l i a y 5 , l!X8
CONVERSION OF ORG.A~-IC CHLORIDES TO ACIDS
phase extracted with ether. After drying over magnesium sulfate, the ether was removed and the residue distilled t o afford 78 g. (62%) of product boiling a t 155-160" ( 8 mm.). Anal. Calcd. for C13HI~Br:C, 62.1; H , 5.97. Found: C, 62.3; H, 5.82. 2-Methyl-4'-bromobiphenyl.-Dehydrogenation of the olefin described above was accomplished by a method developed by v. Braun, et a1.,z6for similar compounds. To a solution of 50 g. (0.2 mole) of l-methyl-2-(p-bromophenylbcyclohexene in 500 ml. of chloroform, kept a t 0", was added 32 g. (0.2 mole) of bromine dropwise. After the addition, the chloroform was distilled off and the residue heated a t a bath temperature of 170-180" and a t the full vacuum of the oil-pump. Hydrogen and hydrogen bromide were evolved and the substituted biphenyl distilled over. After washing with carbonate and drying over magnesium sulfate the oil was distilled t o give 30 g. (63%) of the desired product boiling a t 303-306' .27 Oxidation of a small quantity of this material with neutral permanganate gave a n acid which was cyclized via the acid chloride and aluminum chloride t o 2-bromofluorenone, m.p. 148-149O.27 i l n attempt a t dehydrogenating the olefin with chloranil led t o only a very low yield of the biphenyl. 2-Methyl-4'-trimethylsilylbiphenyl.-A mixture of 22 g. (0.089 mole) of 2-methyl-4'-bromobiphenyl and 10.8 g. (0.1 mole) of chlorotrimethylsilane was added dropwise t o 5 g. (0.22 g. atom) of sodium sand in 100 ml. of ether. After most of the bromide had been added, the solution began t o reflux and the sodium turned dark blue. Refluxing continued spontaneously for 40 minutes. After this, heat was applied and the mixture was refluxed for an additional 3 hours. Working up in the usual manner gave 11 g. (52%) of silane boiling a t 295', which gave a negative Beilstein test for halogen. Anal. Calcd. for CIGH&: .C, 80.0; H , 8.35; Si, 11.66. Found: C, 79.85; H , 8.71; Si, 11.50. Isolation of Cleavage Products.-A solution of 10 g. (0.044 mole) of 4-trimethylsilylbiphenyl in 150 ml. of the cleaving medium was allowed t o stand a t room temperature for a week. After pouring into an excess of water, the mixture was extracted thoroughly with ether. After drying over magnesium sulfate, the ether was removed and the residue distilled. There was obtained 2.8 g. (73%) of hexamethylethyldisiloxane, b.p. 98", X ~ D1.3776, and 4.5 g. (6673 of biphenyl, b.p. 253-256', m.p. 70". (26) J. V. Braun, G. Irmisch and J. Nelles, Be?., 66B,1471 (1933). (27) hl. Gomberg and J. Pernert, THIS JOURNAL, 48, 1372 (19261, report a b.p. of 303-305' for 2-methyl-4'-bromobiphenyl prepared by a diazo coupling method. They converted this material to 2-bromofluorenone, m.p. 149".
[CONTRIBUTION FROM
THE
-3287
Trimethyl-I-naphthylsilane was prepared by the method described by Gilman and co-workers28; b.p. 115-116' (1 mm.), %'OD 1.5806, d W 4 0.981; MRD (calcd.) 67.40, MRD (found) 67.60. Trimethyl-2-naphthylsilane was prepared from 2-iiaphthyllithium and trimethylchlorosilane; b.p. 93-9,5" (0.5 mm.), 72% 1.5613, d204 0.968; MRD (calcd.) 67.40, d i h (found) 67.08. Anal. Calcd. for C13H16Si: Si, 14.02. Found: Si, 13.63. Dimethylethylphenylsi1ane.-Over a period of 4 hours 150 ml. of anhydrous ether containing phenylmagnesium bromide (from 19.5 g. (0.8 g. atom) of magnesium and 73.5 ml. (0.7 mole) of bromobenzene) was added t o 103 g. (0.8 mole? of dimethyldichlorosilane. This mixture was heated t o reflux during this addition. The ether was then distilled off and the residue refluxed overnight. Approximately 0.9 mole of ethereal ethylmagnesium bromide was added, and the solution again was refluxed overnight. The product was hydrolyzed with water and worked up in the usual fashion. I t was distilled through a Todd continuous wire spiral column and 19 g. of a middle cut was collected for the kinetic work; b.p. 195", %*OD 1.4938, dzo, 0.878; M R D (calcd.) 54.73, MRD (found) 54.47. Thecompound was reported previously," and these constants given: nZoD 1.4928, dm, 0.877. Anal. Calcd. for CloHlaSi: C, 73.09; H , 9.28. Found: C, 73.10, 73.08; H , 9.89, 9.98. Triethylphenylsilane was prepared from ethylmagnesium bromide and phenyltrichlorosilane in the usual manner. The sample used for the kinetic studies had b.p. 73" ( 1 mm.), nZoD1.5025, d204 0.893; MRD (calcd.) 63.96, M R D (found) 63.63. The compound was reported previouslyzgwith the constants f i z o1.5024, ~ dm4 0.891. Triisopropylphenylsilane was prepared from phenyltrichlorosilane and isopropyllithium. The sample used for kinetic studies had b.p. 95" ( 4 mm.), nZoD 1.5104, dZ04 0.904. The reported30 constants were nZoD 1.51115, dZo4 0.905.
Acknowledgment.-The authors are grateful to the Ethyl Corporation and the National Science Foundation whose financial assistance made this work possible. (28) H. Gilman, R . A. Benkeser and G.E.D u m , THIS JOUIWAL, 72, 1689 (1950). (29) A. Bygden, Uppsala Dissertation, Sweden, 1916; C. A . . 14, 1974 (1920). (30) H. Gilman and R. N . Clark, THIS JOURNAL, 69, 1409 (1947).
LAFAYETTE, IND.
DEPARTMENT OF CHEMISTRY OF
THE
USIVERSITYOF W ~ s c o ~ s r s ]
The Stereochemistry of the Conversion of Organic Chlorides to Acids by Carbonation of the Grignard Reagents1 BY HARLAN L. GOERINGAND FREDH. RICCARRON~ RECEIVEDXOVEMBER 4, 1957 The stereochemistry of the conversion of (a) optically active 3,3-dimethylcyclohexyl chloride, (b) cis-( Ia) and frans-3methylcyclohexyl chloride ( I b ) and (c) cis-( I I I a ) and trans-5-metbyl-2-cyclohexenyl chloride ( I I I b ) to acids by carbonation of the Grignard reagents has been examined. Under the mildest conditions that the chlorides could be converted to the Grignard reagents (refluxing ether) no stereospecificity was observed with any of these three cyclic systems. T h e optically active system gave completely racemic acid and in the other two systems, epimers gave products having the same configurational composition. The 3-methylcyclohexanecarboxylic acid derived from the 3-methylcyclohexyl chlorides contained 26% of the trans isomer and the acid derived from the 5-methyl-2-cyclohexenyl chlorides contained 68% of the trans isomer.
There is considerable evidence that the two-step (1) This work was supported in part by the Research Committee
of the Graduate School of the University of Wisconsin with funds given by the Wisconsin Alumni Research Foundation and in part by a grant from The Upjohn Co. (2)- Shell Oil Co. Fellow 1955-1956.
conversions of alkyl halides to various products via the Grignard reagents are non-stereospecific, i.e., enantiomeric and epimeric halides give the Same product. It has been found in several cases that optically active halides in which the halogen atom
2288
H.~RI,AN L. GOERING A N D FRFDH. LICC.IRROI\'
1-01, SO
is attached to the only asymmetric center give com- the acid in this optically active cyclic system is pletely racemic product^.^ It also has been found non-stereospecific. that cholestanyl and epicholestanyl bromide are Carbonation of the Grignard Reagents Derived converted to the same acid, cholestane-3B-carbox- from cis- and trans-3-Methylcyclohexyl Chloride.ylic acid, by carbonation of the Grignard reagents. The isomeric 3-methylcyclohexyl chlorides were The loss of configuration in such processes is appar- prepared by the reaction of the isomeric 3-methylently consistent with the observation of Letsingers cyclohexanolsll with phosphorus pentachloride in that optically active 1-methylheptyllithium can be chloroform. It has been shown previously that this prepared a t -70" but racemizes rapidly when the reaction is stereospecific-optically active alcohols temperature is raised to 0". give active chloridesSand epimeric chlorides give difI n contrast to the above observations Nousseron ferent products12-and different products were inand co-workers have repeatedly claimed6 that car- deed obtained from the isomeric S-methylcyclohexabonation of the Grignard reagents derived from nols. If it is assumed that the reaction involves inthe isomeric 3-methylcyclohexyl chlorides. and bro- version of configuration, as is evidently the case in mides gives 3-methylcyclohexanecarboxylic acid other ~ y s t e m s , ' ~the , ' ~ trans-chloride I b is obtained with predominant retention of configuration. It from the cis-alcohol and the cis-chloride Ia isobtained also has been reported7 that the epimeric trans-2- from the trans-alcohol. It is noteworthy that the chlorodecalins are stereospecifically converted relative physical properties (indices of refraction to the epimeric trans-2-decanols by oxidation and densities) are consistent with this assignment of of the Grignard reagents. Because of these con- configuration.'? The infrared spectra of the two flicting reports we have carefully examined the products were significantly different. The spectrum stereochemistry of the conversion of chlorides to of the chloride derived from the cis-alcohol had characids by carbonation of the Grignard reagents in acteristic bands a t 9.01, 10.42, 12.95 and 14.68 p and three cyclic systems. The chlorides used in the the spectrum of the chloride derived from the transpresent work were (a) (-)-3,3-dimethylcyclohexyl alcohol had characteristic bands a t 7.48,11.12,10.62, chloride, (b) cis-(Ia) and trans-3-methylcyclohexyl 12.38 and 12.78 p . Slight absorption in the specchloride (Ib) and (c) cis-(IIIa) and tr~ns-~5-methyl- trum of each isomer corresponding to the strong 2-cyclohexenyl chloride (IIIb). characteristic bands in the spectrum of the other The Conversion of Optically Active 3,3-Dimethyl- indicated a slight amount of intercontamination. cyclohexyl Chloride to 3,3-Dimethylcyclohexane- When samples of the two chlorides were carefully carboxylic Acid.-Optically active 3,3-dimethyl- fractionated with an efficient all-glass column the cyclohexyl chloride, [ o I z 4 D - 2.37", was prepared spectra of the successive fractions showed only from active 3,3-dimethylcyclohexanol,[ o c ] * ~ D1.13", minor changes indicating that both isomers were by treatment with phosphorus pentachloride.* essentially homogeneous. Careful study of the The chloride was converted to the Grignard reagentg spectra indicated that the upper limits for interwhich was poured onto Dry Ice. -137% yield of contamination were 5% for the chloride derived apparently pure 3,3-dimethylcyclohexanecarboxylic from the trans-alcohol and 370 for the chloride deacid, [oI2'D -0.011 f 0.002", was isolatedfrom the rived from the cis-chloride. reaction. The product was identified by its chemThe isomeric chlorides were converted to 3ical composition and neutral equivalent and con- methylcyclohexanecarboxylic acid by carbonation version to the known10 3,3-dimethylcyclohexylcar- of the Grignard reagentsg and the products were binol by reduction with lithium aluminum hydride. isolated and purified in such a way as to avoid That the trace of activity observed in the product fractionation or isomerization (equilibration) of was not due to active 3,3-dimethylcyclohexanecar- the isomeric 3-methylcyclohexanecarboxylic acids boxylic acid was demonstrated in the following (11). The infrared spectra of the products derived manner. Reduction of (+)-3,3-dimethylcyclohex- from the isomeric chlorides were indistinguishable. anecarboxylic acid, [ Q ] * ~ D1.13', with lithium alu- Authentic &-(Ira) and trans-3-methylcyclohexminum hydride was found to give (+)-3,3-dimeth- anecarboxylic acid (1Ib)lG were prepared for comylcyclohexylcarbinol, [O!]*~D 2.07", i . e . , this con- parison purposes and the spectra for these comversion results in about a twofold increase in ro- pounds were found to differ considerably. The tation. When the same reduction was applied to pure isomeric acids were isolated and purified in the product from the Grignard reaction the result- the same way as the products from the Grignard ing 3,3-dimethylcyclohexylcarbinolwas completely reagents without isomerization. That the prodinactive. Thus the conversion of the chloride to ucts isolated from the Grignard reaction were uncontaminated binary mixtures of IIa and IIb mas (3) R. H. Pickard and J. Kenyon. J . Chem. Soc., 99, 45 (1911); shown by neutral equivalents, carbon--hydrogen C. W. Porter, THISJ O U R N A L , 57, 1436 (1935): A . M . Schwartz and J. R . Johnson, ibid., 63, 1063 (1931). analysis and infrared spectra. The infrared spec(4) G. Roberts and C . W.Shoppee, J . Chem. Soc., 3418 (1954). ( 5 ) R. L. Letsinger, THISJ O U R N A L , 73, 4842 (1950). (6) M, Mousseton and R. Jacquier, Bnll. SOL. chini, France, C80 (1951), and references cited therein. (7) A. Zlatkis and E. A. Smith, Caiz. J . C h e w , 29, 162 (19.51). (8) H. L. Goering and F. H. McCarron. THISJOURNIL, 78, 2270 (1956). (9) T h e Grignard reagents were prepared a t t h e temperature of refluxing ether. Attempts t o prepare t h e reagents at lower temperatures were unsuccessful. (10) W.E. Doering and F. M. Beringer, THISJOURNAL, 71, 2221 (1949).
(11) H. L. Goering and C. Serres, i b i d . , 74, 5908 (1952). (12) R. J. Bridgewater and C. W. Shoppee, J . C h e m . S O L . , 1709 (1953); C. W. Shoppee and G. H. R . Summers, i b i d . , 1790 (1952). (13) \V. A . Cowdrey, E. D. Hughes, C. IC. Ingold, S. RIasterman and A . D. Scott, i b i d . , 1252 (1937); W. Gerrard and R. J. Phillips, Chemistry & l i z d u s l r y , 540 (1952); E. D. Hughes, C. K. Ingold and I. C. Whitfield, N u t w e , 147, 206 (1941). (14) See 1;.L. Allinger, Enperientia, 10, 328 (1954). (15) D. S. Xoyce and R . J. Nagle, THISJ O U R N A L , 76, 127 (1953). (16) F. R . Hew@Il, P. R.Jefferies and A . K . Macbeth, J. Chem. Soc., 699 (1964).
May 5, 1958
CONVERSION OF ORGANIC CHLORIDES TO ACIDS
2289
Carbonation of the Grignard Reagents Derived from cis-(IIIa) and trans-5-Methyl-2-cyclohexenyl Chloride (IIIb).-The Grignard reagents were preparedg from pure samples of cis-(IITa) and trans-5-methyl-2-cyclohexenyl chloride (IIIh)21 using a high ratio of magnesium to allylic chloride in dilute ether solution.22 After carbonation and hydrolysis the ether solutions of the products were hydrogenated (platinum oxide) to convert the unknown isomeric 5-methyl-2-cyclohexenecarboxylic acids (IV) to the known isomeric 3-methylcyclohexanecarboxylic acids (11). In each experiment, an amount of hydrogen equivalent to the amount of allylic halide used in the reaction was absorbed. Thus the unsaturated acid as well as the coupling product was reduced completely and the configurational composition of the saturated acid I1 was the same as that of the unsaturated acid IV. The saturated acid was isolated in 15y0yield from the trans-chloCOzH COvH ride I I I b and 37oj, yield from the cis-chloride IIIa IIa, 74% IIb, 26% in such a way as to avoid fractionation of the isoThe present results clearly show that contrary to mers. A 55% .yield of the hydrogenated coupling the reports of Mousseron and co-workers,6the con- product, 3,3’-dimethylbicyclohexane,was isolated version of the isomeric 3-methylcyclohexyl chlo- from the experiment involving the trans-chloride rides (I) to 3-methylcyclohexanecarboxylic acid IIIb. (11) by carbonation of the Grignard reagent is not The configurational composition of the 3-methylstereospecific. There are several possible reasons cyclohexanecarboxylic acids was determined as defor the apparent stereospecificity observed by scribed in the preceding section. The infrared Mousseron and co-workers. Comparison of phys- spectra of the products derived from the isomeric ical properties’7 clearly shows that the chlorides chlorides were indistinguishable and corresponded used in the present work differed from those used in detail to a composite of the spectra of pure cispreviously. It has been shown1*that the acid ob- (IIa) and trans-3-methylcyclohexanecarboxylic acid tained by carbonation of the Grignard reagent de- (IIb) . Neutral equivalents and physical properties rived from the chloride prepared by the reaction as well as infrared spectra indicated the prloducts of hydrochloric acid with 3-methylcyclohexanol, were pure binary mixtures of I I a and IIb. Infrathe method used by Mousseron and co-workers to red analysis showed that the products contained prepare one of the chlorides, contains considerable 68 5% of the trans-acid. These conversions are quantities of trans-4-methylcyclohexanecarboxylic acid. Thus it seems almost certain that a t least summarized below. one of the “isomeric” acids obtained by hfousseron and co-workers was contaminated with 4-methylcyclohexanecarboxylic. acid. The analytical methodIg used to determine the configurational IIIa c1 IIIb c1 compositions of the 3-methylcyclohexanecarboxylic Lacids would not detect the presence of 4-methylcyclohexanecarboxylic acid. This method involved esterification and then fractionation of the methyl esters which are reportedlg to boil 2” apart. The refractive indices of the supposedly isomeric acids obtained by saponification of the “separated” methyl esters were nearly identical and considerably lower than that observed in the present work for the isomer (cis) with the lowest refractive index. C02H COvH As already has been suggestedz0i t appears likely IT’a (32%) IYb (68%) that the apparent stereospecificity reported for the conversion of the isomeric trans-2-chlorodecalins to the isomeric trans-2-decanols can be exH? plained by the likelihood that one of the isomeric chlorides contained 1-chlorodecalin and thus one of IIa (32%) I I b (68%) the products was largely a mixture of the isomeric The non-stereospecificity of the two-step convertrans-1-decanols. sion of 5-methyl-2-cyclohexenyl chloride (1II;i to 5 (17) M. Mousseron, R. Granger and J. Valette, Bull. sac. chifn. methyl-2-cyclohexenecarboxylic acid (IV) does not Fvance, 244 (1946). appear to be a result of isomerization (equilibration) (18) L. H. Darling, A . K , hfacbeth and J. A. Mills, J . Chem. Soc., tra were an exact composite of the spectra for I I a and I I b and showed that the product contained 26 h 5y0 of the trans-acid IIb. The results of these experiments are summarized below.
*
+
1364 (1953). (19) hl. hlousseron, Bull. sac. chim. Fyance, 605 (1947). (20) W. G. Dauben and R. C. Tweit, THIS JOURNAL, 7 6 , 3187
(1954).
(21) (a) H. L. Goering, T.D. Nevitt and E. F. Silversmith, ibid.,‘7‘7, 4042 (1955); (b) the pure samples of the isomeric 5-methyl-2-cyclohexenyl chloride were supplied by Dr. E. F. Silversmith. (22) W. G.Y o u n g and M. Eisner, THISJOURNAL, 6S, 2113 (1941).
2290
HARLAN L. GOERING ASD FREDH. AICCARRON
1'01. SO
of the reactants (111) or products (IV). trans-5- 1 4556,26p-nitrobenzoate m.p. 56.4-57.2'," acid phthalate Methyl-2-cyclohexenyl chloride (IIIb) (the most m.p. 94°),2i with phosphorus pentachloride gave 82 g. (78%) of trans-3-methylcpcloliexyl chloride, b.p. 46-49' (15 mm.), reactive isomer)21does not isomerize to a detect- and 15 g. (11%) of material, b.p. i4-77' (16 mm.), assumed able extent ( 2 7 , ) when allowed to stand a t the re- to be a mixture of isomeric 1,2-dichloro-3-methylcyclohexaction temperature for four hours (the time required anes and 1,2-dichloro-4-methylcyclohexanes.8After redisfor the reaction). As mentioned in the preceding tillation, the trans-3-methplcyclohexyl chloride had: b.p. (14 Illm.), n Z 5 D 1.4565, d z r 0.980, 11fD 36.8 section the saturated acid I1 is not isomerized or 43.8-44.0" (calcd. 37.2'1. fractionated under the conditions of the reaction A n d . Calcd. for C7H13C1: CI, 26.73. Found: C1, and there is little doubt but that IV is also stable 27.0%. under these conditions. Grignard Reactions. A. (dZ-3,3-Dimethylcyclohexyl The ultraviolet spectrum of the ether solution of Chloride).-To 2.5 g. (0.10 mole) of magnesium was added mole) of dl-3,3-dimethylthe carbonation product was examined prior to 2 ml. of a solution of 14 g. (0.093 cyclohexyl chloride in 50 ml. of anhydrous ether. Two reduction to determine if the P,y-unsaturated acid drops of methyl iodide were added and the mixture was re(IV) was isomerized to the e,B-unsaturated acid, 5 - fluxed for 10 min.; 25 ml. of anhydrous ether was added methyl-1-cyclohexenecarboxylicacid, under the after which the rest of the halide solution was added dropconditions of the reaction. If indeed such an isom- wise. The addition of the halide solution required about hour. After refluxing for 0.5 hour the Grignard reagent erization occurred both allylic halides would neces- 0.5 was carbonated by the method of Hussey.Z8 T h e resulting sarily give the same final product. From the ab- mixture was hydrolyzed with dilute hydrochloric acid. sorption a t 205 p-crotonic acid is reportedz3 to The ether layer was separated, and the aqueous layer eshave an extinction coefficient of lo4 at this wave tracted four times n i t h ether. The combined ether extracts were extracted with four 25-ml. portions of 10% solength-it was established that IV obtained by car- dium hydroxide. The basic layer was acidified (congo red) bonation contains little (
