Part I: A Study of New Selective Brominating Agents. Part II: An Investigation of Certain 1,1-Bis(p-Chlorophenyl)alkanes and Derivatives

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Part I: A Study of New Selective Brominating Agents. Part II: An Investigation of Certain 1,1-Bis(p-Chlorophenyl)alkanes and Derivatives

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PURDUE UNIVERSITY

THIS IS TO CERTIFY THAT T HE THESIS PREPARED U N D E R M Y SUPERVISION

Charles Edgar Mortimer PART I: A STUDY OP NEW SELECTIVE BROMINATING AGENTS PART II: AN INVESTIGATION OP CERTAIN l,l-BIS(pentitded CHLOROPHENYL) ALKANES AND DERIVATIVES

COMPUTES WITH THE UNIVERSITY REGULATIONS O N GRADUATION THESES

A N D IS APPROVED BY M E AS FULFILLING THIS PART OF THE REQUIREMENTS

F O R THE D E G R E E OF

Doctor of Philosophy

June 6,______ iqSO

TO THE LIBRARIAN:--IS THIS THESIS IS N O T TO BE R E G A R D E D AS CONFIDENTIAL.

PROFESSOH IX CHARGE

GRAD. SCHOOL FORM B—3 .4 9 —1M

PART I: A STOUT OF HEW SELECTIVE BROMINATING AGENTS PART II: AN INVESTIGATION OF CERTAIN 1,1-BIS (^CHLOROPHENYL)AIKANES AND DERIVATIVES A Thesis Submitted to the Faculty of Purdue

University by

Charles Edgar Mortimer In Partial Fulfillment Requirements

of the

for the Degree of

Doctor of Philosophy lune, 1950

ProQuest Number: 27714069

All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is d e p e n d e n t upon the quality of the copy subm itted. In the unlikely e v e n t that the a u thor did not send a c o m p le te m anuscript and there are missing pages, these will be noted. Also, if m aterial had to be rem oved, a n o te will ind ica te the deletion.

uest ProQuest 27714069 Published by ProQuest LLC (2019). C opyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C o d e M icroform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106 - 1346

ACKNOWLEDGMENT

The first part

of

this

work was

directed by Dr. E# T. McBee; the second part was co-directed by Dr. E* T. McBee and Dr. H. B. Hass. to express them. The

his help

preparing the

The author

deep of

wishes

appreciation

to

Dr. Z. D. Welch in

thesis is also gratefully

a cknowledged. This investigation on a Purdue Research

was

conducted

Foundation

Fel­

lowship sponsored by the Michigan Chem­ ical Corporation, Saint Louis,Michigan.

TABLE OF CONTENTS Page ABSTRACTS............................................ Part 1. A Study of New Selective Brominating Agents.........................................

i

Part S. An Investigation of Certain l,l-Bis(jDchlorophenyl) alkanes and Derivatives........... PART I. A STUDY OF NEW SELECTIVE BROMINATING AGENTS. ♦

xxiii 1

Introduction.......................................

1

Discussion....................................

B

Experimental........

19

Preparation of N- Br omo ciiloroa ce tami de.........

19

Preparation of N-Bromotrichloroacetamide....... 21 Preparation of N-Bromo tri fluo roace tami de......

23

Reaction of N-Bromotrichloroacetamide with Anisole..........

.»•• 24

Reaction of N-Bromotrifluoroacetamide with Anisole...........................

25

Reaction of N-Bromotrichloroacetamide with Toluene.....................

25

Reactions of N-Bromotrifluoroacetamide with Toluene............. Non-Catalyzed

26 ......................

26

Peroxide Catalyzed.......................

27

Aluminum Chloride Catalyzed. ......

27

Reaction of N-Bromotrifluoroacetamide with Styrene............................

29

Page Reaction of N-Bromotrifluoroacetamide with C yc lohexene............................ N-(2-Bromocyclohexyl)-trifluoroacetamide..

30 32

Reaction of N-Bromo chlor oac e tami de with Cyc lohexene...........

34

Reaction of N-Bromotrichloroacetamide with Cyclohexene... ........................ Preparation of 2-Methyl-2-butene..........

35 36

Reaction of N-Bromotrifluoroacetamide with 2-Methyl-2-butene......................

36

Reaction of N-Bromoohloroacetamide with 2-Methyl-2-butene......................

37

Reaction of N-Bromotrichloroacetami de with 2-Methyl-2-butene •,

..................

38

Reaction of N-Bromotrifluoroacetamide with Propylene...............................

39

Reaction of N-Bromotrifluoroacetamide and Cyclohexanone* • ............. Preparation of N-Bromo-1,8-naphthalimide..

40 42

Reaction of N-Bromo-1,8-naphthalimide with Cyclohexene.

.........

Preparation of N-Bromo-4-nitrophthalimide♦

43 44

Reaction of N-Bromo-4-nitrophthalimide with Cyclohexene.............................

45

Preparation of Dibromomalononitrile.......

46

Page Beaction of Dibromomalononitrile with Cyclohexene.................. *

*

Determination of "Active^ Bromine........... Bibliography.

......

46 47 50

PART II. AN INVESTIGATION OP CERTAIN 1,1-BIS(^-CHLOROPHENYL )ALKANES AND DERIVATIVES.......

52

Introduction. ...........

52

Discussion..........».....

53

Experimental.......

73

Condensation of Chlorobenzene with Methylene Chloride.....................

73

Preparation of Bis (]>-ehl©rophenyl )methane from DDT. ........

75

Preparation of £,j>f~Diehlorobenzophenone. *•.

76

Preparation of 1,1-Bis (]>»chlorophenyl)ethanol............

77

Preparation of 1,1-Bis(^-ehlorophenyl)ethene

79

Preparation of 1,1-Bis (j>-ehlorophenyi) ethane

79

Action of Nitric Acid on Bis (^-chlorophenyl) methane «.............................

79

Action of Nitric Acid on 1,1-Bis (j>-ehlorophenyl )ethane

......

81

Preparation of 1,1-Bis (j£-chlorophenyl) *2,2,2tri fluor ©ethane

.......

•••

81

phenyl )-2,2,2-tr if luor ©ethane.............

82

Action of Nitric Acid on 1,1-Bis (]>-ehloro-

Page Friedel-Orafts Condensation of Chlorobenzene ......

and 1 $1-Diehloro-l-ni troethane

83

Reaction of jg^Chlorophenylstagnesium Bromide and 1,1-Di br omo -1-nitro ethane.............

83

Reaction of ^-Chlorophenylcadmium Chloride and 1,1-Dibromo-l-nitroethane. *. • .......

84

Reaction of Phenyleadmium Chloride with 1.1-Di bromo-l-nitro ethane.

............

85

Reaction of ^-Chlorophenylmagnesium Bromide and Ethyl Trifluoroacetate.•

.........

86

Preparation of Bis (£-ehlorophenyl)chloro86

methane.......................... Condensation of Silver Nitrite with Bis(jo-chlorophenyl) methane.

...........

67

Attempted Additions of Anhydrous Hydrogen Halides to 1,1-Bis(^-chlorophenyl)ethene.♦

88

Chlorination of 1,1-Bis(jg-chlorophenyl)ethane

89

Reaction of Anhydrous Hydrogen Chloride with 1.1-Bi s (jD-chlorophenyl )ethanol

*....

90

Reaction of Thionyl Chloride with 1,1-Bis(£-chlor ©phenyl) ethanol.

............

Bibliography........... VITA............................................. .

91 92

(Contribution from the Department of Chemistry and Purdue Research Foundation, Purdue University) A STUDY OF NEW SELECTIVE BROMINATING AGENTS1

(1) Contains material from Mr, Mortimerfs doctoral thesis.

By E, T. McBee and C. E. Mortimer AN ABSTRACT p N-Bromoacetamide ,

N-bromophthalimide

3

and

(2)

Wohl, A., Ber. 52, 51 (1919).

(3)

Wohl, A. and Jaschenowski, K . , Ber. , 54, 476 (1921).

N-br omo suc cinimi de4 are used extensively as brominating (4)

Ziegler, K . , Spaeth, A., Schaaf,

E . , Schumann, W,

and WinkeImann, E . , An n . , 551, 80 (1942). agents in the Wohl-Ziegler reaction. On the other hand N-ch lor oacetami de, N~ehlorophthalimide and N-chlorosuccinimide have been reported to be completely ineffective as allylic chlorinating agents^.

This may be explained by

noting that chlorine is more electron attracting than bromine* Hence any grouping of a molecule which would drain electrons away from a bromine atom of the molecule, thus making the bromine relatively positive, would not necessar­ ily affect a chlorine atom in the same manner or to the same

ii

extent. This is also borne out by the fact that whereas N~chloroacetamide did not chlorinate cyclohexene, N-chlorotrichloroacetamide produced 3-chlorocyclohexene in a low yield from cyclohexene^#

The alpha chlorine

atoms of N-chlorotrichloroacetamide would provide a strong inductive effect away from the nitrogen substituted chlorine and thus render it more positive than the nitro­ gen substituted chlorine of H-chloroacetamide# In this investigation, N-bromochloroacetamide, N-bromotriehioroacetamide and N-bromotrifluoroacetamide were made and tested as brominating agents. These compounds were synthesized by using an adaptation of the method of Franseconi and de Plato^# The mercury derivative of the (5) Francesconi, I. and de Plato, G, , Gazz, chim, ital,, 33, 226 (1903), amide was prepared and this compound was brominated in chloroform. Thus with trifluoroacetamide the equations are: 2 CF3C0NH2 + (CF3C0NH)2Hg +

HgO

►(CF3C0NH)2Hg

4- HgO

2 Br2-- >»2 CFgCCXNHBr 4

EgBr2

Using this method, N-bromochloroacetamide, melting at 63° C , , was prepared in a 68% yield; N—bromotriehloroacetamide, melting at 120° C . , was prepared in a 86% yield; and N-bromotrif luoroacetamide, melting at 59° C, ,

ill

was prepared in a 75# yield# These compounds reacted with anisole to produce £-bromoanisole# The reactions of anisole with N-bromotrichlor oac etamide and N-bromotrif luoroacetamide both gave a 64# yield of jD-bromoanisole#

These reactions probably

proceeded by an ionic mechanism, as is usually postulated for aromatic substitutions#

While the mechanism for

allylic brominationd of the Wohl-Ziegler type has not been established firmly, there is strong evidence for a g free radical mechanism and such is favored . Significantly, (6) Djerassi, C. , Chem. Rev., 45, 271 (1948) and references cited there* the reaction of anisole with N-bromoacetamide has been re­ ported to give a 75# yield of j^-bromoanisole^ ; while N-bromosuecinimide, which is a better agent for allylic brominations than N-bromoacetamide, reacts with anisole to give a 32# yield of jD-bromoanisole7# (7) Buu-Hoï, N. P . , Ann., 556 1 (1944). A trace of benzyl bromide and a 26# yield of jo-bromo­ to lu ene were obtained from the reaction of N-bromotri chlor oacetamide and toluene, while the reaction of N-bromotrifluor oacetami de and toluene gave a 8# yield of benzyl bromide and a 6# yield of £-bromotoluene# The benzyl bromide in which the alpha hydrogens may be considered to be allylic to the double bonds of the benzene ring, was probably

iv

produced by a free radical reaction, while the jD-bromotoluene was probably the product of an ionic reaction* When a trace of dibenzoyl peroxide, which catalyzes free radical reactions, was used in the reaction of N-bromo­ trif luoroacetamide and toluene, a 61% yield of benzyl bromide was obtained. When toluene was reacted with N-bromotri fluor oacetami de in the presence of molar quan­ tities of aluminum chloride, a catalyst generally em­ ployed in bringing about aromatic substitutions by an ionic mechanism, a 68% yield of £-br omo toluene was ob­ tained. Since these compounds probably react by at least two mechanisms, the reactions of these N-bromoacetamide derivatives with olefins would not be expected to be clean cut. Additions to the double bond, which presum­ ably occur through an ionic mechanism; polymerizations, which are catalyzed by free radicals; and reactions of the brominated products with the very reactive regenerated amides are among the reactions which could be predicted. N-Bromotrifluoroacetamide and cyclohexene gave a 42% yield of N- (2- bromoc yc lohexy 1 )-tr i fluor o ac et ami de , which would be the addition product if N-bromotrif luoro­ acetamide added to the double bond of cyclohexene* Kharasch and Priestly® have reported additions of certain (8)

Kharasch, M. 8* and Priestly, H* M. , THIS J'OTJRNAL, 61,

5425 (1959).

V

N-br omo sulfonamide a to styrene and other olefins, N-Bromotrifluoroacetamide and styrene gave a viscous brown material from which no pure products could be isolated. Polymerization (evidence for free radicals) of the styrene and/or its derivatives was extensive and rapid. In addition to N-(2-bromocyclohexyl)-trifluoro­ acetamide, the reaction of N-bromotrif luoroacetamide and cyclohexene also gave a small quantity of and oil which was similar to a product Howton9 obtained from the reaction (9) Howton, D. B . , THIS JOURNAL, 69, 2060 (1947), of N-bromosuccinimide and cyclohexene. He described it as a mixture composed primarily of 5 ,6-dibromocyclohexene and l ,2-dibromocyclohexane. This oil was also the product of the reaction of N-bromochloroacetamide and cyclohexene and of the reaction of N-bromotr ichlor oac etami de and cyclohexene. With B-methyl-2-butene, N-bromochloroacetamide and N-bromotrifluoroacetamide, gave low yields of a dibrominated derivative, Wohl

has reported that N-bromoacetamide

and 2-methyl-2-butene give a similar product, N-Bromotrifluoroacetamide and propylene gave a 8% yield of allyl bromide and a 50% yield of a dibrominated derivative. The production of dibrominated olefins instead of the expected mono brominated derivatives is frequently observed with N-bromoacetamide^»^ * and it wDuld appear

vi

that this is also the case with other acetamide deriva­ tives* N-Bromotrifluoroacetamide was also reacted with cyclohexanone, and a 41% yield of 2-bromoeyclohexanone was produced» Carbonyl compounds could not enter into some of the side reactions which are possible with olefins* It would appear that the alpha halogen atoms of N-bromochloroacetamide, N-br omotric hloroa ce tami de and N-br omotri fluoroacetami de activate the nitrogen substi­ tuted bromine to such an extent that these agents react by ionic, free radical, and possibly other mechanisms to produce a mixture of a great many products. A good agent for the Wohl-Ziegler reaction, on the other hand,probably reacts almost exclusively by free radicals* In addition to the halogenated N-bromoacetamide de­ rivatives, N-bromo-1,8-naphthalimid e , N-bromo-4-nitrophthalimide and Dibromomalononitrile were reacted with cyclohexene. N-Bromo~l,8-naphthalimide was made by brominating a solution of 1,8-naphthalimide in dilute aqueous potassium hydroxide. The reaction of N-bromo-l,8naphthalimide and cyclohexene yielded 1,8-naphthalimide (substantial quantitative recovery), an 8% yield of 3-bromocyclohexene and a small amount of tar. N-Bromo4-nitrophthalimide was made by brominating potassium 4-nitrophthalimide in chloroform. It reacted with cyclo­ hexene to give a small amount of tar and the theoretical

vii

amount of 4-nitr ophthalimide. Both N-br omo-1,8-naphtha limi de and N-br omo-4-ni tr ophtha limi de are high molecular weight, high melting solids of low solubility in most organic sol­ vents, and these results are not surprising# It has been reported that dibromomalononitrile brominates N,N-dimethylaniline and malononitrile^• (10) Ramberg, L. and Wideqvist, S., Arkiv Kemi, Mineral. Geol. 12A, No. 22, 12 pp.

(1937).

In this investigation the reaction of dibromomalononitrile and cyclohexene was found to give a 41% yield of 1,2-di­ br omo cyclohexane. EXPERIMENTAL N-Bromochloroacetamide.-Yellow mercuric oxide was made by treating a solution of 50.0 g. (0.15 mole) of hydrated mercuric nitrate in 500 ml. of water with a solution of 14*0 g. (0*35 mole) of sodium hydroxide in 100 ml. of water at room temperature (not higher). The precipitated mercuric oxide was collected by suction filtration and washed well with water. Dry, red mercuric oxide as supplied by chemical houses could not be used in the preparation# Ethyl chloroacetate was prepared using chloroacetic acid, ethanol and concentrated sulfuric a c i d ^ , and chloro(11) Conrad, M . , Ann., 188, 218 (1877). acetamide was made by treating this ester with twice its

viii

volume of concentrated ammonium hydroxide at 0° C.5 The freshly prepared yellow mercuric oxide, in the form of a damp paste, was added to a solution of 18.5 g, (0.2 mole) of chloroacetamide dissolved in a minimum quantity of water. The mixture was stirred and allowed to stand ÿe permit the bis(chloroacetamido)mercury and excess mercuric oxide to settle completely# The solid was separated by suction filtration and dried under vacuum in a round bottom flask which was heated on a steam cone. The dried solid was suspended in 150 ml. of dry chloroform and 15 ml.

(48.0 g . ; 0#3 mole) of

bromine was added. The mixture was suction filtered and the chloroform evaporated from the filtrate under a current of dry air. N-Bromochloroacetamide separated from the chloroform solution in glistening white plates; it was recrystallized from chloroform. The N-bromochloro­ acetamide obtained weighed 23.3 g. (0.135 mole) which represents a 68% yield based on the chloroacetamide used. The product melted at 63° C. N-Bromotrichloroacetamide.-Ethyl trichloroacetate was prepared by bubbling anhydrous hydrogen chloride gas through an ethanolic solution of trichloroacetic acid^-2 ; (12) Spiegel, L. and Spiegel, P., Ber., 40, 1730 (1907)# this ester was converted to trichloroacetamide by treatment 13 with concentrated ammonium hydroxide #

il

(13) Clermont, A , , Comp, rend., 133, 738 (1901)» N^Bromotrichloroacetamide was prepared from trichloroacetamide in substantially the same manner as was N-bromo­ chloroacetamide from chloroacetamide with the following exceptions. Trichloroacetamide is only slightly soluble in water, therefore, a slurry of this amide in water was treated with the yellow mercuric oxide» In the final step, the chloroform was removed under vacuum at room temperature instead of evaporating it.

From 8.2 g . (0.5

mole) of tri chloroacetamide, 1(^4 g. (0.43 mole) of N-bromotrichloroacetamide was obtained [86% yield based on the trichloroacetamide used)*

The product melted at 120° C*

Anal. Calcd. for C2HBrCl3N0: C, 9.95; H, 0.42; N, 5.80. Found: C, 9.95; H, 0.44; N, 5.82. N-Bromotrifiuoroacetamide.-Trifluoroacetamide was prepared using the method of Oilman and Jones^» (14) Oilman, H. and Jones, B. G. , THIS JOURNAL, 65. 1458 (1943). The procedure used in the preparation of N-bromotrifluoroacetamide from trifluoroacetamide was essentially the same as that used in the preparation of N-bromotrichloroacetamide. Trifluoroacetamide is very soluble in water ; its hydrolysis to trifluoroacetic acid and ammonia is very easily accomplished and very rapid.

For this reason, a thick

paste of yellow mercuric oxide in water was added to the

X

dry trifluoroacetamide. This mixture was stirred for five minutes and then the entire slurry was dried under vacuum without filtration. The remainder of the procedure was identical to that described in the preparation of N-bromo­ tri chlor oac etamide. From 56.5 g. (0.5 mole) of trifluoro­ acetamide , 72 g. (0.38 mole) of N^bromotrifluor oacetami de was obtained!75# yield). The product melted at 59° C. Anal. Calcd. for CgHBrF^NO: C, 12.50; H,0.52, Found: C, 12.62; H, 0.53. Reaction of N-Bromo tri chloroacetamide with Anisole.- The following were placed in a 250 ml. Erlenmeyer flask in the order named: 10.8 g. (0.1 mole) of anisole, 65 ml. of dry acetone and 24.14 g. (0.1 mole) of N-bromotrichloroacetamide. The flask was stoppered and set aside at room temperature for twenty-four hours. The acetone was removed under vacuum and 4.5 g. of trichloroacetamide was removed by suction filtration. Fifty milliliters of carbon tetrachloride was then added and this solution was washed with 5% sodium carbonate followed by distilled water. The organic layer was then dried over anhydrous sodium sulfate. Vacuum dis­ tillation of this solution gave after removal of the carbon tetrachloride, only one fraction boiling at 60-84° C./7 mm. Redistillation of this fraction gave 12 g. (0.064 mole) of p-bromoanisole boiling at 100° C./16 mm.

(64# yield). The

product melted at 11-2° C. and had a normal boiling point of 215° C . ; the nitro derivative melted at 88° C.

xi

Reaction of N-Bromotrifluoroacetamide with Anisole.- This experiment was conducted in a manner similar to that of N-bromotrichloroacetamide with anisole*

From the reaction

of 21*6 g. (0.2 mole) of N-bromitrifluoroacetamide, 12 g# (0.064 mole) of j>-bromoanisole was obtained. Reaction of N-Bromotrichloroacetamide with Toluene.-The following were placed in an Erlenmeyer flask in the order named: 18.4 g. (0.2 mole) of toluene, 100 ml. of acetone, and 24.1 g. of N-bromotrichloroacetamide. The flask was stoppered and set aside at room temperature. After two days, the mixture still gave a positive starch-iodide test; the acetone was removed under vacuum and 100 ml. of toluene added. This mixture was allowed to stand an additional two days; after which it no longer gave a starch-iodide test. The unreacted toluene was removed under vacuum and precipitated trichloroacetamide removed by suction filtration. The trichloroacetamide weighed 15.4 g. which is 96% of the amount expected on the basis of the N-bromotrichloroacetamide used. Distillation of the fil­ trate gave a fraction which boiled at 66° C./8 mm. This was redistilled at atmospheric pressure and boiled at 184° C. The material was a solid at room temperature (m.p. 28® C* ) and was identified as £- bromotoluene by the oxidation of it to ^-bromobenzoic acid (m.p. 251° C. ). Reactions of N-Bromotrifluoroacetamide with Toluene : A:Non-Catalyzed.- To a solution of 46.0 g. (0.5 mole) of toluene in 50 ml. of dry acetone, 19.2 g. (0.1 mole)

xii

of N-bromotrif luoroacetamide was added. The solution turned yellow immediately, and the flask was stoppered and set aside at room temperature. After twenty-four hours the mixture no longer gave a starch-iodide test. The acetone was removed under vacuum. The precipitated trif luoroaceta­ mide was removed by suction filtration. This solid was washed with 50 ml. of carbon tetrachloride and the wash­ ings added to the filtrate. The regenerated trifluoroacet­ amide weighed 8.6 g. which is 76% of what would be expected on the basis of the N-bromotrifluoroacetamide used. The carbon tetrachloride solution was washed with 5% sodium carbonate followed by distilled water and then dried over sodium sulfate. The solution was then vacuum distilled. After the excess toluene and carbon tetrachloride were re­ moved the products were collected in a fraction boiling at 64-80° C./lO mm. A tarry residue was left. Fractiona­ tion of the 64-80° portion, under atmospheric pressure, gave 1.1 g. of ]D-bromotoluene (0.006 mole; 6.4% yield) boiling at 184° C. and 1.4 g. of benzyl bromide (0.008 mole ; 7.9% yield) boiling at 198° C. B:Peroxide Catalyzed.-To a solution of 18.4 g. (0.2 mole) of toluene in 100 ml. of carbon tetrachloride, 0.5 g. of dibenzoyl peroxide and 19.2 g. (0.1 mole) of N-bromotrifluoroacetamide were added in the order named. The solu­ tion turned amber colored immediately and the flask was stoppered and set aside at room temperature for twentyfour hours. At the end of that period the mixture still

xiii

gave a positive starch-iodide test, so it was transferred to a Glas-col heated 500 ml* round-bottom flask equipped with a reflux condenser, and refluxed for thirty minutes* At the end of that time the mixture no longer gave a starch-iodide test, and upon cooling crystals of trifluoro­ acetamide were precipitated. The yield of regenerated trifluoroacetamide was approximately quantitative (11 g * ); the solid was removed by suction filtration* The liquid was fractionated under vacuum. After the unreacted toluene and carbon tetrachloride were removed, a fraction boiling at 66-80° C*/10 mm. was collected. This was redistilled at atmospheric pressure to give 10.4 g. of benzyl bromide boiling at 198° C.

About 5 g. of a mixture of higher boil­

ing products was also obtained* This represents a 61% yield of benzyl bromide based on the N-bromotrifluoroacet­ amide used* C Aluminum Chloride Catalyzed*-Anhydrous aluminum chloride (13.4 g. ; 0.1 mole) was mixed with 40 ml. of dry toluene* This mixture was cooled in an ice-salt bath and 19.2 g. (0*1 mole) of N-bromotri fluor oac etamide was added in small portions over a period of an hour. The reaction was very vigorous, and the solution turned a dark red-brown in color* After the addition was complete, the reaction flask was kept in the cooling bath for an additional two hours and then allowed to stand at room temperature overnight. The mixture was poured into ice-water and this then

xiv

extracted with ether. The ether solution was washed with cold water and dried over anhydrous sodium sulfate. The ether was removed and the residue distilled under atmospheric pressure using a Vlgreaux column* A 68% yield of jd-bromo to lue ne (11.6 g.) was obtained which boiled at 182-4° C. In all of the experiments the products were confirmed by melting points (j^-bromotoluene, 28° C. ;benzyl bromide, -4° C*), boiling points (as reported previously) and the preparation of derivatives. ^-Bromotoluene was oxidized to p-bromobenzoic acid (m,p. 251° C * ) and the anilide was prepared from benzyl bromide (m.p* 117° C * ). Reaction of N-Bromotrifluoroacetamide with Cyclohexene*~ The following materials were mixed in a 250 ml. Erlenmeyer flask in the order named: 24,6 g. (0.3 mole) of cyclohexene, 100 ml. of carbon tetrachloride, and 28.8 g* (0.15 mole) of N-bromotrifluoroacetamide. The flask was cooled in an ice-bath for three hours and then allowed to stand for twenty-four hours at room temperature. It was found that without this initial cooling the mixture got very warm, darkened in color and precipitated a red, sticky material. At the end of twenty-four hours the mixture no longer gave a starch-iodide test, and N - (2-bromocyclohexyl)-trifluoro­ acetamide precipitated. The carbon tetrachloride was re­ moved at room temperature under vacuum and the mixture filtered. The solid N - (2-bromocyclohexyl)trifluoroacetamide was set aside and the filtrate was dissolved in an additional

XV

50 ml* of carbon tetrachloride. This solution was washed with 5% sodium, carbonate followed by distilled water and finally dried over anhydrous sodium sulfate. Fractiona­ tion under reduced pressure gave, after removal of the carbon tetrachloride and excess cyclohexene, a fraction which boiled at 84-7° C./5 mm»

Redistillation of this

fraction gave 8 g* of material which boiled at 55-7° C./ 1 mm*,

This boiling point does not correspond to the

boiling point of any pure brominated cyclohexene. The product gave unsaturation tests and a positive test with alcoholic silver nitrate ; it was similar to a liquid ob­ tained by Howton9 from the reaction of N-bromosuccinimide and cyclohexene which he identified as a mixture contain­ ing 1,3-dibromocyclohexane and 5 ,6-dibromocyclohexene* The solid N-(S-brbmocyclohexyl)-trifluoroacetamide was recrystallized twice: first, from ethanol-water; second, from carbon tetrachloride. The yield was 17.3 g. (43% based on the N-bromotrifluoroacetamide used) of white crystalline material melting at 153° C. The product did not give unsaturation tests, and gave a precipitate with alcoholic silver nitrate only after heating. Qualitative analysis confirmed the presence of fluorine, nitrogen and bromine. Anal* Calcd. for C0H_.BrF^NO: C, —— — —

o

1-L

o

35*03; H, 4.01;

H, 5.11. Found: 0,35.37; H,4.03; N, 4*98. The same products were isolated in approximately the same ratio when dibenzoyl peroxide (0*3 g* ) was added to a similar reaction mixture in another experiment. Further,

xvi

it was found that the results were similar when ether was employed as the reaction solvent in place of carbon tetra­ chloride. N-(2-Bromocyclohexyl)-trifluoroacetami de.-your grams of this compound, obtained from the reaction of N-bromotrifluoroacetamide and cyclohexene, was dissolved in 25 ml. of 20% potassium hydroxide solution and the mixture warmed on a steam bath. A gas was liberated which was identified as ammonia by its odor and effect on moist red litmus paper. The solution was evaporated to dryness on the steam bath. The dry salts were placed in a 125 ml. Claisen flask and a solution of 25 ml. of concentrated sulfuric acid in 20 ml. of absolute ethanol (at room temperature) was added. The distilling flask was equipped with a condenser and receiver and was heated by a heating mantle.

Ethyl trifluoroacetate distilled over at 60-2° C . ;

1.6 g# (77% yield) of this compound was obtained. Treatment of this ester in anhydrous ether with ammonia gas gave,after removal of the ether, 1.2 g. of trifluoroacetamide (m.p. 75° C.). Reduction of N-(2-bromocyclohexyl)-trifluoroacetamide by sodium in amyl alcohol was conducted according to the method of Kharasch and Priestly®. Cyclohexylamine was ob­ tained and isolated as the hydrochloride*

From 2 g. of

N-(2-bromocyclohexyl)-trifluoroacetamide, 0.75 g . (75% yield) of cyclohexylamine hydrochloride was obtained melting at 206° C.

xvii

Reaction of N-Bromotrifluoroacetamide and 2-Methyl-2brrtene*-S^Methyl-E-butene was prepared by dehydrating 15 t-azoyl alcohol according to the method of Norris and Joubert . (15) Norris, J. F. and Joubert, J. M, , THIS JOURNAL, 49, 873 (1927). The following were mixed in a 125 ml. Erlenmeyer flask : 14 g. (0.2 mole) of 2-methyl-2-butene, 0.2 g. of dibenzoyl peroxide, and 50 ml. of carbon tetrachloride. To this solution, 19.2 g. (0.1 mole) of N-bromotrifluoroacetamide was added, in small portions, with shaking. The flask became warm but no color developed; trifluoracetamide started precipitating immediately. The flask was stoppered and set aside at room temperature for twenty-four hours. At the end of that time the mixture was filtered, the carbon tetrachloride removed from the filtrate under vacuum, and the distillation residue filtered again. A total of 9 g. of trifluoroacetamide was recovered from the two filtrations (80% of the theoretical). The filtrate was vacuum distilled and a fraction was collected which boiled at 49**60° C./13 mm. Redistillation of this fraction gave 3.2 g. of a dibrominated unsaturated derivative of 2-methyl2-butene (38% yield) boiling at 54-5° C.

Wohl2 obtained

a similar product from the reaction of N —bromoac et amide and 2-methyl-2— butene which he identified as 1,4—dibromo2-methyl-2-butene.

xviii

Reaction of N-Bromotrifluoroacetamide and Propylene.N-Bromo trif luoroacetamide (19.2 g. ; 0.1 mole) was dissolved in 100 ml. of anhydrous ether. Propylene was bubbled through this solution, at room temperature, for six hours. At the start the flask got quite warm and a red color developed; however, evaporation of the ether soon cooled the flask and the color disappeared. The ether had to be continually replaced due to evaporation losses; the volume was main­ tained at approximately 100 ml.

It was found that it was

not advisable to cool the flask in an ice-bath as this slowed the reaction too much. At the end of six hours, at room temperature, no starch-iodide test was obtained and the mixture was distilled at atmospheric pressure. After the ether distilled, 1 g. of allyl bromide distilled at 70-1° C. (8.3% yield) followed by 5.0 g. (50% yield) of a dibrominated unsaturated derivative of propylene boiling at 136-8° C. The second corresponds to a product obtained p by Wohl from the reaction of N-bromoacetamide and propylene which he reported was 2 ,3-dibromo-1-propene* Reaction of N-Bromotrifluoroacetamide with Cyclohexanone.To a solution of 24.9 g. (0.3 mole) of cyclohexanone and 0.2 g. of dibenzoyl peroxide in 100 ml. of carbon tetra­ chloride, 19.2 g. (0.1 mole) of N-bromotrifluoroacetamide was added.

The mixture, in a stoppered 500 ml. Erlenmeyer

flask, was set aside at room temperature. The contents of the flask became yellow which gradually changed to red and finally purple. At the end of two days, the mixture

xix

no longer gave a starch-iodide test and the solution was a rose color. The solution was washed with 5% sodium carbonate solution followed by distilled water and dried over anhydrous sodium sulfate. Vacuum distillation of the solution gave 7.3 g. (41% yield) of 2-bromocyclohexanone boiling at 90° C./14 mm. N-Bromo-1.8-naphthalimide.-1.8-Naphthalic acid was prepared by the oxidation of acenaphthene according to the method of Gkraebe and G-feller

.

This 1,8-naphthalic acid was

(16) Graebe, C. and Gfeller, E . , Ber., 25, 652 (1892). converted to 1,8-naphthalimide according to the method of Jaubert^. 1,8-Naphthalimide (19.7 g. ; 0.1 mole) was (17) Jaubert, G. F . , Ber., 28, 360 (1895). dissolved in a solution of 22.4 g. (0.4 mole) of potassium hydroxide in 1500 ml. of water. The mixture was stirred well and filtered. The filtrate was then cooled to around 0° C. in an ice-bath and 40 g. (0.5 mole) of bromine was added. N-Bromo-1,8-naphthalimide precipitated immediately; it was removed by suction filtration. The crude N-bromo-1,8-naphthatimide was dried in a round bottom flask under vacuum and the dried material then recrystallized from benzene. The re­ crystallized product melted at 268-70° C. ; 12 g. (43% yield) was obtained. Anal. Calcd. for G^H^BrNOg: C, 52.17; H, 2.17; N, 5.07. Found: C, 52.00; H, 1.95; N, 5.13.

Reaction of N-Bromo-1.8-naphthalimide with Cyclohexene.A mixture of 20 g. (0*072 mole) of N-bromo-1,8-naphthal­ imide, 50 ml.

(40.5 g * ; 0.49 mole) of cyclohexene and

50 ml* of benzene was refluxed until it no longer gave a positive test with starch-iodide paper (two hours). At the end of this time the reaction mixture was cooled and filtered. The residue was 1,8-naphthalimide (m.p# 298-300° C. ) ; 14 g. (98% recovery) was obtained. Fractionation of the filtrate gave 0.95 g. (8.2% yield) of 3-bromocyclohexene boiling at 45-7°C./lO mm. A small quantity of a brown tar was left from the distillation. N-Bromo-4-nitrophthalimide.- Fhthalimide was nitrated to yield 4-nit ropht ha limide according to the method of Huntress and Shriner

1A

• 4-Nitropht ha limide (19.2 g. ;

(18) Huntress, E* H. and Shriner, R. L . , Org. Syntheses, Coll. Vol. II, 459 (1943). 0.1 mole) was dissolved in 500 ml. of hot 95% ethanol and a solution of 16.8 g. (0.3 mole) of potassium hydrox­ ide in 50 ml. of ethanol was then added. The potassium salt of 4-nitrophthalimide precipitated immediately. The mixture was filtered hot,and the potassium 4-nitrophthalimide air dried. This compound was then suspended in 500 ml. of dry chloroform and 24 g. (0.3 mole) of bromine added to the mixture.

The mixture was stirred and allowed

to stand for 0.5 hour. At the end of that time the mixture was filtered, the residue discarded and the filtrate

xx i

evaporated to dryness. The crude N-bromo-4-nitrophthalimide was recrystallized from chloroform; 13 g. (48% yield) of the compound (m.p* 193° C. ) was obtained. Anal. Calcd. for CgHgBrNgO^ C, 35.42; H, 1.11; N, 10.33. Found: C, 35.40; H, 1.20; N, 10.41. Reaction of Dibromomalononitrile with Cyclohexene.- The method of Ott and Weissenburger^-® was used to prepare (19) Ott, E. and Weissenburger, H . , Ber., 70. 1829 (1937). di bromoma lononitrile as well as the addition complex of dibromomalononitrile and sodium chloride.

A reaction was

run in which 11.2 g. (0.05 mole) of dibromomalononitrile, 16.4 g. (0.2 mole) of cyclohexene and 50 ml. of carbon tetrachloride were re fluxed together for two hours. The unreacted cyclohexene and carbon tetrachloride were distilled from the reaction mixture at atmospheric pressure and the remainder was fractionated under vacuum. Five grams of 1,2-dibromocyclohexane boiling at 101-3° C./13 mm. was obtained; this represents a 41% yield based on the quantity of dibromomalononitrile used. A mixture of 14 g* (0.015 mole) of NaCl*4CBr,> (CN)g (equivalent to 0.06 mole of dibromomalononitrile), 16 g. (0.195 mole) of cyclohexene and 50 ml. of carbon tetra­ chloride was refluxed for two hours. At the end of this time the mixtur e no longer gave a positive test with starch-iodide paper, and it was cooler and filtered. The carbon tetrachloride and unreacted cyclohexene was

xxii

distilled f r o m ,the filtrate at atmospheric pressure. The remainder from this distillation was distilled under vacuum* 1,2-Dibromocyclohexane (5.5 g . ; 38% yield) was obtained boiling at 101° C./13 mm. ACE]HOWLEDGrMENTe-This work was carried out on a Purdue Research Foundation fellowship sponsored by the Michigan Chemical Corporation, Saint Louis, Michigan. SUMMARY (1) N-Bromo chi or oa cet ami de, N-bromotrichloroacetamide and N-bromotrifluoroacetamide have been prepared and studied as bfominating agents* (2) These compounds have been observed to be fair brominating agents for aromatic and carbonyl compounds. However, with olefins they react to produce a mixture of products among which was a dibrominated derivative of the olefin. (3) N-Bromo-1,8-napht ha limide and N-bromo-4-nitrophtha limide were prepared and reacted with cyclohexene. These reactions gave a small quantity of brominated tar and the imide from which the brominating agent was derived. (4) Dibromomalononitrile and cyclohexene reacted to give a 41% yield of 1,2-dibromocyclohexane. Lafayette, Indiana.

xxiil

(Contribution from the Department of Chemistry and Purdue Research Foundation, Purdue University) AN INVESTIGATION OF CERTAIN 1,1-BIS (^.-CHLOROPHENYL)AIKANES AND DERIVATIVES1

(1) Contains material from Mr. Mortimer's doctoral thesis.

By E. T. McBee, H. B. Hass and C. E. Mortimer AN ABSTRACT The compounds 1,1-bis (]3-chlorophenyl)~2-nitroethane and 1 ,1-bis (]>~chlorophenyl)-2-nitropropane have been found to be useful insecticides and far less toxic to warm 2^4. blooded animals than DDT * ' . Also, 1,1-bis(jD-chlorofE) Muller, P., U. S e Pat. 2,397,802 (1946) (3) Blickenstaff, R. T., Ph. D. Thesis, Purdue University (1948). (4) Neher, M. B. , Ph. D. Thesis, Purdue University (1946). phenyl)ethanol is an effective agent for the control of mitesIn

view of the activities of these compounds, it

(5) Michigan Chemical Corporation, private communication. was expected that the 1,1-bis (js-chlorophenylJ-l-nitroalkanes would be useful miticides. Bis(jD-chlorophenyl)methane has been made by many methods; however, most of the preparations reported in the literature

xxlv

offer disadvantages in that low yields of a product are obtained the final purity of which is questionable. The condensation of chlorobenzene and methylene chloride, which is not reported in the literature, was found to give a very small amount of an oil from which no pure bis(jD-chlorophenyl) methane could be isolated. The isomers of bis(jD-ehlorophenyl)methane are difficult to separate; hence, prepara­ tions involving compounds in which the ]>-chlorophenyl groups are already present in the molecule (such as the reduction of ^ j s ’-dichlorobenzophenone ) are more satisfac(6) Montagne, P. J . , Bee. trav. chim., 25, 390 (1907). tory than condensations in which a mixture of o-chlorophenyl and £-chlorophenyl derivatives may be formed (such as the condensation of chlorobenzene and formaldehyde^). (7) Nastjukow, A. and Andre jew, W. , J. Russ. Phys. Chem. Soc., 47, 552 (1916). A method was developed to prepare bis(^-chlorophenyl)methane by the alkaline hydrolysis of DDT. This is probably the best source of the methane derivative, for, in one step from DDT, an excellent yield of very pure bis(p^chlorophenyl)methane may be obtained. It has been reported that alcoholic potassium hydroxide with DDT, at room temperature or reflux temperature, gives dichloroethene8 »9 »

1,1-bis(£-ehlorophenyl)-2,2-

. At a higher temperature (ca.l50° C . )

XXV

(8) Gatzi, K* and Stammbach, W. , Helv. Chim. Acta. , 29, 563 (1946)• (9) Grummitt, O . , Buck, A. C. and Egan, R . , Org* Syntheses, 26, 21 (1946)* (10) Grmmnitt, 0*, Buck, A. C. and Stearns, J. , THIS JOURNAL, 67, 156 (1945). the reaction yields 2 ,2~bis(£-chlorophenyl)acetic acid^^ ^ In this investigation the reaction of potassium hydroxide with DDT in ethanol at a still higher temperature (180° C . ) in an autoclave has been found to yield bis(]D-chlorophenyl)methane in substantially quantitative yield* The use of pure 1,1-bis(£-chlorophenyl)~2,2,2-trichloroethane, obtained by the recrystallization of technical DDT, yields bis(£-chloro~ phenyl)methane which is free from o-chlorophenyl isomers. Cl

Cl

Cl

Cl

HCC0oH

The higher members of the bis(£-chlorophenyl)alkanes may be prepared by synthesizing the l,l-bis(£-chlorophenyl)1-hydroxyalkanes, dehydrating these compounds and hydrogenat­ ing. 1,1-Bis(£-chlorophenyl)ethanol is best made by one of two methods:

(1) The reaction of méthylmagnésium bromide11 or (11) Grummitt, 0., Buck, A. C . and Becker, E. I* THIS JOURNAL, 67, 2265 (1942) . méthylmagnésium iodide12 with £ ,£1~dichlorobenzophenone: (12) Bergmann, E. and Bondi, A., Ber., 64, 1455 (1931)* Cl

Cl

(2)

Cl

The reaction of jD-chlorophenylmagnesium bromide

and ethyl acetate : Cl

CH3C02C2H5+2 p-ClC6H4MgBr

►CHgÔOMgBr

4- Mg(0C2H 5 )Br

xxvii

1,1-Bis (£-chlorophenyl)ethano1 may be dehydrated by treatment with 20% sulfuric acid to give an 88% yield of 1.1-bis(£-chlorophenyl)ethene11.

The hydrogenation of this

compound gives a 62% yield of 1,1-bis(£-chlorophenyl)11

ethane•

Ring nitration of the bis(£-chlorophenyl)alkanes may 13 be accomplished by fuming nitric acid • There is no mention (13) Forrest, J ., Stephenson, 0, and Walters, W. A. J Chem. Soc., 1946, 335* in the literature of the action of concentrated or dilute nitric acid on these compounds. However, from the reaction of 1,1-diphenylethane and concentrated nitric acid in glacial acetic acid, which ultimately yields benzophenone, a series of intermediate oxidation products has been isolated: 1.1-diphenyl-2-nitroethanol, 1,l-diphenyl-2-nitroethene and l,l-diphenyl-2,2-dinitroethene^. Konowaloff^ has ni(14) Anschutz, R. and Hilbert, A., Ber. , 54, 1854 (1921). (15) Konowaloff, M. , J. Russ# Phys. Chem. Soc. , 25, 389 (1893); ibid., 26, 68 (1894); Ber., 29, 2195 (1896), trated diphenylmethanè with 12.7% nitric acid at 100° C. in a sealed tube and obtained diphenylnitromethane. The product was not very stable ; it decomposed at room temperature and difficulty was encountered in regenerating it from its salts. The action of dilute nitric acid (12.7% by weight) and a nitric acid-acetic acid mixture (13% nitric acid by

xxviii

weight) on bis (]D-chlorophenyl)methane and 1,1-bis {£-chlorophenyl)ethane was studied. The only product obtained from any of the reactions was E^j^-dich-lorobenzophenone, and no intermediate oxidation products were isolated* l,l~Bis(]D~ chlorophenyl)ethene when treated with nitric acid under similar conditions was readily oxidized to this ketone# Hence it may be postulated, in the case of 1,1-bis(£-chlorophenyl)ethane, that this compound is initially oxidized to 1,1-bis(^-chlorophenyl)ethanol and this alcohol is then dehydrated, cleaved and oxidized to p^ja’-dichlorobenzophenone. This ketone has been reported as the product of the irradiation of DDT with a mercury vapor l a m p ^ and is (16) Fleck, E. E. , THIS JOURNAL, £1, 1034 (1949). an unpredicted product of many reactions of the 1,1-bis(£chlorophenyl)aIkanes and derivatives# It would appear that the activating effect of the two

chlorophenyl groups

renders certain derivatives of the bis(^-chlorophenyl)alkanes very susceptible to oxidation. However, 1,1-bis(£chlorophenyl)-3,2,2-trifluoroethane when treated with dilute aqueous nitric acid under similar conditions was not affected* It is well known that the Friedel-Crafts reaction is not an efficient method of synthesizing nitro compounds. 17 However, the preparation of the isomeric phenylnitropropanes (17) Silverberg, I# B . , Ph. D. Thesis, Purdue University(19421

xxix

as well as the preparation of 1 - (j)-ch.lorophenyl)-3-nitro1Q

propane*1-0 have been reported using condensations of this (18) Patrick, T. M, , Ph. B. Thesis, Purdue University (1943). type* When an attempt was made to condense chlorobenzene and 1,1-dichloro-l-nitroethane, almost all of the starting materials were recovered unchanged together with a very small amount of an oil from which no pure product could be isolated. The reactions of jD-chlorophenylmagnesium bromide and jD-chlorophenylcadmium chloride with 1,1-dibromo-l-nitroethane were studied. Newman and S m L t h ^ have reported a (19) Newman, M. S. and S#ith, A. S., J. Org. Chem., 15, 592 (1948). successful condensation between phenylmagnesium bromide and m-nitrobenzldehyde at -70° C . ; and therefore the reactions were run at the temperature of a dry-ice-trichloroethylene bath in addition to experiments conducted at room tempera­ ture. However, in all cases the products were a high melting, insoluble, yellow solid (presumed to be a phenylene polymer), unreacted starting materials and traces of

-dichloro-

biphenyl. An experiment with phenylcadmium chloride and 1,1-dibromo-l-nitroethane yielded only unreacted starting materials and a trace of biphenyl. As a matter of interest, £-chlorophenylmagnesium bromide

XXX

was reacted, with ethyl trifluoroacetate ; however no pure product could be isolated from the reaction mixture. A condensation of silver nitrite with bis (jD-chlorophenyl)chioromethane was run; it was expected that the two ^-chlorophenyl groups would activate the aliphatic chlorine atom of the bis (js-chlorophenyl)chloromethane to such an ex­ tent that this condensation would be effected and the nitro derivative made in good yield. There was evidence that the reaction proceeded in the expected manner since silver chloride was produced; however, a high yield of j^P^-dichlorobenzophenone was obtained. It may be postulated that bi s (]3-chlorophenyl )ni tr ome thane is actually produced in this reaction, and as soon as it has been formed, undergoes transformation to the ketone: Cl

Cl

HCNO

This is similar to the Net synthesis of aldehydes and ketones from nitroalkanes. The two £-chlorophenyl groups may activate the bis(£-chlorophenyl)nitromethane to such an extent that this decomposition is spontaneous. Attempts were made to synthesize alpha halogen derivatives of

1

,1-bis(^-chlorophenyl)ethane in order that a

xxxi

silver nitrite condensation could be run with one of them. However, neither anhydrous hydrogen chloride gas nor an­ hydrous hydrogen bromide gas could be made to add to 1.1-bis(^-chlorophenyl)ethene.

The failure of hydrogen

chloride gas to add to 1,1-bis(^-chlorophenyll-S,2-dichloroethene has been reported^. (20) Grummitt, 0., Buck, A. C . , Jenkins, A., Stearns, J., Becker, E. X. and Joseph, R . , "Review of Alternate Syntheses of DDT", Western Reserve University, Cleveland, Ohio. The chlorination of 1,1-bis(^-chlorophenyl)ethane, as a source for 1,1-bis(p-chlorophenyl)-1-chloroethane, 20 was no more rewarding. Grummitt et al have chlorinated 1.1-bis(£-chlorophenyl)ethane and obtained an oil the chlorine content of which corresponded to that of 1,1-bis(]>-chloro­ phenyl)- 2 ,2-dichloro ethene. In this investigation the chlorin­ ation of 1,1-bis(^-chlorophenyl)ethane was carried out under milder conditions than those of Grummitt; however, it was found that either no reaction occurred or else it proceeded as reported by Grummitt. Sheibley and Prutton

21

isolated

(21) Sheibley, F. E. and Prutton, C. P., THIS JOURNAL, 62, 840 (1940). no 1,1-diphenyl-1-chloroethane from the chlorination of 1.1-diphenylethane, but rather they obtained 1,1-diphenyl2.2-dichloroethene* They postulated that the rate of

xxxii

formation of 1,1-dipheny1-1-chloroethane was slower than its dehydrohalogenation. Shoepfle and Byan2^ claim to have made (22) Shoepfle, C. S. and Ryan, J. D. THIS JOURNAL, 52, 4027 (1930). 1.1-diphenyl-1-chloroethane by the action of hydrogen chloride gas on 1,1-diphenyl-l-ethanol. The reaction solvent was removed from the product under vacuum at 0° C . ; however, no other purification was attempted. The product was an unstable oil which gave off hydrogen chloride at room temperature. When the procedure of Shoepfle and Ryan was followed with 1,1-bis(£-chlorophenyl)ethanol, a gummy solid was obtained which was found to be mainly unreacted starting materials and 1,1-bis(^-chlorophenyl)ethene• Treatment of 1,1-bis(p-chlorophenyl)ethanol with thionyl chloride in toluene resulted in the production of a good yield of 1,1-bis(^-chlorophenyl)ethene. The Friedel-Crafts condensation of chlorobenzene and 1.1.1-trichloroethane does not give 1,1-bis(^-chlorophenyl)1#chloroetbane, but rather it produces 1,1-bis(p-chloro­ phenyl) ethene2^. (23) Mortimer, C. E. , M. S. Thesis, Purdue University(1948). From the foregoing references and experimental evidence it may be assumed that

1

,1 -bis(^-chlorophenyl)-1-chloro­

ethane is relatively unstable. Since the nitro group is larger

xxxiii

than the chloro and of comparable negativity, the stability of the alpha nitro derivatives of the 1,1-bis(jd-chlorophenyl) aIkanes is questionable* EXPERIMENTAL Bis (p-chlorophenyl )methane*- 1,1-Bi s (£-c hloro phenyl )-2,2,2trichloroethane was obtained by recrystallizing technical DDT from 95% ethanol9 ; 212 g* (0.6 mole) of this compound was dissolved in 1500 ml. of absolute ethanol and 168 g. (3.0 moles) of potassium hydroxide was added to the solution. The mixture started reacting immediately (the production of 1,1-bis(^-chlorophenyl)-2,2-dichloroethene); it was placed in a 2000 ml. capacity steel autoclave. The autoclave was rocked and heated to 180° C. for a total of sixteen hours* At the end of this time the autoclave was cooled and the mixture removed. The ethanol was distilled at atmospheric pressure and the dry crude material added to 1000 ml. of water. This aqueous solution was extracted with ether and the ether extracts evaporated to dryness. No 2,2-bis(]D-chloro phenyl)acetic acid was obtained upon acidification of the aqueous solution left after the ether extraction, and there­ fore decarboxylation must have been complete under the condiditions of the experiment. The yield of crude bis(jD-chlorophenyl)me thane from the ether extracts was 140 g. (98%). This was recrystallized from 95% ethanol to give 128 g . (90%) of bis(p-chlorophenyl)methane melting at 55-6° c.

xxx iv

Bis(p-chlorophenyl)ethanol.- A 1000 ml., 3 necked, round bottom flask was equipped with a mercury sealed stirrer, dropping funnel, and reflux condenser. A mixture of 12.4 g. of magnesium (0.515 mole) and 100 ml. of anhydrous ether was placed in the flask and a solution of 95.7 g. of £-bromochlorobenzene (0.5 mole) in 300 ml. of anhydrous ether was added through the dropping funnel. The

bromo-

chlorobenzene was supplied by the Michigan Chemical Corpor­ ation. The reaction was initiated by the addition of a small crystal of iodine and the ether solution in the dropping funnel was added at such a rate so as to cause •vigorous refluxing. After all of the solution had been added (about 1.5 hours) the mixture was stirred an additional 0.5 hour. A solution of 19.8 g. of ethyl acetate (0.225 mole) in 150 ml. of dry toluene was then added through the dropping funnel. The addition took one hour after which the reaction mixture was stirred an additional two hours. Hydrolysis was accomplished by pouring the reaction mixture into a chilled 10% acetic acid solution. The organic layer was separated and suction filtered ; about 0.5 g. of an insoluble organic material was removed.

The ether solution

was washed with water followed by a wash using a 10% sodium carbonate solution. The organic mixture was then steam dis­ tilled in the presence of sodium carbonate, and the ether and toluene thus removed. The viscous liquid left in the distilling flask was poured into a beaker to crystallize. The crude was recrystallized from petroleum ether. The

XXXV

yield of pure product was 48 g. (80% yield) melting at 67°Co C.

l,l~Bis(^-chlorophenyl)ethanol may also b e prepared

by the reaction of j^p^-dichlorobenzophenone with either méthylmagnésium bromide^ or méthylmagnésium iodide^2. 1,1-Bis(p-chlorophenyl)ethane.- l ,l-Bis(^-chlorophenyl)ethanol was dehydrated to 1 ,1-bis (j^-chlorophenyl) ethene and this compound then hydrogenated to 1,1-bis (jo-chloro­ phenyl )ethane according to the method of Grummitt, Buck and Becker^. Action of Nitric Acid on Bis(p-chlorophenyl)methane»- Two grams of b i s (£-chlorophenyl)methane together with 35 ml* of dilute nitric acid (specific gravity 1.075-13.7% nitric acid by weight) were sealed in a Carius tube. The tube was com­ pletely immersed in a well protected bath of boiling water» Experiments were run using a reaction time of from 0.5 to three hours. At the end of the alloted time the tube was Cooled, opened, and the contents added to 150 ml. of dis­ tilled water. This mixture was then extracted with ether. The ether solution was then extracted with several portions of 10% sodium hydroxide in order to remove any nitro derivative. However, neutralization of this sodium hydroxide solution did not precipitate any organic material; upon evaporation of the ether solution approximately two grams of organic product was obtained. This product consisted of either pure bis(p-chlorophenyl)methane (m.p. 55-6oc»), pure p ,p *-dichlorobenzophenone (m.p. 145° C.) or a mixture

xxxvi

of the two which could be readily separated by fractional crystallization from ethanol. The identities of the pure compounds was also confirmed by mixed melting points, and, in the case of the ketone, a positive test with 2,4-dinitrophenylhydrazone. A reaction time of from 0.5 to one hour induced no change in the

bis (^-chlorophenyl)methane,

whereas three hours gave approximately a quantitative yield of £,£it-dichlorobenzophenone# Similar experiments were run using a nitric acidacetic acid mixture (15% nitric acid by weight) in place of the aqueous nitric acid. At the temperature of the reaction, all of the methane derivative used (2 g# ) was soluble in the 25 ml. of nitric acid-acetic acid mixture employed. The bis(]>-chlorophenylJmethane was completely converted to £ , £ ,-dichlorobenzophenone in one half hour in a sealed tube at 100° C. Experiments were also conducted by refluxing 2 g. of bis(jd-chlorophenyl)methane with 25 ml. of dilute nitric acid or the nitric acid-acetic acid mixture. The results were essentially the same. Complete conversion to

-di­

chlor obenzophenone took approximately three hours with the aqueous nitric acid and about one hour with the nitric acid-acetic acid mixture. Action of Nitric Acid on 1 »l-Bis(p-chlorophenyl)ethane»Experiments were conducted in the same manner as those in which the action of nitric acid on b i s ( j D - c h l o r o p h e n y l ) methane was studied. The results were similar ; either un-

xxxvii

changed 1,1-bis(£-chlorophenyl)ethane, g

•-dichloro-

benzophenone, or a mixture of the two was obtained. One experiment was run in which 2 g. of 1,1-bis (^-chlorophenyl)ethane and 25 ml. of dilute nitric acid (specific gravity 1.075; 12.7% by weight) was heated to 60° C. with stirring, instead of refluxing. However, the outcome of the reaction was the same; complete conversion to 2*2/-dichlorobenzophenone took longer (six hours). Treatment of 1,1-bis (j3chlorophenyl)ethene with dilute nitric acid under similar conditions, also resulted in the production of

-di­

chlor obenzophenone • Action of Nitric Acid on 1 .l-Bis(p-chlorophenyl)-8.2m8tri fluoroethane.-1,l-Bis(p-chlorophenyl)-2,2,2-trifluoroethane was prepared from DDT according to the method of Kirkwood and Dacey

OA.

** Two grams of this compound together

(24) Kirkwood, S. and Dacey, J. R. , Can. J. Research,24, 69 (1946). with 25 ml. of dilute nitric acid (12.7%) were refluxed together for twelve hours. The mixture was then cooled, and the solid separated by filtration. The product was recrystallized from ethanol and found to be unchanged 1,1-bis(^-chlorophenyl)-2,2,2-trifluoroethane (m.p. 64-5° C. - no depression when mixed with authentic 1,1-bis(2" chlorophenyl)-2,2,2-trifluoroethane). The use of 25 ml. of a nitric acid-acetic acid mixture (13% nitric acid by weight) in place of the aqueous nitric acid did not change the results.

xxxviil

Condensation of Silver Nitrite with Bis(p-chlorophenyl)chlorome thane.-p.p*-Dichlorobenzophenone was reduced to bis (^-chlorophenyl)methanol and this alcohol then treated with thionyl chloride to give bi s(j£-chloro phenyl )chloro30 methane according to the method of Grummitt et al » Silver nitrite was prepared from silver nitrate and sodium nitrite ; this compound was thoroughly dried by warming it in a round bottom flask under vacuum. A slurry was made with 17 g. of this freshly prepared silver nitrite (50% excess over the theoretical) and 50 ml. of anhydrous ether. This was placed in a 500 ml* 3 necked round bottom flask equipped with a Hershberg stirrer, reflux condenser and a dropping funnel. All operations were performed in the dark. The stirrer was started and a solution of 20 g. bis(£-chlorophenyl)chloromethane in 100 ml* of anhydrous ether was admitted drop-wise through the dropping funnel. Since it appeared that no reaction had occurred at the end of six hours, the mixture was stirred for a total of forty-eight hours with gentle re­ fluxing for the last six hours. The reaction mixture was filtered and the solid was found to contain silver chloride (insoluble in dilute nitric acid)* The ether was removed under vacuum and the solid recrystallized

from hexane.

Eighteen grams of p,p^f-dichlorobenzophenone was obtained (97% yield based on bis(p-chlorophenyl) chloromethane)# It melted at 145° C . , did not depress the melting point of

xxxix

known ^

1-dichlorobenzophenon e , and gave a positive test

with 2 ,4-dinitrophenylhydrazine. Experiments were also run at room temperature for three days and in an ice-bath for five days; jd ^ ^ d i chloro benzophenone in substantially quantitative yield was produced in each, ACKNOWLEDGMENT.This work was carried out on a Purdue Research Foundation fellowship sponsored by the Michigan Chemical Company, Saint Louis, Michigan. SUMMARY (1) Methods are described for the preparation of 1,1-bis(£-chlorophenyl)alkanes. (2) Bis(p-chlorophenyl)methane and 1,1-bis(p-chlorophenyl)ethane reacted with dilute nitric acid and nitric acidacetic acid mixtures to give j^,^1-dichlorobenzophenone; none of the expected alpha nitro derivatives was isolated# (3) 1,l-Bis (j>-chlorophenyl)-l-nitroethane could not be prepared by the Friedel-Crafts reaction of chlorobenzene and 1 ,1-dichloro-l-nitroethane or by the reactions of £-chlorophenylmagnesium bromide or £-chlorophenyleadmium chloride with 1,1-dibromo-l-nitroethane. (4) The condensation of silver nitrite with bis(^-chloro phenyl)chloromethane gave

2 ,,£t-dichlorobenzophenone

and

not the expected bis(^-chlorophenyl)nitromethane. A alpha halogen derivative of bis(p-chlorophenyl)ethane could not be prepared and hence a Victor Meyer condensation could not be run with the ethane analog. Lafayette, Indiana#

PART I: A STUDY OF NEW SELECTIVE BROMINATING AGENTS

INTRODUCTION

In 1919, Wohl (35) introduced N-bromoacetamide as a brominating agent which replaces an allylie hydrogen of an olefin without addition to the double bond# CH3C0NHBr +

- C H = C H — CHg- -» - C H = C H — CHBr~~ +

Ct^CONHg

Although the yields of brominated olefins reported were not good (ca#15 to 30%) and dibromo olefins were frequently obtained, this work demonstrated the feasibility of a general reaction of this type# Wohl later introduced N-bromophthalimide as an a H y l i c brominating agent, which, however, was not as efficient in this capacity as N-bromoacetamide (36)# For many years very little work was done with N-bromoacetamide or N-bromophthalimide, and no attempts were made to discover better agents for this type of halogénation. In 1942, Ziegler and coworkers (37), as a result of an empirical study of more than thirty compounds, introduced N-bromosuccinimide as a compound which would ef­ fect a H y l i c brominations. N-Bromosuccinimide is vastly superior to N-bromoacetamide or N-bromophthalimide in this respect. The yields using N-bromosuccinimide, while in some instances are low, are usually fair. The compound is more widely applicable than N-bromoacetamide or

2

N-bromophthalimide*

The production of dibrominated olefins

is infrequent; if a reaction occurs, it generally gives the expected mo nobrominated olefin* The replacement of an allylic hydrogen of an olefin with a halogen, by use of a selective halogenating agent such as those previously mentioned, has been named the Wohl-Ziegler reaction*

In recent years, an amazing

quantity of research on the reaction, and especially the use of N-bromosuccinimide, has been reported (12).

DISCUSSION A valid generalization as to the exact structural requirements of a good agent for the Wohl-Ziegler reaction is difficult to make* However, a few conclusions may be drawn, and theoretical explanations advanced, from the behavior of the compounds which have been studied in this capacity. The first and most obvious consideration, of course, is that the halogen in the prospective agent be relatively "positive"* All of the compounds which have shown any allylic halogenating powers at all have contained a "positive" halogen* These include N-halo compounds derived from amides and imides of carboxyl!c and sulfonic acids and certain N-halo-imines* It is inconceivable, for instance, that an alkyl bromide, without any substituents to render the bromine atom positive, would make a good brominating

3

agent for the Wohl-Ziegler reaction. The degree to which the halogen must be rendered positive will be discussed later♦ A second consideration may be derived from an exam­ ination of the postulated reaction mechanism. Although the mechanism or mechanisms of the reaction are not known with certainty, there is strong evidence for a free radical mechanism and such is favored (12). (1)

^N-Br

+•

(2) - C H

CH=CH—

(3) — C H

CH==CH— +

(4) - C H

CH=CH-+^N-Br

Br*

-ÔH— CH=CH- + Br-

— CHBr-- C H = C H — — CHBr

CH =

CH-+

It must be mentioned that this mechanism is postulated only for allylic brominations; in addition the agents for the Wohl-Ziegler reaction are used for the bromination of carbonyl compounds and the nuclear bromination or aromatics. Other mechanisms probably are involved in these latter uses as well as in certain side reactions which will be discussed later.

The fact that the point of attack on the olefin by

the brominating agent usually corresponds to that of other reagents believed to react by free radicals as well as the observed catalysis by light and peroxides are among the evidence for a free radical mechanism in the allylic brominations. Hence it might logically be expected that a good

4

brominating agent for the Wohl-Ziegler reaction would be one which would readily give up its bromine as a bromine atom, therefore, a bromo compound which would form a relatively stable free radical upon removal of the bromine atom* It is interesting to note that the free radical produced from N-bromosuc cinimide must be relatively stable, and hence possess a comparatively low activity, since an attack on the solvent, in which the reaction is run, by the sue cini ml do radical is seldom observed (12), (19), (20)* The free radical produced from N-bromosuccinimide may be a resonance hybrid of the following forms: CUz — C:

0*

CH-— C = 0

2s

2

CH-— C = = 0

\

N*

yN

/

CH-— C f=0 d==o

^

CH—— C = 0

3

\

2

> CH—— C

2

2

0-

A report favoring an 0-Br rather than the N-Br structure for N-bromosuccinimide has been published (28)* It is easily seen that the free radical derived from N-bromoacetamide, which possess only one carbonyl group, would not be stabilized to the same extent by resonance*

/

CHg— C

N#

/*

CH 3 -— C = N

Hence it is probable that an N-bromoacetamide molecule does not dissociate into a free radical and a bromine atom with as much ease as an N—bromo sue cinimide molecule, and there­ fore it is to be expected that N-bromoacetamide is not as

5

good an allylic brominating agent as N-bromosuc cinimide* N-Bromoglutarimide has been proven to be entirely ineffective as an agent for the Wohl-Ziegler reaction (37)* At first glance one might expect that the glutarimido radical would have similar resonance forms to those of the suocinimldo radical*

However, the succinimido radical is

probably planar, or nearly so, whereas the glutarimido radical probably exists in boat and chair forms.

In either

of these forms it is impossible to draw a plane through the glutarimido radical which would include the nitrogen atom, both carbon atoms of the carbonyl groups and both oxygen atoms.

It Is this

0 0 //. H -6 -N-C-

grouping about which the

electronic configuration would resonate.

Hence the reso­

nance of the glutarimido radical is probably damped due to the non-planarity of the radical, and the ineffective­ ness of N-bromoglutarimide as an allylic brominating agent may thus be explained. In the light of these resonance considerations, the fact that N-bromophthalimide is not as effective as is N-bromo sue cinimide in the Wohl-Ziegler reaction may be slightly baffling,

A phthalimido free radical probably

would be planar, and would be expected to have more reso­ nance forms, due to the possible interaction of the elec­ trons of the benezene nucleus, than a succinimido radical. On this basis, therefore, one might falsely predict that N-bromophthalimide would be a better allylic brominating

6

agent than N-bromosuc cinimide* To refute this It is necessary to bring in a third consideration as to the general structural requirements of a Wohl-Ziegler halogenating agent* In N-bromophthalimide the benezene nucleus exerts an inductive effect away from the bromine atom; hence the bromine of N-bromophthalimide may be considered to be rela­ tively more positive than that of N-bromosuc cinimide. Therefore, in the phthalimlde derivative there is a strong tendency for the compound to dissociate into positive bro­ mine ions and negative phthalimido ions as well as into free radicals*

Ions of the type derived from N-bromo-

phthallmide probably do not react to brominate olefins in the allylic position; rather, they probably add to the double bond of the olefin or enter into other side reactions* Thus the overall yield of the desired allylically brominated olefin is less when N-bromophthalimide is employed than when N-bromosuecinimide is used*

When N-bromophthali­

mide is reacted with cyclohexene we therefore obtain two products: a 50# yield of 3 -bromo-l-cyclohexene (37) (through a free radical mechanism) and a 21# yield of N- (2-bromocyclohexyl)phthalimido (37) (through an ionic mechanism)* Thus while activation to render the bromine positive is necessary, it must not be excessive*

That the magnitude

of this activation may be critical is shown below* The i n e f f e c t i v e n e s s o f N - c h l o r o s u c c i n i m i d e a s o p p o s e d

7

to the reactivity of N-bromosuc claim! de can be explained by the fact that chlorine is more electron attracting than bromine#

Hence a grouping or structure of a compound which

draws electrons away from the bromine atom of that compound, thus leaving this bromine relatively positive, would not necessarily affect a chlorine atom substituted for the bromine atom in the same manner or to the same extent# This idea is borne out not only by the succinimide derivatives, but also by the fact that N-chloroacetamide and N-chlorophthalimlde are completely ineffective in bringing about allylic chlorinations whereas N-bromoacetamide and N-bromo­ phthalimide are capable of effecting some allylic bromina­ tions (37)# Further, in the light of the ineffectiveness of N-chloroacetamide, it is interesting to note that N-chlorotrichloroacetamide produces 3-chloro-l-cyclohexene, in a poor yield however, from cyclohexene (37)# The chlorine atoms of the trichloroaeet&mido group would provide a strong inductive effect away from the nitrogen substituted chlorine of N-chlorotrichloroacetamide# Hence, the nitrogen substi­ tuted chlorine of N-chlorotrichloroacetamide would be ex­ pected to be relatively more positive than that of N-chloroacetamide# In t h i s i n v e s t i g a t i o n N - b r o m o c h l o r o a e e t a m l d e , N - b r o m o trlchloroaoetamide, and and

tested as

was

the

brominating agents#

only compound

prepared and

N-bromotrifluoroacetamide

it h a d

of the

not

were

made

N-Bromochloroacetamide

series

which had

been tested as

been

an agent

for

previously the

8

Wohl-Ziegler reaction* The literature contains the fol­ lowing methods for making N-bromo compounds: (1)

The method of Behrend and Sehreiber (1 ) and Wohl (3 5 )

of the addition of a molar amount of bromine to the amide followed by the addition of a molar amount of concentrated aqueous potassium hydroxide to this ice-cold mixture* The N-bromo compound is extracted from the reaction mixture by an organic solvent e. g« benzene* This method is used in the preparation of N-bromoacetamide* (8 )

Bromination of an ice-cold alkaline solution of the

amide or imide (4), (37) * This method is used for the preparation of N-bromosuc cinimide (37) and N-bromophthalimide (4), (37)* (3)

Treatment of an aqueous solution of molar amounts of

bromine and the amide with an equivalent quantity of calcium carbonate (15)* (4)

The method of Bolsmenu (2) wherein bromine is added

in small portions to an ethyl acetate solution of the amide*

After each bromine addition the solution is agi­

tated with a small amount of silver oxide until the bromine color is discharged*

Isolation of the N-bromo compound is

accomplished by filtering off the inorganic salts and evap­ oration of the solvent* (5)

The method of Selwanow (32) and Bolsmenu (3) of treat­

ing the amide, in water, with mercuric oxide and bromine* (6 )

The method of Franseconi and de Plato (13) wherein the

mercury derivative of the amide is brominated*

9

In addition, amides have been chlorinated directly to produce the N-ohloro derivative by treating the molten amide with anhydrous chlorine gas (18) and by adding the amide to chlorine water at room temperature (7 ), (3 4 ); however there are no reports of this process being carried out with bromine* Chloroacetamlde, trlchloroacetamide, and trifluoro­ acetamide were made according to standard methods reported in the literature*

It was found that, of the methods for

synthesizing N-bromo compounds mentioned above, those in­ volving water in the bromination step were unsuccessful in preparing the N-bromo derivatives of the halogenated ac etami des*

These acetamlde derivatives are derived from

relatively strong acids; in the presence of bromine vmter they readily decompose*

Likewise direct bromination of

these amides did not meet with success nor did the method of Bolsmenu (2) employing silver oxide*

The N-bromo com­

pounds may be prepared by an adaptation of the method of Franseconi and de Plato (13) * The mercury derivative of the amide is made by treating the amide, in water, with freshly prepared yellow mercuric oxide*

It is best to keep the amount of water at a minimum;

a slight excess of mercuric oxide was used*

The solid mix­

ture of mercuric oxide and the desired mercury derivative was carefully dried and a suspension of this in chloroform was brominated* The mercuric bromide was removed by filtra­ tion and the chloroform removed under vacuum* The product

10

was re crystallized from chloroform. Thus with trif luoro­ acetamide the equations are: 2

CFgCONHg +

HgO

(CF3 C0MH)2Hg + 2Brg

----- w-

(CF^CONHjgHg + HgO

----------2 CF^CONHBr +

HgBr^

Using this method, N-bromochloroacetamide, melting at 63° C . , was prepared in 68 % yield; N-bromotrichloroacetamlde, melting at 120 ° C. f was prepared in 86 % yield; and N-bromotrif luoroacetamide, melting at 59 ° C . , was prepared in a 75% yield* In water, as well as acetone, ethanol, and ether, they decompose to the amide.

Alcoholic or aqueous solutions

give positive silver nitrate tests, turn starch-iodide paper blue, and possess bleaching power. Upon melting they decompose and turn a red-brown color*

The compounds are

relatively stable, however, and may be stored without substantial decomposition in a vacuum desiccator for a few days. If these solid compounds are added to pure cyclo­ hexene , without a diluent, they react violently with the evolution of much heat and produce a brown tarry mixture♦ These compounds were found to be brominating agents and they reacted with anisole to produce j>-bromoanisole* The reactions of anisole with N-bromotrichloroacetamlde and N-bromotrif luoroacetamide both gave a 64% yield of |>-bromoanisole•

However, it is doubtful that these anisole

brominations proceeded by a free radical mechanism.

11

Rather they probably went by way of an ionic mechanism, involving a positive bromine ion, as is usually postulated for aromatic substitutions*

Significantly the reaction of

anisole with N-bromoacetamide gives a 75# yield of £*br omoanl sole (35), while that with N-bromo succinimide gives a 33# yield of g-bromoanisole (5 )• With toluene, two products were obtained. The reaction with N-bromotrichloroacetamlde gave a trace of benzyl bro­ mide and a 36# yield of

-bromo to lue no, while that with

N-bromotrifluoroacetamide gave an 8 # yield of benzyl bro­ mide and a 6 # yield of

bromo toluene •

In both cases

these two compounds were the only pure products which could be isolated from the tarry reaction mixture. The 2>-bromo toluene was probably produced via an ionic mechanism

as was the j^-bromoanisole♦

The benzyl bromide, in which

the bromine of the bromomethyl group may be considered as allylic to the double bonds of the ring, is probably the product of a free radical reaction. Hence, from these reactions and others which follow, it may be deduced that these N-bromoacetamide derivatives react In two ways. In the first, a bromine atom is removed leaving a free radical; in the second a positive bromine reacts leaving a negative halogenated aeetamldo ion. These conclusions are strengthened by the results of catalyzed reactions of N-bromotrifluoroacetamide and toluene. Peroxides generally catalyze free radical reactions. When a trace of dibenzoyl peroxide was added to the reaction of

12

N-bromotrif luoroacetamide and toluene, a 61% yield of benzyl bromide was secured* Aluminum chloride, on the other hand, catalyzes aromatic substitutions presumably through an ionic mechanism* The use of molar quantities of aluminum chloride, in the reaction of N-bromotrif luoro­ acetamide and toluene, resulted in the production of jKbromotoluene in 68 % yield*

Both types of reactions are

therefore possible for N-bromotrif luoroacetamide with toluene, and by a suitable choice of a catalyst one may be made to predominate at the expense of the other* The reaction of N-bromosueclnlmlde with toluene has been reported to yield a 64% yield of benzyl bromide (30) when dibenzoyl peroxide is used as a catalyst, and a 71% yield of 2 *bromotoluene when a molar quantity of aluminum chloride is employed (31)* Unfortunately the product or products of the non-catalyzed reaction of N-bromo sue cinimide and toluene are not reported* The reactions of the N-bromoacetamide derivatives investigated, with olefins were not as clean cut as the reactions of these brominating agents with aromatic com­ pounds*

Since it seems that these agents react by two

mechanisms, complications might be expected. Additions to the double bond, which presumably occurs through an ionic mechanism; polymerizations, which are catalyzed by free radicals; and reactions of the brominated hydrocarbon products with the regenerated acetamlde derivatives, could be predicted*

13

N-bromo tr 1fluoroa ce taraid© reacts with cyclohexene to give a 42# yield of N-(2-bromocyelohexyl)-trlfluoro­ acetamide •

This would be the product If the positive

bromide and negative trlfluoroacetamldo ions added to the double bond of cyclohexene*

Such an addition is reported

for the reaction of N-bromophthalimide and cyclohexene—bromobenzoic acid (m. p. 251° C. ) and the anillde was pre­

pared from benzyl bromide (m* p. 117° C.)*

In the non— cata­

lyzed reaction the lack of complete recovery of trifluoro-

29

acetan&de was probably due to the use of a large excess of toluene in which this amide is soluble# Reaction of N-Bromotrlfluoroaeetainîde and Styrene Kharaseh and Priestly (24) in their study of the ad­ dition of N-bromosuIfonamides to styrene, added the N-bromo-compound to an excess of styrene and separated the solid addition product#

When 19#2 g# (0*1 mole) of N-bro-

motrifluoroacetamide was added in small portions to 30#8 g# (0*2 mole) of styrene the solution got warm and a red color developed#

The mixture gave a positive starch-io-

dide test until one week had elapsed, after which it was filtered and a gummy mass removed*

Recrystallization of

this material from carbon tetrachloride gave 5 #6 g# of trifluoroaeetamlde (theoretical recovery should have been 11#2 g * )#

The liquid, which was very viscous, was vacuum dis­ tilled and 8 g# of styrene was recovered (boiling at 33° C#/10 mm#)*

The rest of the material could not be made

to distil but, upon reduction of the pressure and eleva­ tion of the temperature, started to darken and decompose# This residue was probably a polymeric product and was a sticky semi-solid material from which nothing could be isolated by crystallization technics# In a second experiment, 19*2 g* (0*1 mole) of N-bromotrifluoroaeetamlde was added to 10*4 g* (0*1 mole) of

30

styrene containing 0*5 g« of hydro qui none •

At the end of

24 hours the mixture still gave a positive starch-iodide test, but was dissolved in 50 ml. of carbon tetrachloride and washed with several portions of distilled water. The solution was then dried over anhydrous sodium sulfate and distilled under vacuum.

The distillation was similar to

the previous one, in that, after the carbon tetrachloride and a trace of unreacted styrene had distilled the polymeric residue started decomposing. Preparation of Cyelohexene Cyclohexene was prepared by dehydrating cyclohexanol according to the Organic Syntheses preparation of Coleman and Johnston (8 )» Reaction of N-Bromotrifluoroaeetamlde and Cyclohexene The following materials were mixed in a 250 ml. Erlenmeyer flask in the order named: 24.5 g. (0.3 mole) of cyclo­ hexene, 100 ml. of carbon tetrachloride, and 26.8 g. (0.15 mole) of R-bromotrifluoroacetamlde.

The flask was

cooled in an ice bath for three hours and then allowed to stand for twenty-four hours at room temperature.

It was

found that without this initial cooling the mixture got very warm, darkened in color, and precipitated a red,sticky material.

At the end of twenty-four hours the mixture no

longer gave a starch-1odide test. A white flocculent perclpitate (N-(2 -bromocyclohexyl)-trifluoroacetamide) had

31

formed e The carbon tetrachloride was removed at room tempera­ ture under vacuum and the solution filtered» The white solid was recrystallized twice: first, by dissolving It In a minimum quantity of ethanol and reprecipitatlng It by the addition of water; second, re crystallization from carbon tetrachloride# Trifluoroaeetamlde Is very soluble In water while N-( 2 -bromocyclohezyl)-trifluoroaeetamlde is not; therefore, the first recrystallization removed any trifluoroaeetamlde present* The second recrystallization removed other organic impurities and facilitated drying* The yield was 17.3 g. of the N-(2-bromocyclohezyl)-trifluoro­ aeetamlde (4Z% based on N-bromotrifluoroaeetomlde used)* The compound was a white crystalline material which melted at 153° C . , did not give unsaturation tests, and gave a pre­ cipitate with alcoholic silver nitrate only after heating* It burned with a smokey flame; a qualitative analysis confirmed the presence of fluorine,nitrogen,and bromine* Analysis gave: % C

Calculated Found

for OgH ^ B r F g N O

U n

a N

35*03

4*01

5*11

35*37

4*02

4*98

The filtrate was dissolved in 50 ml* of carbon tetrachloride and the solution washed with 5% sodium carbonate solution followed by distilled water. The solution was dried over anhydrous sodium sulfate. Fractionation under reduced pressure gave, after removal of the carbon

32

tetrachloride and unreacted cyclohexene, a fraction which boiled at 84-7° C./5 mm#

Redistillation of this fraction

gave 8 g. of material which boiled at 55-7° C+/1 mau

This

k°iii&g point does not correspond to the boiling point of any pure brominated cyclohexene*

The liquid was similar to

a mixture reported by Howton (19) to be at least partially composed of 3, 6 -dibromocyclohexene and l,2 -dibromocyclohexane*

The product gave unsaturation tests and a positive

test with alcoholic silver nitrate# The same products were isolated. In approximately the same ratio, when dibenzoyl peroxide (0*3 g. ) was added to a similar reaction mixture in another experiment*

further,

it was found that the results were similar when anhydrous ether was employed as the reaction solvent in place of carbon tetrachloride* N- (2-Br omoc yc lohexyl )-trifluoroaeetamlde four grams of N (2 -bromocyclohexyl)-trifluoroacetamide was dissolved in 25 ml# of 20 # potassium hydroxide solution and the mixture warmed on a steam bath*

A gas was liberated,

which from the odor and the effect on moist red litmus paper, was identified as ammonia#

The solution was evaporated to

dryness on the steam bath* The dry salts were placed in a 125 ml* Claisen flask and a solution of 25 ml* of concentrated sulfuric acid in 20 ml* of absolute ethanol (at room temperature) was added* The dis­ tilling flask was equipped with a condenser and receiver and

33

was heated with a heating mantle*

Ethyl tr ifluoroa c e tat e

distilled over at 60-2° C*, 1,6 g* (ca* 77# yield) of the compound was obtained*

Treatment of this ester in anhydrous

ether with ammonia gas gave* upon removal of the ether and ethanol, 1,2 g* of trifluoroaeetamlde melting at 75° C, The remainder of the Nw (2 -bromocyclohexyl)*trifluoroacetamide molecule could not be isolated* Reduction of N- (2-bromocyclohexyl)-trifluoroaeetamlde was conducted according to the directions of Kharaseh and Priestly (24) ♦

Two grams of the compound was dissolved in

60 ml, of n-amyl alcohol*

The solution was heated to boil**

ing and 2,5 g, of metallic sodium was added gradually in small pieces to the hot solution over a period of an hour# The mixture was cooled and extracted several times with 10# hydrochloric acid*

This aqueous acid solution (about 150

ml* ) was evaporated to a smaller volume (about 30 ml* ) and extracted with ether to remove traces of amyl alcohol*

The

aqueous solution was then made basic with solid potassium hydroxide and extracted with ether*

This extraction thus

removes the cyclohexylamlne from potassium bromide or other water soluble compounds which may have been carried along in the original hydrochloric acid extraction. The ether extract was extracted with three 10 ml* portions of 10 # hydrochloric acid and these washes combined and evaporated to dryness*

The white solid, thus obtained

was recrystallized by dissolving it in a minimum quantity of water, filtering, and removing the water under vacuum*

34

The cyclohexylamlne hydrochloride melted at 206° C • and weighed 0*75 g* (75% yield based on the amount of N-(2-bromocylcohexyl)-trifluoroaeetamlde used)• Base liberated the free amine from an aqueous solution of the hydrochloride* Reaction of N-Bromochloroacetamide With Cyclohexene To a mixture of 32*8 g* (0*4 mole) of cyclohexene in 125 ml, of carbon tetrachloride, 17.3 g. (0.1 mole) of N-bromochloroacetamide was added.

The N-bromochloroaceta-

mide was added in small portions, and the mixture was stirred during the addition.

The mixture was set aside at

room temperature for twenty-four hours at which time it no longer gave a starch-lodlde test. Chloroacetamide which had precipitated from the reac­ tion solution was removed by suction filtration. The un­ reacted cyclohexene and carbon tetrachloride were removed under vacuum, and the residual liquid was suction filtered to remove additional chloroacetamide which had precipitated upon removal of the solvent.

The filtrate was distilled

under reduced pressure.

No. 3-bromocyclohexene was obtained

(b.p. 45-7° C./10 mm.).

The pressure was reduced and a

fraction distilled at 51-7° C./l mm. secured.

No other products were

Redistillation of the 8 g. fraction which distilled

at 51-7° C./l mm. did not separate it into its components. It gave positive unsaturation tests and a precipitate with alcoholic silver nitrate.

Howton (19) obtained a similar

35

product from the reaction of N-bromosuccinimide and cyelo** hexene ; he was able to isolate 3, 6 -dibromocyclohexene and 1,2-dlbromocyclohexane from this product*

The liquid from

this experiment upon long standing in a refrigerator pre­ cipitated a small amount of solid which melted at 1080 C. (3,6 -dibromocyclohexene melts at 108° C. ). When a similar experiment was run with the reaction vessel cooled in an ice bath, the same product, in the same yield was obtained* Reaction of N-Bromotrichloroacetamide and Cyclohexene A solution of 24*6 g* (0*3 mole) of cyclohexene in 200 ml* of carbon tetrachloride was placed in a beaker sur­

rounded by an ice bath* To this, 48*2 g* (0*2 mole) of N-bromotrichloroacetamide was added in 5 g* portions* After each addition the solution was tested until it no longer gave a positive starch-iodlde test before the next portion was added*

At the end of the additions the mixture was

filtered and trichloroacetamide removed*

The excess cyclo­

hexene and carbon tetrachloride was distilled (under vacuum) from the filtrate*

The residue from the distillation was

filtered and the two precipitates combined,

A total of

21*8 g* of trichloroaeetamide was recovered which is 67#

of the amount expected on the basis of the N-bromotrichloroacetamide used* Successive vacuum distillations gave ultimately 13 g* of a liquid boiling at 52-4° C./l mm.

The remainder of the

36

material decomposed as the temperature was raised; nothing more was secured from it.

The 52-4° fraction decolorized

bromine in carbon tetrachloride and gave a precipitate with alcoholic silver nitrate ; it was a clear oily liquid. How­ ton (19) obtained a similar product from the reaction of N-bromosucclnlmide and cyclohexene ; he was able to isolate 3, 6-dibromocyclohexene and 1 ,2 -dibromocyclohexane from it* Similar results were obtained when anhydrous ether or glacial acetic acid were used as reaction solvents. In no experiment m s

any 3-bromocyclohexene obtained.

Preparation of 2 -Methyl-2-Butene t-Amyl alcohol purified by rectification was dehydrated with sulfuric acid using the method of Norris and Joubert (26). Reaction of N-Bromotrifluoroacetamide and 2-Methyl~2—butane The following were mixed in a 125 ml. flask: 14 g. (0.2 mole) of 2 -methyl-2 -butenet 0.2 g. of dibenzoyl perox­ ide, and 50 ml. of carbon tetrachloride.

To this solution,

19.2 g. (0.1 mole) of N-bromotrifluoroacetamide was added, in small portions, with shaking.

The flask became warm but

no color developed; trifluoroacetamide started precipitating immediately.

The flask was stoppered and set aside at room

temperature for twenty-four hours.

At the end of this time

the mixture was filtered, the carbon tetrachloride removed from the filtrate under vacuum, and the distillation

37

residue filtered again* A total of 9 g* of trichloroacetamide was recovered in the two filtrations (80% of the theoretical)* The filtrate was vacuum distilled* No monobrominated derivative was isolated (boiling points reported by Ziegler in the range 34-40° C*/l5 mm.)* Instead, a fraction was collected which boiled at 49-60° C./13 mm. Repeated fractionation of this liquid gave 3,2 g* boiling at 54-5° C./12 mm. The product was a dibrominated deriva­ tive of 2-methyl-2-butene* Wohl (35)obtained a similar product from the reaction of N-bromoacetamide and 2-methyl2 -butene ; he assumed the compound to be l,4-dibromo-2 -methyl2 -butene.

Reaction of N-Bromochloroacetamide and 2-Methyl-2-butene This experiment was conducted in a manner similar to that of Wohl (35) who brominated 2-methyl-2-butene with N-bromoacetamide. Ten grams of 2-methyl-2-butene was placed in a beaker which was surrounded by an ice-water bath* A solution of 5 g* of N-bromochloroacetamide in 50 ml, of dry acetone was then added and the mixture stirred* The solution was allowed to stand until it no longer gave a starch-iodide test, and then a second 5 g* portion of N-bromochloroacet­ amide, dissolved in acetone, was added. This procedure was continued until the amount of N-bromochloroacetamide added was equivalent to the amount of 2 -methyl-2 -butene employed (24.6 g. of N-bromochloroacetamide). The solution was filtered and the acetone removed from

38

the filtrate under vacuum.

The residue was then filtered

a second time and the two precipitates combined# The solid was chloroacetamide ; 8 g. was recovered (60% of the expected) ♦

Vacuum distillation of the filtrate gave 11*5 g*

of a liquid boiling at 42-58° C./10 mm* Redistillation yielded 3 g. of material boiling at 54-5° C ./12 mm*

The

material gave a testfbr halogen and positive unsaturation tests* From a rough quantitative analysis for bromine and the boiling point this product was proved to be a dibrominated derivative of 2-methyl-2-butene♦

Wohl (26) obtained

a similar product from the reaction of N-bromoacetamide and 2-methyl-2~butene and reported this compound to be 1,4-dibromo-2-methyl-2-butene ♦

The amount obtained in the above

reaction would represent an 18% yield based on the N-bromochloroacetamide used# Reaction of N-Bromotrichloroacetamide and 2 -Methyl-B-butene An experiment was run similar to that in which N-bromochloroacetamide was reacted with 2 -methyl- 2—butene except that chloroform was used as the reaction solvent in place of acetone*

Ten grams of 2 —methyl-2-but ene and 34*5 g* of

N-bromotrichloroaeetamide were used*

Nothing but a brown,

viscous, high-boiling residue was obtained from an attempted vacuum distillation of the product. In a second experiment, a one liter, 3 necked, round bottom flask was equipped with an all-glass, mercury-sealed

39

stirrer and placed in an ice bath.

A mixture of 14 g*

(0*3 mole) of 2 -methyl-2 -butene and 300 ml# of acetone was placed in this flask#

The solution was stirred until

it was thoroughly chilled, and 40 g# (0*17 mole) of N-bromotrichloroacetamide was added in small portions, dissolved in acetone, over a period of time.

The reaction mixture

was tested with starch-iodide paper until it no longer gave a positive test before each subsequent addition. volume of acetone used was 500 ml#

The total

The acetone was removed

under vacuum and 15 #4 g. of tri chloroacetamide was recovered (60% of what was expected)#

The filtrate was dissolved in

100 ml. of carbon tetrachloride and this solution then

washed with 5% sodium carbonate followed by distilled water# The organic solution was dried over anhydrous sodium sul­ fate and then vacuum distilled.

After the carbon tetra­

chloride was removed the material got darker in color and started to decompose as the temperature was raised. No pure compound could be obtained from this reaction product. Reaction of N-Bromo tr i fluor oacetamide and Propylene N-Broffiotrifluoroacetamide (19#2 g # ; 0.1 mole) was dis­ solved in 100 ml. of anhydrous ether.

Propylene vas bubbled

through this solution, at room temperature, for six hours. At the start the flask got quite warm and a red color devel­ oped 5 however, evaporation of the ether soon cooled the flask and the color disappeared.

The ether had to be continually

replaced due to evaporation losses; the volume was maintained

40

at approximately 100 ml*

It was found that it was not ad­

visable to cool the flask in an ice bath as this slowed the reaction too much*

At the end of six hours, at room

temperature, no stareh-iodide test was obtained and the mixture was distilled at atmospheric pressure* After the ether distilled, 1 g. of allyl bromide dis­ tilled at 70-1° C. (6.3# yield) followed by 5.0 g* (50# yield) of a dibrominated derivative boiling at 136-8° C* A brown tarry residue was left. ation tests.

Both products gave unsatur­

The second corresponds to a product obtained

by Wohl (3 5 ) from the reaction of N-bromoacetamide and propylene which he reported was B ,3-dibromo-l-propens* In another experiment, dioxan was used as the solvent* The reaction was much more rapid; the mixture no longer turned starch-lodlde paper blue after one hour*

However,

no products could be isolated from the reaction mixture* Fractionation at atmospheric pressure or under reduced pressure failed since there was no plateau in the boiling curve.

Likewise, extraction procedures were not successful

in separating the mixture into its components* Reaction of N-Bromotrifluoroacetamide and Cyclohexanone To a solution of 24.9 g* (0*3 mole) of cyc lohexanone and 0.2 g, of dibenzoyl peroxide in 100 ml* of carbon tetra­ chloride, 19.2 g. (0*1 mole) of N-bromotrif luoroacetamide was added*

The mixture in a stoppered 500 ml* Erlenmeyer

flask was set aside at room temperature*

The contents

41

of the flask became yellow which gradually changed to red then purple*

At the end of two days, the mixture no longer

gave a starch-lodlde test and the solution was a rose color# The carbon tetrachloride was removed under vacuum but no trifluoroaeetamlde precipitated, presumably due to the solubility of this compound In the excess cyelohexanone used*

Therefore, the carbon tetrachloride was replaced

and the solution washed with 5% sodium carbonate solution followed by distilled water to rid It of trifluoroaeetamlde# The washing caused the color of the solution to change from rose to a honey color# After drying the carbon tetrachloride solution over anhydrous sodium sulfate, the mixture was fractionated In vacuo# 2-Bromocyelohexanone distilled at 90° C#/14 mm#

The yield was 7#2 g# which Is 41# of what

would be expected on the basis of the N-bromotrlfluoraeetamlde used* Analysis of the compound for bromine gave: calculated for CgHçGBr

45.1#, found 44*9##

The

material decomposes readily at room temperature turning a deep brown# With silver nitrate the bromine in the compound is quantitatively precipitated as silver bromide# In one experiment the reaction mixture of cyelohexanone, N-bromotrifluoroaeetamlde and carbon tetrachloride was refluxed instead of allowing the reaction to proceed at room temperature* A violent reaction resulted; the mixture charred and had to be discarded*

42

Preparation of N-Bromo-1,8 naphthalimide 1.8-Naphthalic acid was prepared by the oxidation of acenaphthene with sodium di chromât e and sulfuric acid ac­ cording to the method of Graebe and Gfeller (17). Recrystallization of this 1,6-naphthalie acid from concen­ trated nitric acid gave 1,8-naphthalie acid anhydride (17)* (S3).

1,8-Naphthalimide was prepared by treating

1,8-naphthalic acid anhydride with aqueous ammonia according to the method of «Taubert (23). The imide was recrystallized from concentrated nitric acid* 1.8-Naphthalimide (19*7 g.; 0*1 mole) was dissolved in a solution of 22.4 g* (0.4 mole) of potassium hydroxide in 1500 ml. of water.

The mixture was stirred well and

filtered. The filtrate was then cooled to around 0° C* in an ice bath and 40 g* (0*5 mole) of bromine was added* N-Bromo-1,8-naphthalimlde precipitated immediately; it was removed by suction filtration. The crude N-bromo-1,8-naphthalimide was dried in a round bottom flask under vacuum and the dried material then recrystallized from benzene. The recrystallized product melted at 268-70° C* (corrected) and gave the following analysis: # C

# H

# N

Calculated for C ^ H ^ B r N O ^

52.17

2*17

5*07

Pound

52.00

1*95

5,13

The yield was 12 g. or 43# based on the amount of

43

1,8-naphthalimide used» If 1,8-naphthalimide is added to concentrated aqueous potassium hydroxide, the imide decomposes to 1,8-naphtha1ie acid and naphthalene*

Hence it is recommended, in the

first step of this procedure, that the 1,8-naphthalimide be dissolved in very dilute potassium hydroxide solution at a temperature not exceeding room temperature* Francesconi and Recchi (14) have reported that they prepared N-bromo-1,8-naphthalimide by a procedure similar to the one previously described*

However, they gave no

analysis for their product which they stated melted at 200° C* Reaction of N-Bromo-1,8-naphtha limide with Cyclohexene A mixture of 20 g* (0*073 mole) of N-bromo-1,8—naph­ tha limide , 50 ml* (40.5 g* ; 0.49 mole) of cyclohexene and 50 ml* of benzene was refluxed until it no longer gave a positive test with st&rch-iodide paper (two hours). At the end of this time the reaction mixture was cooled and fil­ tered* The residue, which weighed 14 g* » was 1,8-nap ht ha limide.

It melted at 298-300° C. and did not depress the

melting point of known 1,8-napbthalimlde.

This represents

a 98% recovery of 1,8-naphthalimlde based on the amount of N-bromo-1,8-naphthalimide used. The benzene and unreacted cyclohexene was distilled from the filtrate at atmospheric pressure, and the residue

44

from this distillation was fractionated under reduced pressure*

A fraction was collected which boiled at

60-4° C*/l6 mu*, upon redistillation it boiled at 45-7°C*/10 flun*

It gave positive unsaturation tests and a precipi­

tate with alcoholic silver nitrate*

This product was iden­

tified as 3-bromocyclohexene; 0*95*g* was obtained which would represent a 8*2# yield based on the quantity of N-bromo-l,6-naphtha11mide used*

No other pure component

could be isolated from the reaction mixture, a small quan­ tity of a brown tar was left from the distillation* Preparation of N-Bromo-4-nitrophthalimide Fhthalimide was nitrated to yield 4-nltrophthalimide according to the method of Huntress and Shriner (21)* Bredt and Hof (4) prepared N-bromophthalimlde by brominating an Ice cold solution of phthalimide in aqueous potassium hydroxide*

However, 4-nitrophthalimide is very easily

hydrolyzed to 4-nitrophthalie acid; hence N-bromo-4-nitrophtha limide could not be prepared from 4-nitrophtha limide using Bredt and Hof’s procedure# 4-Ni tr op htha 1 Imide (19#2 g. ; 0.1 mole) was dissolved in 500 ml* of hot 95% ethanol and a solution of 16.8 g* (0*3 mole) of potassium hydroxide in 50 ml. of ethanol was then added.

The potassium salt of 4-nitrophthalimide

cipitated immediately*

pre­

The mixture was filtered hot and

the potassium 4 —nitrophthalimide air dried*

This compound

was then suspended in 500 ml* of dry chloroform and 24 g*

45

0*5 mole) of bromine added to the mixture* The mixture was stirred and allowed to stand for 1/2 hour* At the end of that time the mixture was filtered, the residue was discarded and the filtrate evaporated to dry­ ness*

The crude N-bromo-4-nitrophthalimide was re crystal­

lized from chloroform, 13 g* (48# yield) of the compound melting at 193° C* was obtained*

Analysis gave: # C

# H

# N

Calculated for CaHJB N^O, 8 3 r 2 4

35*42

1.11

10*33

Found

35*40

1*20

10*41

Reaction of N-Bromo-4-nitrophthalimide With Cyclohexene A mixture of 20*3 g* (0*075 mole) of N -bromo-4-nitrophthalimide, 24.6 g. (0*5 mole ) of cyclohexene and 50 ml* of carbon tetrachloride was refluxed until it no longer gave a positive test with starch-iodide paper (two hours)• The reaction mixture was then

cooled and filtered. The

residue from the filtration was 4-nltrophthalimide which melted at 198° C* and did not depress the melting point of known 4-nitrophthalimide ; 14 g* of this compound was re­ covered which is 97# of the amount which would be expected on the basis of the quantity of N-bromo -4-ni tr ophtha limid e used* When the unreaeted cyclohexene and carbon tetrachloride were removed from the filtrate by distillation at atmos­ pheric pressure, 5 g* of a dark brown oil was left* No pure compound could be obtained from this oil by vacuum distil­ lation*

46

Preparation of Dibromomalononitrlie Malononitrile was made using a series of preparations reported in Organic Syntheses# Ethyl cyanoacetate was pre­ pared (22); and this compound was converted, by treatment with aqueous ammonia, to cyanoac eta mide (11) # Malononitrile was obtained by dehydration of cyanoac et ami de with phosphorous pentachloride (10)# The method of Ott and Welssenburger (27) was used to prepare dibromomalononitrlie, as well as the addition complex of dibromomalononitrlie and sodium chloride, from malononitrile# Malononitrile in an aqueous solution con­ taining sodium chloride was treated with bromine and the insoluble complex, NaCl+4CBrg(CN)g, precipitated# Dibromomalononitr lie was prepared by steam distillation of this complex# Reaction of Dibromomalononitrlie and Cyclohexene A mi store of 14 g# (0#015 mole) of NaCl+40Brg (CN)g (equivalent to 0#06 mole of dibromomalononitrlle), 16 g# (0#195 mole) of cyclohexene and 50 ml# of carbon tetra­ chloride was refluxed for two hours#

At the end of this

time the mixture no longer gave a positive test with starch iodide paper, and it was cooled and filtered#

The residue

was 2#5 g# of a black material which, from its behavior on ignition, probably was a mixture of sodium chloride and tarry by-products#

47

The carbon tetrachloride and unreacted cyclohexene was distilled from the filtrate at atmospheric pressure* The remainder from this distillation was distilled under vacuum*

1,8-Dibromocyclohexane (5*5 g«; 38# yield) was

obtained boiling at 101° C*/l3 mm* A black tarry residue was left In the distilling flask but no pure compound could be isolated from it by distillation or crystallization* When 26 g* (0*027 mole) of NaCl#4CBrg(CN)g was refluxed with 30 g* (0*37 mole) of cyelohexene, without any carbon tetrachloride, and the experiment conducted as described previously, a brown tar was obtained from which no pure compound could be isolated* A reaction was run In which 11*2 g*

(0*05 mole) of

dibromomalononitrlle, 16*4 g* (0*2 mole) of cyclohexene and 50 ml, of carbon tetrachloride were refluxed together for two hours* The unreacted cyclohexene and carbon tetra­ chloride were distilled from the reaction mixture at atmos­ pheric pressure and the remainder was fractionated under vacuum,

Five grams of 1,2-dibromocyclohexane boiling at

101-3° C*/13 mm* was obtained; this represents a 41# yield based on the quantity of dibromomalononitrlle used* Determination of "Active* Bromine Ziegler (37) described a simple method of determining bromine (or other halogens) in compounds in which it is "loosely bound* or "active". This method has been used in

48

this investigation for the determination of bromine In N-bromo compounds, allylically brominated olefins, and bromo c yc lohe xanone ♦ An amount of the sample, the bromine content of which corresponded to about 30 ml. of 0.1 N silver nitrate, was weighed carefully into a 250 ml. Erlenmeyer flask.

It was

dissolved in 50 ml. of methanol, ethanol, or acetone and 5 ml. of 6 N nitric acid was added.

An excess of 0.1 N

silver nitrate was then added from a burette.

The mixture

was heated strongly for at least 0.5 hour to Insure com­ plete precipitation of the silver bromide.

The mixture was

then cooled to room temperature and 1 ml. of indicator added.

The indicator used was a saturated aqueous solution

of ferric ammonium sulfate.

The excess of silver nitrate

was titrated with a 0.1 N ammonium thiocyanate solution. The end point is a red brown color due to the complex ferric thiocyanate. The standard silver nitrate was prepared by weighing out the proper amount of pure, dried, silver nitrate, dis­ solving it In water and diluting to volume.

The ammonium

thiocyanate solution was standardized against this silver nitrate solution.

With 2-bromocyclohexanone, the weighed

sample was dissolved in alcoholic potassium hydroxide and the solution heated on a steam bath for two hours. At the end of that time, the flask was cooled, the potassium hy­ droxide neutralized with nitric acid, 5 ml. of 6N nitric acid was added in excess, and an excess of standard 0.1 N silver nitrate added from the burette.

After the silver

49

bromide had precipitated, 1 ml* of ferric ammonium sulfate indicator was added and the excess silver nitrate titrated with the standardized 0*1 N ammonium thiocyanate

solution*

50

BIBLIOGRAPHY Behrena, R* and Schreiber, H , , Ann, 318, 371 (1901). Bois menu, E., Compt. rend. 153, 678 (1911). Boismenu, E . , Compt. rend. 1 5 5 . 1482 (1911). Bredt* J. and Hof, H . , Ber 33, 21 (1900). Buu-Hoï, N. P., Ann. 556. 1 (1944). Clermont, A., Compt. rend. 155. 738 (1901)• Cloez, S., Ann. chlm. (3) 17, 297 (1846). Coleman, G. H. and Johnston, H. F . , Org. Syntheses Coll. Vol. I, 183 (1941) Conrad, M. , Ann. 1 88. 218 (1877). Corson, B. B . , Scott, R. W. and Vdse, C. E. ,0rg. Syntheses Coll. Vol. II, 379 (1943). Corson, B. B . , Scott, R. W. and Vose, C. E . , Org. Syntheses Coll. Vol. I, 179 (1941)* Djerassi, C . , Chenu Rev. 43, 271 (1948)♦ Franseconi, L. and de Plato, G . , Gazz. chlm. ital. 55, 226 (1903). Francesconi, L. and Recchi. V., Gazz. chlm. Ital. 32, 45 (1902). Francois, M . , Compt. rend. 147. 680 (1908). Gilman, H. and Jones, R. G * , J. Am. Chem. Soc• 65. 1458 (1943). Graebe,

C.

and Gfeller, E . , Ber 25, 652(1892).

Hof man,

A.

W . , Ber 15, 410 (1882).

Howton,

D.

R . , J. Am. Chem. Soc. 69, 2060 (1947).

Howton,

D.

R. and Buchman, ÏÏ. R . , J . Am.Chem. Soc.

51

70, 2517 (1948). (21)

Huntress, E. H. and Shriner, R. L. Org. Syntheses Coll. Vol. H ,

(22)

459 (1943).

Inglis, J. K. H., Org. Syntheses Coll. Vol. I, 254 (1941)

(23)

Jaubert, G. V. , Ber. 28, 360 (1895).

(24)

Kharaseh, M. S. and Priestly, H. M . , J. Am. Chem. Soc. 61, 3425 (1939).

(25)

Menschutkin, N. and Jeroalojeff, M . , 2. Chem. %, 5 (1871); Jahresber. Chem. 1871. 728.

(26)

Norris, J. F. and Joubert, J. 11., J. Am. Chem. Soc. 49, 873 (1927).

(27)

Ott, B. and Welssenburger, H., Ber. 70, 1829

(1937).

(28)

Putokhin, N. 1., J. Gen. Chem. (XT. S. S. R. ) 15, 332 (1945).

(29)

Ramberg, !.. and Wideqvist, S., Arkiv Kemi, Minerai. Geol. 12A. No. 22, 12 pp. (1937).

(30)

Schmid, H», and Karrer, P., Helv. Chlm. Ac ta 29,, 573 (1946).

(31)

Schmid, H., Helv. Chlm. Acta 29, 1144 (1946).

(32)

Selwanow, T . , Ber 26 , 423 (1893).

(33)

Spiegel, L. and Spiegel, P., Ber 40,

(34)

Steiner, A., Ber. 15, 1607 (1882).

(35)

Wohl, A., Ber. 52, 51 (1919).

(36)

Wohl, A. and Jaschenowski, K . , Ber 54, 476 (1921)

(37)

Ziegler, K . , Spaeth, A., Schaaf, B . , Schumann, W. and Winkelmann, E . , Ann 551. 80 (1942).

1730 (1907).

52

PAST II: AN INVESTIGATION OF CERTAIN 1,1-BIS (£-CHmROFHENTL )AIKANES AND DERIVATIVES

INTRODUCTION The 1,1-bis(£»ehlorophenyl)ethane skeleton is to be found in many insecticides and mit ici des*

The discovery

that 1,1-bis (ja-chlorophenyl)*2,2,2-trichloroethane (DDT) was a superior insecticide initiated many investigations as to the nature of and reason for its insecticidal ac­ tivity as well as the capacities of similar compounds as insecticides. 1$1-Diphenylsthane is ineffective as an insecticide; in comparison to DDT* 1*l-diphenyl-2*2*2-trichloroethane and 1,1-bis (jg^ehlorophenyl)ethane have a greatly reduced insecticidal action*

These facts, along with others, have

lead to the theory that the insecticidal power of DDT is due to the "£ bridged 4,4f-dichlorophenyl structure” aug­ mented by the effect of the "chloroform residue" (18). The jd bridged structure supposedly acts by an "enzyme blocking mechanism" while the d o r o f o r m residue is claimed to "act as a lipophilic group which causes the molecule to have an affinity for the nerve lipoids" (20).

The theory

was supported by the insecticidal activities of compounds which had structures similar to DDT but with residues of inhalation anaesthetics other than chloroform (20). Further, it has been found that compounds with either

53

aliphatic or aromatic ehloro groups, but not both, are not as toxic to warm blooded animals as those containing both (40), Hence, compounds with other groups replacing either the aliphatic or aromatic chloro groups in DDT. (e.g# methoxy groups replacing the aromatic chloro groups) are being considered for use as parasite killers in human medication (16).

The advantages of effective insecticides

with little or no toxic effect on warm blooded animals are obvious. The compounds 1,1-bis (jD-chlorophenyl) -2-nit roe thane and 1,1-bis (]3-chlorophenyl)-2-nitropopane have been found to be useful insecticides and far less toxic to humans than DDT (4), (27), (29)# Further, 1, 1-bis (£-chlorophenyl)ethanol is an effective agent for the control of mites (23) # In view of the activities of these compounds it was ex­ pected that the l ,l-bis (^-chlorophenyl)-l-nitroalkanes would be useful mitlcides. DISCUSSION Preparation of 1,1-Bis (£-chlorophenyl)alkanes Bis(j>-ehlorophenyl)methane has been made by many methods.

However, all of the preparations reported in the

literature offer the disadvantage that low yields are ob­ tained.

The compound has been produced in poor yield, to­

gether with unidentified by-products, by the reduction of p,pt—dichlorobenzophenone by red phosphorous and hydroiodie

54

acid (34) and by zinc and either acetic or sulfuric acid (35) e The reduction of p , p 1wdlchlorobezophenone hydrazone (obtained in 56# yield from p ,p *«"dichlorobenzophenone ) has recently been reported to give a 21% yield of bis (£-efaloropheny 1 )-methane (15). Bis (jg^chlorophenyl)methane has been made from the diazonium salt of b is (£—ami nophenyl) methane with cuprous chloride in concentrated hydrochloric acid (19)* The isomers of bis (j>»chlorophenyl) me thane are very difficult to separate; this fact has led to erroneous con­ clusions*

Nastjukow and Andrejew (28) reported that the

reaction of formaldehyde and chlorobenzene in the presence of sulfuric acid yielded bis(m-chlorophenyl)methane* Bentley and Catlow (2) later showed that this condensation resulted in a mixture of isomeric dichloro diphenylmethanes in which the

and o,]>* diehloro derivatives predominate.

In a Frlede 1-Crafts type reaction, chlorobenzene and 2 -chlorobenzyl chloride in the presence of sulfuric acid

have been reported to yield bis (j>-chlorophenyl)methane(4l)* There is no mention in the literature of the Friedel-Crafts condensation between chlorobenzene and methylene chloride; this reaction was studied in this investigation as a possible source of bi8(£-chl©rophenyl)methane* The reaction was conducted using conditions which had been previously outlined for successful condensations of this typeî chlorobenzene—carbon tetrachloride (32), and chlorobenzene— 1 ,1 ,1 —triehloroethane (25)* In no experiment

55

was any pure bis(j^chlorophenyl)methane isolated* The low yield of product, the boiling point of which deviated widely from that of the expected bis (£-chlorophenyl)« methane, was probably a mixture of the o-chlorophenyl and ]>»ehlorophenyl isomers of this compound*

The small amount

of bis (j>*ehlorophenyl)methane, which was probably produced, was not isolated from this oil since it was evident that this reaction was not a convenient source of the compound sought* A method was developed to prepare b i s (£-chlorophenyl)* methane by the alkaline hydrolysis of DDT* This is probably the best source of this methane derivative, for, in one step from DDT, an excellent yield of very pure bis(^chlorophenyl )me thane may be obtained* Potassium hydroxide acts on an alcoholic solution of DDT at room temperature or at reflux temperature to give 1.1-bis(j)»chlorophenyl}« 2 ,2-dichloroethane (4), (12),(14)* At higher temperatures, potassium hydroxide reacts with 1.1-bis(i>-*ehlorophenyl)~2,2-dichloroethene or DDT (this reaction goes through the e the ne derivative) to give 2,2-bis(j>-chlorophenyl)-acetic acid*

This reaction proceeds at a

temperature higher than the boiling point of ethanol (ca* 150° C* ) and so it has been run in 95% ethanol in a sealed tube (14) or autoclave (9), or in ethylene glycol under reflux (12)* In this investigation, the reaction of potassium hy­ droxide with DDT in 95% ethanol at a still higher

56

temperature (180° C*)

In an autoclave has been found to

give bis (j>~ohlorophenyl)methane in a substantially quanti­ tative yield.

O

HCGCl^

-- ^

C=CClg

--

The recrystallization of technical DDT from 95# ethanol yields pure 1,1-bis (2>-chlorophenyl)-2s2,2-trichloroethane uncontaminated by o,-chlorophenyl isomers (12)♦ Using this pure p^-chlor ophenyl derivative in the alkaline hydrolysis, bis(jD-chlorophenyl)methane is obtained free from o-ehlorophenyl isomers»

One recrystallization of the product direct

from the autoclave yields very pure bis(gchlorophenyl)methane. 1,1-Bis (£-eh lor ophenyl )ethane has been prepared in several ways»

Cook and Chambers (6) obtained a low yield of

1.1-bis (]>-chlorophenyl) ethane from the condensation of chlorobenzene and acetylene in the presence chloride.

of aluminum

Grummitt, Buck and Becker (11) have obtained

1.1-bis (£-chloro phenyl) ethane in 38# yield from chloroben­ zene and acetaldehyde with aluminum chloride or sulfuric acid and in 51# yield from chlorobenzene and 1,1-dichloroethane with aluminum chloride» 1,1-Bis (£-chlorophenyl)ethane is a white crystalline solid melting at 54-5° c»

However, all of

the products from the above condensations, while giving

57

substantially the correct analysis for 1,1-bis(£- chlorophenyl)ethane were high-boiling fluorescent oils*

The

authors report unsuccessful attempts to purify their products and obtain crystalline

l s1-bis (jo-chlorophenyl) eth­

ane * The Friedel and Crafts condensation of chlorobenzene and 1,1,1-trichloroethane in the presence of aluminum chloride gives a 24% yield of l s1-bis(£-ehlorophenyl)ethene (26)*

This could be hydrogenated to the ethane deriva­

tive, but the overall yield would be very low and therefore this procedure does not represent a convenient source for the compound*

The reduction of DDT with zinc and concen­

trated hydrochloric acid in boiling ethanol has been found to give a small yield of 1,1-bis (£-chlorophenyl)ethane along with 1,2-bis(£-chlorophenyl)ethene and l,l-bis(£-ehlorophenyl)- 2 ,2-dichloroethane (8)• The chlorination of 1,1-diphenylethane has been found to yield 1,2-diphenylethane and 1, l-diphenyl-2,2-di chloroethene (36).

Also the condensation of bis (£-chlorophenyl )chloro-

methane and méthylmagnésium bromide gave no 1,1-bis(jwchlorophenyl)ethane but rather a 95% yield of 1,1,2,2-tetrakis— (£-chlorophenyl) ethane (11). The best preparations of 1,1-bis (j>-chlorophenyl)ethane involve synthesizing 1 ,1 -bis(£-chlorophenyl)ethanol, dehy­ drating this compound to the ethene derivative, and hydrogen­ ating the 1 ,1 -bis (]>-chlorophenyl)ethene. All of the steps in these syntheses give good yields of products, the purity and

58

Identity of which is unquestionable* 1,1-Bis(£-chlorophenyl)ethanol is best made by one of two methods: (1)

The reaction of a Grignard reagent derived from a

methyl halide with

O

0— 0

(2)

— SB^M g-Bp ^

«dichlorobenzophenone (3),(11)

CH^COMgBr

CH3C0H

The reaction of j9«ehlorophenylmagnesium bromide

with ehtyl acetate (23) 01

CH3C02C2H 5+

O

2 £ C l C ^ M g B r — ► CH^COMgBr

+

MgtOC^jBr

CH^COH

The £,]>*«dichlorobenzophenone for reaction (1) may be made

59

by: (a) Hydrolysis of the £,£-dichlorobenzophenone dichloride produced by the aluminum chloride catalyzed con­ densation of chlorobenzene and carbon tetrachloride (26), (32). (b) Chromium trioxide oxidation of 1,1-bis(£-chlorophenyl)-2 ,2-dichloroethene which is obtained by the alkaline hydrolysis of DDT. Reaction (1) gives a 89# yield of 1,1-bis (j>~chlorophenyl )ethanol; both méthylmagnésium bromide (11) and méthylmag­ nésium iodide (3) have been used. Details of reaction (2) are not included in the litera­ ture; they may be found in the experimental section of this thesis.

The method gives an 85 to 95# yield of the ethanol

derivative. 1,1-Bis(£-ehlorophenyl)ethanol may be dehydrated by treatment with 20# sulfuric acid to give an 88# yield of 1,1-bis (£-chlorophenyl) ethene (11) .

The hydrogenation of

this compound with platinum black as a catalyst gives a 62# yield of l,l-bis(j>-chlorophenyl)ethane (11). Direct reduc­ tion of 1,1-bis (2>~chlorophenyl)ethanol gave only a 14# yield of 1,1-bis (|>-chlorophenyl)ethane (11) • The higher homo logs of the 1,1-bis (£-ehlorophenyl )alkanes may be made by methods analagous to those used in the preparation of 1 ,l-bis (js-chlor ophenyl) ethane.

60

Action of Nitric Acid on 1,1-Bis {]>~chlorophenyl )alkanes Ring nitration of the 1,1-bis(£-chlorophenyl)alkanes may be accomplished by the use of fuming nitric acid (8)* Treatment of 1,1-bis (^-chlorophenyl}ethane with fuming ni­ tric acid in glacial acetic acid at 100° C* gives 1,1-bis(4-chloro-3-nitrophenyl)ethane*

If concentrated sulfuric

acid is used in place of the acetic acid in this reaction, 1,1-bis(4-chloro-3,5-dinitrophenyl)ethane is produced (8)* Analagous results are reported in the nitration of DDT (8). The yields of aromatically nitrated products in these reac­ tions are not reported nor is any mention made of aliphatic nitro derivatives or other oxidation products being pro­ duced.

One may safely conclude, from this work, that ring

nitration of these compounds requires fairly rigorous con­ ditions and fuming nitric acid* There is no reference in the literature of the action of concentrated or dilute nitric acid on these compounds* However, the reaction of concentrated nitric acid in glacial acetic acid on 1,1-diphenylethane has been reported to yield a series of compounds: l,l-diphenyl-2-nitroethanol, 1,1-diphenyl-2-nltroethene, and 1,l-diphenyl-2,2-dintiroethene (1)* It is significant that the treatment of 1 ,1-diphenylethene with a similar nitrating mixture and under similar conditions gives the same products (1)* Also by the reaction of nitrogen dioxide on 1,1-diphenylethene in petroleum ether containing a trace of water, l ,l-diphenyl-2-nitroethanol is

61

obtained and this compound is easily dehydrated to 1,l-di­ phenyl-2 -ni troethene (42) * The following series of reactions has been postulated to explain the formation of the observed products:

oxlAatiqa*. (c 6h 5)2c (o h )c h 3 (c6h 6)80 = c h 3

*

(C6H5 )2C(N02 )CH8N03_ _ ^ 0 --- _

(G6ag)2C(0H)CE8N02 . , . ^ 0 ^ ( C ^ C ^ C H N C ^ tCgH g)gC (NOg) CH(NO_).

- h co

U zO r

NOg____^

(CaH_).C(OH)CH(NO^). -H^.0 ,

This reaction ultimately yields benzophenone*

No mention

is made of the reaction of diphenylethane with dilute ni­ tric acid or with nitric acid - acetic acid mixtures con­ taining less than a 1:1 molar ratio of nitric acid. Konowaloff (16) has nitrated diphenylmethane with dilute aqueous nitric acid and obtained dlphenylnitromethane♦ He ran the reaction at 100° C. in a sealed tube using an aqueous solution which was 12,7% nitric acid by weight. The product was not very stable; it decomposed at room tem­ perature into a yellow oil and difficulty was encountered in regenerating the compound from its salts. The reactions of dilute nitric acid with bis (^-chlorophenyl) methane and with l,l-bis(£-ch lor ophenyl) ethane were studied.

Experiments were run using dilute aqueous nitric

acid (12.7# nitric acid by weight) in a sealed tube at 100°Ce using the method of Konowaloff (18) and at open reflux.

62

Also the reactions of bis(

hlorophenyl)methane and 1,1-

bis (£-chlorophenyl)ethane with an nitric acid-acetic acid mixture (13% nitric acid by weight) were studied in sealed tubes and at open reflux* —Dichlorobenzophenone was the only organic product isolated from any of these reactions*

The reactions in

sealed tubes were more rapid than those conducted under re­ flux*

Further, the nitric acid - acetic acid mixture, while

resulting in a homogeneous reaction solution, oxidized the compounds more rapidly than the aqueous nitric acid* Complete conversion of the bis (])-eh lor ophenyl) methane and 1,1-bis(£-chlorophenyl)ethane to

dichlorobenzophenone

was ac­

complished by the nitric acid-acetic acid mixture in onehalf hour in a sealed tube at 100° C. or in one hour at reflux*

Using the aqueous nitric acid solution the trans­

formation was complete in approximately three hours* In no instance was any compound other than unreacted starting material or £-£»-dichlorobenzophenone isolated* If any in­ termediate compound or compounds are involved, as is the case in the nitration of diphenylethane, it would appear that their oxidation to the ketone is a more rapid reac­ tion than that of their formation from the starting com­ pound* It is significant that the reaction of 1,1-bis(g-chloropheny1)ethene, under similar conditions, was found to give £ ,£f—dichlorobenzophenone readily* Further, it has been reported (8), that fuming nitric acid, under conditions

63

that give ring nitration in the case of DDT, gives £,£*dichlorobenzophenone and no aromatic nitration with 1,1bis ( p ^ c h l o r o p h e n y l ) ,2,-dichloroethene• Hence it may be postulated, in the case of 1,1-bis(£-chlorophenyl)ethane, that the compound is initially oxidized to 1,1-bis(2>-chlorophenyl)ethanol, and this compound is dehydrated, cleaved, and oxidized to

-dichlorobenzophenone.

In the reactions of bis (jy-chlorophenyl)alkanes with dilute nitric acid, the ease of formation of £,£,-diehlorobenzophenone as well as the lack of the isolation of any intermediates is more reasonable if viewed in the light of the following.

Throughout this investigation as well

as others, £ , £ f-dichlorobenzophenone has been observed to form with amazing ease and hence has been an unpredicted product of many of the reactions of the 1,1-bis(£-chlorophenyl)alkanes•

If the recrystallization of 1,1-bis(p-chlo-

rophenyl)ethanol is attempted at too high a temperature, p,p*-dichlorobenzophenone is formed.

This ketone has been

reported as having been produced in approximately 20% con­ version (100% yield) by irradiating DDT for forty hours with a mercury vapor lamp (7). It would appear that the activating effect of the two £-chloropheny 1 groups renders certain derivatives of the 1,1-bis(£-chlorophenyl)alkanes very susceptible to oxidation. It was decided to nitrate 1,1-bis(£-chlorophenyl)-2, 2 ,S—trifluoroethane in order to test the stability of alpha nitro analogs. 1,1—Bis(p-chlorophenyl) —2,2,2-tri—

64

fluoroethane was prepared from DDT and mercuric fluoride using the method of Kirkwood and Dacey (17) ♦ It was found that the compound was recovered unchanged In nitrations using dilute nitric acid (specific gravity 1,075) or nitric acid - acetic acid mixture (13# nitric acid by weight). The 1,1-bis(3>"»chlorophenyl )-3-nitroalkanes are not made by nitrating the corresponding alkanes. Rather, the fol­ lowing series of reactions is used to prepare them (4),(27),

(20 ). 0= C H

NaOC (H) CHgNO^

Cl

Cl Condensation of Chlorobenzene and 1,1-Dichloro-l-nitroethane It is well known that the Friede 1-Crafts reaction is not an efficient method of synthesizing nitro compounds. The inert character of nitrobenzene with regard to this reaction has led to its use as a high boiling solvent for many Friede1-Crafts condensations.

Many investigators (5),(21)

have reported unsuccessful attempts with halo nitro paraffins which they ascribed as due to the inherent inhibition of the

65

reaction by the nitro group and the predominance of byreactions* However, several investigators have reported success­ ful condensations of this type* Triphenylnitromethane has been prepared from benzene and chloropicrin (34); phenylnitromethane has been prepared from benzene and bromonitromethane (37)•

The condensations of benzene with the chlo-

ronitropropanes produced the corresponding phenylnitropropanes in varying yield (39) ♦ When chlorobenzene was used in place of benzene with the chloronitropropanes the only successful condensation was that with l-chloro-3-nitropropane in which the chloro group was as far as possible away from the nitro group (22)*

The yields in all of the reac­

tions were very poor* The condensation of chlorobenzene and 1,1-dlchloro1-nitroethane in the presence of aluminum chloride was at­ tempted using the method of Silverberg (39)* Most of the starting materials were recovered unchanged*

The only

organic product of the reaction was a small quantity of a fragrant red oil from which no pure product could be isolated* This was to be expected in view of the work with chlorobenzene and the monochloronitropropanes (22) * Reactions of 1,1-Dibromo-l-nitroethane with jD-Chlorophenylmagnesium Bromide and p^Chlorophenylcadmium Chloride Although the condensations of Grignard reagents with compounds containing a nitro group are usually not

66

successful, the reaction of £-chlorophenylinagnesium bromide and 1,1-dlbromo-l-nitroethane was studied. ]>-Chlo~ rophenylmagneslmn bromide was prepared from p-bromoehlorobenzene and magnesium In anhydrous ether and l ,1-dibromo-lnltroethane was added slowly to this Grignard reagent. A vigorous reaction resulted, but the only organic products were a high melting yellow solid, insoluble in the usual organic solvents, and £-bromochlorobenzene. Neither cooling the reaction with an ice salt bath, nor reversal of the order of addition of the reactants (i* e. adding the Grig­ nard reagent drop-wise to the 1,1-dibromo-l-nitroethane) gave different results. Newman and Smith (30) have reported a successful con­ densation between phenylmagnesium bromide and m-nitrobenzaldehyde at -70° C.

Therefore, the reaction between

]>-ehlorophenylmagnesium bromide and 1,1-dibromo-l-nitroethane was repeated at the temperature of a dry-ice-trlchloroethylene cooling bath.

The reaction proceeded as

before, starting materials and a yellow polymer were re­ covered. Since cadmium reagents are generally not as reactive as Grignard reagents, the reaction of

chlorophenylcad—

mium chloride and 1,1 -dibromo-l-nitroethane was studied. The cadmium reagent, p-chlorophenyl ca dmium chloride, was prepared from

chlorophenylmagnesium bromide by the ad­

dition of anhydrous cadmium chloride to the Grignard re­ agent.

To this, 1 ,1 -dibromo-l-nitroethane was added

67

dr op-wise and the mixture was cooled by an ice bath. The products isolated were: a small quantity of a high melting yellow solid similar to that obtained In the reaction of jD-chlorophenylmagneslum bromide and 1,1-dibromo-l-nitro­ ethane , £-bromochlorobenzene » and j^E^-dichlorobiphenyl. A similar experiment was conducted using phenylcadmium chloride, in place of ]>-ehlorophenylc&dmium chloride, which might yield 1,1-diphenyl-1-nitroethane.

Only bi­

phenyl and unreacted starting materials were isolated. From this reaction it may be assumed that the high melting yellow solid obtained in the previous experiments was a phenylene polymer or a polymer derived from the £-dihalogenated benzene, since it was not obtained in the reaction using phenylcadmium chloride. As a matter of interest, |>-chlorophenylmagnesium bro­ mide was reacted with ethyl trifluoroacetate• It was ex­ pected that 1,1-bis(p-chlorophenyl)-2,2,2-trifluoroethanol would result in the same way as 1,1-bis (p-chlorophenyl)ethanol is the product of £-chlorophenylmagnesium bromide and ethyl acetate. However, the reaction yielded a yellow solid, insoluble in common organic solvents, and a small quantity of a tan syrup from which no pure product could be isolated.

The reaction was repeated using a dry-ice-

trichloroethylene cooling bath but the results were similar. The reaction of phenylmagnesium bromide and ethyl trichloroacetate has been reported to give poor yields of bi­ phenyl and chlorobenzene; none of the expected

68

1,l-diphenyl-2,2,2-trichloro-l-ethanol was isolated (15), Silver Nitrite Condensations With 1,1-Bis (2>-chlor ophenyl )-1-haloalkanes A condensation of silver nitrite with bis(^-chlorophenyl)chloromethane was run.

In Victor-Meyer condensa•

tions, alkyl brojaides and Iodides are generally used; it has been reported that alkyl bromides give better yields than do alkyl iodides and also that primary alkyl halides give better yields than do seconary or tertiary alkyl halides (35) • However, in the case of bis(jg^chlorophenyl)chloromethane, it was expected that the aliphatic chlorine atom, would be activated by the two |>-chlorophenyl groups to such an extent that a silver nitrite condensation could be effected and the nitro derivative made in good yield. The bis (g-c hlor ophenyl )chlor omethane was made in a four step synthesis from DDT,

Dehydro ha lo gena t ion of DDT

by refluxing with alcoholic potassium hydroxide, gave 1,1bis(£-chlorophenyl)-2,2-dichloroethene which was oxidized by chromium trioxide to jj-jjj^dichlorobenzophenone.

This

ketone was then reduced to 1,1-bis(jy-chlorophenyl)methanol by zinc dust and sodium hydroxide, and the alcohol con­ verted to the chlor omethane derivative by refluxing with thionyl chloride. Thoroughly dry silver nitrite was mixed with a solu­ tion of bis(js-chlorophenyl)chloromethane in anhydrous ether ; the reaction was run in the dark and provisions were

69

made for the exclusion of moisture* As is the case in this type of condensation, the reaction was a slow one and took days for completion* Experiments were run at room tempera­ ture, reflux temperature, and at 0 ° C* There was evidence that the condensation proceeded in the expected manner since silver chloride was produced; however, in all experi­ ments a high yield of £

-dichlorobenzophenone was obtained*

It may be postulated that bis (£-chlor ophenyl) nitromethane is actually produced in this reaction, and as soon as it has been formed, undergoes transformation to the ketone : Cl

2

Cl

HÇN0

This is similar to the Nef synthesis of aldehydes and ketones from nitro alkanes*

The activating effect of the

two £-chlorophenyl groups might be expected to displace the equilibrium between the true nitro form and the aci form of bis(£-chlorophenyl)nitromethane t o m r d the aci side. Thus it may be that the compound is a strong enough acid to bring about its own decomposition* Attempts were made to synthesize alpha halogen deriva­ tives of 1 ,1 -bis(£-ehlorophenyl)ethane in order that a sil­ ver nitrite condensation could be run with one of them.

70

However, from the many methods tried no such halogen derivative could be made. Neither anhydrous hydrogen chloride gas nor anhydrous hydrogen bromide gas could be made to add to 1 ,1 -bis(2 ~ohlo­ ropheny 1) ethene.

Additions were attempted in anhydrous

ether, carbon tetrachloride and glacial acetic acid, at room temperature and at- 10 ° C. at reaction times ranging from four to eighteen hours.

%n all cases the bis(g-chlo-

rophenyl)ethene was recovered unchanged.

Failure of hydro­

gen chloride gas to add to l,l-bis(j>-chlorophenyl>e,2 ,-dichloroethene has been reported (15).

The ethylenic bond of

1 .1-bis(£-chlorophenyl)- 2 ,2 -dichloroethene is very unreactive

as it does not add bromine in carbon tetrachloride at room temperature. The chlorination of l,l-bis(£-chlorophenyl)ethane, as a source of 1 ,1 -bis (£-chlorophenyl)-l-ch lor oethane, was no more rewarding.

Grummitt et al (13) chlorinated 1,1-biste­

chier ophenyl) ethane in carbon tetrachloride at temperatures in the range of from 25° C. to 80° C.

The product was an

oil, the chlorine content of which corresponded to that of 1 .1 -bi s (£-chlor ophenyl)- 2 ,2 -di chloro ethene; however, this

compound is a solid.

This type of reaction product is

similar to that obtained in the chlorination of diphenyl­ ethane (36). From the work of Grummitt, it was evident that if any 1 .1 -bis(£-chlorophenyl)-l-chloroethane were to be obtained

in the chlorination of 1 ,1-bis(£-ehlorophenyl)ethane the reaction must be conducted under mild conditions. However,

71

it was found that either no reaction occurred or else it proceeded as reported by Grummitt* The chlorination of 1 ,1-diphenylethane has been re­ ported to proceed as follows(36):

U)

(C6H5)3C(H)CH3+ C13 - ^ -chlorophenyl)ethene, and a small amount of

«•dichlorobenzophenone were isolated. 1,1-Bis (^-chlo-

rophenyl )ethene is extremely susceptible to oxidation, as has been mentioned earlier ;hence, the production of a small amount of p,p*-dichlorobenzophenone is not surprising* Bis (]>-chlorophenyl) chlor omethane may be made by a method similar to the above, or as was done in this inves­ tigation, by ref luxing the bis (jD-chlorophenyl) me thetnol in toluene with thionyl chloride.

When 1 ,1 -bis(j^-chlorophenyl)**

ethanol, in toluene, was re fluxed with thionyl chloride, a good yield of 1 ,1-bis (j)-chlorophenyl)ethene resulted. Boyk and Mortimer (26) in a study of the Friede 1-Crafts condensation of chlorobenzene and 1 ,1 ,1-trichloroethane obtained a 24)6 yield of 1 ,1-bis(£-chlorophenyl)ethene to­ gether with polymerization products derived from this olefin and/or c^-chloro-£-chlorostyrene* None of the ex­ pected 1 ,1-bis(g-chlorophenyl)-l-chloroethane was obtained, nor could any 1 ,1 -bis (2 -ehlorophenyl)ethanol be secured by the hydrolysis of the crude product and subsequent isola­ tion procedures*

73

ITrom the foregoing references and experimental evi­ dence it may be assumed that 1 ,1-bis (^-chloro phenyl)-!chloroethane is relatively unstable*

Since the nitro

group is larger than the chloro# and of comparable nega­ tivity, one would wonder about the stability of the alpha nitro derivatives of the 1 ,1 -bis(j^-chlorophenyl)alkanes*

EXPERIMENTAL Condensation of Chlorobenzene With Methylene Chloride A 100 ml* 3 necked round bottom flask was with a mercury

sealed Hershberg stirrer, a

equipped dropping funnel

(open end supplied with a calcium chloride tube), and a reflux condenser*

The open end of the condenser was con­

nected via* a calcium chloride tube to a long rubber tube which served as an exit for hydrogen chloride gas* Anhydrous aluminum chloride (133*5 g* ; 1 mole) and chlorobenzene (175 ml*; 192*5 g*; 1*73 moles) were placed in the flask* A mixture of methylene chloride

(65*5 ml»;

85 g* ; 1 mole) and chlorobenzene (100 ml* ; 100

g* ; 0*97

mole) was poured into the dropping funnel*

The total amount

of chlorobenzene used was 2*7 moles* The methylene chloride - chlorobenzene mixture was admitted drop-wise with stirring during one hour*

The reac­

tion mixture gradually turned a deep red color; hydrogen chloride was evolved slowly at first and then rapidly

74

throughout the remainder of the reaction*

The mixture

was stirred for seven hours and then allowed to stand overnight♦ The aluminum chloride complex was decomposed by pouring the mixture into a beaker containing 150 g* of ice and 250 ml* of water*

The organic layer was separated

and the water layer was extracted with several portions of benzene*

The organic fractions were combined and

washed with dilute hydrochloric acid (10 % by weight) fol­ lowed by distilled water* Treatment of this solution with Norite did not completely decolorize it; the material was a clear amber-red*

The solution was dried over anhydrous

sodium sulfate* The benzene was evaporated on a steam bath and a viscous orange-brown material was left* was obtained by cooling this syrup*

No solid product

Vacuum distillation

gave two fractions : one boiling at 170° C*/5 mm*, the other at 260° C*/5 mm*

No crystals could be obtained from

the first fraction by diluting this oily liquid with pentane and cooling the solution in a dry-ice-trichloroethylene bath* ature*

The second fraction m s a solid at room temper­

Recrystallization of this product from ethanol gave

a material which melted above 220° C,

Bi stfc-chloro phenyl )-

methane is a solid which melts at 55—6° C* and boils at 208-10° C*/15 mm* In a second experiment, 300 ml* of carbon—disulfide was added to the contents of the flask*

The experiment was

75

conduc"ted in a similar manner to that previously described# The same two fractions were obtained ; no pure bis (g—chloro— phenyl)methane was isolated from them* Preparation of Bis (]>»ôhlorophenyl)methane from DOT Pure £»