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P U R D U E U N IV E R S IT Y
THIS IS TO CERTIFY THAT THE THESIS PREPARED U N D E R M Y SUPERVISION
by________ John A *
THE PREP/lRa TION AND REACTIONS OF CERTAXN
_______ ALIPHATIC HALOGEN_COMPOUNDS________________
COMPLIES WITH THE UNIVERSITY REGULATIONS O N GRADUATION THESES
A ND IS APPROVED BY M E AS FULFILLING THIS PART OF THE REQUIREMENTS
FOR THE DEGREE OF
_______________Doctor of Philosophy_______________
S c h o o l ,o r D
( ? / % .
TO THE LIBRARIAN:--
■±S'THIS THESIS ÏS-Wer TO BE REGARDED AS CONFIDENTIAL.
GRAD. SCHOOL FORM 9—3 -4 9 — 1M
THE PREPARATION AND REACTIONS OF CERTAIN ALIPHATIC HALOGEN COMPOUNDS
A Thesis Submitted to the Faculty of Purdue University
John A. Barone
In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August, 1950
ProQuest Number: 27714173
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 27714173 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 author is deeply grateful to Dr. E. T. MoBee for directing this research.
The helpful suggestions
of D r s. H. C. Brown, 0* R. Pierce, and Z. D. Welch are also appreciated. The suggestions and companionship given by the other members of the Department of Chemistry have been welcome.
Special thanks are due to J. Burch, M, Fein,
J. Higgins, I. M. Robinson, K. Taylor, and A. Truchan. This investigation was financed by a grant from the Mallinckrodt Chemical Works administered by the Purdue Research Foundation.
TABLE OF CONTENTS
PAGE ABSTRACT PART 1.
THE PREPARATION AND PROPERTIES OF FLUORINATED DERIVATIVES OF ACETALDEHYDE
PART 2*.. THE REACTIONS OF ESTERS OF TRIFLUOROACETIC ACID WITH S O D I U M ............... xv PART 3.
THE PREPARATION OF SOME POLYCHLORINATED ISOBUTANES AND IS O B U T E N E S .............xx
THE PREPARATION AND REACTIONS OF SOME POLYHALOGENATED BRANCHED ALIPHATIC C O M P O U N D S ........................... xxvii
THE PURITY AND STABILITY OF F LUO R INATED ............... .xxxiü COMPOUNDS
THE PREPARATION AND PROPERTIES OF FLUORIDATED DERIVATIVES OF ACETALDEHYDE
EXPERIMENTAL..................................„ . .
Preparation of Fluoral ........................ 5 8 Polymerization of Fluoral.................. Hydration of Fluoral . ...................... 8 Preparation of Fluoral 2 ,4-Dinitrophenyl9 hycLrazone ................................... Preparation of 3,3,7,7-Tetramethyl-1,9-dioxo10-(trifluoromethyl)octahydroxanthene . . . 9 Preparation of 4,4,4-Trifluoro-3-hydroxybutanoic Acid..................................... 9 Preparation of 1,1,1-Trifluoro-2-propanol. . . 10 Preparation of 3-Aza-l,1,1-trifluoro-4-oxo-2pentanol.................................. 12 Preparation of 3,5-Diaza-l,1,1-trifluoro-4oxo-2 -pentanol............................ 12 Preparation of Chlorodifluoroacetaldehyde. . . 13 Polymerization and Hydration of Chlorodifluoroacetaldehyde.............................. 14 Preparation of Chlorodifluoroacetaldehyde 2 ,4-Dinitrophenylhydrazone............... 15
PAGE Preparation of 3,3,7,7-Tetramethyl-l,9-dioxo10-(chlorodifluoromethyl)octahydroxanthene. . Preparation of 3 -Aza-l-chloro-l,1-difluoro-4oxo-2 -pentanol............................... Preparation of 3,5-Diaza-l-chloro-l,1-difluoro4 -oxo-2 -pentanol............................. Preparation of Difluoroacetaldehyde............ Polymerization and Hydration of Difluoroacetal dehyde ....................................... Preparation of Difluoroacetaldehyde 2,4-Dinitrophenylhydrazone.................. Preparation of 3,3,7,7-Tetramethyl-l,9-dioxo-10(difluoromethyl)octahydroxanthene ..........
15 16 16 16 18 18 19
S U M M A R Y ............................................
REACTIONS OF ESTERS OF TRIFLUOROACETIC ACID WITH SODIUM
Preparation of Butyl Trifluoroacetate.......... Reaction between Sodium and Butyl Trif luoroacetate Reaction of Ethyl Trifluoroacetate and Sodium. .
23 24 26
S U M M A R Y ...........................................
THE PREPARATION OF SOME POLYCHLORINATED ISOBUTANES AND ISOBUTENES
EXPER M E N T A L ....................................... Identification of the Polychlorinated Starting M a t e r i a l s ................................... Chlorination of Hexachloroisobutene............ Preparation of Heptachloroisobutene............ Attempted Chlorination of Heptachloroisobutene . Chlorination of Heptachloroisobutane ..........
34 34 35 38 38 39
PAGE Preparation of Octachloropropane ............ Chlorination of Methallyl Chloride ..........
S U M M A R Y ..........................................
THE PREPARATION AND REACTIONS OF SOME POLY HALOGENATED BRANCHED ALIPHATIC COMPOUNDS
DISCUSSION .. .. .................................
Preparation and Attempted Fluorination of 1,1,3Triohloro-2-methylpropene ................ Preparation of 2-Methyl-l-nitro-2-propanol . . Preparation of 2-Methyl-l-nitropropene . . . . Preparation of l,l,2-Tribromo-2-methyl-l-nitrop r o p a n e ................................... Preparation of 2,2-Dimethyl-l,3-dinitropropane Preparation of 1,1,3,3-Tetraehloro-2,2-dimethyl1 .3-d init ropropane......................... Halogenolysis of 1,1,3,3-Tetraohloro-2,2-dimethyl1.3-dinitropropane by Antimony Pentachloride The Reaction of 1,1,3,3-Tetrachloro-2,2-dimethyl1.3-dinitropropene with Antimony (V) Chlorof luoride............................. Reaction of 1,1,3,3-Tetrachloro-2,2 -dimethyl1, 3-dinitropropane with Antimony Triflucride .......... and Antimony Pentachloride. . Reaction of 1,1,3,3-Tetraohloro-2,2-dimethyl1.3-dinitropropane with Antimony Pentafluoride ............................. Preparation of 1,1, l-Trichloro-2,2-dimethylprqpane Preparation of 1,l-Dichloro-l-fluoro-2,2dime thy Ipropane ........................... Attempted Reaction of t-Butylmagnesium Chloride with Dichlorodifluoromethane. . . . . . . . Attempted Reaction between t-ButyImagnesium Chloride and Chlorotrifluoromethane . . . . Reaction between t-ButyImagneslum Chloride and Bromotr if luoromethane..................... Reaction between Isopropylmagnesium Chloride and Carbon Tetrachloride ..................... Reaction between Isopropylmagnesium Chloride and Trichlorofluoromethane. . . . ............ Reaction of Butyllithium and Fluoroform. . . .
50 50 51 51 52 53 53 54 55 56 56 57 58 58 58 59 59 60
PAGE Attempted Reaction of 1,1,1,3,3,3-Hexafluoropropane with Lithium....................... Reaction of 1,1,1,3,3,3-Hexafluoropropane with Phenyllithium......................... Reaction of Methyllithium and 2-Bromo-l,1,1trif luoroethane........................... Reaction of 1,l,2-Trichloro-3,3,3-trifluoro propane with Aluminum Chloride............ Attempted Prins Reaction with 1,1-Dichloropropene and Carbon Tetrachloride............
61 61 62 62 63
S U M M A R Y .........................................
THE PURITY AND STABILITY OF FLUOR INATED COMPOUNDS
EXPERIMENTAL..................................... Stability of 1,1,1,3,3,3-Hexafluoropropane toward Very Dilute Potassium Permanganate . Stability of 1,1,1,3,3,3-Hexafluoropropane toward Dilute Sodium H y d o x i d e ............ Reaction of 1,1,1,3,3,3-Hexafluoropropane with 20% Aqeous Potassium Hydroxide............ Infrared Cuirve ....................... Method for Flammability Determination........ Flammability Data.............................
S U M M A R Y .........................................
70 70 71 72 72 73
LIST OF TABLES Page Table 1.
Flammability D a t a .........................
(Contribution from the Department of Chemistry and the Purdue Research Foundation, Purdue University) THE PREPARATION AND PROPERTIES OF FLUORINATED DERIVATIVES OF ACETALDEHYDE 1 by E. T. McBee and I. A. Barone 1.
Contains material from Mr. BaroneTs doctoral thesis.
AN ABSTRACT Fluorinated aldehydes have been a source of interest for some time because of their possible pharmacological significance.
During the course of this research, Shecter
and Conrad2 reported the preparation of fluoral as a by2.
Shecter and Conrad, J. Am. Chem. Soc., 72, oooo (1950).
product of the nitration of 1,1,1-trifluoropropane. and Ahlbrecht 3.
prepared heptafluorobutyraIdehyde by the
Husted and Ahlbrecht, Abstracts of Paper, 116th Meeting American Chemical Society, p • I0ÏU~(1949).
reduction of heptafluorobutyric acid with lithium aluminum hydride. In this laboratory, trifluoroacetic acid, difluoroacetic acid, and chlorodifluoroacetic acid were reduced to the corresponding aldehydes.
It was found that a procedure
comprising the addition of the acid to an ether solution of
lithium aluminum hydride was more convenient for laboratory preparations than the reverse addition.
and chlorodifluoroacetaldehyde were isolated for the first time as a result of these reactions.
It was also found that
difluoroethanol, on oxidation with sodium dichromate and sulfuric acid, yielded a product from which the 2,4-dinitrophenylhydrazone of difluoroacetaldehyde was prepared. Fluoral was obtained in 46% conversion along with 29% trifluoroethanol.
Chlorodifluoroacetaldehyde and difluoro
acetaldehyde were obtained in conversions of 39% and 10% respectively.
Some chlorodifluoroethanol and difluoroethanol
were also produced.
Trifluoroethyl p-nitrobenzoate, chloro
dif luoroethyl p-nitrobenzoate and difluoroethyl 3,5-dinitrobenzoate were prepared to show the formation of the corres ponding alcohols. Derivatives of the aldehydes were readily formed.
2 ,4-dinitrophenylhydrazones were prepared according to the usual method.
Previously, similar reactions
Shriner and Fuson, "The Systematic Identification of Organic Compounds," 2nd e d ., John Wiley & Sons, Inc., New York, N. Y . , 1940, p. 143.
Huntress, "Organic Chlorine Compounds," John Wiley & Sons, Inc., New York, N. Y . , 1948, p. 624.
with chloral had led to the formation of various products obtained from the hydrolysis of the trichloromethyl grouping. Reactions of the aldehydes with methone 6 gave the
Shriner and Fuson, "The Systematic Identification of Organic Compounds , 11 3 rd ed., John Wiley & Sons, Inc., New York, N. Y . , 1948, p. 172.
corresponding substituted octahydroxanthenes to show evi dence of the ability of the fluorinated aldehydes to react with active methylene groupings.
This was further demon
strated by the reaction of fluoral with maIonic acid to give 4,4,4-trifluoro-3-hydroxybutanoic acid, 7.
J . Am. Chem. Soc., 65, 389 (1943).
chloral ,5 which gave 4,4,4-trichloro-3-hydroxybutanoic acid. Polymerization of the aldehydes readily occurred in the presence of pyridine in a manner similar to chloral .8 8.
Boeseken and Schimmel, Rec. trav. chim., 32 , 112 (1913).
The polymers could be used as sources of starting materials for further synthesis.
The aldehydes also could be polymer
ized by concentrated sulfuric acid.
However, the polymer
of difluoroacetaldehyde obtained in this manner turned black on standing, probably due to the fact that the group alpha to the carbonyl group is not perhalogenated.
chlorodifluoroacetaldehyde and fluoral readily formed solid hydrates, whereas difluoroacetaldehyde formed a liquid hydrate. Fluoral reacted with methyl magnesium iodide with subsequent hydrolysis to give 1 ,1 ,1 -trifluoro-2 -propanol^
Swart s , Bull. scjL. aoad. roy. Belg,, LsJ , 13, 175 (1927 } .
in 67% yield•
A 3 ,5 -dinitrobenzoate of 1,1,1-trifluoro-2 -
propanol was obtained.
This alcohol was also obtained by
the reduction of 1 ,1 ,1 -trifluoroacetone with lithium aluminum hydride using the general method of Nystrom and Brown. 10.
Nystrom and Brown, J. Am. Chem. Soc,, 69, 1197 (1947). Chloral, unlike acetaldehyde, has been shown to form
an addition compound^ with acetamide and urea.
ide, fluoral gave 3-aza-l,1,1-trifTuoro-4-oxo-2-pentanol. Urea and hydrated fluoral formed 3 ,5-diaza-l,l,1-trifluoro4-oxo-2-pentanol.
Chlorodifluoroacetaldehyde formed 3-aza-
1-chloro-l,1-difluoro-4-oxo-2-pentanol and 3,5-diaza-lchloro-1,1-difluoro-4-oxo-E-pentanol with acetamide and urea respectively. EXPERIMENTAL Fluoral. — Lithium aluminum hydride (28.5 g . , 0.75 mole) was dissolved in 800 ml. of anhydrous ether and the solution was cooled to 0°.
Trifluoroacetate acid (114 g.,
1.0 mole), dissolved in 200 ml. of ether, was added dropwise
in four hours.
The mixture was allowed to stir for one
hour longer at 0 ° and for one hour at room temperature. After being refluxed for 1/2 hour, the mixture was cooled to 0°.
Fifty milliliters of water was added, followed by
1100 g. of 20% sulfuric acid.
The mixture was refluxed for
four hours and then left overnight. separated and dried.
The ether layer was
The water layer was extracted continu
ously with ether for two days.
The ether extract was dried
and combined with the ether layer.
After the ether was dis
tilled, 39 g. (29% conversion) of trifluoroethanol, b.p. 73-74°, was obtained.
Trifluoroethanol was identified by
its p-nitrobenzoate ester, m.p* 47-48°. Anal. Calcd. for C 9H 5O4 NF 3 :
The material left after the distillation of the trifluoroethanol was heated with 300 g. of concentrated sulfuric acid to give 45 g. (46% conversion) of fluoral, b.p. -19 to -17°.
The odor of fluoral was similar to that
of chloral but milder and sweeter.
A sample of fluoral did
not polymerize on standing for one week at -70°. A reaction was carried out wherein 0.25 mole of lithium aluminum hydride was added to 0.5 mole of trifluoro acetic acid.
After the ether had been distilled from the
ether solution, the residue was decomposed with sulfuric acid to yield 16 g. (33% conversion) of fluoral and 20 g. of trifluoroethyl trifluoroacetate. Catalytic amounts of pyridine and sulfuric acid caused the polymerization of fluoral.
Using pyridine, the
polymerization of liquid fluoral (at -70°) to an amorphous white solid took place overnight.
Fluoral vapors polymer
ized immediately with pyridine. A sample of polymer in a small corked vial evidently hydrated to form hygroscopic white needles around the cork.
This product was soluble in water, acid to Hydrion paper, and had a melting point of 83-83° in a sealed tube.
tion occurred at 73 ° in an open tube• Fluoral 3,4 -Dinitrophenylhydrazone.— Fluoral 2,4dinitrophenylhydrazone,1 m . p . 151-152°, was prepared from fluoral polymer by the usual method.^
b.p. 105°, obtained from the reduction of trifluoroacetic acid, gave the same derivative. Anal. Calcd. for C 8H 5 O 4 N 4F 3 :
Found : 23, 3D.3.
5,3,7,7-Tetramethyl-l,9-dioxo-10-(trifluoromethyl)octahydroxanthene.— The product from the piperidine-catalyzed reaction^ of fluoral polymer and methone in absolute ethanol was treated with concentrated hydrochloric acid to yield 3,3,7,7-tetramethyl-l-9-dioxo-10-(trifluoromethyl)octahydrox anthene, m.p. 188-189°* Anal. Calcd. for CigHg^O^Fg: Found :
C , 63.2; H, 6.1.
C, 63.2; H, 6.1. 4,4,4-Trifluoro-5-hydroxybutanoic Acid.--Three grams
(0.032 mole) of malonic acid and 3.1 g . (0.032 mole) of fluoral polymer were placed in a 50 ml. flask equipped with a Dry Ice condenser and drying tube.
Two drops of pyridine
were added and the mixture was heated with an oil bath at 100° until frothing ceased.
The temperature was then
increased to 160° where it was maintained for one hour. The reaction product was crystallized from ether-benzene to give 3.5 g. of a white solid.
After several recrystalli-
zations from ether-benzene and drying in a vacuum dessicator, a melting point of 74-76° was obtained.
this to be 4,4,4-trifluoro-&-hydrôxybutanoic acid (69% yield). Anal. Calcd. for C 4 H 5 O 3F 3 : 158.
C, 30.4; H, 3.2; N.E.,
C, 30.5; H, 3.2; N.E., 157.
1,1,1-Trifluoro-2-propanol.— A Grignard reagent was prepared from 71 g. (0.5 mole) of methyl iodide.
was cooled to 0° and 39 g. (0.4 mole) of fluoral was bubbled in during two hours.
The reaction mixture was stirred for
one hour longer at 0 ° and for one hour at room temperature. The mixture was then poured unto ice and acidified with dilute hydrochloric acid.
The ether layer was separated and the
water layer was washed twice with ether. were combined and dried.
The ether solutions
Rectification gave 31 g. (67%
yield) of 1,1t1-trifluoro-2-propanol.
from concentrated sulfuric acid, these physical properties were obtained, b.p. 77.5-77.7°, n§^ 1.3168.
benzoate was prepared with a melting point of 89-90° after recrystallization from ethanol-water. Anal. Calcd. for CioHyOgNgFs:
This same alcohol was prepared by the reduction of 1,1,1-trifluoroacetone with lithium aluminum hydride.
grams of 1,1,1-trifluoroacetone was passed into 1.9 g. (0.05 mole) of lithium aluminum hydride dissolved in 200 ml. of ether at 0° during 1 1/2 hours.
The reaction was completed
according to the procedure of Nystrom and B r o w n . T w e l v e
grams (60% yield) of 1,1,1-trifluoro-2-propanol, b.p. 77.477.7°, was obtained by distillation of the crude alcohol from 10 ml. of concentrated sulfuric acid.
zoate was prepared. 5-Aza-l,1,1-trifluoro-4-oxo-2-pentanol.— One gram of fluoral polymer and 0.5 g. of acetamide were dissolved in 10 ml. of absolute alcohol and heated for three hours using
a Dry Ice-trichloroethylene-cooled condenser.
obtained after evaporation of the solvent was recrystallized several times from ether-carbon tetrachloride to give 3 -aza1,1,1-trifluoro-4-oxo-2-pentanol, m.p. 117-118.5°. Anal. Calcd. for C 4 % 0 2 N&&ir&:
5,5-Diaza-l,1,1-trifluoro-4-oxo-2-pentanol.— A sample of fluoral polymer was depolymerized by heat and bubbled into water.
The resulting water solution was ether
extracted and the ether was evaporated.
Five-tenths gram of
the resulting hydrated fluoral and 0.5 g. of urea were dissolved in 1.5 ml. of water and allowed to stand in a small test tube for four days.
A white solid was obtained
from this solution with a melting point of 146-147° after several recrystallizations from ethanol-benzene.
analyzed for the addition compound, 3,5-diaza-l,1,1-trifluoro4-oxo-2-pentanol. Anal. Calcd. for CgH^OgNaFg:
Chlorodifluoroacetaldehyde.— Lithium aluminum hydride (14.3 g . , 0.375 mole) dissolved in 400 ml. of anhydrous
ix ether was added dropwise to 65 g. (0.5 mole) of* chlorodifluoroacetic acid, dissolved in 200 ml. of ether, in three hours.
The resulting reaction mixture was stirred for one
hour longer and then refluxed for 1/2 hour.
was hydrolyzed, separated and. extracted in a manner similar to that described in the preparation of fluoral.
ether was distilled from the combined ether solutions, the higher boiling residue was decomposed by treatment with 150 g. of concentrated sulfuric acid to give 22 g. of chloro dif luoroacetaldehyde , b.p. 18.2-18.5°, collected in a Dry Ice-trichloroethylene-cooled receiver. this experiment was 39%. distilling at 86-92°.
The conversion in
Nine grams of liquid was obtained
A portion of this was extracted with
water and the water solution was ether extracted.
solution was dried and the ether was removed by rectification. The residue had a boiling point of 93-94°.
From the boiling
point, the odor, and the preparation of a p-nitrobenzoate ester, m.p. 54-55°, it was concluded that this material was crude chlorodifluoroethanol. Anal. Calcd. for C 9H 5O 4NCIFg :
Found : N, 5.3.
In other reduction experiments, the residue from the ether distillation was rectified before treatment with concentrated sulfuric acid.
A fraction distilling at 104°
was obtained from which chlorodifluoroacetaldehyde was isolated.
However, this method gave lower yields.
odor of chlorodifluoroacetaldehyde was similar to that of fluoral.
Chlorodifluoroacetaldehyde was depolymerized by catalytic amounts of pyridine.
Polymerization was also
induced by concentrated sulfuric acid.
ization of the liquid aldehyde at -70° was not noted. Chlorodifluoroacetaldehyde polymer hydrated in the same manner as that from fluoral but more slowly.
melting point was 77-78° in an open tube. Chlorodifluoroacetaldehyde 2,4-Dinitrophenylhydrazone.-• Chlorodifluoroacetaldehyde 2,4-dinitrophenylhydrazone was prepared from the polymer and the fraction boiling at 104° from the reduction.
Purification was effected by recrystalli
zation from chloroform-petroleum ether (90-100°) to give the 2,4-dinitrophenylhydrazone, m.p. 138-139°.
compound, when in an acidic alcohol-water solution, was not stable to prolonged heating. Anal. Calcd. for C 8H 5 O4 N 4 CIFg:
3,3,7,7-Tetramethyl-l,9-dioxo-10- (chlorodif luor omet hyl)octahydroxanthëne.— 3,3,7,7-Tetramethyl-l,9-dioxo-10-(chloro dif luoromethyl) octahydroxanthene , m.p. 139-140°, was prepared from chlorodifluoroacetaldehyde polymer. Anal. Calcd. for CiaHgiOgClFg: Found :
C, 60.4; H, 5.8.
C, 60.5; H, 5.4. 3-Aza-l-chloro-l,1-difluoro-4-oxo-2-pentanol.--One
gram of chlorodifluoroacetaldehyde polymer and 0.5 g. of acetamide were dissolved in 10 ml. of absolute ethanol and refluxed for three hours.
The resulting solid was recry
xi stallized several times from ether-carbon tetrachloride to give a compound which analyzed for 3-aza-l-chloro-l,1 -difluoro4-oxo-2-pentanol, m.p. 109-li0°. Anal. Calcd. for C 4H6 O 2 CIF 2 :
3 ,5 -Diaza-l-chloro-l,1 -difluoro-4-oxo-2-pentanol.—
One gram of chlorodifluoroacetaldehyde polymer and 0.5 g. of urea were used to prepare 3,5-diaza-l-chloro-1,1-difluoro4-oxo-2-pentanol, m.p. 120-121.5°.
The experiment was
carried out as that above and the product was recrystallized from ethanol-carbon tetrachloride. Anal. Calcd. for CgH^OsNgClFg:
N, 16.0. Difluoroacetaldehyde.— Fifteen grams of sodium dichromate was placed in a 500 ml. flask equipped with a dropping funnel and a water-cooled condenser followed by a bubbler and a Dry Ice-trichloroethylene-cooled receiver with drying tube.
A solution of 15 ml. of concentrated
sulfuric acid and 32 g. (0.39 mole) of difluoroethanol in 60 ml. of watei’ was added dropwise in 1 1/2 hours.
evolved but no gas evolution was noted.
After the addition,
the mixture was refluxed for 1/2 hour.
The mixture was then
continuously extracted for two days, and the ether extract was rectified.
Twenty-three grams of material distilling
from 60° to 107° was obtained.
This included 9 g. of
recovered alcohol and 7 g. of material, b.p. 105-107°. Difluoroacetaldehyde 2 ,4-dinitrophenylhydrazone was prepared
xii from the higher boiling fraction.
Although this fraction
analyzed for the difluoroethanol hemiacetal of difluoroacetal dehyde, no evidence of a hydroxyl grouping could be obtained. Anal. Calcd. for C 4 H 6O 2F 4 : Found:
C , 29.6; H, 3.7.
C, 29.8; H, 3.8. The reduction of 48 g. (0.5 mole) of difluoroacetic
acid with 14.3 g . (0.375 mole) of lithium aluminum hydride was accomplished, in the manner described for the reduction of trifluoroacetic acid.
Rectification of the ether solution
of the product gave 33 g. of material boiling above 80°. This included 5 g. of difluoroethanol, b.p. 94-95°, 11 g. of a fraction, b.p. 104-108°, and 8 g. of recovered acid, b.p. 130-135°.
The difluoroethanol was identified by the
formation of its 3,5-dinitrobenzoate, m.p. 67-68°. Anal. Calcd. for CgEgOgN^F^:
Decomposition of the fraction, b.p. 104-108°, by dropping it on phosphorus pentoxide gave 4 g. (10% conversion) of difluoroacetaldehyde, b.p. 19.8-20.7°.
Treatment of a
similar fraction with concentrated sulfuric acid in a previous experiment had
only to tar formation.
similar tothat of fluoral.
Polymerization of difluoroacetaldehyde to a white solid was induced by pyridine and concentrated sulfuric acid. With the sulfuric acid,
subsequent tarformation occurred.
The liquid aldehyde did
However, in one experiment, exothermic polymerization occurred
xiii during distillation of the aldehyde.
The formation of a
liquid hydrate was observed. Difluoroacetaldehyde 2,4-Dinitrophenylhydrazone.— Difluoroacetaldehyde 2,4 -dinitrophenylhydrazone, m.p. 156-157°, was prepared by the usual method 4 from the fraction, b.p. 105-107°, obtained by the oxidation of difluoroethanol. This same derivative was prepared from a fraction, b.p. 105106°, obtained in the reduction of difluoroacetic acid. Anal. Calcd, for CgH^O^Êi^Fg : Found :
C , 56.8; H, 2.3; N, 21.5.
C, 36.7; H, 2.3; N, 21.2. 3,3,7,7-Tetramethyl-l,9 ~d ioxo-lO ~d ifluoromethyl-
octahydroxanthene.— The piperidine-catalyzed reaction of difluoroacetaldehyde polymer and methone in absolute ethanol yielded a dimedone, m.p. 152-153°.
This product was treated
with hydrochloric acid 6 to yield 3,3,7,7-tetramethyl-l,9dioxo-10-(difluoromethyl)octahydroxanthene, m.p. 183-184°. This product was also formed from a similar sequence using the fraction, b.p. 105-106°, obtained from the reduction of difluoroacetic acid. Anal. Calcd. for CisHggOgFg: Found :
C, 66.7; H, 6 .8 .
C, 67.2; H, 6.9. Acknowledgment.--The authors express their thanks to
the Purdue Research Foundation and Mallinckrodt Chemical Works for the financial aid which made this work possible.
SüMtÆART Fluoral, chlorodifluoroacetaldehyde, and difluoro acetaldehyde have been prepared by the lithium aluminum hydride reduction of the corresponding acids.
ponding alcohols were obtained as by-products.
dinitrophenylhydrazones and substituted octahydroxanthenes have been prepared from the aldehydes.
been oxidized to a product from which the 2 ,4-dinitrophenylhydrazone of difluoroacetaldehyde was obtained.
polymerization and hydration of the aldehydes are discussed. 1,1,1-Trifluoro-2-propanol has been prepared from fluoral and méthylmagnésium iodide.
This alcohol has also
been prepared by the reduction of 1 ,1 ,1 -trifluoroacetone with lithium aluminum hydride. The preparation of 3-aza-l,1,1-trifluoromethyl-4oxo-2-pentanol, 3,5-diaza-l,1,1-trifluoromethyl-4-oxo-2pentanol, 3-aza-l-chloro-l,1-difluoro-4-oxo-2-pentanol, 3,5-diaza-l-chloro-l,l-difluoro-4-oxo-2-pentanol and 4,4,4-trifluoro-3-hydroxybutanoic acid are reported.
(Contribution from the Department of Chemistry and Purdue Research Foundation, Purdue University) THE REACTIONS OF ESTERS OF TRIFLUOROACETIC ACID WITH SODIUM 1 By E. T. McBee and J. A. Barone 1.
Contains material from Mr. Barone's doctoral thesis.
AN ABSTRACT In order to prepare 1,1,1,4,4,4-hexafluoro-3-oxo-2butanol, the ethyl and butyl esters of trifluoroacetic acid were treated with sodium.
The sodium reacted vigorously
with the esters, possibly by a free radical reaction involv ing the alpha fluorine atoms of the esters.
quent hydrolysis of the reaction mixtures, the corresponding esters of /", low yields.
^-trif luoroacetoacetic acid were obtained in The acyloin was not obtained in either case.
Butyl 7/,-)^,x-trif luoroacetoacetate was isolated from the reaction of butyl trifluoroacetate and sodium.
product formed a copper chelate and a 2,4-dinitrophenylhydrazone.
Hydrolysis of the compound with 10% sulfuric
acid yielded 1 ,1 ,1 -trifluoroacetone which was identified by conversion to its 2 ,4-dinitrophenylhydrazone. In the reaction of ethyl trifluoroacetate with sodium, ethyl >",7^>-trifluoroacetoacetate was prepared as shown by the formation of a copper chelate 2.
and also the
Henne, et al., I. Am. Chem. Soc., 69, 1819 (1947).
xv i 3-trifluoromethyl-1-(2 1 ,41-dinitrophenyl)pyrazolone by reaction with 3 ,4 -dinitrophenylhydrazine.
A water soluble,
acidic solid was also obtained which analyzed for fluoroacetoacetic acid, EXPERIMENTAL Butyl Trifluoroacetate.— Butyl trifluoroacetate, b.p. 104° (750 nun.) was prepared according to the usual g method for ethyl trifluoroacetate. 3.
Gilman and Jones,
Am. Chem. Soc., 65, 1458 (1943) .
Reaction between Sodium and Butyl Trifluoroacetate.— Twenty-three grams (1 mole) of sodium sand was prepared in xylene.
The xylene was replaced by 300 ml. of ether
(Mallinckrodt A. R.) in a one-liter, three-necked flask. The flask was equipped with a dropping funnel, a mercurysealed stirrer, and a water-cooled condenser. gen atmosphere was utilized.
A dry nitro
Eighty-six grams (0.5 mole)
of butyl trifluoroacetate was added as fast as reflux permitted.
The mixture turned yellow and then dark red.
The mixture was allowed to stand for one hour and then a cold solution of 53 ml. of 96% sulfuric acid in 85 ml. of water was added slowly with the reactor cooled in an ice bath.
After precipitation of the sodium sulfate decahydrabe,
the ether layer was separated and the residue washed with ether. sulfate.
The combined ether solutions were dried with sodium The ether was distilled and then 39 g. of butyl
xvii alcohol—ester azeotrope was obtained, b.p. 98-100°, followed by butyl alcohol.
Rectification of the residue gave 11 g.
of yellow liquid, from which 6 g. of butyl trifluoroacetoacetate, b.p. 63-65° (19-20 mm.), n§^ 1.3852, was isolated.
A black residue remained.
Qualitative tests on butyl
showed that it was soluble in 5% sodium hydroxide but insoluble in water.
It gave a white precipitate with
mercuric chloride-sodium ethoxide reagent and decolorized a dilute potassium permanganate solution and a 5% solution of bromine in carbon tetrachloride (hydrogen bromide evolved). Anal. Galcd. for C g H n O ^ g :
Two ml. of the ester was refluxed for 10 days with 30 ml. of 10% sulfuric acid.
The gas evolved was passed
into a solution of 2,4-dinitrophenylhydrazone and the solid which precipitated was filtered and recrystallized several times from alcohol-water to give an orange solid, m.p. 137.5-138.5°.
This was shown to be the 2,4-dinitro-
phenylhydrazone of 1 ,1 ,1 -trifluoroacetone by preparing an authentic sample, m.p. 138-138.5°, and by finding that no noticeable depression occurred in a mixed melting point. A 2,4-dinitrophenylhydrazone, m.p. 87-88°, was prepared from butyl >; x,>"-tr if luoroacetoacetate, Anal. Calcd. for C 14 H 15 O 5N 4 F 3 : Found:
A copper chelate was prepared by shaking one ml. of butyl •>-,'7';T^t rif luoroacetoacetate with 5 ml. of saturated copper sulfate solution.
The organic layer turned green
immediately and after standing several hours, crystalliza tion took place.
Two recrystallizations from ethanol-water
were performed and green crystals obtained.
blue on standing even in a vacuum dessioator and melted at 91-92°. Anal. Calcd. for Ci 6H 2 o0 6F 6 Cu: Found;
C, 39.4; H, 4.1.
C, 39.2; H, 4.3. Reaction of Ethyl Trifluoroacetate and Sodium.—
Seventy-one grams (0.5 mole) of ethyl trifluoroacetate, b.p. 61.5-61.7°, in fifty ml. of ether (Mall. A. R.) was added to 36 g . (1.5 mole) of sodium sand covered with 300 ml. of ether (Mall. A. R . ).
The time of addition was
five hours, after which reflux was self-sustained for fifteen minutes.
It was further refluxed for 1/2 hour
by external heating and then allowed to cool.
qualitative test for fluoride ion in the solution was positive.
About 0.75 mole of 96% sulfuric acid in 100 ml.
of water was added slowly. because sodium was present.
Extreme care was exercised After the addition, the
reaction mixture was stirred for two hours and the ether layer was separated and dried.
In addition to ethyl triflu
oroacetate and ethanol, 5 g. of ethyl ^ acetate, b.p. 60-65° (80 mm.) was obtained.
trif luoroaceto Nine
milliliters of higher boiling liquid was distilled together with 1 g. of solid.
Considerable gummy residue remained.
The solid was separated and recrystallized twice from benzene. It had a melting point of 104-105°, was soluble in ether and water, and was acid to Hydrion paper.
and the analysis indicated that it was fluoroacetoacetic acid. Anal. Calcd. for C 4 H 5 O3 F: Found:
C, 40.0; H, 4.2.
C, 39.7; H, 4.0. A copper chelate was prepared from the fraction
thought to be ethyl x, >7 7">>>>,-trifluoroacetoacetate was formed.
This was shown
by the formation of the copper chelate and the 2 ,4-dinitro phenylhydrazone and the elementary analyses of the various products.
Location of the fluorine atoms was proven by acid
hydrolysis of the ester to 1 ,1 ,1 -trifluoroacetone which was
identified by conversion to its 2,4-dinitrophenylhydrazone. In the reaction of ethyl trifluoroacetate and sodium, ethyl
7-,^,^-trifluoroacetoacetate was isolated.
identified by the formation of its copper chelate3 and also 3 -trifluoromethyl-1 -(2 1 ,4 T-dinitrophenyl)pyrazolone by
reaction with dinitrophenylhydrazine.
A small quantity of
a water soluble, acidic solid was also obtained.
evidence suggested that this was ^-fluoroacetoacetie acid. It has been suggested that the reactions were due to contamination by esters of acetic acid since the products were obtained in small yields.
Since the esters were pre
pared from sodium trifluoroacetate obtained by the oxida tions of fluorinated olefins, the presence of esters of acetic acid seemed unlikely. In view of the many free radical reactions between sodium and halogenated compounds, the initial step in the reaction which occurred may have involved a reaction between sodium and the alpha fluorines of the esters.
possible first step in the reaction may have been the forma tion of the CF3 Ç -0 free radical which would be postulated for the ordinary acyloin reaction.
Regardless of the simplicity
of the first step, the succeeding ones were probably complex. EXPERIMEMAL Preparation of Butyl Trifluoroacetate.
grams of moist sodium trifluoroacetate was added to a mixture of 338 g. of butanol and 282 g. of concentrated sulfuric acid and allowed to stand overnight.
The azeotrope of butanol,
£4 water, and butyl trifluoroacetate was distilled•
layer was separated and dried over calcium chloride *
rectified and two main fractions were obtained: A. B.
100° (748 mm.) 104° (750 mm.)
nlî*5 ng 5
Fraction A probably was an alcohol-ester azeotrope.
treated with phosphorus pentoxide until heat was no longer evolved.
This product was then rectified giving a large
fraction boiling at 104°.
A total of 196 g. of butyl trio fluoroacetate was obtained. Henne reported that butyl trifluoroacetate boils at 100 ° but he probably isolated only the azeotrope.
A quantity of crude ester was recovered by
treating the phosphorus pentoxide with ice-water. Reaction between Sodium and Butyl Trifluoroacetate. Twenty-three grams (1 mole) of sodium sand was prepared in xylene.
The xylene was replaced by 500 ml. of ether in a
one-liter, three-necked flask.
The flask was equipped with a
dropping funnel, a mercury-sealed stirrer, and a water-cooled condenser.
A dry nitrogen atmosphere was utilized.
six grams (0.5 mole) of butyl trifluoroacetate was added as fast as reflux permitted. dark red.
The mixture turned yellow and then
The mixture was allowed to stir for one hour longer
and then a cold mixture of 52 ml. of concentrated sulfuric acid in 85 ml. of water was added slowly with the reactor cooled in an ice bath.
After precipitation of sodium sulfate
decahydrate, the ether layer was separated and the residue washed with ether. with sodium sulfate.
The combined ether solutions were dried The ether was removed by distillation,
25 followed by a mixture of butyl alcohol, butyl trifluoroacetate, and water, leaving a higher boiling residue.
The water was
separated from the mixture; the organic layer was dried. Rectification gave 29 g. of material boiling from 98-100°C. (alcohol-ester azeotrope) and 7 g. of butyl alcohol.
residue obtained above was rectified at 19-20 mm. pressure to give the following: A. B. C*
58-63° 63-65° 65-80°
3 g. 6 g.
yellow liquid yellow liquid (ngu 1.3852) yellow liquid
A considerable black residue remained.
qualitative tests on A and B were obtained: Solubility— insoluble in water, insoluble in 5% sodium bicarbonate, soluble in hot 5% sodium hydroxide. Classification— with ferric chloride solution, gave a red color; with eerie nitrate, a dark red color was obtained; with mercuric chloride-sodium ethoxide reagent, a white solid precipitated.
Further, dilute potassium permanganate was
decolorized as was 5% solution of bromine in carbon tetra chloride (hydrogen bromide). Fraction B was identified as butyl aoetate.
The analyses for the compound and two derivatives
were obtained. Anal. Calcd. for Found:
0, 45.6; H, 5.2; F, 26.8.
C, 45.4; H, 6.1; F, 25.6. A 2,4-dinitrophenylhydrazone, m.p. 87-88°, was prepared. Anal. Calcd. for O 14 H 15 O 6N 4F 3 : N, 14.3.
A copper chelate was prepared by shaking one milliliter
of fraction B with 5 ml. of saturated copper sulfate solution. The organic layer turned green immediately and after standing several hours, crystallization took place.
tions from ethanol-water were performed and green crystals obtained.
These turned blue on standing even in a vacuum
dessicator and melted at 91-92°. Anal. Found;
Calcd. for Ci 6H 20 ° 6F 6Ou:
C, 59.4; H, 4.1.
C, 59.3; H, 4.5. Two milliliters of the butyl >;>> v'-trif luoroacetoacetate
was refluxed for 10 days with 50 ml. of 10% sulfuric acid. The exit gas was passed into a solution of 2,4-dinitrophenyl hydrazone and the solid which precipitated was filtered and recrystallized several times from alcohol-water to give an orange solid, m.p. 157.5-138.5°.
This was shown to be the
8,4-dinitrophenylhydrazone of 1,1,1-trifluoroacetone by preparing.an authentic sample, m.p. 138-138.5°, and by finding that no noticeable depression occurred in a mixed melting point. When the reaction was carried out using a molar ratio of sodium to ester, about one-half as much product was obtained and twice as much ester was recovered.
Although the sodium
was added in slices to the ether at reflux temperatures, the nature of the main product was not affected as shown by the formation of the copper chelate. Reaction of Ethyl Trifluoroacetate and Sodium.
one grams (0.5 mole) of ethyl trifluoroacetate (prepared by the usual method and distilled from phosphorus pentoxide) in
fifty ml* of ether was added to 36 g . (1*5 mole) of sodium sand covered with 300 ml* of ether (Mallinokrodt A. R*).
time of addition was five hours, after which reflux was selfsustained for fifteen minutes.
It was further refluxed for
1/S hour and then allowed to cool.
A qualitative test for
fluoride ion in the solution was positive.
About 0.75 mole
of 96% sulfuric acid in 100 ml. of water was added slowly. Extreme care was used because excess sodium was present.
the addition, the mixture stirred for two hours and then the ether layer, separated and dried. About 16 g. of alcohol-water-ester-azeotrope was obtained at 56-57° followed by ethyl alcohol.
was further dried and distilled at reduced pressure*
grams of ethyl x, ?■',>-trif luoroacetoaoetate, b.p. 60-65° (80 mm.) was obtained. Jïine milliliters of higher boiling liquid was also distilled together with 1 g. of solid. gummy residue remained.
The solid was separated and recry
stallized twice from benzene.
It had a m.p. of 104-105°, was
soluble in ether and water, and was acidic to Hydrion paper. A copper chelate was prepared from ethyl -k, ^ >-trifluoroacetoacetate and recrystallized from ethanol.
point was 187-189°, which is the same as that listed^ for the derivative of ethyl x, v,>-trifluoroacetoaoetate.
with 2 ,4 -dinitrophenylhydrazine gave a yellow solid with a m.p. of 104-105°.
The analysis indicated that this was
3-trif luoromethyl-1- (2*,4*- d initrophenyl )pyrazolone. Anal. Calcd. for C10 H 5 O 5 N 4F 3 :
The boiling point of the compound, the qualitative reactions (similar to those for the butyl ester) and the derivatives established the principal product as ethyl >", trifluoroacetoaoetate*
The higher boiling fractions may have
contained compounds with one or two fluorine atoms.
analysis obtained for the solid product indicated that it was a monofluorinated derivative of acetoacetic acid, probably v-fluoroacetoacetic acid. Anal. Calcd. for G 4H 5 O3 F: Found:
C, 40.0; H, 4.2.
C, 39.7; H, 4.0. SUMMARY
Sodium has been found to react with the butyl and ethyl esters of trifluoroacetlc acid to give ultimately the corres ponding esters of y,i^r-trifluoroacetoaeetic acid.
chelates of these esters and the derivatives with 2 ,4 -dinitrophenylhydrazone have been prepared.
was cleaved to 1 ,1 ,1 -trifluoroacetone which was identified by its 2 ,4-dinitrophenylhydrazone.
Blatt, A., ed., ”Organic Synthesis,” John Wiley and Sons, Inc., 1943, Vol. II, p. 114.
Henne, A., "Organic Reactions,” John Wiley and Sons, Inc., 1944, Vol. II, p. 89.
Henne, A*, et al., J. Am. Chem. S oc., 69, 1819 (1947).
McElvain, S. M . , "Organic Reactions,” John Wiley and Sons, Inc., 1948, Vol. XV, p. 250.
THE PREPARATION OP SOME POLYCHLORINATED ISOBUTANES AND IS0BUTENE8 INTRODUCTION An examination of the fluorinated compounds prepared at Purdue University and tested as anesthetics by Robbins
showed that all the compounds producing anesthesia have a hydrogen alpha to a highly negative group, usually a trifluoromethyl group.
Compounds with high molecular weights, due to
increased halogen content, often proved more effective anesthetics.
However, a relatively low boiling point was
found to be necessary for the practical application of inhalation type anesthetics.
The preparation of branched
chain compounds results in isomers with lower boiling points than the normal isomers.
Thus branching could provide for
increased molecular weights without increasing boiling points. The compound which would best satisfy the above requirements is 1 ,1 ,1,5,3,3-hexafluoro-2 -(trifluoromethy:}propane. The best intermediate for the preparation of this compound would be octachloroisobutene.
The purpose of this investiga
tion was to prepare octachloroisobutene and other highly chlorinated isobutanes and isobutenes which might be useful in the synthesis of 1,1,1,3,5,3-hexafluoro-2-trifluoromethy])propane.
A good method for obtaining octachloroisobutene
would be to prepare nonachloroisobutane and dehydrohalogenate it. DISCUSSION A survey of the published literature revealed that the
most highly chlorinated isobutane was 1 ,1 ,2 ,2 -tetrachloro-2 (chloromethyl)propane prepared by Kleinfeller ,4
work. Frost 2 and Gryting3 reported the polychlorination of t-butyl chloride and rectification of the product into three fractions.
The two higher boiling products were available.
These products were found to be hexachloroisobutene and heptaehloroisobutane.
Dehydrohalogenation of the sample of hepta-
chloroisobutane gave material with the same boiling range as the hexachloroisobutene. Isolation of one solid isomer of the five possible hexachloroisobutene isomers which might be present in the liquid product was accomplished by fractional crystallization in a methanol solution using Dry Ice as coolant. was found to add chlorine readily.
The exhaustive chlorination
of the hexachloroisobutene mixture led to the isolation of still another isomer.
Chlorination of hexachloroisobutene in
a quartz flask in the presence of ultraviolet light gave addition to form octachloroisobutane in 40% conversion and 74% yield.
Chlorination of the solid heptachloroisobutane
gave substitution in 15% conversion and 62% yield to form octachloroisobutane. Since further chlorination could not be effected by a substitution type reaction, octachloroisobutane was dehydrohalogenated to heptachloroisobutene.
In one case a crystalline
product with a sharp melting point was obtained.
chlorination of this sample gave only recovery of material with the same boiling range as the starting material.
recovered material was separated into the crystalline starting material and a liquid with the same boiling range.
possible that during the chlorination, isomerization occurred through a free radical intermediate giving a mixture of the two possible isomers of heptachloroisobutene.
It nias interest
ing to note that the chlorination of liquid heptachloroisobutene did not produce any of the crystalline isomer. Thus nonachloroisobutane was not obtained by substitution or addition.
An examination of the Fischer-Hirschfelder model
for nonachloroisobutane revealed that the molecule would be highly strained and this steric effect would make the formation of the compound difficult.
On the other hand, it would be quite
simple for an octachloroisobutyl free radical to eject a chlorine free radical and form heptachloroisobutene. An investigation was carried out simultaneously on the polychlorination of methallyl a reasonable cost.
chloride which is available at
By the use of relatively high temperatures
^ it was considered possible that octachloroisobutene would be a reaction product.
However, cleavage occurred and
octachloropropane was isolated in 85% yield.
To aid in its
identification, this product was cleaved by the method of Ghao*^ to tetrachloroethylene and carbon tetrachloride • The rectification of most of the crude product from the chlorination of methallyl chloride at a lower temperature than above gave two main fractions.
One fraction had a boiling
range similar to that of the hexachloroisobutene and the other had a range similar to that of heptachloroisobutane.
the reactions of the lower boiling liquid indicated it is a mixture of hexachloroisobutane and hexachloroisobutene with the former probably predominating.
of the compound with a boiling range near that of heptachloro isobutane gave a product with a somewhat higher boiling range than hexachloroisobutene and a higher index of refraction. This indicated that the solid product may have been a mixture of heptachloroisobutane containing some octachloroisobutane. This product has been designated as G^Cly+H#-.
product discussed above has been represented by G^ClgHx. The remainder of the crude product from the low tempera ture chlorination of the methallyl chloride was chlorinated further.
A quartz flask and a mercury vapor lamp were used
in obtaining a mixture of products containing six, seven and eight chlorine atoms with the isobutane structure being maintained. For the preparation of octachloroisobutane (and hence octachloroisobutene), it is recommended that the chlorination of methallyl chloride be first carried out in an ordinary glass chlorination tube and that the crude product be then further chlorinated in a quartz flask.
For the first chlorin
ation, initially a source of diffuse light should be used and then a fluorescent light is advisable.
For the second
chlorination, a mercury vapor lamp should be used.
should be carried out until there is no increase in density.
34 EXPSIRIMENTAL Identification of the Polychlorinated Starting Materials. The two higher boiling products from the chlorination of 1,3dichloro-2-methylbutane by Frost^ and Gryting*^ were a liquid containing 81,2% chlorine and a solid containing 84.0% chlorine. The liquid sample containing 81.2% chlorine was shown to be hexachloroisobutene (Theor. 81.0% Cl.) by the chlorine analysis and the physical properties. for hexachloroisobutene were:
These physical properties
b.p. 107-108° (10 mm.),
ng° 1.5486, dt3 1.641. Fractional crystallization of a 40 g. sample of hexa chloroisobutene from methanol using Dry Ice as coolant showed that this contained approximately 31 g. of a crystalline isomer of hexachloroisobutene, m.p. 39-40°. Anal. Calcd. for C4 H 2 CI 6 : Found:
C , 18.2; H, 0.76.
C, 17.9; H, 0.84. The methanol was evaporated from the filtrate and the
residue rectified to give about 14 g. distilling at 105-107° at 10 mm.
Both the solid and the liquid gave chlorine addition
when dissolved in carbon tetrachloride and chlorinated in a quartz flask using a mercury vapor lamp for activation. The solid containing 84% chlorine had a boiling point of 156-160° at 24 mm. and a boiling point of 131-133° at 10 mm.
It was found to have a melting point of 67-68°.
boiling point and elementary analysis indicated that it was heptachloroisobutane.
Anal. Caled. for O 4H 3 CI 7 : Found;
C, 16.0; H, 1.02; 01, 83.0.
C, 15.6; H, 1.07; Cl, 84.0. This compound was dehydrohalogenated by treatment with
potassium hydroxide in methanol to give a liquid with a boiling range of 108-109° at 10 mm.
This was hexachloroisobutene.
Anal. Calcd. for C4 H 2 CI 6 Î 0, 18.2; H, 0.76.
C, 18.3; H, 0.76. Ghlorination of Hexachloroisobutene.
A number of attempts
were made to add chlorine to hexachloroisobutene.
chlorine into a solution of hexachloroisobutene in carbon tetrachloride contained in a test tube failed to give chlorina tion.
Using no solvent, hexachloroisobutene was treated with
chlorine in a test tube illuminated by diffused light at 85± 3° for 10 hours.
Only starting material was obtained.
An attempt to use antimony pentachloride to catalyze the reaction was to no avail as expected. The need for more light activation was realized.
use of two fluorescent lights did not effect the chlorination of hexachloroisobutene contained in a test tube at 0°.
a mercury vapor light through a quartz plate into a quantity of the starting mixture contained in a 250 ml. three-neeked flask was, also, unsuccessful.
In that experiment, chlorine
was bubbled in for twenty-four hours and the material held at 0 °. A Vycor tube was found to transmit sufficient ultra violet light for chlorination to take place. experiment was performed;
About 132 g. of hexachloroisobutene was chlorinated In a Vycor tube at 0° for twenty-four hours utilizing a mercury vapor lamp.
The solution was purged and the product distilled
in a Glaisen flask to give recovery of starting material ana 18 g. of product at 141-145° at 5 - 6 miu.
of a similar fraction showed this to be octachloroisobutane. It was then decided that an investigation using quartz apparatus was justified.
Reactions were carried out at three
different temperatures which could be conveniently obtained. One hundred grams of hexachloroisobutene was chlorinated for twenty-four hours in a quartz flask equipped with a dispersion disk and an exit tube and cooled to 0° in a Dewar flask. was then purged and distilled.
Eighty-three grams was recovered
at 106-112° (10 mm.) and 13 g . of solid remained.
crystallization of this solid from methanol gave a wax-like product. Eighty-five grams of hexachloroisobutene was chlorinated as above, but the temperature was kept at 30t2°.
gave 51 g. of liquid at 106-114° (10 mm.) and 26 g. of solid at 142-146° (5-6 mm.).
This solid was found to be octachloro
isobutane . Anal. Calcd. for C^HgClg:
C, 14.4; H, 0.60.
C, 14.2; H, 0.67. Seventy-five grams of hexachloroisobutene was dissolved in 100 ml. of carbon tetrachloride.
The quartz flask was
equipped with an inlet disk, a condenser and an exit line. The solution was added and heated to the reflux temperature
of carbon tetrachloride and illuminated with a mercury vapor lamp.
After twenty-four hours, it was cooled and purged.
considerable amount of the solvent was lost during the chloroination and purging.
The remainder was vaporized and the
residue distilled in a Glaisen flask.
Only 36 g. of starting
material was recovered from 105-115° (10 mm.) and 22 g. of octachloroisobutane was obtained in the range 139-144° at 5-6 mm. The following yields and conversions were obtained: Temperature
0° 30° 76°
9 24 23
Yield 55 60 44
Since 30°, gave the best conversion and yield, it was used for the following experiment: Two hundred grams of hexachloroisobutene was placed in a 500 ml. quartz flask, a mercury vapor lamp was turned on and chlorine dispersed in at a rate of 1/2 mole/hr.
At the end
of each day, 1 ml. was withdrawn, the chlorine boiled out and the index of refraction taken.
Between the second and third
days no change in index was noted. 3 days was n§0 1.5545. mixture purged.
The index at the end of
The chlorination was stopped and the
Distillation gave 92 g. of hexachloroisobutene
and 102 g. of solid residue, with a boiling range of 141-144° at 5-6 mm.
This represents a 40% conversion and 74% yield of
octachloroisobutane. An exhaustive chlorination performed on 70 g. of the recovered material (b.p. 89-92 at 5-6 mm.) gave only 8 g . more of product.
The recovered hexachloroisobutene had an
38 index of n§° 1.5412.
Crystallization of this from methanol
solution using a Dry Ice bath gave a solid, m.p♦ 27-28°.
isomer of hexachloroisobutene apparently will not add chlorine. Preparation of Heptachloroisobutene.
Using the sample
of octachloroisobutene obtained above in 40% conversion, crystalline heptachloroisobutene was obtained.
ha loge nat ions had led to a liquid product. A solution of 101 g. (0.3 mole) of octachloroisobutane in 150 ml. of methanol was placed in a three-necked 500 ml. flask with stirrer, dropping funnel and condenser.
About 17 g.
(0.3 mole) of potassium hydroxide in 200 ml. of methanol was added dropwise in two hours.
It was then stirred for 1/2 hour
longer and the solid filtered.
The filtrate was washed with
water and the chlorinated hydrocarbon obtained was dried with calcium chloride.
Rectification gave a product whose main
fraction boiled at 129-130° at 10 ram. with the index being 20
Exothermic crystallization took place giving a
total of 46 g. of product with m.p. 45-46°. octachloroisobutane remained in the pot. Anal. Pound:
Calcd. for C4H0l7:
Eight grams of
The conversion was 51%.
0, 16.2; H, 0.34.
C, 16.3; H, 0.48. Attempted Chlorination of Heptachloroisobutene.
five grams (0.12 mole) of crystalline heptachloroisobutene was dissolved in 40 ml. of freshly distilled carbon tetrachloride and placed in a 500 ml. quartz flask, equipped with a dispersion disk and exit tube.
Chlorination at 1/12 mole/hr. for twenty-
four hours at 30-3° led only to the recovery of material in
the same range as the starting material.
Seeding it with a
crystal of starting material led to a mixture of the solid and a liquid.
From this, 3 g. of starting material was recovered.
The remaining liquid had the same boiling range as the start ing material. place.
This seemed to indicate that isomerization took
The seeding of recovered heptachloroisobutene from an
attempted chlorination of the liquid isomer did not give any crystals.
Apparently then there were two isomers, one liquid
and one solid, neither of which will add chlorine. Chlorination of Heptachloroisobutane.
Ninety grams of
heptachloroisobutane (m.p. 67-68°) was dissolved in 100 ml. of carbon tetrachloride and the solution poured into a quartz flask equipped with a dispersion disk and exit tube. A twentyfour hour chlorination at 0° was carried out.
The mixture was
purged, the solvent distilled and the solid distilled at 5-6 mm. About 71 g. of starting material was recovered at 121-126° and 13 g. of product obtained at 142-146°.
This product had the
same boiling point as that compound previously identified as octachloroisobutane and represented a 13% conversion and a 62% yield.
A similar experiment was tried at 30° but the conversion
was only 11 %. Preparation of Octachloropropane.
About 331 g. (3.67
moles) of methallyl chloride was chlorinated in a chlorination tube equipped with a condenser and cooling coils.
source of light was used for seven hours, diffuse light was used for twenty-two hours and light from fluorescent lamps was used for sixty-nine hours.
Water was circulated for
eighteen hours, no outside heat was used for twenty-six hours "f* o and then the mixture was heated at 120_5 for fifty-four hours. At that time, so much solid was present in the reactor that the reaction had to be discontinued.
The crude product weigh
ing 1002 g. was placed on drying paper in the hood until it became almost white.
This product was not dehydrohalogenated
by potassium hydroxide in methanol.
The product was purified
and found to melt at 160-161°, and boil at 262-263° (une.). The melting point of octachloropropane was listed as circa 160°.
The boiling point had been given as 268° and 257°.
The following experiment was performed to prove the presence of the compound : One hundred grams of crude product was placed in a 250 ml. stillpot and attached to a column.
The mixture was
heated to 120 ° (mantle temp.) and kept there for two hours at total reflux.
Take-off was instituted and continued for
three hours with the mantle temperature being raised in the course of the rectification.
The following fractions were
obtained : o 76-76.5 76.5-119° 119-120°
30 g . 4 g. 33 g .
carbon tetrachloride tetrachloroethylene
Ghao^ reported that 28 g. of carbon tetrachloride and 29.6 g. of tetrachloroethylene from octachloropropane were prepared in a similar experiment.
The conversion to and yield of
octachloropropane were 85%. Anal. Calcd. for C 3 C18 :
41 Chlorination of Methallyl Chloride.
About 271 g.
(3 moles) of methallyl chloride was placed in a chlorination tube with condenser and cooling coils.
For eight hours,
chlorine was dispersed in with water circulation and no extra source of light.
Then for eleven hours, water was circulated
and diffuse light used. The water circulation in the coils was stopped and the chlorination was continued for twenty-five hours longer.
Then, 2 fluorescent lamps were added and
chlorination continued for twenty-eight hours more, after which no change in color intensity of the solution was noted even though no more chlorine was added.
The chlorine was
purged, and the mixture was rectified at 10 mm.
fractions were obtained : A. B. C.
78-89° 89-90° 90-100° 100-101° 101-108 108-112° 112-117°
3.5 ml 39 ml. 18 m l . 34 ml. 44 ml. 232 ml 15 m l .
1.5131 1.5198 1.5329
After 93 g. of a solid (D) was distilled at 120-124° (5-6 mm.), a quantity of extremely viscous oil remained. Fractions A and B were presumed to be isomers of pentaohloroisobutane and were not studied further.
Fraction C had the
proper boiling range for a hexachlorinated product.
tion and dehydrochlorination indicated that this was a mixture of hexachloroisobutane and hexachloroisobutene.
it will be designated as C4 CI 5H X . Anal. Found:
Calcd. for C4 CI 5H 4 :
0, 18.0 ; H, 1.0.
C, 18.1; H, 1.5.
A similar experiment was carried out using 6 moles of methallyl chloride•
For eight hours, chlorine was dis
persed in at a rate of 1/6 mole/hr. with water circulation and no extra source of light.
Then for ten hours water was
circulated and diffuse light used.
The water circulation
was stopped and chlorination with diffuse light was contin ued
for twenty-four hours longer,
Two fluorescent lights
were added and the chlorination continued for forty-eight hours*
The rate was increased to just below that which
caused foaming and then chlorinated for another forty-eight hours before purging.
A total of 1575 g. of product was
obtained of which 1243 g. was rectified at 10 mm.
products were a liquid obtained at 109-114° (n§° 1.533) and a solid distilling at 141-144°.
Approximately 1/3 of the
product distilled below 109° at 10 mm.
The solid had a
boiling range somewhat higher than that compound identified as heptachloroisobutane.
Furthermore, on dehydrohalogena
tion the index of refraction and the boiling point of the product was higher than that of the compound identified as hexachloroisobutene.
It must be concluded, therefore, that
this is a heptachloroisobutane containing a small amount of octachloroisobutane and will be designated as
The remaining crude material (331 g.) from the above experiment was further chlorinated at 301:3 in a quartz flask for six days.
A mercury vapor lamp was used for illumination
and the chlorine rate was about 1/8 mole/hr.
43 109-112.5° 140-146° 140 —146°
(10 mm.) (10 mm.) (5—6 mm. )
39 ml. 145 g. 53 g .
0^C1^H% C^Cly^Hg. 0^.Cl^Hg
The main product of* the reaction was changed from one contain ing six chlorine atoms to one containing seven chlorine atoms. A negligible amount of material was obtained containing less than six chlorine atoms.
Moreover, a quantity of octachloro
isobutane was isolated. SUMMARY A mixture of isomers of hexachloroisobutene has been further chlorinated by the use of a quartz flask and a mercury vapor lamp to prepare octachloroisobutane.
Two solid isomers
of hexachloroisobutene have been isolated. Octachloroisobutane has been dehydrohalogenated to heptachloroisobutene.
The isolation of a crystalline isomer
of heptachloroisobutene which did not add chlorine is reported. A mixture of isomers of heptachloroisobutane has been chlorinated by the use of a quartz flask and a mercury vapor lamp to prepare octachloroisobutane. Methallyl chloride has been chlorinated to a mixture of isobutanes including those containing six, seven, and eight chlorine atoms.
Chlorination of methallyl chloride
at 120Î5 led to the formation of octachloropropane.
Chao, T. H . , Ph.D. Thesis, Purdue University (1940).
Frost, L., Research Reports, Purdue University (1947).
Gryting, H . , Research Reports, Purdue University (1947).
Kleinfeller, H . , Ber., 62, 1590 (1929).
5. Robbins, B . , J. Pharmacol., 8 6 , 197 (1946).
PART IV THE PREPARATION AND REACTIONS OF SOME POLYHALOGENATED BRANCHED ALIPHATIC COMPOUNDS INTRODUCTION The pharmacological possibilities of a compound with the three trifluoroiaethyl group alpha to a carbon containing one hydrogen was discussed in Part II.
A study of those
isobutanes containing one and two trifluoromethyl groups also seemed advisable for comparison purposes.
It was postulated
that the polyfluorinated isobutanes would have labile hydrogen atoms which might be responsible for anesthetic activity.
further study was instituted to prepare compounds that would contain the trifluoromethyl groups present in compounds which have good anesthetic properties but would not include the alpha hydrogens which may be responsible for that activity. One type of compound that would satisfy these requirements would be the fluorinated neopentanes. DISCUSSION It was found that Young-*-5 in an unpublished thesis reported the preparation of a number of the less highly fluorinated isobutanes including 2 ,3-dichloro-l, 1,1,S a pent afluoro~2-me thy Ipropane .
It was decided, therefore, not
to study the fluorination of the lower chlorinated compounds further at this time.
Young, however, had failed to fluorinate
1,1,5-trichloro-2-methylpropene which had been prepared by chlorination.
When it was found that this compound could be
readily prepared from chloretone5 by dehydration and rearrange ment , its fluorination was attempted.
However, the result "1 12
obtained applying the method used by T o l a n d ^ for the prepara tion of 1,1,1-trifluoropropane substantiated the experience of Young. It seemed best, then, to prepare the lower fluorinated compounds from an entirely new starting material.
bromine atoms were found to be more effective than chlorine atoms in increasing the anesthetic index (ratio of concentra tions necessary for anesthetic dose to fatal concentrations), the compound chosen was 1,1,B-tribromo-2-methyl-l-nitropropane. Lambert and Lowe^ had prepared 2-methyl-l-nitro-2-propanol by condensing acetone and nitromethane.
They had dehydrated
it on a small scale to 2-methyl-l-nitropropene, by acétylation followed by an elimination reaction using sodium acetate. The olefin was prepared from the alcohol in 68% yield by the application of this method.
The olefin was converted to the
desired l,l,2-tribromo-2-methyl-l-nitropropane by bromination, dehydrobromination and bromination.
The method of S u s i e ^ for
the bromination of nitroolefins was applied.
from the olefin to the crude product desired was 65%.
time involved in the first step and the amount of material which had to be handled deterred from the usefulness of the brominated compound.
Further, the results from the flammability
testing (see Part V*) indicated that a compound containing a low halogen to hydrogen ratio would be unsatisfactory as an ideal anesthetic because it would burn in oxygen.
47 to prepare isobutanes containing fewer than six fluorine atoms was therefore abandoned.
The attempts to prepare such
compounds to be discussed subsequently were made before the flammability data had been obtained. T h o m a s ^ and Gillette*** reported the fluor inat ion of 1.1-dichloro-l-nitropropane with a mixture of antimony (V) chlorofluoride and hydrogen fluoride,
that the reaction of chloropicrin and antimony pentachloride gave carbon tetrachloride.
This indicated that the nitro
groups and the chlorine atoms in such compounds could be replaced,
Gryting2 , however, found that attempts to fluorinate
1.1-dichloro-l-nitro-2-(dichloronitromethyl)-2-methylbutane with active metal halides were unsuccessful due to the decomposition of the starting material by the f luor inat ing agents* The desired starting material was prepared in a two step synthesis according to the method of Larrison^ with some modifications.
It was demonstrated that the 1,1,3,3~tetrachloro-
2.2-dimethyl-1,3-dinitropropane was decomposed to varying degrees by antimony halides.
When antimony pentachloride was
used, a 27% conversion to 1,1,l,2-etrachloro-2-methylpropane4 was obtained.
With antimony (V) chlorofluoride a compound
with the formula C 6H 2 CI 6F 2 was obtained presumably by halogenolysis followed by coupling.
Using antimony trifluoride
(with 10% antimony pentachloride), and antimony pentafluoride, the products of decomposition could not be identified. Kinney and Spliethoff6 reported that the reaction of butylmagnesium chloride and carbon tetrachloride at Dry Ice
48 temperatures produced 1,1,1-trichloropentane in 16.5% yield. The low yield was a result of the violence of the reaction which also produced olefinic by-products,
A reaction with
carbon tetrachloride and t-butylmagnesium chloride gave 1,1,1trichloro-2,2-dimethylpropane.
t-butylmagnesium chloride gave 1,l-dichloro-l-fluoro-2,2dimethylpropane in poor yield.
In each case, the reaction m s
extremely violent and olefinic by-products resulted.
difluoromethane and chlorotrifluoromethane did not react. With bromotrifluoromethane, t-butylmagnesium chloride reacted in such a manner that qualitative tests for both bromide and fluoride ions were obtained.
A trace of material
which might be 1,1,l-trifluoro-2,2-dimethylpropane was isolated. Is opropylmagnesium chloride reacted with carbon tetra chloride and trichlorofluoromethane but the dehydrohalogena tion occurring during the reaction and/or the distillation caused mixtures to be obtained.
thane and chlorotrifluoromethane failed to react. Another possibility for the preparation of branched compounds would be the coupling of trifluoromethyllithium with isopropyl bromide or t-butyl bromide.
It was thought
that the metalation of fluoroform, where the hydrogen should be made labile by the inductive effect of the trif luor ornethyl group, offered a method of synthesis.
However, a reaction
of fluoroform with butyH i t h i urn gave é-nonene.7
fluoroform was bubbled into the butyllithium, an excess of organometallic was present and the lithium compound evidently
reacted with two fluorine atoms to produce coupling and then acted, as a base to split out hydrogen fluoride. The hydrogen atoms of 1,1,1,3,3,3-hexafluoropropane were not sufficiently active to react with metallic lithium. An attempt to metalate the compound with phenyllithium was unsuccessful.
However, olefinic material was observed and the
presence of fluoride ion was noted in the reaction mixture. A metal-halogen interchange was attempted using methyl lithium and 3-bromo-l,1,1-trifluoroethane.
The only product
of the reaction when the 2-bromo-l,1,1-trifluoroethane was bubbled into the
methyllithium was a combustible olefinic gas
which boiled at Dry Ice temperatures.
This gas was probably
1,1-difluoroethane. Using aluminum chloride as condensing agent, the reaction of trichloroethylene and carbon tetrachloride carried out by PrinslO gave symmetrical heptachloropropane.
that the attack by the trichloromethyl carbonium ion was directed to the carbon containing the hydrogen atom and away from that containing the two vinyl chlorine atoms.
possible that carbon tetrachloride could be condensed with substituted propenes containing a terminal dichloromethylene group bonded to the next carbon by a double bond.
of carbon tetrachloride, aluminum chloride and 1,1-dichloropropene led only to the formation of tar-like materials. A reaction with 3,3,3-trifluoro-1,1,2-trichloropropene, aluminum chloride and carbon tetrachloride gave a quantity of hexachloropropene corresponding to the amount of aluminum
50 chloride used.
Inactive3 aluminum fluoride remained.
A similar reaction was observed with 3,3,3-trifluoro1,1-dichloropropene prepared according to the method of Truchan.^
A compound thought to be 1,1,2,3,3,3-pentachloro-
propene was obtained. EXPERIMENTAL Preparation and Attempted Fluorination of 1,1,3-Trichloro2-methylpropene.
One hundred fifty grams (0.85 mole) of
chloretone was obtained in the anhydrous state by the distilla tion of chloretone hydrate.
The chloretone was mixed with
105 g. (0.87 mole) of dimethylaniline and 180 g. (1.2 moles) of phosphorus pentoxide and heated.
Rectification of the
crude product from this reaction gave a 72% yield of 1,1,3trichloro-2-methylpropene, b.p. 54-56° (24 mm.). An autoclave was loaded with 136 g. (0.8 mole) of 1,l,3-trichloro-2-methylpropene. and cooled.
The autoclave was evacuated
Then 200 g. (10 moles) of hydrogen fluoride was
distilled into the reactor.
It was heated to 120° and this
temperature was maintained for two days. 600 lbs. was produced. bled.
A pressure of about
The autoclave was cooled to 50° and
No organic material was obtained in the traps.
reactor was cooled to room temperature and opened.
mixture remaining was poured into dilute ammonium hydroxide and black tar-like material was obtained which did not steam distil.. Preparation of 3-Methyl-l-nitro-2-propanol.
To 100 ml.
of methanol in a two-liter flask equipped with a dropping
51 funnel, ball-joint stirrer and a water-cooled condenser (with drying tube) was added 4 g. of sodium.
After the sodium had
reacted, 1 liter of acetone and 244 g. of nitromethane were added* week.
The mixture was stirred at room temperature for one The mixture was acidified with 10 N hydrochloric acid,
filtered and dried*
The filtrate was rectified to give 79 g*
of 2-methyl-1-nitro-2-propanol, b.p* 77-79° (10 mm.).
subsequent experiment using recycled acetone, a maximum yield of 111 g* (26.5% conversion) was obtained. Preparation of 2-Methyl-I-nitropropene * About 107 g. (0.9 mole) of 2-methyl-1-nitro-2-propanol (2 moles) of acetic anhydride were refluxed for six hours and then allowed to cool. The mixture was poured into ice-water, stirred, and allowed to come to room temperature. The organic layer was separated, dried over sodium sulfate and then placed in a 250 ml. distilling pot with 2 g. of anhydrous sodium acetate.
The mixture was
heated under 10 mm. pressure for one hour and then 61 g. of 2-methyl-l-nitropropene was collected at 55-62°.
was 68%. Preparation of 1,1,2-Tribromo-2-methyl-l-nitropropane. Approximately 16.7 g. (0.166 mole) of 2-methyl-l-nitropropene was mixed with 25 ml. of carbon tetrachloride and placed in a 500 ml., three-neeked flask with dropping funnel, stirrer and condenser with drying tube.
The mixture was stirred and 32 g.
(0.20 mole) of bromine in 80 ml. of carbon tetrachloride was added dropwise in two hours keeping the temperature at about 20° during the addition.
The reaction mixture was stirred at
85* 3° for one day and allowed to stand for an additional day before being purged and washed with 5% sodium carbonate solution. About 9.3 g. (0.17 mole) of potassium hydroxide dissolved in methanol was added dropwise in one hour to the solution of 1,2-dibromo-S-methyl-l-nitropropane.
The mixture was allowed
to stand for one hour and the potassium bromide was filtered and washed with methanol.
The filtrate was washed with water
and the organic layer was separated and dried. Thirty-two grams (0.20 mole) of bromine in 30 ml. of carbon tetrachloride was added dropwise to the carbon tetrachlor ide solution of l-bromo-2-methyl-l-nitropropene, keeping the solution at 85* 3°.
The solution was stirred for one day and
refluxed for one day longer.
Much of the bromine was purged
and the rest removed by a sodium carbonate treatment.
tetrachloride was distilled under reduced pressure and a crude solid amounting to 35 g. resulted.
Recrystallization of this
gave 1,1,2-tribromo-2-methyl-l-nitropropane, m.p. 198-199°. This is a conversion of 65% to the crude product from the first olefin. Anal. Found :
Calcd. for C ^ e O g N B r g :
C, 14.1; H, 1.8; N, 4.1.
C, 14.2; H, 1.9; N, 3.9. Preparation of 2,2-Dimethyl-l,5-dinitropropane.
hundred twenty-two grams (2 moles) of nitromethane, 85 g. (1 mole) of piperidine and 58 g. (1 mole) of dry acetone was prepared in a 500 ml. flask equipped with a condenser and a drying tube.
Heat was evolved and the mixture was darkened.
It was allowed to stand for one week and then poured into water
and acidified with dilute hydrochloric acid to destroy the 2.2-dimethyl-l,3 -dinitropropane-piperidine complex.
solution was extracted with ether several times and the ether solution dried with sodium sulfate.
The ether was evaporated
and the mixture was distilled in a Glaisen flask.
tion boiling at 126-131° (10 mm.) was collected, solidifying in the receiver.
It was recrystallized from ether and dried
on a porous plate, becoming water-white.
The melting point
was 93-94° and the conversion was 37%. Preparation of 1,1,3,3-Tetrachloro-2,2-dimethyl-1,3dinitropropane.
A methanol solution of 32.6 g. (0.8 mole) of
8 .2-dimethyl-1,3-dinitropropane was stirred into 59.2 g.
(0.8 mole) of calcium hydroxide suspended in 1300 ml. of water. Chlorine was bubbled into the stirred mixture until it was acid.
The reaction required about four hours at 0-5°.
mixture was purged with air and the solid was filtered. product was washed and dried,
quantitative conversions to
1,1,3,3 -tetrachloro-2 ,2-dimethyl-l,3-dinitropropane, m.p. 147-148°, were obtained. Halogenolysis of 1,1,3,3-Tetrachloro-2,2-dimethyl-l,3dinitropropane by Antimony Pentachloride.
A solution of 75 g.
(0.25 mole) of 1,1,3,3-tetrachloro-2,2-dimethyl-l,3-dinitropropane in 150 ml. of tetrachloroethylene was placed in a two-liter, three-necked flask equipped with a dropping funnel, Hershberg-type stirrer with a ball-joint seal, and a watercooled condenser with drying tube attached.
The solution was
heated to 100° and 150 g. (0.50 mole) of antimony pentachloride
54 was added dropwise during two hours.
The heating was continued
for one hour with the mantle temperature being gradually raised to 130°.
After cooling and settling, the supernatant liquid
The residue was washed with concentrated
hydrochloric acid and the organic layer combined with that decanted.
The mixture was then washed with concentrated
hydrochloric acid and steam distilled.
A small organic
residue (starting material) remained in the pot. distillate was dried and distilled.
The odor of phosgene was
noted during the steam distillation and an exhaust line from the steam still to the hood was utilized. After distillation of the tetrachloroethylene in the organic layer, a residue of 13 g. was obtained which was crystallized from ether and sublimed several times at reduced pressure.
The 1,1,1,2-tetrachloro-8 -methyl propane (27%
conversion) was obtained.
This was crystallized from methylene
chloride to give a melting point of 177-178°. Anal. Found:
Calcd. for G 4 H 3 CI 4 ;
C, 24.5; H, 3.03; Cl, 72.4.
C, 24.6; H, 3.18; 01, 71.9. The Reaction of 1,1,3,5-Tetrachloro-2,2-dimethyl-l,3-
dinitropropene with Antimony (V) Chlorofluoride. Antimony (V) chlorofluoride was prepared by the chlorination of 179 g. of antimony trifluoride (with 15 g. of antimony pentachloride). When the mixture became liquid, the reaction was stopped.
two-liter, three-necked flask was equipped with a dropping funnel, a mercury-sealed stirrer and an air-cooled condenser, followed by an ice trap, a sodium hydroxide wash bottle, a
calcium chloride drying tower and a Dry Ice-trichloroethylene cooled receiver* The mixture was cooled by an ice-water bath.
Then 75 g.
of 1,1,3,3-tetrachloro-2,2-dimethyl-l,3 -dinitropropane in 150 ml. of tetrachloroethylene was added and the mixture was allowed to come slowly to room temperature (two hours). instituted as soon as possible.
The mixture was allowed to
react at room temperature for two hours and then heated at 75° for one hour.
It was allowed to pool and settle and the
supernatant liquid was decanted.
The black residue was washed
with concentrated hydrochloric acid and the organic layer added to that decanted.
Then the mixture was washed with acid and
steam distilled. The organic distillate was separated and dried. Distillation gave recovery of the tetrachloroethylene and a white solid (7 g . ).
This had a melting point of 157-158° and
the composition C^EgClqQFg.
This was probably formed by
halogenolysis followed by coupling. Anal. Caled. for GgHgCljo^S 1 Found:
°» 15.4; H, 0.43; Cl, 76.0.
C, 15.4; H, 0.39; 01, 76.3. Reaction of 1,1,5,3-Tetraehloro-3,3-dimethyl-1,5-
dinitropropane with Antimony Trifluoride and Antimony Pentachloride.
Using apparatus similar to that above, 100 ml.
of tetrachlorethylene was added to a mixture of 179 g. (1.0 mole) of antimony trifluoride and 30 g. (0.10 mole) of antimony pentachloride.
Then 75 g. (0.35 mole) of 1,1,3,3-tetrachloro-
3,3-dimethyl-l,3 -dinitropropane dissolved in 100 ml. of tetra-
56 chlorettiylene was added slowly with no heat evolution.
mixture was heated for four hours at a mantle temperature of 135-140°.
The reaction mixture was treated as above.
distillation gave only tetrachlorethylene in the distillate. A 47% recovery of 1,1,3,3-tetraehloro-2,2-dimethyl-l,3dinitropropane was made from the residue in the stillpot. The odor of phosgene was noted as in the two previous experiments described. Reaction of 1,1,3,3-Tetrachloro-2,2-dimethyl-l,3dinitropropane with Antimony Pentafluoride.
151 g. (0.7 mole) of antimony pentafluoride was added dropwise to 105 g. (0.35 mole) of 1,1,3,3 -tetrachloro-2,2-dimethyl1,3-dinitropropane suspended in 50 ml. of perfluoromethylnapthalane .
The copper reactor used was equipped with an
inlet tube, an exit tube, and a stirrer sealed with perfluoromethylnapthalane.
An absorption "train" similar to that used
for the reaction with antimony (V) chlorofluoride followed. The reaction was kept at 0° during the addition and for two hours afterwards. temperature.
It was then allowed to warm to room
Examination of the reactor showed that only a
charred solid remained. Preparation of 1,1,l-Trichloro-2,2-dimethylpropane. One mole of t-butyl chloride was reacted with 1 mole of magnesium to form a Grignard reagent.
A one-liter, three
necked flask was equipped with a dropping funnel, a mercurysealed stirrer and a condenser followed by a bubbler and drying tube.
In a dry nitrogen atmosphere, 150 ml. of ether
was added to the flask and then 308 g. (2 moles) of carbon tetrachloride was added.
The flask was cooled in a Dry Ice-
triohloroethylene bath and the Grignard reagent dropped in over a two hour period.
The reaction mixture was kept at
-70° overnight and then allowed to come to room temperature. The mixture was poured unto cracked ice and the ether layer washed with water.
The ether layer was separated and dried♦
The low boiling components were distilled and the residue rectified to give 21 g . (12 % yield) of 1 ,1 ,l-triehloro-2 ,2 dimethylpropane, most of which distilled at 53-55° (22-23 mm.). The physical properties were nfp 1.461, d^5 1.205 and M.R., 40.0 (calcd. 39.9). Anal. Found:
Calcd. for C 5H 9CI 3 :
C, 34.1; Cl, 60.5.
C, 33.8; Cl, 61.9. Preparation of 1,1-Dichloro-l-fluoro-2,2-dimethylpropane.
About 0.75 mole of t-butylmagnesium chloride was prepared and added dropwise to 211 g. (1.5 mole) of trichlorofluormethane in ether solution at -70° during three hours.
was carried out in the same manner as the preceeding one. Rectification of the higher boiling residue gave 10 g. (5% yield) of 1 ,1 -dichloro-l-fluoro-2 ,2 -dimethylpropane most of which boiled at 108-110°. 1.1135 and n§ 5 1.4135.
The physical properties were d ^
The molar refraction calculated was
35.0 and the observed was 35.7. Anal.
Calcd. for C 5H 9 C1 2F:
Found 01, 41.8; F, 11.2.
01, 44.7; F, 11.9.
58 Attempted Réaction of t-Butylmagnesium Chloride with Dichlorodifluoromethane.
About 0.90 mole of t-butylmagnesium
chloride was prepared• Then 182 g. of dichlorodifluoromethane was forced into a one-liter, three-necked flask containing about 200 ml. of ether at -70° using nitrogen pressure on dichlorodifluoromethane also at -70°.
The Grignard reagent
was added over 3 hours but no reaction was noted.
reactor was allowed to come to room temperature, the dichloro dif luoromethane with some ether boiled out and was collected. This was then bubbled into the Grignard at room temperature but no reaction was noted. Attempted Reaction between t-ButyImagnesium Chloride and Chlorotrifluoromethane.
One mole of t-butylmagnesium
chloride was prepared. Then about 50 g. of chlorotrifluoro methane was bubbled in, but no reaction was observed. Reaction between t-Butylmagnesium Chloride and Bromotrifluoromethane.
Using 8.1 g. (0.33 mole) of magnesium
and 30.9 g. (0.33 mole) of t-butyl chloride, a Grignard reagent was prepared according to standard technique.
solution was transferred to a 500 ml., three-necked flask with an inlet tube and a Dry Ice-trichloroethylene condenser. After the first two hours and the addition of 6 g. of bromo tr if luoromethane , the reaction started as evidenced by salt formation.
In the next two hours, 24 g . more was bubbled in;
at the end of this time a test with Gilman1s reagent was negative.
From this reaction, 2 g. of material was obtained
boiling at 20-22°.
This boiling point is within the range
estimated, for 1,1,1 -tr if luoro-2,2-dimethylpropane. quantity of high boiling material remained.
on the solid which precipitated during the reaction showed the presence of both bromide and fluoride ions. Reaction between IsopropyImagnesium Chloride and Carbon Tetrachloride.
Using isopropyImagnesium chloride and carbon
tetrachloride, an experiment similar to that with t-butylmagnesium chloride was performed.
Rectification of the material
boiling above 80° gave 6 g. of product between 126-130° and a quantity of prerun.
The physical properties for that boiling
from 128-130° were n|p 1.4587 and d ^
analysis was 8.7% low, indicating that some dehydrohalogenation had taken place. Reaction between Is opropyImagne sium Chloride and Trichlorofluoromethane.
Using one mole of is opropyimagne s ium
chloride and two moles of trichlorofluoromethane, a reaction was carried out as before.
Rectification of the material
boiling above 35° gave 9 ml. of material between 67° and 110° but no plateau was obtained in the curve.
This was probably
due to some dehydrochlorination and some dehydrofluorination giving a variety of products. No reaction was observed between isopropyImagnesium chloride and dichlorodifluoromethane or between that Grignard reagent and chlorotrifluoromethane.
The experiments were
carried out in the same manner as the corresponding experiments with t-butylmagnesium chloride.
B ut yl lithi urn and Fluorof orm.
of butyllithium was prepared from butyl bromide and lithium according to standard technique in a one-liter, three-necked flask.
Then the fluoroform was allowed to bubble in after
having been dried over calcium chloride and phosphorus pentoxide. An exothermic reaction occurred for approximately 1/2 hour and then subsided. Exit gases decolorized a 5% potassium perman ganate solution.
Fluoroform was passed in for about 2 hours.
The mixture was carbonated in an ether-Dry Ice slurry. then acidified and continuously ether extracted.
of the combined ether solutions from two such experiments gave 6 g. of material boiling at 143-146°.
valeric acid was isolated.
No trifluoroacetic or
This product was insoluble in water
and decolorized a potassium permanganate solution, as well as a 5% solution of bromine in carbon tetrachloride.
properties of the main fraction were n§ 0 1.4186 and d| 6
These properties and the boiling range resembled those given by Kirrman4 for 4-nonen e .
They suggested, as did the analysis,
that the product might contain some 5 -fluorononane, which would boil at about the same temperature. Anal. Calcd. for
C, 85.7; H, 14.3.
C, 83.5; H, 14.0. It is thought that the compound was formed by the condensation of two moles of butyllithium with one mole of fluoroform, followed by dehydrohalogenation of this product. Since the gas was bubbled into the organometallic solution initially there was a sufficient excess to accomplish this.
Attempted Reaction of 1,1,1,5,3,5-Hexafluoropropane with Lithium*
Fourteen grams of 1 ,1 ,1,3,5,3-hexafluoropropane was
collected in a dry Carius tube (at -70°).
Then 15 ml. of anhydrous
ether and a lump of calcium hydride was added.
About 0.7 g.
(0.1 mole) of lithium was pounded into a sheet, cut into small triangles and dropped into the Carius tube utilizing a nitrogen stream as inert atmosphere.
About 0.5 ml. of ethyl bromide
was added to initiate the reaction.
The tube was sealed and
allowed to stand for five days with the lithium remaining substantially unchanged. two days.
The mixture was heated to 110° for
At the end of that time, the pieces of lithium had
curled but otherwise seemed intact. Reaction of 1,1,1,3,3,3-Hexafluoropropane with Phenyllithium. Forty-seven grams (0.3 mole) of bromobenzene and 4.3 g. (0.6 mole) of lithium were used to prepare 0.3 mole of phenyl lithium in ether according to standard technique.
lithium bromide was filtered and the solution was poured into a 500 ml., three-necked flask equipped with an inlet tube and a Dry Ice condenser.
Then 1,1,1,3,3,3-hexafluoropropane was
bubbled into the solution.
For a short time the reaction was
exothermic with refluxing in the condenser which was followed by a Dry Ice-trichloroethylene cooled receiver. color was noted.
A deep red
The exothermic reaction abruptly ceased but
the organic was bubbled in until 37 g. had been added.
small quantity of liquid in the trap decolorized a potassium permanganate solution. The main reaction mixture was carbonated using a
62 Dry Ice-et&er slurry. after acidification.
However, no organic acids were isolated A quantity of inorganic material was
obtained which gave a positive fluoride test (zirconium nitrate and sodium alizarin sulfonate solution) and, of course, a positive lithium flame test. Reaction of Methyjl lithium and 2-Bromo-l,1,1-trifluoroethane.
In a nitrogen atmosphere, about 28.2 g. (0.2 mole)
of methyl iodide was added to 2.8 g. (0.4 mole) of lithium according to standard technique to form methyAH ithium.
33.6 g. (0.2 mole) of 2-bromo-l,1,1-trifluoroethane was bubbled into the mixture contained in a three-necked flask equipped with an ice-water cooled condenser*
A slightly exothermic
reaction took place and a gas was produced, some of which was held by a Dry Ice-trichloroethylene cooled receiver, but most of which escaped*
The gas escaping was combustible.
the addition, a test with Gilmanfs reagent indicated the absence of an organolithimn reagent * A test for the fluoride ion was positive.
Examination of the liquid in the trap
showed it to be material boiling circa -70° and small quantity of ether.
The low boiling material, which was also
unsaturated, was probably 1 ,1 ,-difluorethene. Reaction of 1,1,2-Trichloro-5,5,3-trifluoropropane with Aluminum Chloride.
A 308 g. (2.0 moles) quantity of
carbon tetrachloride was placed in a one-liter flask and 20 g. (0.15 mole) of aluminum chloride was added.
mixture was stirred and heated to reflux and 200 g. (1 mole) of 1 ,1 ,2 -trichloro-3,3,3-trifluoropropane was added in two
63 hours and then the mixture was allowed to reflux for two hours longer.
It was cooled and poured into an ice-water mixture.
The organic layer was washed with water, separated and dried. Rectification gave starting materials and the following higher boiling material: A. B. C.
73-79 79-79.5 79.5-80.5
9 g. 10 g.
The water washings were tested for fluoride ion and found to give a positive test.
The index of refraction for
B and an authentic sample of 1,1,2,3,3,3 -hexachloropropene were taken and found to be n§^ 1.5429 and n§^ 1.5423 respectively.
These values and a converted boiling point
for B of 208° indicated that the allylic fluorines were replaced by chlorines from the aluminum chloride. Reaction of 1,1,2-Dichloro-5,3,3-trifluoropropene with Aluminum Chloride. A reaction similar to the preceding one was carried out using 123 g. (0.8 mole) of carbon tetrachloride, 8 g. of aluminum chloride and 66 g. (0.4 mole) of 1,1,3-trichloro-3,3,3-trifluoropropene.
higher boiling material was isolated: 57-58 (11-12 mm.) 58-59 (11-12 mm.)
3 g. 6 g.
In view of the preceding experiment and the physical properties of the product, this is probably 1 ,1 ,3,3,3-pentachloropropene. Attempted Brins Reaction with 1,1-Dichloropropene and Carbon Tetrachloride * Three experiments were carried out in an attempt to condense 1 ,l-diohlaropropene and carbon tetrachloride using aluminum chloride as a condensing agent to produce an
The temperature of the reactions were
76°, 40°, and 30° respectively.
The lowering of the tempera
ture led to the formation of less tar-like material and the recovery of more starting material but no condensation products were isolated.
In each case 0.5 mole of 1,1-dichloro-
propene was dropped into 1 mole of carbon tetrachloride. After the addition, the mixture was steam distilled and the organic layer separated, dried, and rectified.
and carbon tetrachloride could not be separated by rectifica tion due to the similarity in boiling points. SUMMARY 2-Methyl-l-nitropropene has been prepared in good yield from 2 -methyl-l-nitro-2 -propanol by modifying a known method.
This compound has been brominated, dehydrobrominated
and again brominated to prepare the desired l,l,2 -tribromo-2 methyl-l-nitropropane. Attempts to use exchange reactions to further halo gens te 1,1,3,3-tetrachloro-2,2-dimethyl-1,3-dinitropropane have been unsuccessful due to the instability of this compound to active metal halides. In a reaction with antimony pentachloride, 1,1,3,3tetraohloro-2 ,2 -dimethyl-l,3-dinitropropane has been converted to 1 ,1 ,1 ,2 -tetrachloro-2 -methylpropane. 1,1,l-Trichloro-2,2-dimethylpropane has been prepared by reacting the Grignard reagent of t - butyl chloride with carbon tetrachloride.
65 dimethylpropane has been prepared in a reaction with the same Grignard reagent and trichlorofluoromethane. Reactions of the above two halogenated methanes with the Grignard reagent of isopropyl chloride has given a mixture of saturated and unsaturated products in each case. :Btityllithium has been found to react with fluoroform to give 4-nonene. Lithium does not react with 1,1,1,3,3,3 -hexafluoropropane. Brins type reactions have been shown to be unsuccessful in the preparation of halogenated isobutanes.
Gillette, L., Ph.D. Thesis, Purdue University (1944).
Gryting, H . , Progress Reports, Purdue University (1947).
Henne, A., and Newman, M . ,