[CONTRIBUTION FROM NOYESCHEMICAL LABORATORY, UNIVERSITYOF ILLINOIS]
SOME REACTIONS O F 1 ,2-bis(/3-CHLOROETHYLTHIO)ETHANE1 CHARLES C. PRICES
AND
ROYSTON M. ROBERTS3
Received August 19, 1946
1,2-bis(@-Chloroethylthio)ethane (I) and the corresponding glycol, IV, were first reported by Bennett and Whincop (1). The purpose of the present investigation was to study the hydrolysis of the former and to characterize the oxidation products of both. The various transformations studied are indicated in the chart below. CHzSCHzCHzCl
HzOI
I
HOAc'
CHZSCHeCHzCI
CHzSO CHzCHz C1
I
CHZSOzCHzCH2Cl
H A
CHzSOCHzCHzCI
CH2SOzCHzCH2CI
I1
1 C7H7SO2NC1Na
I
, 1
I11
(a-Disulfoxide, m.p. 180"; 8-disulfoxide, m.p. 152')
(Disulfone, m.p. 206")
m.p. 149" CHgSCHzCHzOH
I
CH2SCHzCHzOH
HsOz
HOAo'
IV (Glycol)
(CHzSOCHzCHz0H)z
(CHzSOnCHaCH,OH)t
VI
V (Glycol a-disulf oxide, m.p. 139";
I
(Glycol disulfone, m.p. 115')
glycol 8-disulfoxide, m.p. 105') ( CHzSO CHz CHz 0C 0 CzHz)2 H,O'+ (CHzSCHzCHz0COCeHa)z H&+'
1
VI1 (Dibenzoate, m.p. 92')
VI11 (Dibenzoate a-disulfoxide, m.p. 172"; le-, m.p. 127")
I I
(CHzSOzCHzCH,OCOC,H,) IX
2
(Dibenzoate disulfone, m.p. 166")
Considerable difficulty was encountered in establishing suitable conditions for the various oxidations. For example, it was only by slow, room-temperature oxidation with hydrogen peroxide in acetic acid that it was possible to isolate crystalline sulfoxides from the glycol IV. The separation of the stereoisomeric forms of the &sulfoxides was accomplished only by extensive fractional crystallization. 1 The work reported herein was carried out under a contract, recommended by the National Defense Research Committee, between the Office of Scientific Research and Development and the University of Illinois. 2 Present address: University of Notre Dame, PIIotre Dame, Indiana. 3 Present address: University of California, Los Angeles, Calif. 255
256
C. C. PRICE A4mR . M. ROBERTS
The rate of hydrolysis of I in water could not be conveniently studied because of extreme insolubility. By extrapolation of the rate in aqueous dioxane solutions it has been estimated that the fmt-order rate constant in water a t 25" should be about 0.4 min.-'. This is four times that of p-chloroethyl sulfide, kZ5 = 0.10 min.-l [half-life a t 25", seven to eight minutes (2, 3, 4)], and about twice the value reported for P-(p'-chloroethy1thio)ethyl ether (X) by Brookfield and Moelwyn-Hughes (5). (ClCHzCHzSCHzCH2)2 (XI
0
From unpublished observations of Bergmann and Fruton ( 6 ) , it has been possible to estimate that the hydrolysis of the sulfonium salt XI, formed from I and two equivalents of thiodiglycol, is a first-order reaction, as is that for the corresponding salt, XII, from 6-chloroethyl sulfide. The half-life for XI1 is about nine days, that for XI about one and one-half dags. Furthermore, the half-life of the similar sulfonium salt (XIII) from X has an intermediate half-life of about 3.8 days (7).
S[CHZCH&( CH2 CHZ0H)z 12
[CH2SCH2 CH2;( CHzCH2 OH)2]2 c1XI
c1-
XI1 -k
0 [CH2C X 2 SCHz CHz S( CH2 CHz OH212 c1XI11 The rates thus parallel those of the corresponding chloro compounds but are about 1500 times slower. In connection with speculation concerning the mechanism of hydrolysis of p-chloroethyl sulfides (2, 3, 4), it is of interest to compare this order of reactivity for chloro compound and sulfonium salt with examples known to proceed by SN1 and by S Nmechanisms. ~ For example, the rate constant for the first-order (SN1) hydrolysis of dimethylt-butylsulfonium hydroxide has been determined by Gleaves, Hughes, and Ingold (8) to be 20.5 hrs.-1 at 100". From the data of Hughes (9) for the hydrolysis of t-butyl chloride in aqueous alcohol a t 5 to 45", we have estimated the first-order rate constant to be dependent on about the fifth power of the water concentration and the rate constant in pure water a t 100" to be about 6 X lo4 hr.-l. The ratio of klfor the chloride and the sulfonium ion would thus be about 3000 in this case. The second-order (SN~) rate constants for the reactions of ethyl chloride (10) and triethylsulfonium ion (8) with hydroxyl ion in ethanol a t 100" differ by a factor of about 200, in this case favoring the sulfonium ion. The first-order kinetics, the effect of solvent medium and the ratio of re-
REACTIONS OF 1,2-b?k(~-CHLOROETHYLTHIO)ETHANE
257
activity of chloride to sulfonium ion thus all seem t o favor an interpretation of the hydrolytic reactions of the p-chloroethyl sulfides as true “SN~” solvolytic reactions. This conclusion is further supported by the ease of conversion of p-thioalcohols to chlorides, which is accomplished readily and rapidly by treatment with concentrated hydrochloric acid with much the same ease as the conversion of t-butyl alcohol to the chloride. It thus appears that the cyclic ethylene sulfonium salt postulated as an intermediate for many reactions of 0-chloroethylsulfides (4) must be the result of the stabilization of the cation so formed but that this cyclization must not be the factor supplying the principal driving force for the reactions. RSCHZCHzCl
HpO
,
RSCHzCHz+ 1 CH,
Fd’
\
+
C1-
1
CH2
EXPERIMENTAL
Approximate solubility of I ,8-bis(~-chloroethylthio)ethane4 ( I ) in water. One gram of I was dissolved in 100 cc. of absolute ethanol by shaking at room temperature. When 1 cc. of this solution was added to 100 cc. of distilled water, solid precipitated and did not redissolve. The alcohol solution was then added dropwise to 100 cc. of water shaking after each drop was added, and it was found that the addition of five drops led t o separation of fine solid particles which floated on the surface of the water. This indicated that the solubility was below 25 mg. per liter of water. Reaction of 1 ,I-his(@-chloroethy1thio)ethane ( I ) w i t h sodium thiosulfate. The method used for the determination of the rate of hydrolysis of p-chloroethyl sulfide (4)was applied with certain modifications. A 1% solution of I in purified dioxane(l1) waa prepared. When 1 cc. of this solution was added to 25 cc. of aqueous 0.01 N thiosulfate solution, fine particles of solid separated. The experiments were therefore carried out by adding at least 10 cc. of dioxane to the thiosulfate before the addition of the solution of I;no solid precipitated under these conditions. After various intervals, 25 cc. of 0.01 N iodine in potassium iodide solution was added and the excess iodine was titrated with thiosulfate. A blank containing only dioxane and thiosulfate was always run concurrently and the small correction applied to the analytical data. Thenormality of the standard solutions was checked every few hours. The results are summarized in Figs. 1 and 2 and in Tables I and 11. .In extrapolation of the values for kl in Table I1 (see Fig. 3) indicates a value for kl i n pure water of 0.4 m h - 1 and a dependence of kl on approximately the fourth power of the water concentration. Hydrolysis of 1 ,I-bis(p-chloroethy1thio)ethane( I ) determined by use of sodium thiosulfate reaction. T o 25 cc. of distilled water and 10 cc. of dioxane in six flasks was added 1 cc. of the dioxane solution of I. After five, ten, fifteen, twenty-five, forty, and eighty minutes, 22.20 cc. of thiosulfate solution was added. Forty minutes after the thiosulfate was added t o each flask, 25.00 cc. of iodine solution was run in and the excess iodine was back-titrated with thiosulfate. On the basis of the results of the preceding experiments i t was assumed that the 1,2-bis(@-chloroethylthio)ethane which had not been hydrolyzed at the time the thiosulfate was added would react with it t o the extent of 90% within forty miniites. The results are summarized graphically in Fig. 4. 4 This vesicant and toxic material was handled with great care, using rubber gloves over polyvinyl alcohol gloves.
258
C. C. PRICE AND R.
M. ROBERTS
1 ,B-bis(8-ChEoroethylthio)ethane a- and 8-disulfoxides ( I I ) . To a solution of 30 g. (0.137 mole) of I in 150 cc. of dioxane in a beaker was added 30 cc. (0.291 mole) of 30% hydrogen peroxide, and the solution was warmed on a hot plate. When the temperature reached 75", the solution began to boil; it was removed from the hot plate but continued to boil
0
0 I
I
5
IO
I
15 20 25 T I M E IN MINUTES
30
FIG:1: Rate of Reaction of I with Thiosulfate in 32% Aqueous Dioxane
16
1.4
L 10
,
I
I
20 30 40 TiME IN MINUTES
I
I
50
60
FIG.2. Rate of Reaction of I with Thiosulfate in Aqueous Dioxane. @,43.2%dioxane;
a , 48.6% dioxane; 0,55.8% dioxane; 0 , 6 0 . 7 % dioxane. vigorously for three or four minutes, the temperature having risen to 90". As the solution cooled to about 80°, crystals began to form, and by the time room temperature was reached, the beaker contained a mass of white solid. After cooling in ice, the white crystals were collected and dried in I.'UCUO for thirty-six hours. They weighed 28 g. (81%) m.p. 147-159".
259
REACTIONS OF 1,2-b'k(@-CHLOROETHYLTHIO)ETHANE
These crystals were dissolved in 130 cc. of hot glacial acetic acid. The solution was filtered hot and cooled in ice. The white crystals which separated, when dry, melted at 174-176" and amounted t o about 13 g. The filtrate was evaporated t o dryness under a n air stream, and the 15 g. of white powdery residue had the melting point 150-156'. The higher-melting fraction was recrystallized from 1 liter of methanol; the melting point was then 175-177'. Another recrystallization from a mixture of 150 cc. of methanol and 70 cc. of glacial acetic acid gave fine shiny white crystals of a-disulfoxide melting at 176-178'. A sample of this material recrystallized from glacial acetic acid and then from methanol melted a t 179-180". The material has been referred to herein as the a-disulfozide. Anal. Calc'd for C&H12Cl?O?S2:C, 28.69;H, 4.82;S, 25.53. Found : C, 29.02;H , 5.08;S, 24.68. A 12-g.sample of the lower-melting, more soluble crude p-disulfoxide above was purified by suspending it in 200 cc. of absolute ethanol and boiling under reflux for half a n hour. TABLE I REACTIOXO F 1 ,2-biS(~-CHLOROETHYLTHIO)ETHANE (I) WITH THIOSULFATE AT ROOM TEMPERATURE ( C A . 28') I N DIOXANE % DIOXANE
2.13 1.35 1.35 1.35 0.95 .74
7.15 7.00 7.00 7.40 5.05 3.88
32.6 31.4 31.2 31.4 32.0 32.4
0.072 .lo5 .081
.OS7
.os1 .091
0.086 I ,008 TABLE I1
REACTION OF
io1 x
1110
(I) WITH THIOSULFATE AT ROOM TEMPERATURE IN AQUEOUS DIOXANE
1,2-bis@-CHLOROETHYLTHIO)ETHANE
I
108
x [~ioa-lo
1.82 1.07 1.07 1.07
6.12 5.54 4.50 4.25
1
%DIOXANE
ca. 32 43.2 48.6 55.8 60.7
0.086 .071 .032 .025 ,014
The mixture was filtered hot to remove insoluble material, and the filtrate was cooled t o 15". The precipitate which formed in the filtrate was collected and dried in vacuo; 7.6 g., m.p. 151-152". A sample of this material, referred t o as @-disulfoxide,was recrystallized for analysis from ethanol as fine microcrystals, m.p. 151-152". Anal. Calc'd for CsH&1202S2: C, 28.69; H, 4.82. Found : C, 28.57; HI 5.00. The mixture of the two isomers above was found to be very slightly soluble in ether, benzene, carbon tetrachloride, acetone, and petroleum ether (b.p. 9 0 - 1 1 0 O ) . It was more soluble in chloroform, dioxane, methanol, and ethanol and quite soluble in glacial acetic acid. The pure 8-disulfoxide was found to be appreciably more soluble in methanol, ethanol, and chloroform and much more soluble in glacial acetic acid than the a-disulfoxide. The solubility of the two isomers in dioxane was about the same.
260
C. C . PRICE AND R. M. ROBERTS
The aqueous solubility of the a-disulfoxide was found to be 0.229 g. per 100 cc. of water a t 30". The p-disulfoxide was soluble to the extent of 1.09 g. per 100 cc. of water a t 30". 1,8-bis(B-ChZoroethylthio)ethane disulfone (111). T o a suspension of 0.83 g. (0.0038 mole) of the a-disulfoxide (m.p. 174176") in 85 cc. of dioxane was added 5 cc. (0.0049 mole)
FIG.3. Variation of the Rate Conatant for the Hydrolysis of I with the Composition of the Aqueous Dioxane Solvent.
-
1
1.4 -
t
\ \
\ \
I
20
I
40
60
80
TIME IN MINUTES
FIG.4. Hydrolysis of I in 31.2% Aqueous Dioxane. 0, First Chlorine, kt Second Chlorine, kl = 3.98 X 10-3.
=
0.085;
0,
of 30% hydrogen peroxide, and the mixture was heated to gentle reflux. All the solid went into solution and the heating was continued for five hours. The cold reaction mixture was diluted with 100 cc. of water. The flocculent precipitate of white solid was collected and dried in vacuo. The yield was 0.75 g. of powdery solid melting at 203-205'. In like
REACTIONS OF
1,2-b'k(&CHLOROETHYLTHIO)ETHANE
261
manner, the 6-disulfoxide (m.p. 151-153") was converted t o disulfone, m.p. 201-203'. After two recrystallizations from methanol-acetic acid, i t melted at 205-206" (6). A n a l . Calc'd for C6HI2Cl2O1S2:C, 25.45; H, 4.27; S, 22.64. Found : C, 25.46; H, 4.47; S,22.84. A mixture of the a- and 8-disulfoxides (7.8 g., 0.031 mole) was dissolved in 50 cc. of hot glacial acetic acid and treated with 12 cc. (0.12 mole) of 30% hydrogen peroxide. The solution was heated to gentle reflux. After fifteen minutes a voluminous white precipitate appeared. The heating was maintained for an hour with occasional shaking and the mixture was allowed to cool overnight. It was then filtered and the solid was washed with 200 cc. of water and dried in a vacuum desiccator. The yield was 8.03 g. (91.5%) of white powder melting a t 204206". 1,2-bis(8-Chloroethylthio)ethane was similarly oxidized with hydrogen peroxide in acetic acid to form the disulfone in 84% yield directly. The aqueous solubility of the disulfone was only 0.008 g. per 100 cc. of water at 30". Stability of the disulfoxides (11)and disulfone (111)toward hydrolysis. A 0.1-g. sample of the a-disulfoxide was dissolved in 100 cc. of distilled water in a 250 cc. volumetric flask and more distilled water was added to the mark. A solution of 0-disulfoxide was prepared in the same way. I n 140 cc. of distilled water was placed 0.1 g. of the disulfone. The mixture was shaken for forty-eight hours and then the undissolved disulfone was collected on a filter. The filtrate was poured into a 250-cc. volumetric flask, and more distilled water was added t o the mark. These solutions were allowed to stand in the glass-stoppered flasks for a month. At intervals during this time each solution was tested for chloride ion by adding a few cubic centimeters t o a 5% silver nitrate solution. No precipitate was ever obtained. After the solutions had stood for a week, 95 cc. of the disulfone solution was poured into a 125-cc. Erlenmeyer flask and 5 g. of sodium bicarbonate was added. The mixture was stirred until all the bicarbonate dissolved. This solution was then stoppered and allowed t o stand for twenty-five days. It was frequently tested for chloride ion by acidifying a 5-cc. sample with nitric acid and adding silver nitrate solution. KO precipitate was ever obtained. Reaction of chloramine-T with 1 ,B-bis(6-chloroethy1thio)ethane( I )in dioxane. Two grama of I was dissolved in 10 cc. of dioxane and 40 cc. of a 12.5% chloramine-?'solution was added. An oily solid precipitated immediately. The oily solid was washed repeatedly with 30-cc. portions of methanol. Less than a gram of the resulting white powder was recrystallized from 650 cc. of methanol t o yield fine, lustrous crystals which melted a t 147.5149". A sample was prepared for analysis by recrystallizing a small amount of these crystals from 35 cc. of methanol. The melting point of this sample was 14&149", and the composition found corresponded to the disulfilimine derivative of I. A n a l . Calc'd for CzoH&lzPI;20rSa: C , 43.08; H, 4.70. C, 43.31; H, 4.67. Found : Treatment of 2 ,d-bis(P-hydroxyethy2thio)ethane( I V ) in acetic acid with hydrogen perozide. T o a solution of 10 g. (0.055 mole) of the glycol I V in 50 cc. of gIacial acetic acid was added with cooling 13 cc. (0.113 mole) of 27% hydrogen peroxide. The solution was allowed t o stand a t room temperature for forty-eight hours and then the solvents and excess hydrogen peroxide were removed by distillation under diminished pressure (25 mm.) . The waterbath beneath the distillation flask was not heated above 50". The residue, which crystallized upon standing, was taken up in 50 cc. of hot absolute ethanol, placed in a stoppered flask, and allowed to cool to room temperature overnight. Fine crystals separated, 5.6 g., m.p. 85-132". The filtrate from these crystals deposited more solid on standing, so it was cooled t o O", and the second crop was collected, 1.3 g. of white powder melting at 9&111", with sintering at 85". Ir'either of these crops of crystals was hygroscopic. After extensive fractional crystallization from ethanol, samples of glycol a-disulfoxide, melting a t 137-139", and of glycol p-disulfoxide, melting at 102.5-105°, were obtained.
262
C. C. PRICE AND R. M. ROBERTS
A n a l . Calc'd for CJf140&: C, 33.63; €1, 6.58. Found: (a-isomer): C, 33.94; H , 6.74. @-isomer): C , 33.71; H, 6.73. When a few crystals of mixed glycol disulfoxides (V) were added to a few cubic centimeters of concentrated hydriodic acid, a distinct reaction took place, as shown by the intense coloration of the solution by free iodine and by the heat which was produced. No precipitation of solid or oily drops occurred when the solution was diluted with water, and i t was presumed that the reaction n-hich took place was the reduction of the disulfoxide to the glycol IV. 1 ,d-bis(B-HydroxyethyEsuZfonyZ~Iethane( V I ) . T o a solution of 20 g. (0.110 mole) of the glycol IV in 100 cc. of glacial acetic acid was added portionwise with cooling 75 cc. (0.652 mole) of 27% hydrogen peroxide. The stoppered flask was allowed to stand for eighty-four hours and the solvents were removed by distillation a t 25 111111. The residue was taken up in 100 cc. of hot absolute ethanol which was filtered and cooled, to give crystals melting at 87-105". Recrystallization from dioxane raised the melting point to 96113", 15 g. This product was treated with 10 cc. of glacial acetic acid and 10 cc. of cold ether, and the mixture was stirred thoroughly while being cooled in an ice-bath. The crystals were washed repeatedly with cold ether and then dried in uacuo. The melting point after this treatment was 108-113", and recrystallization from dioxane brought i t to 112-114', sintering slightly from 102". A small sample was recrystallized from pure dry dioxane yielding crystals which melted at 112-114", sintering from 108'. A second recrystallization from the same solvent raised the melting point of the glycol disulfone (VI) t o 113.5-114.5", sintering slightly a t 110". A n d . Calc'd for CeHl,OeSp: C, 29.26; H, 5.73. Found : C, 29.39; H , 5. 70. I n contrast t o the glycol disulfoxides, which gave an intense color with hydriodic acid, the glycol disulfone gave only a very pale color. One gram of the crude disulfone was dissolved in water and treated with benzoyl chloride by the Schotten-Baumann method. The ester was recrystallized from absolute ethanol, m.p. 163-164", sintering from 156". It was identical with the dibenzoate disulfone (IX) prepared as described below. Oxidation of f ,i?-bis (P-benzoxyethyZthi0)ethaneand separation of the two dibenzoate disulfoxides produced. Fifteen grams (0.08 mole) of the glycol IV was dissolved in 30 cc. of anhydrous pyridine and 18 cc. (0.16 mole) of benzyol chloride was added. The solution was cooled until the initial reaction subsided, then warmed one or two minutes on the hot plate and poured, with stirring, into 100 cc. of water. After cooling, the precipitate was collected, then removed to a beaker and washed with 50 cc. of 5% sodium carbonate. The wash solution was removed, and the precipitate was washed on the filter with another 10 to 15 cc. of the same solution. The product was then recrystallized three times from ethanol, using Darco treatment the last time, and 15.7 g. (50.47,) of nearly white crystalline ester melting a t 90-92" was obtained. A n a l . Calc'd for C2oHppOSs: C, 61.51; H, 5.68. Found : C, 61.33; H, 5.85. Ten grams (0.026 mole) of this product was dissolved in 100 cc. of glacial acetic acid by warming and cooled to room temperature without separation of the solute. T o this solution was added with cooling 6 cc. (0.052 mole) of 27% hydrogen peroxide, and the solution was allowed to stand for forty-eight hours. The solvents were then removed by distillation under diminished pressure (25 nun.), and the solid residue was taken up in boiling ethanol, about 500 cc. being required to dissolve it completely. The alcohol solution was filtered hot and then cooled, giving 8.8 g. of crystals which melted at 128-165". The filtrate from these crystals was evaporated until only 5 cc. of liquid remained, which smelled strongly of acetic acid. This was diluted with water, and the precipitated solid was collected, Recrystallization from 20 cc. of ethanol gave needles melting a t 125.5-127". Five grams of the mixture melting a t 128-165" was fractionated by recrystallizations from ethanol-acetic
REACTIONS OF
1 ,2-biS(p-CHLOROETHYLTHIO)EWE
263
acid and ethanol. A yield of 2.25 g. of crystals melting a t 168-170”, sintering from 160” and 1.9 g. of crystals melting at 126-128’ was obtained. The higher-melting material, dibenzoate a-disulfoxide (VIII), was recrystallized for analysis from ethanol, m.p. 171-172’. Part of the crystals melting at 126-128’ were recrystallized for analysis from 20 cc. of ethanol and then melted at 126-127’ (@-isomer). ~ S56.85; Z: H, 5.25. Anal. Calc’d for C Z O H Z ~ OC, Found: (a-isomer); C, 57.04; H, 5.39. (@-isomer); C, 56.67; H, 5.28. Oxidation of dibenzoate a- and 6-disulfoxides to the same disulfone. One-half-gram (0.0012 mole) samples of the two disulfoxides above were dissolved in 10-cc. portions of glacial acetic acid and 4 cc. (0.035 mole) of 27% hydrogen peroxide was added t o each. No heat was evolved, so the solutions were heated to boiling for a few seconds and then allowed t o cool. Within thirty minutes, long, slender needles had separated from solution in both flasks. After standing overnight these crystals were collected, washed with ether, and dried in vacuo. The melting point of both products was 165-166” and the mixed melting point was the same. The melting point of a mixture of the product from the dibenzoate a-disulfoxide with the starting material was 150-157”, sintering from 140”. The product from the dibenzoate @-disulfoxide was recrystallized from glacial acetic acid, but the melting point was lowered to 163-165”, with sintering from 150”. Therefore, a procedure to avoid the possibility of transesterification was used. The ester was dissolved in hot dioxane, filtered through sintered glass, and reprecipitated by adding cold ether through the sintered filter. This gave material melting a t 164-165”, sintering at 161”. Anal, Calc’d for C ~ O H Z Z O C, ~ S 52.85; Z: H, 4.88. Found : C, 53.15; H, 5.07. SUMMARY
The two sulfoxidesand the sulfone from oxidation of 1,2-bis(p-chloroethylthio)ethane, the corresponding glycol and its dibenzoate have been prepared and characterized. From the rate of hydrolysis of the chloro compound in aqueous dioxane, it has been estimated that it hydrolyzes about four times as rapidly as 8-chloroethyl sulfide. -4comparison of the rates of hydrolysis of three p-chloroethyl sulfides with the corresponding sulfonium salts indicates a remarkable resemblance to processes of the “SN~” rather than the “SN~” type. URBANA,ILL. REFERENCES (1) BENNETTAND WHINCOP,J . Chem. SOC.,119, 1860 (1921). (2) PETERS AND WALKER,Biochem. J . , 17, 260 (1923). (3) MOHLERAND HARTNAGEL, Helv. Chim. Acta, 24, 564 (1941). (4) PRICE ANY WAKEFIELD, J . Org. Chem., 12, this issue (1947). (5) Private communication. (6) Private communication; see also STEIN,FRUTON, AND BERGMANN, J . Org. Chem., 11, 692 (1946). (7) PRICE AND POHLAND, J. Org. Chem., 12,000 (1947). (8) GLEAVES, HUGHES,AND INGOLD, J . Chem. Soc., 226 (1935). (9) HUGHES,J. Chem. SOC.,255 (1935). (10) GRANT AND HINSHELWOOD, J . Chem. SOC .,358 (1935). (11) Fieser, ‘(Experimentsin Organic Chemistry” Part 11,D. C. Heath and Co., New York, 2nd Ed., 1941, p. 369.
