ways: (a) through the s k e l e t a l nitrogen atoms, e.g., N4P4(NHMe)8.PtCl2(1); (b) through a s k e l e t a l and an exocyclic nitrogen atom, e.g., W(CO)4.N4P4(NMe2)8(1); (c) through one s k e l e t a l nitrogen atom while another is protonated, e.g., N4P4Me8.CuCl3(1); (d) through the phosphorus atom i n the ring, e.g.,[N3P3Ph4(CH3)H]2. P d C l ( 2 ) . Instances are also known where a protonated 2

phosphazene species functions merely as a counter i o n without any d i r e c t i n t e r a c t i o n with the metal(1). The f a c t o r s that are responsible f o r the divergent behav i o u r of the cyclophosphazene ligands towards the metal ions are poorly understood and c l e a r l y more work is needed i n t h i s area. A study of the metal com­ plexes of the (amino)cyclophosphazenes N3P3R6[R = NHMe(I), NMe (II)], N4P4R8[R = NHMe(III), R =NMe (IV)] 2

2

and the s p i r o c y c l i c phosphazene, N3P3(HNCH2CH2NH) (NMe )4(V),is undertaken with a view to r a t i o n a l i s i n g 2

the l i g a t i n g a b i l i t y of the cyclophosphazenes i n terms of e l e c t r o n i c and s t e r i c f a c t o r s associated with them. Experimental Procedure A s o l u t i o n of the metal chloride(hydrated or anhydrous) and the cyclophosphazene i n the required s tο i chiome try(metal:ligand 1:1 or 1:2) i n methanol or methyl e t h y l ketone was heated under r e f l u x f o r 0097-615 6/81/0171-0481$05.00/0

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PHOSPHORUS CHEMISTRY

4-8 hrs i n the presence of dimethoxy propane. The solution was f i l t e r e d and the solvent was removed from the f i l t r a t e i n vacuo to obtain a s o l i d . The s o l i d was washed several times with petrol-benzene mixture (1:1) to remove excess l i g a n d ( i f any). The complexes were c r y s t a l l i s e d from acetone or methanol. In the case of mercuric chloride complexes, addition of the warm solutions of the metal s a l t and the cyclophos­ phazene i n methanol resulted i n the p r e c i p i t a t i o n o f the complexes. The following complexes were i s o l a t e d : I.2HgCl (VI) m.p. 230°(d), III.2HgCl (VII) m.p. 225°, I I I . N i C l ( V I I I ) m.p. 192°-195°, V.2HgCl (IX)m.p.198°, ( V ) . H i C l ( l ) m.p. 186° (V) .CoClgiXI) m.p.176°-180° The dimethylamino d e r i v a t i v e s ( I complexes(UV s p e c t r a l evidence). 2

2

2

2

2

2

Discussion The n i c k e l chloride complex(X) of the s p i r o c y c l i c phosphazene(V) i s diamagnetic suggesting a square planar coordination around n i c k e l . The P = Ν stretching v i b r a t i o n f o r the complex appears as two s p l i t bands(1215 and 1185 cm ) compared to a single band at 1200 cm"" observed f o r the l i g a n d . The phos­ phorus chemical s h i f t s move u p f i e l d compared to those of the ligand; the spiro phosphorus atom i s the one most affected [complex: S 21.9; 6 p ( i ) 25.5; 1

P R

2

s p

r 0

26.7; 6 ( p i

J(P-N-P) 31-6 Hz; l i g a n d :

P

S

r 0

) 35 ·5|

2

J(P-N-P) 40.0 Hz]. The proton resonances move downf i e l d upon complexation, the most affected being the N-H and the N-Cg protons (complex: S _QH 2.7; N

2

6 -CH N

3*52* 6N-g · ' 4

2

2

7

ϋδ^·6 .ςΗ 2.6; Ν

3

2

3.34; £ N - H · ) · ^ complex exhibits a low molar conductance i n MeCN. These r e s u l t s are consistent with the structure shown i n Figure 1· The cobalt chloride complex(XI) o f the s p i r o c y c l i c phosphazene(V) has a magnetic moment of 4*6 B.M. and a high molar conductance i n MeCN(280 mhos)· I t s e l e c t r o n i c spec­ trum i n acetone or MeCN i s c h a r a c t e r i s t i c of a t e t r a hedral Co(II) complex φ X ^ Î C H j C N ) : 692(895), 635(sh), 590(358). I t i s l i k e l y that one exocyclic and one endocyclic nitrogen atom from each ligand molecule are involved i n coordination.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

99.

CHANDRASEKHAR ET AL.

CH

Figure L

2

CH

Complexes

of Amino(oyclophosphazenes)

ÇH

2

ÇH

2

Possible structure of the nickel chloride complex of the spirocyclic phazene, N P (NH CH2CH2NH) (NMe2)4. 3

483

2

phos-

3

CI

CI

R = NHMe

Figure 2.

Possible structure of the nickel chloride

complex of N P 4

4

(NHMe) .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

8

8

(NHMe) .

4 4

complex of N P chloride Possible structure of the mercuric Figure 3.

( R=-NHCH3 )

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

99.

CHANDRASEKHAR E T A L .

Complexes

of Âmino(cyclophosphazenes)

485

The n i c k e l chloride complex(VIII) of N^P^(NHMe)g i s paramagnetic (3.2 B.M.). The phosphorus NMR spectrum shows a single l i n e which s h i f t s u p f i e l d by 4.0 6 compared to the l i g a n d . A t e t r a h e d r a l structure i s proposed f o r t h i s complex i n which the metal i s coordinated to two antipodal nitrogen atoms of the ligand (Figure 2 ) . The extreme i n s o l u b i l i t y and high melting points of the mercuric chloride complexes suggest that they are polymeric as i l l u s t r a t e d f o r N^P^lNHMeJg^HgClg (VII) (Figure 3 ) · A number of polymeric mercury complexes are known(4,5) · X-ray cry s taTlôgraphi studie l that both r i n g protonation an zene i n a s i m i l a r way but the e f f e c t o f protonation i s more pronounced(1). For the hydrochloride adducts of aminolcyclophospEazenes)» the proton NMR s h i f t s move downfield whereas phosphorus chemical s h i f t s are markedly u p f i e l d to those observed f o r the free bases. The r i n g P = N s t r e t c h i n g frequency also undergoes an upward s h i f t f o r the hydrochloride adducts( 1 ). S i m i l a r trends are observed f o r the metal complexes prepared i n the present study. The mode of coordinat i o n o f oyclophosphazenes to t r a n s i t i o n metal ions mainly depends upon the r i n g s i z e and the nature of the substituent. The r i g i d six-membered c y c l o t r i phosphazenes have low propensity f o r forming metal complexes and c l e a r l y s t e r i c e f f e c t s predominate. Acknowledgement The authors thank the U n i v e r s i t y Grants Commission and the Council o f S c i e n t i f i c and Indust r i a l Research, New D e l h i and the Overseas Development Administration, U.K. f o r support. Literature

Cited

1. Krishnamurthy,S.S.; Sau,A.C.; Woods,M. Adv. Inorg. Radiochem., 1978, 21, 41. 2. Schmidpeter,A.; B l a n c k , K . ; Hess,H.; Riffel,H. Angew. Chem. I n t . Edn. Engl., 1980, 19, 650. 3. C o t t o n , F . Α . ; Goodgame,D.M.L.; Goodgame,M. J. Am. Chem. S o c . , 1961, 83, 4690. 4. W i r t h , T . H . ; Davidson,N. J.Am.Chem.Soc., 1964, 86, 4325. 5. Cheung,K.K.; Sim,G.A. J.Chem.Soc.,1965, p.5988. RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

100 Structural and Magnetic Investigation on Transition Metal Complexes with Tripodal Polytertiary Phosphines L. SACCONI Istituto di Chimica Generale ed Inorganica, Universitàdi Firenze, Istituto CNR, 39, Via J. Nardi 50132 Firenze, Italy

Tripodal tritertiar phosphinomethyl)ethane ethyl)amine, np3, are capable: a) to act as tridentate or tetradentate ligands; b) to promote several reactions with formation of several types of metal complexes which are presented. By reaction of cobalt(II) aquacation with triphos and HSR (R = H, Me) different dinuclear metal complexes are formed with formulae [(triphos)Co(μ-SR)2Co(triphos)] and [(triphos)Co(μ-S) Co(triphos)] . These dinuclear complexes contain from 32 to 34 valence electrons. Those with 34 electrons present antiferromagnetic behavior. These properties are explained in terms of a molecular orbital treatment of the type suggested by Hoffmann and Burdett for unpuckered dinuclear metal complexes. The ligands triphos or/ and np in presence of compounds of iron, cobalt, nickel, rhodium, iridium and palladium, by reaction with THF solutions of white phosphorus, P4, or yellow arsenic, As4, form mononuclear or dinuclear sandwich complexes containing the cyclo-triphosphorus or cyclo-triarsenic units which behave as 3π-electrons rings. The metal complexes formed have the general formulae I(triphos)N(n -P )] (M = Co, Rh, Ir) and |(np )Co(n -P )]; [(triphos) IT (n -P )N ( triphos)] ' ' (ΙΊ = Co, Ni, Rh, Ir, Pd) . The complexes can be also of the ethero-metal type. An iron complex can be formed by using the ethyl derivative of triphos, p Et : [(triphos)CoCn -P )Fe(P Etg)J . Many of the complexes here presented are paramagnetic. The number of valence electrons range from 30 to 34. This unprecedented magnetic behavior can be accounted for by a molecular orbital treatment of the type suggested by Hoffmann. 2+

2

o,+,2+

3

3

3

3

3

3

M

+

2+

3

3 +

3

3

3

6

2+

3

3

0097-6156/81/0171-0487$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

488

PHOSPHORUS CHEMISTRY In t h e case o f "simple

diffraction and

studies

P-(cyclo]-P(cyclo)

increase

sandwich" complexes t h e X-ray

have shown t h a t t h e N - P ( t r i p h o s ) , distances

M-P(cyclo)

r e v e a l e f f e c t s of both the

i n t h e p r i n c i p a l quantum number and t h e " l a n t a n i d e

contraction". For "triple distances

decrease with

i n c r e a s i n g number o f v a l e n c e

With the l i g a n d np [(np )Π(η-Ρ^)J

formula

d e c k e r s a n d w i c h " c o m p l e x e s t h e M-M

i n c r e a s e whereas t h e P ( c y c l o ) - P ( c y c l o )

3

one c a n o b t a i n

distances

electrons.

t h e complexes of g e n e r a l

(N = N i , Pd) w h i c h c o n t a i n

3

an i n t a c t

t e t r a h e d r a l m o l e c u l e P^ σ-bonded t o t h e m e t a l . Also

t h e c o m p l e x e s formed w i t h

a q u a c a t i o n s and CS2 a r there

f

the ligand t r i p h o s , c o b a l t ( I I )

interest

Amon

thes

compound

i s the CS^-bridge

[(triphos)Co(η-CS )Co(triphos)J

. By u s i n g

2

the ligand

[(p^Etg)Fe

is

obtained.

fivecoordinated

in

a singlet state.

This

i s the f i r s t

The t e r t i a r y

2

3

2

2

+

3

complex o f i r o n ( I I )

3

f o r m d i a m a g n e t i c t r i - and e n n e a n u c l e a r

d i c a t i o n s having formulae 3

[Nig(y -S) (p4-S) ] bipyramidal

2

phosphine P E t , i n the presence o f n i c k e l ( I I )

a q u a c a t i o n s and H2S,

6

p Etg

S C(PEt -CH ) CiCH )2]^

t h e u n e x p e c t e d complex c o m p l e x

2 +

3

3

[Ni (y -S) (PEt ) ] 3

. The f i r s t

2

3

6

2 +

and

complex i s f o r m e d by a t r i g o n a l

k e r n e l o f two a p i c a l s u l f u r atoms and t h r e e

equatorial

n i c k e l i o n s . The s t r u c t u r e o f t h e s e c o n d compound c o n s i s t s o f n i n e n i c k e l ions

located at the apices

o f two c o n f a c i a l o c t a h e d r a .

The s i x p h o s p h i n e s a r e bonded t o t h e s i x e x t e r n a l n i c k e l i o n s . Six

s u l f u r atoms l i e p r a c t i c a l l y

t r i a n g u l a r faces nickel

i o n s . The t h r e e

bridging

i n t h e p l a n e s o f t h e two e x t e r n a l

o f t h e two o c t a h e d r a , t r i p l y

bridging

a l lthe

i n t e r n a l s u l f u r atoms a r e q u a d r u p l y

the n i c k e l ions.

The

contributions

of a l l the coworkers

are greatly

acknowledged.

RECEIVED

July 7,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

101 The Use of Alkylaminobis(difluorophosphines) as Ligands to Stabilize Novel Binuclear Complexes J. H. KIM, K. S. R A G H U V E E R , T. W. L E E , L. N O R S K O V - L A U R I T Z E N , V. K U M A R , M. G. N E W T O N , and R. B. K I N G

Department of Chemistry, University of Georgia, Athens, GA 30602

Alkylaminobis(difluorophosphines) RN(PF)2 (R = CH C6H5 etc.) can function as bidentat plexes by bridging a bonde -memberedchelate ring (I). These bridges appear to hold together metal-metal bonds so that they survive chemical transformations which cleave unbridged metal-metal bonds. This property gives the transition metal coordination chemistry of the RN(PF2)2 ligands a richness which appears to rival that of the most versatile un­ saturated hydrocarbon ligands in transition metal organometallic chemistry such as cyclopentadienyl and cyclooctatetraene. In 1980 we published a survey (1) of our major results in this area as of late 1979. These results include extensive work on binuclear CH3N(PF)2 complexes of cobalt (2,3,4,5) and nickel (6). This paper summarizes our more recent results in this area with particular emphasis on binuclear complexes of chromium, molybdenum, and tungsten as well as some new results on iron carbonyl derivatives. 2

Chromium, Molybdenum, and Tungsten Derivatives Several compounds of the type [ RN(PF ) J M (CO)u -2n (M = Cr, Mo, and W; R= CH and C H ; η = 3, 4, and 5) have been prepared which, at least formally, are derivatives of the un­ known binuclear metal carbonyl s M (CO)ii. Thus pyrolysis of the molybdenum complexes RN(PF )^o(CO) (R= CH3 and C H ) at 100-120 C results in extensive rearrangement to give the yellow binuclear complexes [ RN(PF)^I Mo (CO) (R = CH* and C r%) shown by X-ray diffraction in the case R = C5H5 to nave structure Il (M = Mo). The chromium and tungsten analogues [ RN(PF)2] M (CO) (M = Cr and W) can be obtained by photolysis of the corresponding metal hexacarbonyls with CHQN(Pr ) in a 1 to 1.5:1 ligand/metal mole ratio. Pyrolysis or pnotolysis of mix­ ture of the RN(PF ) ligands and M(CO) (M = Mo and W) in a 2 to 2.5:1 ligand/metal mole ratio gives mixtures of the yellow binuclear complexes [CH N(PF ) 1 Μ^Ο) and [CH N(PF ) ] M CO in the case of CH N(PF ) and the yellow binuclear complexes 2 2

3

6

n

2

5

2

2

2

2

3

2

4

3

2

6

5

5

6

5

2 2

2 2

6

3

3

2

2

2

4

3

3

2

2

5

2

2

0097-6156/81/017l-0489$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

490

PHOSPHORUS CHEMIST

[ C H N(PF ) 1 4Mo (CO) and [C HfeN(PF y Mo (CO)2 în the case of C H N ( P F ) . The complex [ C H ^ N C P F ^ M o ( C O ) has been shown by X-ray diffraction to have structure III (M = M o , R = C H ) . The compounds II and III are rare examples of structurally characterized binuclear molybdenum carbonyl complexes containing bridging carbonyl groups. In II where the two metal atoms are equivalent the carbonyl bridge is symmetrical whereas in III where the two metal atoms are non-equivalent the carbonyl bridge is unsymmetrical. The addition reactions of the RN(PF )o ligands to the metal metal triple bonds in the cy cl opent adi eny Imolybden urn carbonyl s [ R ^ Q M o C C O ) ^ (IV: R = H and C H ) have also been studied Thus reactions of IV with RN(PF ) under relatively mild conditions results in the simple adducts, R N i P F ^ M o i C O ^ Q R ^ of apparent structure V . In additio with C H N ( P F ) under more vigorous conditions also results in C O loss to give [ ( C H ^ C M o ( C O ) ( P F ) N C H ] formulated tentatively as VI because its infrared spectrum indicates the presence of bridging carbonyl s but the absence of terminal carbonyls. 6

5

6

2

?

2

2

2

3

6

2

5

2

2

4

2

3

3

2

1

2

3

2

%

2

1

3

2

2

3

5

2

2

3

2

Iron Carbonyl Derivatives Reactions of iron carbonyls with C r ^ N K P F ^ give products of the type [ RN(PF )J Fe (CO)o_2n which may be regarded as derivatives of Fe (CO)9. The following compounds of this type have been reported in previous papers: (1) C H Ν ( P F ) f e ( C Ο ) (n = 1): This orange complex is formed from the reaction of l-e (CO)9 ' * " C H N ( P F ) in a 1:1 mole ratio; a more major product of this reaction is CrijNÇPFo)^ ?e(CO)£ , a compound with two isolated F e ( C O ) groups without an iron-iron bond (6). (2) t CH N(PF ) ] 2fe?(CQ)5 (n = 2): This orange complex is formed by the photolysis of r e ( C O ) with C H N ( P F ) in a 1:1 mole ratio in diethyl ether or pentane (6,7). An alternate method for preparing this compound involves the reaction of F e ( C O ) | with C H N ( P F ^ ; an intermediate in this reaction is yellow [ CH N(PF ) Fe(CO)3l containing two square pyramidal iron atoms and no iron-iron bond (6,7). (3) [CHps|(PF^) 1/e CO (n= 4): This is formed by the ultraviolet irradiation of i e ( C O ) with excess C H N ( P F ) in diethyl ether (8). The infrared spectrum of this yellow complex indicated a terminal carbonyl group rather than the expected carbonyl group. Since this observation was initially somewhat puzzling, the structure of this complex was determined by X-ray diffraction. This revealed the unexpected structure VII in which one of the four C H N ( P F ) ligands has undergone phosphorus-nitrogen bond cleavage to form separate PF and C H N P F units which function as bridging and terminal ligands, respectively. The final member of this series, orange [ C ^ N i P F o ) ^ F e ( C O ) (n = 3), has now been isolated in low yield from the photochemical reaction of F e ( C O ) | with C H N ( P F ) . The infrared spectrum of 2

n

2

2

3

2

2

7

w

2

n

3

2

2

2

4

3

2

2

5

3

2

2

3

2

3

2

2

2

2

2

2

3

3

3

2

1 2

3

2

2

2

2

3

2

3

3

2

3

2

2

2

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

3

101.

KIM ET AL.

Alkylaminobis(difluorophosphines)

as

491

Ligands

R F P^O PF N

2

oc i / \ i / C O

M

R-N

2

C

v

^Mo

I

oc y

M

Mo'

^

F 2 P

/

F

X

Λ

0

W / 2

2

Ν

N

R

R

0

P

O

O

FP 2

2

ο Ί •l ^ C ^ 1 ^ . P F ^ M < ^ ^ M ^ \|_R R OC-7\ A V " PF FoP. Fo~ " ~

oc^

2

2

Ν

N

R

R

R

FP

o

III

o

IV

CH

PF

2

C c ' I f Mo = M o R' I I C c

2

Λ

R'

FP 0

Ρ

2

o o o

R

T

ÇH

Ρ

3

o

τ

CH CH

3

Λ

VI

3

3

F2 po PF2 p /

CH3

X

:PF--

F

Fe-CO F P F R PF PF i

N

2

K

2

Ν

2

N

CH Ctf 3

3

vil

2

O

P

P F

2

OC— Fe^—-Fe— CO ^\ F2P F2P PF PF V

>
· —P=0 + RX I Figure 1. attack by halide ion and alkyl-oxygen fission are indicated by absence of rearrangement in the neopentyl group and although the process may be considered to be of the S 2-type i t is not 0097-6156/81/0171-0517$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

518

PHOSPHORUS

Table I .

F i r s t - o r d e r decompositions t/°C CI

Ph P(OR)MeX

33 60 33 60 33

2

PhP(0R) MeX 2

(R0) PMeX 3

i n CDCI3 1

lO^/s V

Compound

Br

1.5 92 -

CHEMISTRY

I

1.54 74 114 4670 670

2.75 105 148 5260 1100

b i m o l e c u l a r , as k i n e t i c a l l y s e p a r a t e s p e c i e s a r e n o t i n v o l v e d . A s i m i l a r p r o c e s s has b e e pentyloxytriphenylphosphoniu F i r s t o r d e r k i n e t i c s a r e a l s o c o n s i s t e n t w i t h a sequence w h i c h i n v o l v e s r a t e - d e t e r m i n i n g d i s s o c i a t i o n o f the i o n - p a i r ( F i g u r e 2, k__^ B r > I ) a n d t h a t w h i c h i s observed i n h y d r o x y l i c s o l v e n t s (Cl O N O . R

W N 0

2

R

3 ±

R = PP(0)(0Me) ( 0 A l k ) , R - MeO, R = P ( 0 ) ( 0 A l k ) , R' = Me, 1

5

2

2

MeO, P(0)(0Me)

2

It should be noted that the d e r i v a t i v e s o f TNB both with donor and acceptor groups i n the aromatic r i n g have lower r e a c t i o n rates as compared with TNB,

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

110.

GOLOLOBOV A N D ONYS'KO

Phosphorylation

535

of Aromatics

which i s apparently due t o s t e r i c substituents.

hindrance

o f the 1

N u c l e o p h i l i c phosphorylation o f halogenated TNB s It 3 1 5 - T r i n i t r o c h l o r o ( f l u o r o ) b e n z e n e has been phosphory1ated by p i " compounds e i t h e r by nucleophi­ l i c a t t a c k at CI o r through σ-complex formation: ArF + (MeO) P

ArP(0)(0Me)

5

+ MeF

2

If [(MeO^PF Ar"] N0 I

2

^ MeOH

6

^

~*f

ArP(0)(0Me)

2

~ ArH

+ HP + Me 0 2

Ar = 2,4-, 6 - t r i n i t r o phenyl I t f o l l o w s from t h i s scheme t h a t the use o f a protonic solvent (MeOH) as a t e s t f o r n u c l e o p h i l i c a t t a c k at CI i s not a b s o l u t e l y r e l i a b l e , since i o n i c p a i r s o f type 5 may be formed by an a l t e r n a t i v e path. o^oraplexes 1_ and 2 were obtained i n s o l u t i o n (DMSO, MeCN) and p u r i f i e d by column chromatography. They can be kept a t 20° f o r a few hours, a f t e r which they convert slowly t o corresponding phosphonates. 1

o r 2 (R » AlkO)

D M S 0

-

ArP(O) ( 0 A l k )

2

N u c l e o p h i l i c phosphorylation o f 5-nitropyrimidines 2-R-5-Nitropyrimidines 6 do not form stable σcomplexes with (RO)xP o r ( R 0 T 2 ( ° ) without bases. Stable complexes 7 are formed only with s t r o n g l y nuc­ l e o p h i l i c (R0) P(0)H i n the presence o f Et^N. p

H

2

H P(0)(OAlk) ΝγΧΝ +

2

£

R « H, MeO, Ph; R * H 1

0 (AlkO) Rf^N 2

R R» = MeO

10 R = H, MeO

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

536

In a l l cases formation of complexes was detected only on the nonsubstituted C-4- (C-6) atom of the heter o c y c l e (contrary to many other n u c l e o p h i l e s ) . The r e a c t i o n of 2-R-^methoxy-5-nitropyrimidines 8 with (RO) P(0)H and EtzN takes place very u n u s u a l l y , since i t leads to the s u b s t i t u t i o n of the 5-NO2 group which i s u s u a l l y i n e r t . σ - C o m p l e x e s % are formed r a ­ p i d l y i n the r e a c t i o n and then rearrange to phosphon­ ates 10. ÏÏêspite the f a c t that t r i a l k y l phosphites do not form stable complexes with 5 - n i t r o p y r i m i d i n e s . they e a s i l y react with 6-R-4-chloro-5-niti*opyrimidines (R« MeO, NH2, CI) to give the corresponding p y r i m i d i n y l - A phosphonates or ( f o R CI) p y r i m i d i n y l - 4 , 6 - d i p h o s phonates. In 2 , 4 - d i c h l o r o - 5 - n i t r o p y r i m i d i n e s both c h l o r i n e s can be s u b s t i t u t e d but CI i n p o s i t i o n 4 i s the first to be s u b s t i t u t e d , which agrees with a p r e f e r e n t i a l formation of σ - c o m p l e x e s to the C-4 atom of 5 - n i t r o ­ pyrimidines. It i s quite possible that P-nucleophiles are w e l l s u i t e d to accomplish n u c l e o p h i l i c aromatic s u b s t i t u t ­ ion e i t h e r through σ - c o m p l e x e s formation or through halogen a t t a c k . 2

Literature Cited 1. Cadogan, J.I.J. Quart.Rev. 1968, 22, 222. 2. Gololobov, Yu.G.; Onys'ko, P . P . ; Prokopenko, V . P . Dokl. Akad. Nauk SSSR 1977, 237, 105. 3. Strauss, M . J . Chem.Revs 1970, 70, 667. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

111 Use of X-Ray Structural Results on Phosphorus Compounds in Modeling Reaction Mechanisms R O B E R T R. H O L M E S and J U D I T H C . G A L L U C C I Department of Chemistry, University of Massachusetts, Amherst, M A 01003 J O A N A. DEITERS Department of Chemistry, Vassar College, Poughkeepsie, NY 12601

During the past fou hav determined th crystal structure of over thirt and have established that their structures in the solid state and in solution in general are similar (1 ,2). Recent x-ray struc­ tures in the bis(biphenylylene) series (3,4) show steric effects as the size of R increases.

The structure of 8-MeN-l-Np derivative (3) is at a point 2/3 the way from a trigonal bipyramid (R equatorial) toward the rectangu­ lar pyramid with one of the rings in the unique apical-basal ori­ entation. Dimeric phosphoranes exhibiting unusual bridgehead structures are the difluoro and dichloro triazaphospholes (5). Their structures are half-way between the idealized trigonal bi­ pyramid and square pyramid and exist in the cis-facial arrange­ ment (relative to the trigonal bipyramid). 2

0097-6156/81/0171-05 37$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

538

The first x-ray structure of a P(V)-P(V) derivative, the dimeric cyclen phosphorane [(NCH CH ) P] (6) above, shows a normal P-P single bond length (2.264(2) Å). Using the results of x-ray studies as a structural base, we have parameterized a molecular mechanics program (7) to include terms specific for pentacoordinate phosphorus and have shown that computer simulated structures compare favorably with those ob­ tained by x-ray diffraction. In general, phosphorane structures form a series which may be placed incrementally along a C2 coordinate (Berry coordinate) connecting the idealized trigonal bipyramid (TP) with the square (or rectangular) pyramid (RP) (8,9). In most cases these struc­ tural distortions can be interpreted in terms of inherent molec­ ular properties, ie., substituen philicity), ring strai tions (9). It is determined, for example, that like atoms in a five-membered ring and ring unsaturation are required to form a RP., cf 1 and 2. 2

2

4

2

V

When short intermolecular contacts are apparent in the crystallographic data, their presence is due to either intermolecular hydrogen bonding or steric interactions caused by bulky substit­ uents (9). For some of these situations, we simulated both the isolated molecule and the molecular structure perturbed by neigh­ boring molecules in the unit cell to establish that this is the case (10,11) . With this background data, modeling of a reaction coordinate for a phosphorus compound proceeding by an associative mechanism through a pentacoordinated transition state becomes attractive. We have simulated the steric course of the alkaline hydrolysis of chiral five- (12) and six- (13) membered cyclic phosphonium salts, whose reaction kinetics and product stereochemistries had been studied previously by Marsi and coworkers (14,15) . For this pur­ pose, we determined the absolute configuration of the phospholanium iodide % (12) , and the x-ray structures of the related phosmorinanium salts, h and 5 (13).

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

111.

HOLMES

ET AL.

Use

of

X-Ray

Structural

Results

539

M o l e c u l a r m e c h a n i c s m o d e l i n g (13) o f h y d r o x i d e a t t a c k o n t h e c h i r a l trans benzyl d e r i v a t i v e 6 indicated that s t e r i c control during t r a n s i t i o n s t a t e formation i sa p r i n c i p a l f a c t o r i n the r e d u c e d amount o f i n v e r t e d p r o d u c t formed (15) compared t o t h a t f o r t h e c i s i s o m e r 7. 6 (CH -Ph trans) 3

Ph

7(CH

C

^CH Ph 2

CH

H

3

" ^ ^ ^

3

For t h e c h i r a l phenylphospholanium s a l t s , m o d e l i n g (13) shows, i n a g r e e m e n t w i t h t h e i n i t i a l s u g g e s t i o n o f M a r s i T T 4 ) , t h a t s t e r i c c o n t r o l i n t h e ground s t a t e i s important i n a c c o u n t i n g f o r t h e d e c r e a s e d amount o f i n v e r s i o n a t p h o s p h o r u s f o r 8 com­ p a r e d t o t h a t f o r ^. I n 8, i n - l i n e d i s p l a c e m e n t o f t h e methoxy group r e s u l t s i n g r e a t e r s t e r i c i n t e r f e r e n c e between t h e ap­ p r o a c h i n g h y d r o x i d e i o n and t h e r i n g m e t h y l group.

8

The a p p a r e n t u s e f u l n e s s o f t h e m o d e l i n g a p p r o a c h s u g g e s t e d that p o s s i b l e a c t i v e s i t e i n t e r a c t i o n s important i n understanding t h e mode o f a c t i o n o f t h e w e l l - c h a r a c t e r i z e d enzymes, r i b o n u c l e a s e (16) and s t a p h y l o c o c c a l n u c l e a s e ( 1 7 ) , may be r e v e a l e d . B o t h have b e e n t h e s u b j e c t o f e x t e n s i v e c r y s t a l l o g r a p h i c s t u d i e s (18,19) w i t h s u i t a b l e i n a c t i v e s u b s t r a t e s i n p l a c e . We c o n s i d e r e d t h e f i r s t s t e p o f h y d r o l y t i c a c t i o n o f r i b o n u c l e a s e (RNase) on t h e dinucleotide substrate uridylyl-(3 -5 )-adenosine(UpA). Our r e s u l t s (20) o n t h e enzyme mechanism were c o n s i s t e n t w i t h t h e m a i n f e a t u r e s s u m m a r i z e d b y R o b e r t s e t a l (21) . The f i r s t s t e p i s a t r a n s p h o s p h o r y l a t i o n l e a d i n g t o c l e a v a g e ~oT t h e p h o s p h o d i e s t e r f

1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

540

PHOSPHORUS CHEMISTRY

f

f

bond y i e l d i n g a 2 - 3 c y c l i c p h o s p h a t e i n t e r m e d i a t e . Based o n t h e i n i t i a l x - r a y c o o r d i n a t e s ( 1 8 ) , we show ( 2 0 ) a l o w e n e r g y pathway f o r t h i s c l e a v a g e , w i t h l y s i n e - 4 1 o f l i m i t e d i m p o r t a n c e u n t i l t h e c y c l i c i n t e r m e d i a t e i s f o r m e d . An i n - l i n e a t t a c k o c c u r s g i v i n g a p e n t a c o o r d i n a t e d t r a n s i t i o n s t a t e i n t h e l o w energy p a t h . C o n s i d e r a t i o n o f a d j a c e n t a t t a c k and p o s s i b l e p s e u d o r o t a t i o n s result i n r e l a t i v e l y high a c t i v a t i o n energies f o r h y d r o l y t i c cleavage. I n o u r c u r r e n t s t u d y , e x p l o r i n g t h e p o s s i b l e mechanism o f a c t i o n o f s t a p h y l o c o c c a l n u c l e a s e , computer m o d e l i n g i s b a s e d o n the use o f x - r a y c o o r d i n a t e s (19) determined f o r t h e enzyme-in­ h i b i t o r c o m p l e x w i t h d e o x y t h y m i d i n e 3 - 5 d i p h o s p h a t e (dTdp) and c a l c i u m i o n . X - r a y c o o r d i n a t e s o f t h e atoms o f dTdp and o f enzyme r e s i d u e s i n v o l v e Glu43, Arg35, T y r l l 3 , Hys84 energy o f the system minimized w i t h r e s p e c t t o the p o s i t i o n s o f a l l atoms i n v o l v e d . S e v e r a l enzyme c o n s t r a i n t s a r e i n t r o d u c e d i n t o t h e c a l c u l a t i o n t o m i m i c t h e p o s s i b l e enzyme i n f l u e n c e s o n substrate conformation. By t h e a d d i t i o n o f a p a r a - n i t r o p h e n y l g r o u p t o t h e 5 - p h o s p h a t e , t h e i n h i b i t o r dTdp i s changed i n t o an a c t i v e s u b s t r a t e . F a c t o r s w h i c h c o n t r o l n o n e n z y m a t i c and e n z y ­ m a t i c h y d r o l y s i s o f deoxy thymidine-3 -phosphate-5 -para-nitrop h e n y l p h o s p h a t e a r e e x p l o r e d b y s i m u l a t i o n o f two r e a c t i o n p a t h ­ ways ( F i g . 1 ) . f

f

T

1

Path I

1

Path 2

-OH

leaving group

ribose-3- P 0 I base

4

leaving

Figure I. Reaction

group

pathways.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

111.

HOLMES ET AL.

Use of X-Ray Structural Results

541

The results of the computer simulation show, in agreement with experimental data, that the poorer leaving group is cleaved in enzymatic action, ie. Path 2 is the low energy path. This contrasts with nonenzymatic cleavage where the leaving group is the nitrophenoxide ion, ie. Path 1. Simulation of Path 1 for the enzyme produces a high energy route which is due to the presence of Arg35 blocking the approach of hydroxide ion to in­ line attack. Literature Cited 1. Holmes, R.R. "Pentacoordinated Phosphorus. Structure and Spec­ troscopy", Vol. I, ACS Monograph 175, Washington, D.C., 1980. 2. Holmes, R.R. "Pentacoordinated Phosphorus. Reaction Mechanisms", Vol. II, ACS Monograph 176, Washington, D.C., 1980. 3. Day, R.O., Holmes, R.R Inorg Chem 1980 19 3609 4. Day, R.O., Husebye, 3616. 5. Day, R.O., Holmes, R.R., Tautz, H . , Weinmaier, J . H . , Schmidpeter, A. Inorg. Chem. 1981, 20, 1222. 6. Richman, J.E., Day, R.O., Holmes, R.R. J. Am. Chem. Soc. 1980, 102, 3955. 7. Deiters, J . Α . , Gallucci, J . C . , Clark, T . E . , Holmes, R.R. J. Am. Chem. Soc. 1977, 99, 5461. 8. Holmes, R.R., Deiters, J.A. J. Am. Chem. Soc. 1977, 99, 3318. 9. Holmes, R.R. Acc. Chem. Res. 1979, 12, 257. 10. Brown, R.K., Day, R.O., Husebye, S., Holmes, R.R. Inorg. Chem. 1978, 17, 3276. 11. Meunier, P.F., Day, R.O., Devillers, J.R., Holmes, R.R., Inorg. Chem. 1978, 17, 3270. 12. Day, R.O., Husebye, S., Deiters, J . Α . , Holmes, R.R. J . Am. Chem. Soc. 1980, 102, 4387. 13. Gallucci, J . C . , Holmes, R.R. J. Am. Chem. Soc. 1980, 102, 4379. 14. Marsi, K.L. J . Org. Chem. 1975, 40, 1779. 15. Marsi, K . L . , Clark, R.T. J . Am. Chem. Soc. 1970, 92, 3791. 16. Richards, F.M., Wyckoff, H.R. "The Enzymes", P.D. Boyer, Ed., 3rd ed., Vol. IV, Academic Press, New York, 1971, pp. 647-806. 17. Anfinsen, C.B., Cuatrecasas, P., Taniuchi, H. ibid., pp. 177204. 18. Richards, F.M., Wyckoff, H.W. "Atlas of Molecular Structures in Biology, 1. Ribonuclease-S", D.C. Philips and F.M. Richards, Eds., Clarendon, Oxford, 1973. 19. Cotton, F.A., Hazen, J r . , E . E . , Legg, M.J. Proc. Natl. Acad. Sci. U.S.A. 1979, 76, 2551, and references cited therein. 20. Holmes, R.R., Deiters, J.Α., Gallucci, J.C. J. Am. Chem. Soc. 1978 100, 7393. 21. Roberts, G.C.K., Dennis, E.A., Meadows, D.H., Cohen, J . S . , Jardetzky, O. Proc. Natl. Acad. Sci. U.S.A. 1979, 62, 1151. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

112 Ligand Effects on the Reaction of Alkoxide Ions with Organophosphorus Derivatives Containing Multiple Leaving Groups K E N N E T H Ε. DEBRUIN, C H A R L E S Ε. E B E R S O L E , M O R G A N M . H U G H E S , and D A V I D M . JOHNSON Department of Chemistry, Colorado State University, Fort Collins, C O 80523

Nucleophilic displacement reactions on tetracoordinate phos phorus compounds containin proceed with widely varying stereochemistry particula case of oxyanions as nucleophiles, hydrolysis of phosphonium salts (1-3) alkoxide displacements on phosphonothioates (2, 4-6) and alkoxide displacements on phosphorothioates (5, 6) have been observed to displace the a l k y l t h i o ligand with retention, inver­ sion, and retention stereochemistry respectively. Presumably, these stereochemical differences reflect changes i n the structure of the k i n e t i c a l l y formed trigonalbipyramid intermediates with inversion resulting when the a l k y l t h i o ligand i s co-axial with the attacking nucleophile while retention requires the a l k y l t h i o group to be i n the equatorial position (equation 1). The varying stereochemistry therefore implies that the non-displaced ligands (A and Β i n equation 1) have a major influence on r e l a t i v e ener­ gies of the t r a n s i t i o n states leading to the two intermediates.

Suggestive that the o r i g i n of the stereochemical crossover from displacement with inversion i n the phosphonothioate system (A = Ph, Me; Β = O, S) to retention i n the phosphorothioate sys­ tem (A = OR, Β = O) is a function of the electronegativity of the ligand A, is the observation that phosphoramidothioates (A = NRR') undergo displacement of the a l k y l t h i o ligand with net inversion but considerable racemization (7, 8). The NRR' group i s of intermediate electronegativity between Ph and OR and appears to give intermediate stereochemistry between inversion and retention. However, no mention i s made of possible OR displacement which was observed i n the reaction of phosphonothioates (A = Ph) and would underestimate the amount of intermediate 2 formation or whether the racemization may have occurred after product formation. 0097-6156/81/0171-0543$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

544

PHOSPHORUS CHEMISTRY

We h a v e c a r r i e d o u t a d e t a i l e d p r o d u c t , s t e r e o c h e m i s t r y , and r a t e a n a l y s i s o f the r e a c t i o n of 0,S-dimethyl N - ( 1 - p h e n y l e t h y l ) phosphoramidothioate w i t h sodium ethoxide i n e t h a n o l a c c o r d i n g to t h e Scheme b e l o w . C o n c e n t r a t i o n s o f a l l f o u r s p e c i e s were f o l ­ l o w e d b y gas c h r o m o t o g r a p h y and t h e s t e r e o c h e m i s t r y o f t h e i n i t i a l d i s p l a c e m e n t p r o d u c t s were d e t e r m i n e d and c o r r e c t e d f o r i s o m e r i z a t i o n by i s o l a t i o n o f v a r i o u s t i m e i n t e r v a l s . ^ - n m r a n a l y s i s of

0 H

OEt

A — Ρ — SMe

1

\

OMe OEt

3

0 II ]

A — Ρ — OMe ι OEt

SMe

\

-OMe

0

II

0 M

OEt

A — Ρ — OEt 1 SMe

3

A — Ρ — OEt 1 OEt

SMe

t h e d i a s t e r e o m e r i c P-OMe o r P-SMe g r o u p s a f f o r d e d i s o m e r r a t i o and e x t r a p o l a t i o n t o t i m e z e r o gave t h e i n i t i a l r e a c t i o n s t e r e o ­ c h e m i s t r y ( 7 ) . The r e s u l t s a r e i n d i c a t e d i n T a b l e I and c o m p a r e d t o p h o s p h o n o t h i o a t e and p h o s p h o r o t h i o a t e s y s t e m s . It appears t h a t t h e c o m p e t i t i o n b e t w e e n t h e two modes o f a t t a c k by e t h o x i d e i o n on p h o s p h o r a m i d o t h i o a t e s i s v i r t u a l l y i d e n t i c a l t o t h a t f o r p h o s p h o n o t h i o a t e s and n o t i n t e r m e d i a t e i n b e h a v i o r . Table I . P r o d u c t s and C o m p e t i t i o n s f o r F o r m i n g I n t e r m e d i a t e i n the R e a c t i o n of A l k o x i d e Ions w i t h T h i o a t e E s t e r s of Phosphorus SMe

f

' OMe

A

e

-

OR

?"

e

OR

OR

%

Products

%

Products

Ph

OMe

85

100%-SMe

15

100%-OMe

PhCHMeNH

OEt

80

100%-SMe

20

95%-OMe 5%-SMe

iPrO

OEt

0

100

100%-SMe

pN0 Ph

OEt

62

100%- SMe

38

100%-OMe

Ph

OEt

78

100%- SMe

22

100%-OMe

pMe NPh

OEt

83

100%- SMe

17

100%-OMe

2

Ref, 4

5

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

112.

DeBRUIN E T A L .

Ligand

Effects

on

Alkoxide

Ions

Reaction

545

As a f u r t h e r e v a l u a t i o n o f t h e p o s s i b l e e l e c t r o n e g a t i v i t y c o n t r o l by an e q u a t o r i a l l i g a n d on r e l a t i v e s t a b i l i t i e s o f t h e t r a n s i t i o n s t a t e s l e a d i n g t o a t t a c k by a l k o x i d e i o n c o - a x i a l w i t h an SMe g r o u p v s a n OMe g r o u p , we i n v e s t i g a t e d t h e p r o d u c t s f r o m the r e a c t i o n o f sodium e t h o x i d e w i t h p a r a - s u b s t i t u t e d 0 , S - d i raethyl p h e n y l p h o s p h o n o t h i o a t e s . A s s u m i n g c o m p l e t e i n v e r s i o n o f c o n f i g u r a t i o n , p r o d u c t r a t i o s c o r r e c t e d a s above a c c o r d i n g t o t h e Scheme r e f l e c t modes o f a t t a c k . The r e s u l t s a r e l i s t e d i n Table I . C l e a r l y , for large e l e c t r o n i c v a r i a t i o n s i n l i g a n d A ( r a t e c o n s t a n t s s p a n f o u r powers o f 10) a m i n o r v a r i a t i o n i n modes o f i n t e r m e d i a t e f o r m a t i o n i s o b s e r v e d ; a g a i n suggestive that t h e e l e c t r o n e g a t i v i t y o f l i g a n d A i s a minor c o n t r i b u t o r t o d e t e r m i n i n g c o m p e t i t i v e a t t a c k s by a n u c l e o p h i l e . I n t h e absence o f t r o l l i n g c o m p e t i t i v e mode i n t e r m e d i a t e from a t t a c k by a n u c l e o p h i l e on a t e t r a c o o r d i n a t e o r g a n o p h o s p h o r u s e s t e r must r e f l e c t t h e r e l a t i v e a f f i n i t i e s o f l i g a n d s t o occupy an a x i a l s i t e v e r s u s e q u a t o r i a l s i t e s . To e v a l u a t e t h e s e a f f i n i t i e s , we h a v e measured t h e r a t e s o f r e a c t i o n o f s o d i u m m e t h o x i d e i n m e t h a n o l w i t h a v a r i e t y o f compounds. The r e s u l t s a r e given i nTable I I as logarithm o f r a t e constants f o r a t t a c k b y m e t h o x i d e c o - a x i a l w i t h l i g a n d Y. A c o m p a r i s o n o f t h e r a t e c o n s t a n t s k(Y=SMe) a n d k(Y=0Me) f o r p l a c i n g SMe v s OMe i n t h e a x i a l p o s i t i o n o f t h e t r a n s i t i o n s t a t e r e s p e c t i v e l y i n d i c a t e s a c a . 50-100 f o l d r a t e p r e f e r e n c e by t h e SMe g r o u p f o r a l l compounds s t u d i e d . Therefore, the o r i g i n o f t h e s t e r e o c h e m i c a l c r o s s o v e r between p h o s p h o n o t h i o a t e s and p h o s p h o r o t h i o a t e s l i e s n o t i n t h e k i n e t i c a f f i n i t i e s o f t h e two g r o u p s f o r a n a x i a l p o s i t i o n . I n t h e p h o s p h o n o - s y s t e m (A=Ph) r e p l a c i n g a n e q u a t o r i a l g r o u p B=0Me b y B=SMe p r o d u c e s a c a . 10 f o l d r a t e a c c e l e r a t i o n w h i l e i n t h e p h o s p h o r o - s y s t e m (A=Me0) r e p l a c i n g B=0Me b y B=SMe p r o d u c e s a c a . 500 f o l d r a t e acceleration. Thus, p h o s p h o n o t h i o a t e s k i n e t i c a l l y p r e f e r t o p l a c e t h e SMe g r o u p a x i a l (100/10) w h i l e p h o s p h o r o t h i o a t e s p r e f e r p l a c i n g t h e SMe g r o u p e q u a t o r i a l (500/100) c o n s i s t e n t w i t h t h e stereochemical results. Table I I . Rate Constants f o r Reaction of O r g a n o p h o s p h o r u s E s t e r s w i t h Sodium M e t h o x i d e (0.116M) i n M e t h a n o l a t 20.0°. ABP(0)Y A Β

Y=0Me

Ph Ph Ph Ph MeO MeO

-2.50 -3.19 -3.02 -4.19 -2.84 -5.60

Me Ph SMe OMe SMe OMe

log

k Y-SMe -0.32 -1.52 -0.84 -2.23

σ(Α)

σ(Β)

-1.1 -1.1 -1.1 -1.1 -2.5 -2.5

-0.6 -1.1 +0.9 -2.5 +0.9 -2.5

-1.7 -2.2 -0.2 -3.6 -1.6 -5.0

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

546

PHOSPHORUS CHEMISTRY

To evaluate whether the 10 fold or the 500 fold rate accel­ eration observed by replacing B=0Me by B=SMe is the "normal" effect, we have adopted as a model the σ (inv) constants of Splitter and Calvin (9) defined for the effect of ligands on the pyramidal inversion barriers of amines. A parallel between amines and phosphorus barriers has been demonstrated (10). Pre­ sumably, in the inversion processes, hybridization changes in the bond between the center atom and a ligand upon undergoing pyra­ midal inversion would resemble the changes in placing a ligand into the equatorial position upon forming a trigonal-bipyramid intermediate from tetrahedral reactants in the absence of steric factors. Since a phenyl ligand has a resonance acceleration to pyramidal inversion which would be absent in nucleophilic attack at tetracoordinate phosphorus we estimated the σ constant for phenyl (-1.1) to be intermediat A plot of the logarithm (Y=0Me) agains sum of the σ constants for ligands A and Β gives a good linear correlation for a l l compounds except 0,S-dimethyl phenylphosphonothioate (A=Ph, B=SMe) which reacts by a factor of 50 slower than predicted. Although the validity of this treatment may be in doubt, the results suggest that an alkylthio has a net rela­ tively higher affinity for equatorial placement compared to an alkoxy group upon nucleophilic attack at tetracoordinate phos­ phorus. Thus, attack of the nucleophile co-axial with an alkoxy group should be preferred. The reason for preferred attack of alkoxide ion co-axial with the alkylthio group in phosphonothio­ ates and phosphoramidothioates is at present unresolved but may suggest these compounds are not undergoing rate limiting forma­ tion of a pentacoordinate intermediate. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

De'Ath, N. J.; E l l i s , K.; Smith, D. J . H.; Trippet, S. J.C.S. Chem. Commun. 1971, 714. Farnham, W. B.; Mislow, K.; Mandel, N.; Donohue, J . J.C.S. Chem. Commun. 1972, 120. DeBruin, Κ. Ε.; Johnson, D. M. J . Am. Chem. Soc. 1973, 95, 4675. DeBruin, Κ. Ε . , Johnson, D. M. J. Am. Chem. Soc. 1973, 95, 7921. Cooper, D. B.; Hall, C. R.; Harrison, J . M.; Inch, T. D. J.C.S. Perkin I, 1977, 1969. Inch, T. D.; Lewis, G. J . Carbohydrate Res. 1975, 45, 65. Hall, C. R.; Inch, T. D. Tetrahedron Lett. 1977, 3765. Hall, C. R.; Inch, T. D. J.C.S. Perkin I, 1979, 1646. Splitter, J . S.; Calvin, M. Tetrahedron Lett. 1973, 4111. Baechler, R. D.; Andose, J . D.; Stackhouse, J.; Mislow, K. J . Am. Chem. Soc. 1972, 94, 8060.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

113 Methanolysis of a Phosphate Ester WILLIAM S. WADSWORTH, JR. Department of Chemistry, South Dakota State University, Brookings, SD 57007

In a recent publication, we described the proton catalyzed methanolysis of 2-substituted-5-(chloromethyl)-5-methyl-2-oxo -1,3,2-dioxaphosphorinan trations the configuration at phosphorus was retained while at elevated proton concentrations both retention and inversion oc­ cur with inversion predominating. At low acid concentrations protonation takes place on phosphoryl oxygen, the most basic site. Displacement occurs via a pentavalent intermediate. At high concentrations additional protonation of the leaving group leads to both retention and inversion with the latter a direct displacement. For metal ion catalysis under acidic conditions we confined our study to Zn . While final isomer ratios are not unlike those found at high proton concentrations, there are specific 2+

differences between the two systems. The zinc ion catalyzed re­ actions proceed at a reasonable rate at room temperature. Leav­ ing groups which can coordinate with the ion, i.e., those con­ taining trivalent nitrogen, are particularly effective. Reactions are not first order in catalyst, above one equivalent rates are only slightly effected while below one equivalent the retention­ -inversion ratio increases. In those cases where rates are low, retention i s the only route. Rates are not first order in ester but f a l l off rapidly as reaction proceeds. Addition of product to reaction mixtures causes rates to fall dramatically and at the low effective catalyst concentrations, retention only i s observed. Added trans para methoxyphenyl ester (R=OC H7pΟCΗ ) completely inhibits methanolysis. .

6

3

0097-6156/81/0171-0547$05.00/0 ©1981AmericanChemicalSociety In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

548

PHOSPHORUS

CHEMISTRY

T h u s , m e t h a n o l y s i s o f p h o s p h a t e e s t e r s c a n be c a t a l y z e d b y zinc i o ne i t h e r r a p i d l y with both i n v e r s i o n or r e t e n t i o n i n c a s e s w h e r e b o t h p h o s p h o r y l o x y g e n a n d l e a v i n g g r o u p s a r e compl e x e d o r s l o w l y a n d b y r e t e n t i o n i n c a s e s where c o m p l e x f o r m a ­ t i o n i s through p h o s p h o r y l oxygen o n l y . With phosphates having p o o r l e a v i n g g r o u p s , z i n c i o n i s t i g h t l y bound a n d i t s c a t a l y t i c effect inhibited. Methanolysis of cis-2-chloro-5-(chloromethyl)-5-methyl-2o x o - 1 , 3 , 2 - d i o x a p h o s p h o r i n a n c a t a l y z e d by one e q u i v a l e n t o f base ( C H 3 O " ) p r o c e e d s e n t i r e l y by r e t e n t i o n . U n c a t a l y z e d m e t h a n o l y ­ s i s p r o c e e d s s l o w l y by i n v e r s i o n . P h e n y l e s t e r s do n o t r e a c t u n d e r n e u t r a l c o n d i t i o n s b u t u n d e r g o m e t h a n o l y s i s e x c l u s i v e l y by r e t e n t i o n i n t h e presence o f base. I n t h i s s t u d y c a r e was t a k e n t o i n s u r e t h a t c o n c u r r e n t i s o m e r i z a t i o n o f s t a r t i n g m a t e r i a l s by liberated ion did not phenyl ester (R=OC5H3 p r o b l e m a n d t h e e s t e r was n o t u s e d . Methoxide i o n , present i n v e r y s m a l l c o n c e n t r a t i o n s , i s a more e f f e c t i v e n u c l e o p h i l e t h a n phenoxide i o n s . M e t h a n o l y s i s f o l l o w s f i r s t o r d e r k i n e t i c s , T a b l e I , and g i v e s u s i n g s i g m a v a l u e s , a n a c c e p t a b l e Hammett p l o t . For the m e t h a n o l y s i s o f t h e n i t r o p h e n y l e s t e r (R=0C6H *£N0 ) t r i e t h y l amine a n d s o d i u m n i t r o p h e n o x i d e a r e e q u a l l y a s e f f e c t i v e . The l a c k o f a common i o n e f f e c t , s l o w m e t h a n o l y s i s o f a p h o s p h a t e h a v i n g a b u l k y l e a v i n g group (R^C^H^* 2 . 6 ( C H 3 ) ) , and s l o w e t h a n o l y s i s compared t o m e t h a n o l y s i s w o u l d p o i n t t o t h e f i r s t s t e p , formation of a pentavalent intermediate, as r a t e determining. A number o f a n o m o l i e s e x i s t . The h i g h r e a c t i v i t y o f t h e t h i o p h e n y l e s t e r (R=SC5H^) may be due t o l o w , compared t o o x y g e n analogues, e l e c t r o n d e n s i t y about phosphorus, t h e r e s u l t o f poor 4

2

2

Table I . R OC H *£N0 6

4

1 / 2

12.0

2

12.0 8.0 36 ~350 96 >

OC H -mN0

2

38

OC H -oN0

2

22

OC OC OC OC OC

6

6

6

6

6

6

6

H H H H H

4

4

4

4

4

-mN0 -oN0 -£N0 -£N0 *£N0

2

Base C a t a l y z e d t (hr)

4

4

2

2

b

2

c

2

b

b

b

d

a

Methanolysis o f Trans E s t e r s t (hr) R 1 / 2

0C H *pCH0 6

0 C

H

6 0C OC 0C OC

35

4

F

6

6

6

6

4'£ H *£CH H H -£0CH H -2,6(CH ) 4

1

4

3

3

2

SC6H5

OC H -£N0 6

5

8

142 150 270 550

3

5

3

1

1.5 b

oo »

2

c

a

S o l u t i o n s 0.1 m o l a r i n e s t e r a n d t r i e t h y l a m i n e , room t e m p e r a t u r e . 50% methanol-acetone. 50% ethanol-acetone. ^cis ester. c i s t h i o p h o s p h o r y l (P=S) e s t e r .

b

c

e

b a c k b o n d i n g b e t w e e n p h o s p h o r u s and s u l f u r . U n l i k e i t s para ana­ l o g u e , t h e e s t e r p r e p a r e d f r o m s a l i c y l a l d e h y d e (R=0C^H *£CH0) 4

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

113.

WADSWORTH

Methanolysis

of a Phosphate

549

Ester

does n o t undergo s u b s t i t u t i o n b u t c l e a v e s t o form a c e t a l and s a l t of the a c i d phosphate. I n t e r a c t i o n o f the ortho s u b s t i t u e n t w i t h t h e p h o s p h o r y l g r o u p i s most l i k e l y . A s i m i l a r phenomena may e x ­ p l a i n t h e r a t h e r r a p i d m e t h a n o l y s i s o f t h e o r t h o n i t r o e s t e r (R= OCfcH^'oNC^). The l a c k o f r e a c t i v i t y o f t h e t h i o p h o s p h a t e r e f l e c t s t h e l o w p o l a r i z a t i o n o f t h e p h o s p h o r y l - s u l f u r bond compared t o a p h o s p h o r y l - o x y g e n bond. M e t h a n o l y s i s was e x t e n d e d t o a f e w a c y c l i c s y s t e m s (2). The rate o f methanolysis of jj-nitrophenyl esters again r e f l e c t s d i f ­ f e r e n c e s i n t h e e l e c t r o p h i l i c i t y o f t h e p h o s p h o r u s atom. Ethyl d i - p - n i t r o p h e n y l phosphate l o s e s t h e f i r s t p - n i t r o p h e n o x i d e group upon d i s s o l v i n g i n 5 0 % m e t h a n o l - a c e t o n e . L o s s o f t h e s e c o n d i s much s l o w e r ( t i / = 3 3 5 h r s , 0.1 m o l a r s o l u t i o n s ) . D i p h e n y l £ n i t r o p h e n y l phosphate undergoe a c e t o n e much more r a p i d l molar s o l u t i o n s ) but a g phos p h o r i n a n system, e t h a n o l y s i s i s slower (t-L/ =22hrs). Finally, b i s - d i m e t h y l a m i n o p - n i t r o p h e n y l phosphate does n o t undergo base c a t a l y z e d m e t h a n o l y s i s a t room t e m p e r a t u r e . As w i t h a c i d c a t a l y z e d m e t h a n o l y s i s , added c a t i o n s have a d r a m a t i c e f f e c t on base c a t a l y z e d m e t h a n o l y s i s as w e l l , T a b l e I I . 2

2

Table I I .

E f f e c t o f C a t i o n s on B a s e C a t a l y z e d M e t h a n o l y s i s o f Phosphorinan Esters Inv.(%) Ret.(%) Catalyst t (hr)

R

1 / 2

0C H -£N0 0C H - N0 6

4

6

0 C

4

£

H

2

4

£

2

6

4

£

2

6

a

2

N 0

6

4

CH C00Na Hg(C H 0 )2 Mg(C H 02)2*4H Zn(C H 0 ) -3H Pb(C H 0 ) -3H Mg(C H 0 ) '4H Pb(C H 0 ) -3H 3

2

6 4*£ 2 0C H - N0 0C H - N0 0C6H *pC0CH 0C H '£C0CH 4

b

3

2

2

3

3

3

2

3

3

2

2

2

2

2

2

3

2

2

2

3

2

2

2

2

3

2

2

2

0 0 0 0 0

97 190 31 7 1.25 38 3.4

100 73 70 42 12 52 13

0 27 30 58 88 48 87

R e a c t i o n s 0.1M i n e s t e r a n d c a t a l y s t .

M e t a l a c e t a t e s , due t o t h e i r s o l u b i l i t y i n m e t h a n o l w e r e u s e d . C a r e f u l m o n i t o r i n g o f r e a c t i o n s gave no i n d i c a t i o n t h a t p r i o r i n ­ volvement o f a c e t a t e i o n occurs. Sodium i o n h a s no e f f e c t a n d m e t h a n o l y s i s under the b a s i c c o n d i t i o n s proceeds w i t h complete retention. Lead i o n i s p a r t i c u l a r l y e f f e c t i v e , s t r o n g bonding w i t h the l e a v i n g group, and m e t h a n o l y s i s i s d i v e r t e d t o d i r e c t s u b s t i t u t i o n and i n v e r s i o n . M e t a l a c e t a t e s i o n i z e t o d i f f e r e n t d e g r e e s w h i c h makes r a t e d a t a u n r e l i a b l e . T h e r e i s , h o w e v e r , a rough c o r r e l a t i o n between r a t e s and the degree o f i n v e r s i o n . I n a l l work r e p o r t e d h e r e i n , p r o d u c t m i x t u r e s were o b t a i n e d by swamping a l c o h o l i c s o l u t i o n s w i t h d i l . H C l , e x t r a c t i o n w i t h m e t h y l e n e c h l o r i d e a n d t h e e x t r a c t washed w i t h d i l u t e KOH. P r o ­ d u c t r a t i o s d i d n o t c h a n g e u n d e r r e a c t i o n o r workup c o n d i t i o n s .

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

550

PHOSPHORUS CHEMISTRY

To predict retention and/or inversion a number of factors are important (3). a. Retention is favored by strong nucleophiles which are capable of backbonding to phosphorus. b. Retention is promoted by ligands which enhance the electrophilicity of the phosphorus atom. c. A catalyst which can complex with phosphoryl oxygen will promote retention. d. With the diminished importance of a and b and the pre­ sence of a good leaving group which may complex with a positive ion, inversion becomes favorable. Acknowledgement is made to the Donors of The Petroleum Research Fund, administered by th support of this research Literature Cited 1. 2. 3.

Gehrke, S. H.; Wadsworth, W. S., Jr. J. Org. Chem., 1980, 45, 3921. Bel'skii, V. Ε.; Kudryavtseva, L. Α.; Derstuganova, Κ. Α.; Fedorov, S. B.; Ivanov, Β. Ε. Zh. Obshch. Khim., 1980, 50, 1997. Hall, R. C.; Inch, T. D. Tetrahedron, 1980, 36, 2059.

RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

114 Reactivity of Tricoordinated Phosphorus Compounds A M e c h a n i s t i c S t u d y w i t h a Variety o f Substrates C. DENNIS HALL, ROBERT C. EDWARDS, JOHN R. LLOYD, PAUL D. BEER, PHILIP J. H A M M O N D , ALBERTO O. D'AMORIM , and MELVIN P. MELROSE 1

1

Department of Chemistry, King's College, University of London, Strand, London WC2R 2LS, England

Tricoordinated phosphoru of substrates and a grea available within this area. The classical work involved the quaternization of phosphines with alkyl halides and the famous Arbusov reaction which prompted intensive studies in the field of organophosphorus chemistry. Both reactions involve nucleophilic attack of tricoordinated phosphorus on tetrahedral carbon and show all the characteristics of non-polar reactants combining through polar transition states although the solvent effects are sometimes quite modest. Sub­ sequent studies have demonstrated nucleophilic attack on activated alkenes, activated alkynes, the carbonyl group and halogen whilst in the Perkow reaction (eqn. 1) all four possible sites in 1-3

4

5,6

2

7

7

1-3

8

3

the substrate (halogen, sp C, carbonyl carbon and carbonyl oxygen) have at some time been proposed as the site of nucleophilic attack. In more recent years the range of substrates has broadened to include the O - O bond in various peroxides, the S - S bond, the S - O bond in sulphenate esters, the S - Ν bond in sulphenamides and others which are too numerous to mention. It i s the purpose of this paper to collate much of the available information and in combination with new kinetic data to offer an overall view and rationalization of the reactivity of tricoordinated phosphorus compounds. A selection of the kinetic information available from a variety of substrates i s shown in Table I in which the conditions of temperature and solvent have been maintained as uniform as possible. 2,5,9

10,11

12,13

14,15

16,17

1Theoretical contributions. 0097-6156/81/0171-0551$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS

552

TABLE 1.

CHEMISTRY

Second-order r a t e c o e f f i c i e n t s f o r t h e r e a c t i o n o f Ρ(III) compounds w i t h f o u r t y p e s o f s u b s t r a t e ΙΟ

3

χ k

s"

1

£ mole

2

1

a t 25°C Source

Substrate Ph P

Ph P0R

3

Mel

a

Et00Et

5.0 b

b

3

Ρ(OR)

2

2.2

3.6

4.4 χ 1 0 "

PhSSSPh

PhP(0R)

2

29 χ 1 0 ~

0.35

4.9 χ 1 0 "

3

3

c, d

f

3

c

3.3 12,520

4.6

$8

c, e

^ 5.0

9700

1

R = P r throughout except f o r S /P(0R) f o r which R = E t . a ) i n C H C N b) i n C H C H c ) t h i s w o r k d) Songstad J . A c t a . Chem. S c a n d . ( A ) 1976, 3 0 , 724 e) r e f . 1 2 . f ) v e r y s l o w . 8

3

6

5

3

3

I t i s immediately obvious t h a t w i t h Mel the r a t e s of r e a c t i o n decrease i n the a n t i c i p a t e d order of n u c l e o p h i l i c r e a c t i v i t y , i . e . , P h P > P h P 0 R > P h P ( O R ) > P ( 0 R ) whereas w i t h t h e o t h e r s t h e rate order f o l l o w s t h e sequence Ph P0R > P h P ( 0 R ) > Ph P * (RO) P. The l a t t e r " a n o m a l o u s " b e h a v i o u r has been a s c r i b e d t o t h e d i r e c t f o r m a t i o n o f p e n t a c o o r d i n a t e d p r o d u c t s from P ( I I I ) and t h e sub­ s t r a t e a s d i s t i n c t f r o m n u c l e o p h i l i c d i s p l a c e m e n t by p h o s p h o r u s so t h a t t h e s t a b i l i t y o f t h e T.S. l e a d i n g t o t h e p e n t a c o o r d i n a t e d m o l e c u l e d i c t a t e s t h e rate.£>ϋ> 11 T h e r e i s no d o u b t t h a t s e v e r a l r e a c t i o n s w h i c h d i s p l a y t h e anomalous r a t e sequence (eg w i t h p e r ­ o x i d e s , s u l p h e n a t e e s t e r s a n d d i t h i e t e n e s ) do g i v e p e n t a c o o r d i ­ n a t e d p r o d u c t s and t h e p r o p o s a l i s g i v e n f u r t h e r s u p p o r t by t h e r e a c t i o n o f d i e t h y l p e r o x i d e w i t h a s e r i e s o f c y c l i c phosphines i n w h i c h t h e r a t e sequence p a r a l l e l s t h e s t a b i l i t y o f t h e P ( V ) products.il F u r t h e r m o r e , under t h e a p p r o p r i a t e c o n d i t i o n s p e n t a ­ c o o r d i n a t e d p r o d u c t s a r e a l s o f o r m e d f r o m a l k e n e s ( e q n . 2) and a l k y n e s i i L (eqn. 3) a n d a l t h o u g h r a t e d a t a i s o n l y a v a i l a b l e f o r 3

2

2

3

2

2

OR

R 'ΠΗ Ar P(0R) . n

3

n

+ CH =CHY

3

1

^ >

2

3

(2)

A r P (OR) _ C H C H Y n

3

n

2

2

31

η = 1 or 2

Y = C 0 E t o r CN

δ

2

Ρ (H PO ) 3

l+

-50 (η -35 (η

2) 1)

OR*

1

R *OH Ar POR + PhC5CC0 Et 2

2

>

Ar Ρ(OR)C(Ph)-CHC0 Et 2

2

31

6

Ρ = -54

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

(3)

114.

HALL E T A L .

Tricoordinated

Phosphorus

553

Compounds

p h o s p h i n i t e s a n d p h o s p h o n i t e s , t h e same r e a c t i o n s w i t h p h o s p h i t e s and t r i a r y l p h o s p h i n e s a r e q u a l i t a t i v e l y v e r y much s l o w e r . How­ e v e r , whereas t h e r e a c t i o n w i t h p e r o x i d e i s u n a f f e c t e d by s o l v e n t c h a n g e s , ϋ » 1 £ t h e r e a c t i o n s w i t h M e l , PhSSSPh and SQ show i n c r e a ­ s i n g s e n s i t i v i t y t o s o l v e n t p o l a r i t y s o t h a t r e a c t i o n w i t h Sg appears t oproceed through a h i g h l y p o l a r t r a n s i t i o n s t a t e despite t h e "anomalous" r e a c t i v i t y s e q u e n c e f r o m p h o s p h i n e s t o p h o s p h i t e s . The a v a i l a b i l i t y o f a w i d e r a n g e o f Ρ(III) compounds f r o m the work w i t h a c t i v a t e d a l k e n e s , w h i c h i s r e l e v a n t t o t h e dimer i s a t i o n of a c r y l o n i t r i l e , f a c i l i t a t e d the determination o f p-values ( T a b l e I I ) f o r a number o f s u b s t r a t e s b y s y s t e m a t i c v a r i a t i o n o f t h e p a r a - s u b s t i t u e n t s i n t h e a r y l g r o u p s on p h o s p h o r u s . The d a t a Table I I Rho-values f o variety of substrate a

(°C)

Ρ

Substrate

• Source Ar P

-)c - X (X = C l , B r , I ) CH =CHCN 2

-1.1

2

(30)

-

2

b,c

-1.2

(30)

-2.0

(30)

-1.8 ( 3 0 )

(27)

-0.4

-

b

(37)

b

- 1 . 2 (25)

-1.1 (25)

b

(25)

-3.2

(25)

-3.3

(25)

-3.3

(25)

-2.2 (25)

EtOOEt

-0.4 (28)

-0.3

PhSSSPh

-1.2

(2 5)

-2.5 -3.2

TCNQ

ArP(0R)

Ar P0R

3

a) Maximum e r r o r t h r o u g h o u t ± 1 0 % o f ρ - v a l u e c) r e f . 9 d) r e f . 1 2 .

b,d

(25)

b

b) t h i s w o r k

r e v e a l t h a t a l l t h e r e a c t i o n s a r e a c c e l e r a t e d by e l e c t r o n d o n a t i o n ( i . e . have a n u c l e o p h i l i c component) a n d t h a t t h e r e i s a w i d e range o f s e n s i t i v i t y o f r e a c t i o n r a t e t o t h e e l e c t r o n i c e f f e c t s of s u b s t i t u e n t s a t phosphorus. I t i s also apparent that t h e pv a l u e s a r e v i r t u a l l y i n d e p e n d e n t o f t h e t y p e o f P ( I I I ) compound f o r a g i v e n s u b s t r a t e b u t change w i t h t h e n a t u r e o f t h e s u b s t r a t e . I t seems l i k e l y t h a t t h e m a g n i t u d e o f ρ r e p r e s e n t s t h e " e x ­ t e n t o f e l e c t r o n demand" a t p h o s p h o r u s L i i n t h e T.S. o r i n o t h e r w o r d s i s a measure o f " e l e c t r o n t r a n s f e r " i n t h e T.S., a t e r m (=z) which appears i n t h e semi-empirical equations d e s c r i b i n g t h e n u c l e o p h i l i c r e a c t i v i t y of t r i c o o r d i n a t e d phosphorus.il. This c o n c e p t i s r e i n f o r c e d by ( i ) t h e o b s e r v a t i o n ( f r o m t h e d a t a o f B o k o n o v H and G o e t z u ' u î ) t h a t p - v a l u e s b a s e d o n t h e p K v a l u e s of p r o t o n a t e d phosphines i n c r e a s e w i t h i n c r e a s i n g ρ % , i . e . i n c r e a s e w i t h a s h i f t o f t h e e q u i l i b r i u m (eqn. 4) t o t h e l e f t and a

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

554

(ii) by the fact that reactions of higher ρ value (eg SQ) show a higher sensitivity to solvent. Literature cited 1. Kosolapoff, G.M. and Maier, L.(eds) "Organic Phosphorus Com­ pounds", Vols 1 and 4, Wiley Interscience, New York, 1972/73. 2. Emsley, J . and Hall, C.D. "The Chemistry of Phosphorus", Harper and Row, London, 1976. 3. Trippett, S. Specialist Reports, Royal Society of Chemistry, Organophosphorus Chemistry, Vols 1-11, 1969-1979. 4. Davies, W.C. and Lewis W.P.G J Chem Soc 1934 1599 5. Arbusov, B.A. Pur 6. Aksnes, G. and Aksnes 7. Shaw, M.A. and Ward, R.S. Topics in Phosphorus Chemistry, 1972, Vol 7, p.11. 8. Jarvis, Β.B. and Marien, B.A. J . Org. Chem. 1976, 41, 2182. 9. Borowitz, I . J . ; Firstenberg, S.; Borowitz, G.B. and Schuessler, D. J . Amer. Chem. Soc. 1972, 94, 1623. 10. Denney, D.B. and Jones, D.H. J . Amer. Chem. Soc. 1969, 91, 5821. 11. Denney, D.B.; Denney, D.Z.; Hall, C.D. and Marsi, K.L. J . Amer. Chem. Soc. 1972, 94, 245. 12. Bartlett, P.D. and Meguerian, G. J . Amer. Chem. Soc. 1956, 78, 3710. 13. Feher, F. and Kurz, D. Z. Naturforsch, B. 1968, 23, 1030. 14. Chang, L . L . ; Denney, D.B.; Denney, D.Z. and Kazior, R.J. J. Amer. Chem. Soc. 1977, 99, 2293. 15. Bowman, D.A.; Denney, D.B. and Denney, D.Z. Phosphorus and Sulphur, 1978, 4, 229. 16. Aida, T.; Furukawa, Ν. and Oae, S. Chem. Lett. 1973, 805. 17. Hammond, Ρ. J.; Lloyd, J. R. and Hall, C.D. Phosphorus and Sulphur, 1981 (in press) 18. Beer, P.D.; Edwards, R.C.; Hall, C.D.; Jennings, J.R. and Cozens, R.J. Chem. Comm. 1980, 351. 19. Scott, G.; Hammond, P.J.; Hall, C.D. and Bramblett, J . J. Chem. Soc. Perkin II, 1977, 882. 20. Kosower, E.M. "An Introduction to Physical Organic Chemistry" 1968, J . Wiley, p.54. 21. Hudson, R.F. "Structure and Mechanism in Organophosphorus Chemistry", 1965, Academic Press, Chap. 4. 22. Stepanov, Β . I . ; Bokanov, A.I. and Kovolev, B.A. J. Gen. Chem. USSR (English Ed) 1967, 37, 2029. 23. Goetz, H. and Siegfried, D. Annalen, 1967, 704, 1. 24. Goetz, H. and Sidhu, A. Annalen, 1965, 682, 71. RECEIVED

June 30,

1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

115 A New Stereospecific Synthesis of a P(III) Organophosphorus Ester LEONARD J. SZAFRANIEC, LINDA L. SZAFRANIEC, and HERBERT S. AARON Research Division, Chemical Systems Laboratory, Aberdeen Proving Ground, MD 21010

We have studied the reaction of methyl trifluoromethanesulfonate (methyl triflate and have used this syste stereospecific synthesis of trivalent (P ) organophosphorus esters. Methyl triflate is a powerful alkylating agent, which methylates tetracovalent P=0, P=S, and P=Se systems at the oxygen, sulfur, and selenium atoms, respectively (1,2,3). Its reaction with analogs containing a hydrogen substituent (e.g., phosphinate, phosphonate or secondary phosphine oxide species), however, appears not to have been reported. Neat isopropyl methylphosphinate (1) reacts exothermically on dropwise addition to methyl triflate to form a phosphonium salt (2), P NMR δ +73.4 (downfield from external H PO ) J = 656 Hz, which yields isopropyl methyl methylphosphonite (3), when slowly added to a cold benzene solution containing excess t r i ethylamine (TEA). On warming to room temperature, the product was obtained as a benzene/TEA solution, which separated from a heavier liquid layer that consisted mainly of amine salt byproducts in benzene/TEA. When (R)-(+)-l (25% enantiomorphic excess) was used, a solution of (R)-(+)-3 (δ +176.6) was obtained in 60% yield, 90 mole-% pure with respect to its organophosphorus content. The specific rotation of this product was calculated to be [α]26D + 67.7 (c 2.6, benzene), if optically pure (+)-l starting material had been used. To isolate the neat product, the more volatile ether/trimethylamine combination was used in the reaction, because a higher recovery of product was obtained in trials conducted with the racemic material. However, the neat, distilled, optically active product proved to be stereochemically labile at ambient tempera­ ture, and was considerably racemized compared to that obtained directly in the benzene/triethylamine solution. Moreover, the latter was relatively stable when further diluted in benzene solu­ tion at ambient temperature, showing only a 14% decrease in opti­ cal rotation after 70 hours at 26 . For stereochemical studies, 31

3

4

o

o

This chapter not subject to U.S. copyright. Published 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

-P-H

PHOSPHORUS CHEMISTRY

558

t h e r e f o r e , t h e product i s b e t t e r used d i r e c t l y i n s o l u t i o n , as o b t a i n e d , and n o t i s o l a t e d a s t h e n e a t m a t e r i a l . The benzene/TEA s o l u t i o n o f t h e (+)-3 p r o d u c t d e s c r i b e d above was d i r e c t l y t r e a t e d w i t h s u l f u r and c o n v e r t e d i n t o ( S ) - ( - ) i s o p r o p y l m e t h y l m e t h y l p h o s p h o n o t h i o n a t e ( 4 ) , δ +96.4. The s p e c i f i c r o t a t i o n o f t h e p r o d u c t t h u s o b t a i n e d was c a l c u l a t e d t o equal [ a ] - 1 . 5 5 ° (neat, uncorrected f o r 8 wt-% i m p u r i t i e s ) , i f o p t i c a l l y p u r e ( + ) - l had b e e n u s e d i n t h e i n i t i a l r e a c t i o n . T h i s r o t a t i o n compares t o t h e h i g h e s t l i t e r a t u r e value» [α]^ 1.50 » r e p o r t e d f o r o p t i c a l l y a c t i v e 4, o b t a i n e d f r o m r e a c t i o n o f s o d i u m methoxide w i t h o p t i c a l l y pure i s o p r o p y l methylphosphonochloridot h i o n a t e ( 6 ) ( 4 ) . T h e s e r e a c t i o n s a p p e a r t o be h i g h l y , i f n o t c o m p l e t e l y , s t e r e o s p e c i f i c , and a r e i n agreement w i t h t h e a s s i g n ­ ed r e t e n t i o n o f c o n f i g u r a t i o f o t h c o n v e r s i o f (+)-l t (+) 3, b a s e d on t h e c h e m i s t r of t h e s u l f u r a d d i t i o n ( 5 ) , (4,6 ) relationship b e t w e e n ( R ) - ( + ) - ! , ( S ) - ( - ) - 5 , ( R ) - ( - ) - 6 and ( S ) - ( - ) - 4 , a s summar­ i z e d i n Scheme I .

Scheme I OMe

OMe CF

€ Me

3

—d—±^

Ρ iPrO

I

R N

SO Me

Η

ρ f Me

iPrO

iPrO

Η

Me (R)-(+)-3

(R)-(+)-!

JRa-NJ

OMe

0

II

I

NaOMe

ρ

Ρ iPrO

i

f ^e Me

(S)-(-)-5

SH

iPrO

X

4 Me

(R)-(-)-6

CI

iPrO

f Me

(S)-(-)-4

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

S

115.

SZAFRANIEC ET AL.

P(III) Organophosphorus Ester

559

Literature Cited 1. 2. 3. 4. 5. 6. 7.

Colle, K.S.; Lewis, E.S. J. Org. Chem. 1978, 43, 571. Omelanczuk, J.; Mikolajczyk, M. J . Am. Chem. Soc. 1979, 101, 7292. Omelanczuk, J.; Perlikowska, W.; Mikolajczyk, M. J. Chem. Soc., Chem. Commun. 1980, 24. Mikolajczyk, M.; Omelanczuk, J.; Para, M. Tetrahedron 1972, 28, 3855. Mikolajczyk, M. J . Chem. Soc., Chem. Commun. 1969, 1221. Reiff, L.P.; Aaron, H.S. J. Am. Chem. Soc. 1970, 92, 5275. Michalski, J.; Mikolajczyk, M. Tetrahedron 1966, 22, 3055.

RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

116 A Single Crystal X-Ray Diffraction Analysis of (1R,1'S)-1,1'-Ethylenebis(1,2,3,4-tetrahydro-4,4­ -dimethyl-1-phenylphosphinolinium) Diperchlorate NARAYANASAMY GURUSAMY and K. DARRELL BERLIN Department of Chemistry, Oklahoma State University, Stillwater, OK 74074 DICK VAN DER HELM and M. BILAYET HOSSAIN Department of Chemistry, University of Oklahoma, Norman, OK 73019

Tetrahydrophosphinoliniu ostatic activity as demonstatrate itute during routine screening. Interestingly, a recent discovery 1,2

that certain poly(methylene)bis(triphenylphosphonium) salts have strong anticholinergic activity prompted, in part, our work on bisphosphinolinium salts which possess structural features similar to those of 1 and 2. We report the preparation and separation of diastereoisomers of 1,1'-ethylenebis[1,2,3,4-tetrahydro-4,4-dimethyl-1-phenylphosphinolinium] diperchlorate (3). Although rare such 3

4

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562

PHOSPHORUS CHEMISTRY

salts should be available from bisphosphines 4 which could be alkylated to produce 5. Cyclization of the latter with 115% poly-

5

phosphoric acid (PPA) gave salts 6. Fractional crystallization of the mixture of perchlorates 3, resulted in the separation of the less soluble meso-3 (mp 291-293°C). The residual mixture (enrich­ ed in racemic-3) in methanol and an aqueous solution of sodium tetraphenylborate gave the tetraphenylborates. Fractional cryst­ allization (H CCl -ether) gave the pure racemate (mp 218-219°C). For the resolution work, meso-3. and the racemate of the tetraphen­ ylborate were converted to chlorides via chromatography over Dowex IX-8(Cl ). The racemate of the chloride (hygroscopic) in methanol (anh) was treated with silver L(+)-hydrogendibenzoyltartrate (HDBT). A mixture of diastereomers precipitated, and fractional c r y s t a l l i ­ zation (HCCl -ether) gave pure 2 L(+)-HDBT isomer ([α]2D1 = + 60.5° (c = 1.0 g/100 mL; CH3OH; mp 151-153°C), Treatment of the latter with sodium perchlorate (H2O) at room temp gave optically pure 3, ([α]2D = - 18.5°(c = 1.0 g/100 mL; acetone, mp 262.5-264°C)). This is the first_resolution of a bisphosphinolinium salt. The meso compound (Cl ) gave only the diastereomer 2 L(+)-HDBT [from Ag L(+)-HDBT] was obtained ([a]2D = + 92.5 (c = 1.0 g/100 mL; CH OH; mp 152-154°C)). From Ag D(-)-HDBT, the other diastereomer was found ([ct]|5 = - 91.5° (c = 1.0 g/100 mL; CH3OH; mp 151-153°C)). Conversion to the perchlorates gave meso-j^ as expected. Optically active ^ had a P NMR signal at + 15.40 ppm (DCCl^ + drop of trifluoroacetic acid) while meso-3. had a value of + 14.85 ppm. Thus, 31p NMR anal­ ysis could be used to monitor the resolution. Boiling meso-6 (n =2, Y = Cl) in methanol with aqueous sodium hvdroxide eave Dhosohine 7 and phosphine oxide 8. A l l NMR spectral 2

2

-

3

1

-

4

3

4

3 1

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

116.

GURUSAMY ET AL.

Single

Crystal

X-Ray

Diffraction

Analysis

3

563

d a t a ( l H and ^ P ) a n d e l e m e n t a l a n a l y s e s s u p p o r t e d s t r u c t u r e s 7 and £ w h i c h i n t u r n c o n f i r m t h e b a s i c s t r u c t u r e i n ^3. A s i n g l e c r y s t a l X - r a y d i f f r a c t i o n a n a l y s i s o f meso-3 was p e r ­ f o r m e d on a m o n o c l i n i c c r y s t a l ( s p a c e g r o u p P 2 ^ / c ) . Bond l e n g t h s and atom n u m b e r i n g a r e g i v e n i n F i g u r e 1 a n d bond a n g l e s i n F i g u r e 2. S e l e c t e d t o r s i o n a l a n g l e s a r e g i v e n i n T a b l e I . The two e q u i ­ v a l e n t h a l v e s a r e d e s i g n a t e d "unprimed" and "primed" p a r t s . I n t h e c r y s t a l l i n e s t a t e , t h e p o t e n t i a l symmetry o f t h e s y s t e m i s d e s t r o y e d a s c a n b e s e e n f r o m t h e t o r s i o n a l a n g l e s i n t h e Table.

1*375 Figure 1.

1-377 Bond lengths and atom number for meso-i.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

564

PHOSPHORUS

CHEMISTRY

1 0 7 3 109*9 107*2

II···

I0t-1

108-4

1120

I0S5 C(2)-P(I)-C(I2) C(8i)-P(l)-C(9) C(3)-C(4)-C(il) C(4o)-C(4)-C(K» CC2) -P(l) -C(l2)'

111*0 109*1 106*6 107*6 liai

C^CW-COI) C(4a) -C(4^C(K»

108*9 109*9 110*6

a

a

1

IO0-4X114*8

l

106-7 / S . 108 *8

Figure 2.

Bond angles for


70

0

X = S

20

60

X=N-0

< 5

> 95

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

123.

MAJORAL E T AL.

Photolytic

Rearrangement

of

Azides

599

The d i f f e r e n t r e a c t i v i t y o f phosphorus azides might be i n t e r preted i n terms o f conjugation between phenyl groups and s u l f u r or between phenyl groups and the P=N=0 double bond ; i n these cases the rate o f the phenyl migration decreases and hydrogen abst r a c t i o n reactions dominate. E f f o r t s towards s t a b i l i z a t i o n o f metaphosphonimidates with bulky s u b s t i t u e n t s f a i l e d . P h o t o l y s i s o f 5^ at low temperature d i d not allow us to stabi l i z e 6> or I r r a d i a t i o n o f 5^ i n benzene gave r i s e to dimers and polymers but a l s o to the hydrogen a b s t r a c t i o n product. Moreover we d i d not succeed at the present time i n the preparation o f the phosphorus azide 9 from 8 c e r t a i n l y because o f s t e r i c hindrance.

Taking i n t o account these r e s u l t s i n phosphorus chemistry, i t seemed i n t e r e s t i n g to us to study the same t r a n s p o s i t i o n i n germanium chemistry. In f a c t , p h o t o l y s i s o f the germanium azide 10 i n the presence o f pinacol afforded the dioxagermolanne 12. Un the other hand i n the absence o f trapping agent, p h o t o l y s i s o f 10 gave r i s e mainly to germadiazetidine 13 but a l s o to polymer 14, biphenyle and amine. These l a s t two products came from hydrogen a b s t r a c t i o n from the s o l v e n t by nitrene intermediate JL5. Polymer 14 was a condensed form o f the corresponding germylene 16 whi ch can be trapped with d i m e t h y l d i s u l f u r . Thus two p o s s i b l e mechanisms might e x p l a i n our experimental results:

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

600

PHOSPHORUS

Ph

Ge — Ν

Ph GeN 3

Ph

jph Ge=N-Ph

3

Ph

'p Ν —Ge'

r-> Ph'

CHEMISTRY

M

h

2

10

U — O H

't

>-0H

Ph Ge '

h

2

G

e

:

16

J

[

+

P h N l

"]

15

PhH

0

2

PhNH

(Ph Ge)

+

12

Ph - Ph

14

Since the rearrangement o f s i l i c o n azides i s known, we looked f o r some s y n t h e t i c a p p l i c a t i o n s i n organometallic chemistry. For example, r i n g extension reactions i n v o l v i n g s i l a . i m i n e s interme­ di ates can be described :

( C M

2n

hv

;

->

R-N=Si

R-Si

17

X

n

RO

Si

RO"

2

ROH

ROH R

(CH )

(CM 2^n

N 1

Η

> i

HN ! R

(CH ) 2

n

18

The r a t i o o f _17/ 18 was dependent o f the nature o f the s i 1 icon s u b s t i t u e n t and thus i t was p o s s i b l e to synthesize e i t h e r a endoexo d i f u n c t i o n a l ! z e d s i 1 icon r i n g 17 or a d i e x o f u n c t i o n a l i z e d compound 18.

Literature ci ted : (1) BRESLOW R., FEIRING A . , HERMAN F., J . Am. Chem. Soc., ( 1974) 96, 18, 5937. (2) BERTRAND G., MAJORAL J.P. and BECEIREDO A . , Tetrahedron Letters, 1980, 21, 5015 and ref. included. (3) HARGER M.J.P., STEPHEN,Μ.A., J . Chem. Soc.Perkin I, 1981,737. RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

124 Diphenylphosphinous Acid by UV Irradiation of Aroyl Diphenyl Phosphines K. PRAEFCKE and M. DANKOWSKI Institute of Organic Chemistry, C 3, Technical University Berlin, D-1000 Berlin 12, FRG

Relatively l i t t l e is known about the photochemistry of phos phorus containing organi work on compounds of structur selenoxanthones 3a,b via thiol ester-thiopyrone-, selenol ester­ -seleninone-transformations (1, 2, 3), or photo-Friedel-Crafts­ -reactions (3-6), respectively, (Scheme 1) we have extended our interest to aroyl diphenyl phosphines 1c - k (Schemes 2 - 5) in which X in 1a and b stands for P-phenyl.

As 1c behaves photochemically similar to certain thiol and selenol esters (e.g. 1a and b), yielding heterocycles of type 3 in the first photo-Friedel-Crafts-reaction of an organic phosphorus compound (Scheme 2), the aroyl diphenyl phosphi nes 1d - k show other reactions on u.v. irradiation (7, 8, 9 ) .

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602

PHOSPHORUS CHEMISTRY

However, these latter phosphines 1d - k also suffer photo­ -fragmentations. α-Cleavage occurs under formation of either aldehydes 2d - h , via subsequent H-abstraction of aroyl radicals from solvent (Scheme 3), or hetero- and carbocycle 7 and 8, via cyclization of the correspondi ng aroyl radical s under neighbouring group participation (Schemes 4 and 5). In a competing and novel type of photoreaction, aroyl diphenyl phosphines 1d - k yield diphenylphosphinous acid (4, diphenylphos­ phine oxide) as the photoproduct of a complex transfer of the oxygen from the carbonyl carbon onto the phosphorus atom followed by C-P-bond cleavage and hydrogen abstraction from solvent. The mass spectrometric product analysis of an u.v. irradiation experi-

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

124.

P R A E F C K E A N D DANKOWSKi

Diphenylphosphinous

Acid

603

1. h v [ b e n z e n e ] Î Q £

X

\Q/

|^

2. c c . [ a c e t o n e ] (59%)

OCH3

Θ

ment wi th a 1:1 mixture o f £ θ]-aroyl di phenyl and £ oj-aroyl di t o l y l phosphi ne i n benzene has shown that the photoi nduced oxy­ gen t r a n s f e r r e a c t i o n o f aroyl d i a r y ! phosphi nes a t l e a s t p a r ­ t i a l l y occurs i n t e r m o l e c u l a r l y . Diphenylphosphine oxide ( 4 ) , generated f o r the f i r s t time photochemically i n y i e l d s up to 59%, adds i n s i t u to various c a r ­ bonyl compounds ( e . g . formation o f 5 , 6 and 9 by 1.2- or 1.4additions, respectively).

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

604

PHOSPHORUS CHEMISTRY Acknowledgements

K. Praefcke thanks the Fonds der Chemischen Industrie, Frankfurt/ Main, as well as the Gesellschaft von Freunden der Technischen Universitàt Berlin for their financial support.

References 1. Beelitz, K; Buchholz, G; Praefcke, K. Liebigs Ann. Chem. 1979, 2043. 2. Beelitz, K; Praefcke K Gronowitz S Liebig Ann Chem 1980 1597, and J . Organometal 3. Martens, J; Praefcke, . J . Organometal. Chem. 1980, 198, 321. 4. Martens, J ; Praefcke, K; Schulze, U. Synthesis, 1976, 532. 5. Praefcke, K; Schmidt, D. J . Heterocycl. Chem., 1979, 16, 47. 6. Praefcke, K; Schulze, U. J . Organometal. Chem., 1980, 184, 189. 7. Dankowski, M; Praefcke, K; Nyburg, S. C.; Wong-Ng, W. Phos­ phorus and Sulfur, 1979, 7, 275. 8. Dankowski, M; Praefcke, K. Phosphorus and Sulfur, 1980, 8, 105. 9. Dankowski, M; Praefcke, K; Lee, J.-S.; Nyburg, S. C. Phosphorus and Sulfur, 1980, 8, 359. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

125 Chemical Model Showing Three Phenomena: Phosphorane-->Ylide, Ylide-->Phosphorane, and Phosphorane Ylide RAMON BURGADA, YVES LEROUX, and Y. O. EL KHOSHNIEH Laboratoire des Organo-Eléments, ERA 825, Université P. et M. Curie, Tour 44-45, 4 Place Jussieu, 5230 Paris Cédex 05, France

We have shown without any doubt the formation of carbanions obtained react with an acetyleni carbanionic species with p r o t i c reagents, alcohol for instance,leads to an y l i d A. An alternative pathway involves reaction on the phosphorus atom leading to a phosphorane B.

With c y c l i c phosphite 3, when the trapping reagent used in reaction is phenol, we obtain a quantitative y i e l d of y l i d . Between 0° and 20° this y l i d undergoes a complete rearrangement leading to a phosphorane (1).

Conversely, a phosphorane is obtained at -20°C when the Ρ reagent is trimethylphosphite and methanol is the trapping species. This phosphorane undergo a complete rearrangement in a few minutes at 20°C leading to an ylid. 0097-6156/81/0171-0607S05.00/0 © 1981 American Chemical Society III

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

608

PHOSPHORUS CHEMISTRY

When the Ρ reagent is 3 with benzoic acid as trapping species, we observe an equilibrium between ylid and phosphorane which is strongly solvent dependent, III

for instance in CCl : 8 18%-9 82% and in C H C l : 8 37%-9 63%. If the dichloromethane solution is evaporated and a new solution made with carbon t e t r a ­ chloride then the f i r s t results(8 18% and 9 82%) are found again. In tetrachloride s o l u t i o n , these two species 8 and 9 remained e s s e n t i a l l y unchanged. With d i c h l o r o methane s o l u t i o n , the evolution takes a few hours only; NMR signals appear for 10 (Z+E) whereas the i n t e n s i t y of 8^ and 9_ signals are decreasing. When the percentage of J_0 is 60% the r e l a t i v e r a t i o of y l i d versus phosphorane remains unchanged(36%-64%>. In the end, two isomers (Z + E) corresponding to the phosphonate J_0 can be seen ( Ρ NMR). 4

2

2

3 1

It is also possible to follow the chemical modification of the system with *H NMR technique and in p a r t i c u l a r the appearance and the disappearance of doublets r e l a t i v e to H-C-C=P, H-C=C-P and H-C=C-P . Upon heating, the equilibrium shifts from (50% Z, 50% E) of 10 to isomer E . Another equilibrium ylid«F=^ phosphorane has been reported a few years ago. Nevertheless i t was obtained by addition or loss of a reagent (_2) . V

IV

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

125.

BURGADA E T A L .

Phosphorane-Ylide

(CH.KP

Table

- CH

Μ

β

Chemical

0

( C H ) . P OC H _ 3 4 3

Η

* » - MeOH

?

609

Model

Q

1 summarizes o u r r e s u l t s ,

Trapping

species

Ρ

MeOH

+

PhOH

•f

MeOH

+

PhOH

+

Re s u 11 s

Ί

III

POMe

J—o'

Ylid

C0 Me o

•ι I

C0 Me

POMe ^ L o ^

2

PhC0 H

+

PhC0 H

+

o

2

Ylid

POMe

Ylid Table

1

I n t a b l e 1, t h e t h r e e p h e n o m e n a w h i c h c o r r e s p o n d t o t h e p a p e r ' s t i t l e a r e e n c i r c l e d . We c a n a l s o s e e t h a t t h e same r e a g e n t i . e . m e t h a n o l a l w a y s g i v e s a p h o s p h o r a n e . T h i s one is s t a b l e when t h ep h o s p h i t e r e a g e n t is a c y c l i c species. This phosphorane then undergoes a r e a r r a n g e m e n t t o a n y l i d when t h ep h o s p h i t e r e a g e n t i s a linear species (Ρ(OMe)^)· One c a n s e e a l s o t h a t w i t h t h e same t r a p p i n g reagent, phenol f o rinstance, the k i n e t i c producti s now a n y l i d . When t h e t r a p p i n g r e a g e n t i s b e n z o i c acid we h a v e a t t a i n e d t h e r m o d y n a m i c s t a b i l i t y b e t w e e n ylid and p h o s p h o r a n e . A t l o w t e m p e r a t u r e , t h e y l i d 4^ a d d s m e t h a n o l b e f o r e g i v i n g b y r e a r r a n g e m e n t a p h o s p h o r a n e 5_ wh i c h f i n a l l y lead t o a saturated phosphorane 11 .

t 4

n

OMe

C0 Me 2

P

o/ $c C0 Me 2

CH N

0Ph

MeOH -20

MeO f , 0-P,

0

M

e

OPh

CHCH

c

*Ί

C 0 Me \ ; 0 Me 3 1 P-49ppm 9

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

PHOSPHORUS CHEMISTRY

610

Phosphorane JJ_ is stable enough in solution to be analyzed and i d e n t i f i e d . Nevertheless, in a few days JJ_ loses phenol and not methanol to give a v i n y l phosphorane J_2 (E. s t r u c t u r e ) . MeO |^0Me A M

11

H

»

0 P—C = C ^ ϋ -— / \ •° C0 Me ° 2

+ PhOH

5 + MeOH

1

C

M e

2

We can obtain the same phosphorane J_2 by methano­ l y s i s of phosphorane _5 Concerning the stereochemistry of the phosphorane isomer is the more Table 1 gives Ζ isomer, but only traces of benzoic acid are necessary to provoke instantaneous isomerisation of Ζ to E . The mechanism probably involves an addition-elimination. , MeO OMe MeO Me υ Oune » * \ / Γ Π Mp Η 12Z 0- P ^ 2 c a t a l y t i c Am. 0 - Ρ χ. „ ' 1 2E V / > c -ThcoTs—ry j y \ \ * C0 Me^ H \ ^ ° CO^le C0 Me w

Λ

Λ%

e

v

m

N

7

2

2

Results of Table 1 and the later results seem to sh ow that through out this work we are dealing with k i n e t i c a l l y controlled reactions. Moreover, we demons tr a te that an equilibrium between JT2 and the y l i d form does not exist because this should lead to the isomeris ation of Ζ to E . When the trapping reagent is acetylene dicarboxylate i t s e l f , the reaction yields a new phosphorane which is a pentacoordinated phosphole (3). Li terature cited 1. Burgada, R ; Leroux, Y ; E l Khoshnieh, Y . O . Tetrahedron L e t t . 1980, (21), 925. 2. Schmidbaur, Η ; Stuhler, H. Angew. Chem. Int. Ed. 1972, 2, 145. 3. Burgada, R ; Leroux, Y ; El Khoshnieh, Y.O. Tetrahedron Lett. (in press). RECEIVED

June 30, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

126 Base-Catalyzed Reactions of Phosphonomethyl­ -phosphinates,Bis(phosphonomethyl)phosphinates, and Bis(phosphonomethyl)phosphinic Amides with Aldehydes W. FRANKLIN GILMORE and JOON SUP PARK Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, University, MS 38677

One of the fascinatin aspect f organophosphoru chemistr i s the extent to which t r o l the rate and also the nature of the products of nucleophilic displacements at tetrahedral phosphorus. Our original goal in this work was to design a synthesis of diethylphosphonomethylalkenylphosphinates I I I . Unfortunately the condensation of I with aldehydes occurred primarily by path A (Scheme I) to give II Scheme I

Phosphonomethylphosphinates with Aldehydes Since our initial attempts to direct Scheme I towards path Β by changing the group on the central phosphorus of I failed, we simplified our system to determine what factors control elimina­ tion of a phosphonate or phosphinate phosphorus during carbonyl olefination with PO ylids containing two phosphorus atoms. The results for the condensation of a series of phosphonomethylphos­ phinates IV with aldehydes (Scheme II) are given i n Table I . Scheme II

0097-6156/81/0171-0611$05.00/0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

612

PHOSPHORUS CHEMISTRY

Table I Reaction of Isobutyraldehyde with Phosphonomethylphosphinates R

R

Phenyl 2,4-D imethoxypheny1 4-Methoxyphenyl 3-Chlorophenyl Echyl Phenyl Cyclohexyl

Ethyl Ethyl Ethyl Ethyl Ethy Pheny Ethyl

f

V %

R" Isopropyl Isopropyl Isopropyl Isopropyl

11 13 14 19

Isopropyl

3

VI (yield) % %

(yield) %

89 87 86 81 12

(9) (13) (12) (17)

(67) (62) (54) (59)

97

The data in Table I indicate that the reaction of IV with al­ dehydes can be directed through path A or path Β by changing ster­ ic and electronic factors. The phosphorus atom having the smaller groups is eliminated (compare R=ethyl and cyclohexyl). If the difference in steric factors is not sufficient to completely con­ trol the course of the reaction, the phosphorus atom having the greater positive charge is eliminated (compare R' =ethyl and phenyl when R=phenyl). Bis(Phosphonomethyl)phosphinates with Aldehydes After learning that IV could be directed primarily through path Β by changing steric and electronic factors, we reinvesti­ gated the reactions of I with aldehydes. These results are in Table II. Table II Reaction of Aldehydes with Bis(Phosphonomethy1)phosphinates

R Phenyl Cyclohexyl Isopropyl 2,6-Dimethylphenyl (D,L)-Menthyl Ethyl

f

R

Isopropyl Isopropyl Isopropyl Isopropyl Isopropyl Isopropyl

II % 95 78 93 86 70 100

(yield) %

III %

(48) (51) (36) (53) (57)

5 22 7 14 30 0

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

(yield) % (8) (1) (3) (ID

126.

GILMORE AND

PARK

Base-Catalyzed

Reactions

of Phosphinates

613

The d a t a i n T a b l e I I i n d i c a t e t h a t o u r g o a l o f d i r e c t i n g Scheme I t o p a t h Β was o n l y p a r t i a l l y a c h i e v e d . A s a n a l t e r n a t i v e a n o t h e r method o f i n c r e a s i n g b o t h t h e s t e r i c h i n d e r a n c e and t h e e l e c t r o n d e n s i t y a t t h e c e n t r a l p h o s p h o r u s atom o f I was s o u g h t . B i s ( P h o s o h o n o m e t h y l ) p h o s h i n i c Amides w i t h

Aidehydes

To f u r t h e r s t u d y t h e e f f e c t s o f s t e r i c and e l e c t r o n i c f a c t o r s on t h e c o u r s e o f c a r b o n y l o l e f i n a t i o n w i t h t h e s e d u a l PO y l i d s , we i n v e s t i g a t e d t h e r e a c t i o n s o f V I I w i t h a l d e h y d e s (Scheme I I I ) . D a t a f o r t h e s e r e a c t i o n s a r e shown i n T a b l e I I I . Scheme I I I A [ ( E t O ) , P ( 0 ) C H , ] P ( 0 ) R + R'CHO

—

0

\

î

- R'CH^HP (O)CELP (0) (OEt) Β L i . VIII Table I I I 0

R Phenylamino

f

Isopropyl

II %

(yield) VIII % %

(yield) %

93

(48)

7

(2)

12

(4)

a-Methylbenzylamino

Isopropyl

88

(57)

Cyclohexylamino

Isopropyl

85

(44)

14

(4)

t-Butylamino

Isopropyl

60

(54)

40

(20)

Morpholino

Isopropyl

91

(53)

9

(3)

Piperidino

Isopropyl

67

(38)

33

(11)

Di-n-propylamino

Isopropyl

12

(11)

88

(46)

N-Cyclohexy1-N-methy1amino

Isopropyl

20

(20)

80

(43)

The d a t a i n T a b l e I I I i l l u s t r a t e t h a t c o n d e n s a t i o n o f V I I w i t h i s o b u t y r a l d e h y d e i s a s a t i s f a c t o r y s y n t h e s i s of V I I I which can be h y d r o l y z e d to the d e s i r e d phosphonomethylphosphinic a c i d . T h i s method has b e e n t e s t e d w i t h s e v e r a l o t h e r a l d e h y d e s and found to g i v e r e s u l t s s i m i l a r to those i n T a b l e I I I . Discussion The d a t a p r e s e n t e d i n T a b l e s I - I I I d e m o n s t r a t e t h a t t h r o u g h proper u t i l i z a t i o n of s u b s t i t u t e n t s i t i s p o s s i b l e to d i r e c t c a r ­ b o n y l o l e f i n a t i o n through e l i m i n a t i o n of a p h o s p h i n a t e phosphorus atom (PO) o r a p h o s p h o n a t e p h o s p h o r u s atom (P0„). C o n d e n s a t i o n o f

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

614

PHOSPHORUS C H E M I S T R Y

the anions from I, IV and VII with carbonyl groups forms an anion similar to IX (Scheme IV). Nucleophilic attack of this anion at PO leads to two trigonal bipyramidal (TBP) oxyphosphoranes (X and XI) and attack at PO^ leads to a single TBP oxyphosphorane (XII). Scheme IV 0 -/P(0)(Y)(Z) R'CHC^ P(0)(OR), IX ι

0 OR*

π

•0

l-o

•0 XII

XI

PR

PR r

u

0-P^ 0R

0 R

,

f

II or V

III, VI or VIII

When Y is alkyl and Z=R=ethoxy» PO^ is more positive than PO. Nucleophilic attack at PO2 leads to XII which has a moderate bar­ rier to pseudorotation (PR). Other factors being equal, path Β is less favorable than path A. When Y is ethyl and Z=R=ethoxy, XI is favored due to attack from behind the CH^ of ethyl. If Y is cyclo­ hexyl, formation of X and XI is retarded for steric and electro­ nic reasons; but, to the extent that either forms, XI is favored by steric factors. For Y=phenyl and Z=R=ethoxy, PO is slightly more positive than PO and when R=phenoxy PO^ is much more positive than PO. Thus, when Y=Phenyl, attack at PO is not favored by either electronic or steric factors. To the extent that this oc­ curs, attack should be from the face opposite the phenyl group with formation of XI. Formation of XI also requires a decrease in any resonance interactions which exist between the aromatic ring and PO. For I and VII, Z=alkyl or aryloxy and alkyl or arylamino, while Y is the relatively bulky diethylphosphonomethyl (DEP) group. In I and VII PO is more positive than PO^ and XI is favored unless Ζ is larger than DEP. When Ζ is larger (methyloxy and di-n-propylamino), X is favored and the only reasonable path left is through XII. Literature Cited 1.

Gilmore, W. Franklin and Huber, Joseph W., III. 1973, 38, 1423-4.

RECEIVED

J . Org. Chem.

July 7, 1981. In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

127 Structure-Reactivity Studies on Oxygen­ -Containing Phosphorus-Based Ligands YUAN CHENGYE, YE WEIZHEN, ZHOU CHENGMING, and HUI YONGZHENG Shanghai Institute of Organic Chemistry, Academia Sinica, Peoples Republic of China

Phosphorus ligands bearing phosphoryl oxygen atom are well -known extractants, whic nation compounds with various metals in comparison with other oxygen-containing organic dentates. Structure-reactivity studies of phosphorus-based extractants can, in very practical terms, con­ tribute both to the development of new ligands and to the progress of organophosphorus chemistry in general. As shown by our early studies, the behaviour of extractants are governed chiefly by three structural factors (1). It is proposed that, there is a significant correlation between the extraction properties and some physico­ -chemical constants of ligands. Therefore, i t is interesting to investigate the dependence of chemical structure on the physico­ -chemical properties of phosphorus-based ligands. This paper des­ cribes some new aspects of this problem which have been studied in our Laboratory. Linear Free Energy Relationships. Correlation analysis by LFER is a useful tool for structure-reactivity studies (2). The contri­ bution of charge density of phosphoryl oxygen atom to the coordi­ nation behaviour of neutral organophosphorus compounds is well established. The Lewis basicity of such compounds, as measured by the degree of shift of OD vibration frequency (ΔυOD) of deuterated methanol due to the association of the latter with compound under investigation correlates linearly to the nature of groups attached to phosphorus atom. In a series of phosphate-phosphine oxide, plot of υΡΟ orΔυOD against Taft constant σ* straight lines resulted in both cases. It is well illustrated by the dependence of the nature of substituents (Hammett σvalue) of p-substituted phenylphosphonates on * P0 and ΔΡΟΏ (3). In the case of p-substituted phenyl dibutylphosphinates straight 1ines also resulted when the J> PO and âVOO are plotted versus the Hammett σ constants of the nuclear substituents due to the conjugation effect of ester oxygen atoms (4_) . The 31p NMR studies of p-substituted phenyl- and benzylphosphonates show the linear free energy relationship between the nature of 7

0097-6156/81/0171-0615$05.00/0 © 1981 American Chemical Society

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

616

PHOSPHORUS CHEMISTRY

s u b s t i t u a n t s and c h e m i c a l s h i f t o f 31p n u c l e u s i n b o t h c a s e s t h o u g h t h e i n f l u e n c e o f s u b s t i t u e n t s i s more s t r o n g i n t h e f o r m e r and the s l o p e of s t r a i g h t l i n e i s e v i d e n t l y g r e a t e r than t h a t i n the latter. The s t r u c t u r e - r e a c t i v i t y r e l a t i o n s h i p o f a c i d i c o r g a n o p h o s ­ p h o r u s compounds i s w e l l d e m o n s t r a t e d by m o n o - e s t e r s o f p - s u b s t i ­ t u t e d p h e n y l p h o s p h o n i c a c i d s . The a c i d i t y o f t h e s e o r g a n i c a c i d s i n c r e a s e d as t h e p o l a r n a t u r e o f t h e s u b s t i t u e n t s e n h a n c e d . A l i n e a r f r e e e n e r g y r e l a t i o n s h i p e x i s t s b e t w e e n t h e pKa v a l u e and t h e Hammett σ constants i n a c i d i c p - s u b s t i t u t e d phenylphosphon a t e s . When t h e s e s t r u c t u r e p a r a m e t e r s a r e p l o t t e d e i t h e r a g a i n s t t h e v?00" asym. o r a g a i n s t t h e 31p c h e m i c a l s h i f t o f t h e i r d i c y c l o hexylammonium s a l t s s t r a i g h t l i n e s r e s u l t e d i n b o t h c a s e s . However, a c i d i c p - s u b s t i t u t e to o f f e r such c o r r e l a t i o The q u a n t i t a t i v e i n f l u e n c e o f t h e n u c l e a r s u b s t i t u e n t s on t h e p h o s p h o r y l g r o u p i n d i a l k y l p - s u b s t i t u t e d p h e n y l p h o s p h o n a t e s and t h e i r m o n o - e s t e r s may be due e i t h e r t o t h e c o n j u g a t i o n e f f e c t o f t h e p h o s p h o r y l g r o u p w i t h t h e JT-bonds o f t h e b e n z e n e r i n g o r t o t h e i n d u c t i v e e f f e c t t h r o u g h t h e p h o s p h o r u s atom. I n c o n t r a s t w i t h t h e p o s t u l a t i o n o f K a b a c h n i k ( 6 ) , we a r e o f t h e o p i n i o n t h a t t h e r e s u l t s o f o u r e x p e r i m e n t s m i g h t a l s o be e x p l a i n e d by t h e i n d u c t i v e e f f e c t o f the n u c l e a r s u b s t i t u e n t s toward the p h o s p h o r y l oxygen t h r o u g h t h e p h o s p h o r u s atom, and t h e o x y g e n o f t h e p h o s p h o r y l g r o u p i s l i n k e d t o t h e p h o s p h o r u s by απ-ρπ bond. On t h e b a s i s o f c o r r e l a t i o n a n a l y s i s by LFER b e t w e e n t h e c h e m i c a l s t r u c t u r e and s p e c t r a l d a t a f r o m IR and NMR, Lewis b a s i c i t y , r a t e c o n s t a n t o f h y d r o l y s i s as w e l l as pKa o f v a r i o u s o r g a n o p h o s ­ p h o r u s compounds, i t i s n o t l i k e l y t h a t t h e b e n z e n e r i n g i s c o n j u ­ g a t e d w i t h t h e p h o s p h o r y l g r o u p , and t h a t t h e o x y g e n o f t h e l a t t e r i s l i n k e d t o t h e p h o s p h o r u s by a d o u b l e b o n d , i f t h e g e n e r a l c o n c e p t s o f c o n j u g a t i o n i n t h e c h e m i s t r y o f c a r b o n compounds w o r k as w e l l i n t h e p h o s p h o r u s s e r i e s . H u k e l M o l e c u l a r O r b i t a l M e t h o d . The s t r u c t u r e - r e a c t i v i t y r e l a t i o n s h i p o f p h o s p h o r u s - b a s e d l i g a n d s has b e e n s t u d i e d by H u k e l m o l e c u l a r o r b i t a l (HMO) method. The m o l e c u l e o f t h e s e e x t r a c t a n t s may be c o n s i d e r e d as c o n j u g a t e d s y s t e m c o n t a i n i n g h e t e r o - a t o m s . I n s u c h c a s e , t h e Coulomb and r e s o n a n c e i n t e g r a l s may be a l t e r e d by known e x p r e s s i o n s i n t h e HMO c a l c u l a t i o n . The h i g h d e g r e e s e c u l a r e q u a t i o n i n HMO c a l c u l a t i o n was s o l v e d by t h e s t a n d a r d p r o g r a m i n g o f J a c o b i method, by w h i c h t h e c h a r a c t e r i s t i c r o o t and f a c t o r o f r e a l s y m m e t r i c m a t r i x w e r e s o l v e d . The c a l c u l a t i o n was w o r k e d o u t on t h e e l e c t r o n i c c o m p u t e r C J 719. The s t r u c t u r e p a r a m e t e r s , ^ s u c h as c h a r g e d e n s i t y ( q x ) , bond o r d e r ( P c = x ) , π bond e n e r g y ( E c ) as w e l l as t o t a l e n e r g y o f t h e m o l e c u l a r o r b i t a l s (Σλί) thus c a l c u l a t e d was c o r r e l a t e d w i t h t h e e x t r a c t i o n b e h a v i o u r o f s u c h p h o s p h o r u s - b a s e d l i g a n d s f o r u r a n i u m , t h o r i u m and r a r e e a r t h s (7). The HMO c a l c u l a t i o n s i n d i c a t e t h a t t h e c h a r g e d e n s i t y o f o x y g e n ( 1 . 9 4 5 3 , 1.6125 and 1.5181) and bond o r d e r o f PO and C=0 (0.2318, c = x

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

127.

CHENGYE E T A L .

Oxygen-Containing

Phosphorus-Based

Ligands

617

0.7344 a n d 0.8217) f o r t r i a I k y l p h o s p h i n e o x i d e , N , N - d i a l k y l a c e t a m i d e and d i a l k y l k e t o n e r e s p e c t i v e l y . The s u p e r i o r i t y o f t h e p h o s p h o r u s based l i g a n d s b e a r i n g oxygen over o t h e r oxygen c o n t a i n i n g o r g a n i c dentates i n e x t r a c t i o n o f metals i s w e l l demonstrated. The e x t r a c t i o n a b i l i t y o f n e u t r a l o r g a n o p h o s p h o r u s compounds c l o s e l y r e l a t e d t o t h e charge d e n s i t y o f p h o s p h o r y l oxygen (qo) and p h o s p h o r u s a t o m ( q p ) . I t was f o u n d t h a t t h e d i s t r i b u t i o n r a t i o o f c e r i u m e n h a n c e d a s t h e qo and qp v a l u e s was i n c r e a s e d . M e a n w h i l e a l i n e a r f r e e energy r e l a t i o n s h i p e x i s t s between the Σλί v a l u e s and t h e K a b a c h n i k c o n s t a n t f o r s u b s t i t u e n t s o f p h o s p h o r u s compounds. As e s t i m a t e d b y l e a s t s q u a r e s method, a n e m p i r i c a l e q u a t i o n ^^=-3.84+0.168Σλί was d e d u c e d The e x t r a c t i o n c o n s t a n t o f neodymium, s a m a r i u m , y t t r i u m a n d ytterbium of various a c i d i c h i e f l y by t h e c h a r g e d e n s i t g r o u p i n g > P ( 0 ) 0 H . The p l o t o f Ke o f r a r e e a r t h s v e r s u s qOH(HOMO) v a l u e s o f t h e s e compounds g i v e s s t r a i g h t 1 i n e a s a n t i c i p a t e d , o w i n g t o t h e d i r e c t i n f l u e n c e o f qOH v a l u e o n t h e pKa o f l i g a n d s . A q u a n ­ t i t a t i v e r e l a t i o n s h i p a l s o e x i s t s b e t w e e n t h e Σλί a n d X ^ v a l u e s o f a c i d i c o r g a n o p h o s p h o r u s e x t r a c t a n t s i.e.Zp^=-4.12+0.166Σλί. Pattern Recognition. I n recent years, p a t t e r n r e c o g n i t i o n , an e f f i c i e n t c o m p u t a t i o n a l method f o r t h e a n a l y s i s o f m u l t i v a r i a n t d a t a , was d e v e l o p e d (8) . The p a t t e r n r e c o g n i t i o n p r o c e s s i n g o f t h e i n f l u e n c e o f v a r i o u s s t r u c t u r e f a c t o r s o f some o r g a n o p h o s p h o r u s compounds o n t h e i r e x t r a c t i o n b e h a v i o u r o f u r a n i u m i s d e s c r i b e d . Data p r e p r o c e s s i n g c o n s i s t s o f a u t o s c a l i n g and w e i g h t i n g . The t r a i n i n g s e t i s c l a s s i f i e d a s s o r d i n g t o a g i v e n t h r e s h o l d v a l u e . Two k i n d s o f c l a s s i f y i n g methods a r e u s e d : L i n e a r M a p p i n g Method b y u s i n g K a r h u n e n - L o e v e t r a n s f o r m a t i o n a n d K - N e a r e s t N e i g h b o r Method (KNN). A n unknown compound i s c l a s s i f i e d a c c o r d i n g to the m a j o r i t y v o t e o f i t s K-Neighbors i n t h e f e a t u r e space. Each compound i s i n t u r n t a k e n a s t h e unknown p a t t e r n a n d t h e r e s t a s a t r a i n i n g s e t ( L e a v e - o n e - o u t p r o c e d u r e ) . The p r o g r a m s f o r L i n e a r M a p p i n g and KNN method (LTBP and NBP) were w r i t t e n i n BASIC l a n ­ guage a n d r u n o n a DTS-131 m i n i - c o m p u t e r ( 9 ) . 1. L i n e a r M a p p i n g C l a s s i f i c a t i o n . The~"program LTBP i s a p p l i e d to the c l a s s i f i c a t i o n o f d i s t r i b u t i o n r a t i o o f uranium i n e x t r a c t i o n o f some n e u t r a l o r g a n o p h o s p h o r u s compounds and d i a l k y l a m i n o a l k y l p h o s p h o n a t e s . The g e n e r a l f o r m u l a o f n e u t r a l o r g a n o p h o s p h o r u s com­ pounds i s R 1 R 2 R 3 P O , where R i , R2 a n d R 3 a r e i n d i v i d u a l l y C H 3 - , n - C H , i s o - C H , n - C H , n - C H , C ^ g C H E t C H ^ and C H C H M e o r c o r r e s p o n d i n g a l k o x y 1 g r o u p . The s e l e c t e d n i n e f e a t u r e s a r e : number o f P-O-C bonds i n R^, R^ o r R 3 ; t o t a l number o f P-O-C bonds ; d e g r e e o f b r a n c h o f c a r b o n c h a i n ; number o f c a r b o n atoms i n l o n g e s t and s h o r t e s t c h a i n ; r a t i o o f t h e l e n g t h o f c a r b o n c h a i n a n d t o t a l number o f c a r b o n atoms. The c l a s s i f i c a t i o n t h r e s h o l d (Du) i s 3 0 0 . I n t h e s e v e n t e e n n e u t r a l o r g a n o p h o s p h o r u s compoounds s t u d i e d , t h e r e a r e s i x w i t h Du > 300 a n d e l e v e n compounds w i t h Du 1 0 f o r t h e N - a c y l c l e a v a g e , and k ( 7 ) / k ( 8 ) = 3 x l 0 f o r the d e - t e r t - b u t y l a t i o n r e a c t i o n . This r e s u l t i s i n f u l l agreement w i t h t h e p o s t u l a t e d s t r u c t u r e s o f t h e r e s p e c t i v e c o n j u g a t e a c i d s . I n t h e h i g h l y d e l o c a l i s e d benzamidonium i o n IPh-C(0H)NH-t-Bu|+ c a r b o n y l c a r b o n i s o n l y w e a k l y e l e c t r o p h i l i c and t h e N - t - B u bond i s n o t s i g n i f i c a n t l y weakened. F o r t h e N - p r o t o n a t e d f o r m o f ( 7 ) | P h P ( 0 ) N H - t - B u | + on t h e o t h e r h a n d , h i g h e l e c t r o p h i l i c i t y o f t h e p h o s p h o r u s , as w e l l a s t h e h i g h tendency f o r t h e unimolecular a b s t r a c t i o n o f t h e t - b u t y l carbo nium i o n would be e x p e c t e d . S i n c e t h e r e i s n o t much o f c o n j u g a t i o n between t h e P=0 g r o u p and t h e n i t r o g e n i n ( 2 ) , 0 and Ν atoms c a n i n p r i n c i p l e behave as t w o i n d e p e n d e n t b a s i c c e n t e r s . Medium e f f e c t s upon t h e PMR s h i e l d i n g parameters o f phosphoramidates demonstrated t h a t i n s u c h a s t r o n g a c i d a s t r i f l u o r o m e t h a n e s u l f o n i c amides ( 2 ) i n d e e d e x i s t , a t l e a s t p a r t l y , a s t h e 0 and Ν d i p r o t o n a t e d s p e c i e s . 5

2

2

Solvolytic

2

Behavior

A c i d - c a t a l y s e d s o l v o l y s i s o f b o t h c l a s s e s o f amides ( 1 ) a n d ( 2 ) p r o c e e d s a c c o r d i n g t o t h e A-2 mechanism. I n c o n s e q u e n c e , variation i n the polar effects o fsubstituents atthe nitrogen has two o p p o s i t e e f f e c t s . E l e c t r o n d o n a t i o n i n c r e a s e s t h e c o n c e n ­ t r a t i o n o f s u b s t r a t e ' s c o n j u g a t e a c i d b u t a t t h e same t i m e s l o w s

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the r a t e - d e t e r m i n i n g step - t h e n u c l e o p h i l i c a t t a c k o f a s o l v e n t m o l e c u l e a t t h e c a r b o n y l o r p h o s p h o r y l c e n t e r . However, t h e n e t s t r u c t u r e - r e a c t i v i t y dependence i s d e t e r m i n e d b y r e l a t i v e s e n s i ­ t i v i t y o f b o t h , t h e p r e e q u i l i b r i u m s t e p and t h e s l o w s t e p , t o polar effects of substituents. For the a c i d - c a t a l y s e d h y d r o l y s i s o f b e n z a n i l i d e s s u b s t i t u ­ t e d i n t h e a r o m a t i c amine m o i e t y ρ = 1.66. (jO.The p o s i t i v e s i g n o f t h e r e a c t i o n c o n s t a n t c a n be e a s i l y u n d e r s t o o d i n t e r m s o f t h e h y d r o l y s i s mechanism. The p r o t o n a t i o n o f t h e c a r b o n y l o x y g e n s h o u l d n o t be v e r y much a f f e c t e d b y t h e p o l a r i t y o f a r e m o t e s u b s t i t u e n t i n t h e N - a r y l g r o u p . On t h e o t h e r h a n d , t h e r a t e o f a p p r o a c h o f a n u c l e o p h i l e depends upon t h e e l e c t r o p h i l i c i t y o f the c a r b o n y l c a r b o n , which i n t u r n i s m o d i f i e d by the e l e c t r o n releasing o r electron - donatin propertie f th N-substituent Acid-catalysed solvolysi c h a r a c t e r i s e d by the negativ (p = - 1 . 2 ) . T h e s e i n v e r s e d s u b s t i t u e n t e f f e c t s i l l u s t r a t e t w o p o i n t s d i s c u s s e d b e f o r e . F i r s t , i f the N-protonated form r e p r e s e n t s t h e r e a c t i v e i n t e r m e d i a t e i n s o l v o l y s i s o f ( 2 ) , much s t r o n ­ g e r dependence o f t h e p r o t o n a t i o n p r e e q u i l i b r i u m o n t h e e f f e c t o f N - s u b s t i t u t i o n i s expected. S e c o n d l y , i f the resonance e f f e c t s a r e p o o r l y t r a n s m i t t e d t o t h e Ρ atom t h r o u g h t h e -NH- b r i d g e , s t r u c t u r a l v a r i a t i o n i n t h e N - a r y l s u b s t i t u e n t s h o u l d have weak e f f e c t upon t h e a b i l i t y o f p h o s p h o r u s t o a c c e p t a n u c l e o p h i l e . As a c o n s e q u e n c e o f t h e d i f f e r e n t e l e c t r o n i c i n t e r a c t i o n s w i t h i n t h e p h o s p h o r a m i d a t e g r o u p , P-N bond c l e a v a g e i n p h o s p h o r i c a m i d e s , c o n t r a r y t o t h e b e h a v i o r o f a n a l o g o u s c a r b o x y l i c compounds, i s a c c e l e r a t e d b y t h e e l e c t r o n - d o n a t i o n a t t h e n i t r o g e n atom. Acknowledgements and

The f i n a n c i a l a s s i s t a n c e o f t h e U n i v e r s i t y o f Cape Town t h e C.S.I.R. i s g r a t e f u l l y a c k n o w l e d g e d .

Literature Cited 1. Koizumi, T . ; Haake, P. J. Am. Chem. Soc. 1973, 95, 8073. 2. Robin, M. B.; Bovey, F. A.; Basch, H. "The Chemistry of Amides"; Zabicky, J.; Ed., Wiley, London, 1970; p 7. 3. Burdon, J.; Hotchkiss, J. C . ; Jennings, W.B. J. Chem. Soc. Perkin Trans. 1 1976, 1052. 4. Modro, T. A. Phosphorus and Sulfur 1979, 5, 331. 5. Hehre, W. J.; Taft, R. W. Progr. Phys. Org. Chem. 1976, 12, 159. 6. Peltier, D.; Pichevin, A.; Bonnin, A. Bull. Soc. Chim. Fr. 1961, 1619. 7. Modro, Τ. Α.; Lawry, M. A.; Murphy, E. J. Org. Chem. 1978, 43, 5000. 8. De Lockerente, S. R.; Brandt, P. V . ; Bruylants, A.; de Theux, T. Bull. Soc. Chim. Fr. 1970, 2207. RECEIVED

July 7, 1981.

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

POSTER PRESENTATIONS Reaction of Lignin with Chlorophosphazenes H . Struszczyk—Institute of Man-made Fibers, Technical University of £ o d z , Poland J. E . Laine—Rauma-Repola O Y , Rauma, Finland

Formation of Phosphinidenes by Thermolysis of 7-Phosphanorbornene Derivatives L . D . Quin, K . A . Mesch, and K . C . C a s t e r Gross Chemical Laboratory, Duke University, Durham, N C 27706

Tris(aminomethyl)phosphine Oxide and Its Derivatives Arien W . Frank—Southern Regional Research Center, U S D A , S E A , P.O. Box 19687, New Orleans, L A 70179

3//-Benzo-2,1-oxaphospholenes: Stereochem­ istry of Nucleophilic Substitution at Tricovalent Phosphorus Otto Dahl—Department of General and Organic Chemistry, The H . C . Jgfrsted Institute, University of Copenhagen, Universitetsparken 5, D K - 2 1 0 0 Copenhagen, Denmark

Synthesis of S-Alkyl S-(Carbamoylmethyl)ethylphosphonotrithioates W u Kiun-houo and Sun Yung-min—Depart ment of Chemistry, Fudan University Shanghai 201903, China Cyclic Acetals of Formyl Phosphonic Acid Esters S. Yanai, A . K . Singh, M . Halmann, and D . Vofsi-—The Weizmann Institute of Science, Rehovot, Israel Phosphorus Heterocycle Synthesis by RPXo · A1X Addition to R - C ( = Z H C H ,),-C(=CH,) R"