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FREDERICK R. JENSEN [CONTRIBUTION FROM THE
AND
LAIRDH.GALE
DEPARTMENT O F CHEMISTRY
1-01. s2
O F THE UNIVERSITY OF CALIFORNIA]
A Stereochemical Study of the Cleavage of Organomercurials by Various Brominating Agent~l-~ B Y FREDERICK R. JENSEN AND LAIRDH. GL%LE4 RECEIVED MARCH21, 1959 The cleavage by brominating agents of cis- and trans-4-methylcyclohexylmercuric bromides to yield 4-methylcyclohexy1bromide has been studied under a variety of conditions. The reaction with bromine in non-polar solvents occurs by a free ) - trans(52.6~~70-4-methplradical mechanism with both mercury compounds to give the identical mixture of c i ~ ( 4 7 . 4 7 ~and cyclohexyl bromides. Under other conditions, the reaction also occurs by a polar mechanism. The polar reaction occurs completely stereospecifically with retention of configuration. This is the first example using simple stereoisomers indicating that the steric course of electrophilic substitution of organometallic compounds is retention of configuration.
Considcrable speculation has been made concerning the stereochemical path of electrophilic aliphatic substitution. Hughes and Ingolds early postulated that S Ereactions ~ proceed with inversion while SEI reactions proceed with retention of configuration. Similarly, Dewar6 predicted that the steric course of electrophilic and nucleophilic aliphatic substitution are identical. In 1955, Winstein, Traylor and Garner’ considered that retention of configuration might be an entirely plausible and possibly general stereochemical outcome of concerted electrophilic substitution. These authors reported that mercuric chloride cleavage of cis-2-methoxycyclohexylneophylmercury proceeded with predominant retention of configuration but cautioned that the presence of a P-alkoxy1 group prevented these results from being generalized to other reagents and systems. More recently brright,s while discussing the interchangeability of the anionomercury proup by bromine or iodine, stated that it is expected that configuration is lost whenever replacement occurs a t carbon-metal linkages. These views, which represent the entire spectrum of possible stereochemical results of electrophilic aliphatic substitution, point out the need for definitive experimental evidence on this type of substitution. The lack of experimental data has arisen primarily because there have been few suitable stereoisomers available for electrophilic studies.$ A preliminary account has been reported of the results of a study of electrophilic substitution a t saturated carbon for carbanion-type reactions. lo These results indicate that carbanions may react with partial inversion or partial retention of configuration or complete racemization. N o examples have been reported for the concerted or bimolecular type of substitution using simple stereoisomers, although studies have been reported (1) Electrophilic Aliphatic Substitution I\‘, Organomercurials 11. (2) This work has been supported in part by a grant from t h e Research Corporation. (3) For a preliminary account of some of these results see F. R. Jensen and I-. H. Gale, THISJOCRIAL, 81,1261 (1959). (4) Allied Chemical and Dye Corp. Fellow, 1958-1959, ( 5 ) E. D . Hughes and C . K. Ingold, J . Chem. SOC.,2-11 (19353. (6) M. J. S. Dewar, “The Electronic Theory of Organic Chemist r y , ” Oxford University Press, Oxford, 1949, p. 81. (7) S. Winstein, T . G. Traylor and C. S. Garner, THISJOURNAL, 77, 3741 (1955). (8) G. Tz. Wrig-ht, A ? i ? t . S . Y.A c n d . Sci., 65 (Art. 5 ) , 436 (1957). (0) F. R.Jensen and I,. € I . Gale, THISJ O U R N A L , 81, 145 (1959). (IO) D . J. C r a m , J . Allinger and A. Langemann, C h e m i s t r y b I n d w t r y , ‘31’3 (1956).
using compounds which have stereochemical features which might alter the course of the reactions.” The availability of cis- and trans-4-methylcyclohexylmercuric bromidesg has now made possible a broad and definitive study of various types of electrophilic aliphatic substitution. In this paper the stereochemical results of the bromine cleavage of cis- and trans-4-methylcyclohexylmercuric bromides are reported. Some evidence indicating the stereochemical course of the halogen cleavage of organomercury compounds has been reported. Van Loon and Carter,I2in repeating the earlier work of Schrauth and Geller,13 reported that the brominolysis of a pure diastereomeric 3-acetoxy-2-bromomercuri-3phenylpropanoic acid gives a mixture of the two diastereomeric 2-bromo-3-phenylpropanoic acids. They found that the relative amounts of the two diastereomers obtained depends upon the temperature, solvent and other experimental conditions. Whitinore, Whittle and HarrimanI4 found that neopentylmercuric chloride is converted by halogen to the corresponding bromide or iodide without rearrangement. More recently, Winstein and Traylor16 have studied the iodine cleavage of 4camphylmercuric iodide. They postulated from kinetic evidence that, depending upon reaction conditions, the reaction proceeds by either a free radical or polar mechanism. Furthermore, they found that the polar reaction does not have a large preference, if any, for a mechanism which proceeds by rearward attack; 4-camphylmercuric iodide and n-butylmercuric iodide are cleaved a t about the same rate by triiodide ion. Results and Discussion The results of preliminary experiments indicated that no detectable rearrangement occurs in the cleavage of cis- and trans-4-methylcyclohexylmercuric bromides with various brominating agents. However, i t was found that the relative amounts of the cis- and trans-4-inethylcyclohexyl bromides obtained varies markedly with reaction conditions. I n order to determine the various factors influencing the isomer distribution, small samples (0.0053 mole) of the cis- and trans-mercury compounds (11) For a review of these results see ref. 9. (12) E. J. Van Loon and H. E. Carter, THISJOURNAL,69, 2555 (1937). (13) W.Schrauth and H. Geller, Ber.. 56, 2783 (192?). (14) 17. C. Whitmore, I?. L. Whittle a n d B. I98 73
100
100
100
100
18
19
KZ Air N2
7G
cis N2 46 54 0 20 Brz with ZnBrz Cis" N2 54 46 18b Pyridinium bromide perbromide cis" Air 80 20 79b 21 22 Pyridinium bromide perbromide cis" hTZ 72 28 60b 100 0 100 cis Air 23 Bromine-pyridine complex Cis" Nz 91 9 looh 24 Bromine-pyridine complex Corrected for trans isomer present in Impure cis-4-methylcyclohexylmerc~ricbromide containing 10% trans isomer. starting mercury compound. (I
disulfide as solvent in the presence of air, complete loss of retention occurs (expt. 8). These results suggest that the reaction occurs CH,- ( q - I T < B €31.. C H , O B r + HgRr2 by two pathways. One process occurs through a very reactive intermediate with loss of configuraof the cis- and trans-4-methylcyclohexyl bromides tion and is inhibited or not favored by oxygen and produced were determined by infrared analysis. traces of alcohol. It is likely that this process The results obtained by cleaving the mercury proceeds by a free radical mechanism involving compounds with bromine in a variety of solvents the 4-methylcyclohexyl radical as the reactive under an atmosphere of air or nitrogen are given in intermediate. The other pathway, which is reTable I. In non-polar solvents such as carbon ferred to here as the polar reaction, occurs a t tetrachloride and carbon disulfide, both isomers least partially stereospecifically with retention of yield the identical mixture of cis- and trans-4- configuration. These results do not indicate methylcyclohexyl bromides (expts. 1,2,3,8). Under whether the preponderance of the polar reaction in these conditions the reactions likely proceed the polar solvents is due to assistance of the through a common intermediate which allows polar reaction or inhibition of the radical reaccomplete loss of configuration. Since the product tion. distribution is 47.4 0.2% cis- and 52.6 A 0.2% I n an attempt to cleanly separate the polar trans-alkyl bromide, or nearly the statistical reaction, the cleavage was investigated using distribution, the common intermediate must be various brominating agents (Table IT). More than very reactive and have low selectivity. 90% retention is obtained with four sources of posiIn more polar solvents, or solvents containing a tiveor partially positive bromine (expts. 13,14,15,17) trace of alcohol, the reactions occur with partial under a n atmosphere of nitrogen. With pyridinretention of configuration (expts. 4,5,6,7). Under ium bromide perbromide a s the cleavage agent, the these conditions, the addition of air to the reaction reaction is more stereospecific in air than in nitrovessel results in a marked increase in the amount of gen (expts. 15,16). The bromine-pyridine complex retention (expts. 9,10,11). However, in pure carbon cleaves the mercury compound completely stereowere cleaved with different brominating agents under a variety of conditions. The relative amounts
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L
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150
FREDERICK R. JENSEN
specifically both in the presence and absence of air (expts. 17,18). Similarly, samples of cis-4-methylcyclohexylmercuric bromide were cleaved with various brominating agents (expts. 19-24). The cis isomer is more sensitive to the free radical reaction as indicated by the lesser amount of retention obtained. As with the trans compound, the cis isomer yields less retention in nitrogen than in an air atmosphere (expts. 21,22). The czs isomer is cleaved completely stereospecifically both in air and nitrogen atmospheres by the bromine-pyridine coinplex (expts. 23.24). Larger samples of the cis- and trans-mercury compounds were cleaved by the bromine-pyridine complex to yield pure samples of cis- and trans-4nicthylcyclohexyl bromides for use as infrared standards for the product distribution analyses. The trans-mercury compound yielded a product which solidified in the condenser of the distillation apparatus and was identified as trans-4-methylcyclohesyl bromide by its infrared spectrum. The spectrum contained a strong equatorial C-Br and contained no absorption a t IT04 axial C-Br absorption. Similarly, when the cis isomer was cleaved. cis-4-nicthylcyclohexyl bromide was obtained which showed strong axial C-Br absorption a t 6% ern.-' and weak equatorial C-Rr absorption shifted to 707 cm.-'. The prcsence of weak equatorial C-Br absorption is not surprising. From the known AF(a-e) values for the bromine (0.6 kcal. mole)" and methyl (l.S kcal. mole)lJ groups, it is calculated that cis-4niethylcyclohexyl bromide exists as approximately 12yoof the confoiniation where the C-Br bond is equatorial a t 2,;'. ('I I
