RECEIVED KOVEMBER 20, 1956 For study of their seroflocculating activity, a number of 30-chloro bile acid derivatives were prepared by a new method Several new acetates, tosylates and other involving replacement of a tosylate group in pyridine with pyridinium chloride, related compounds are reported, When the synthesis of ethyl 3~-chloro-ll-cholenate (28) by the method previously described5 was attempted on a larger scale, the yield and quality of product were found to be considerably Iowered. Various other direct methods for preparing halides also proved unsatisfactory for this compound. The presence of 28 among the products of a tosyl chloride reaction in pyridine described in the preceding paper' furnished a clue for a satisfactory new method for preparing the compound.Since 28 obviously resulted from an intermediate tosylate, the commonly used reaction of a tosylate with lithium chloride in acetone (and in dioxane) was tried on the tosylate of ethyl 3a-hydroxy-11cholenate. Intractable mixtures of unsaturated and chloro compound resulted. However, by substituting pyridine and pyridine hydrochloride for the solvent-halide system, a good quality chloro product was obtained in 51%. yield. The yield is only moderate, and the superiority of the method lies in the purity of the product, which is very little contaminated by dienic impurity. A mixture of chloro compound containing more than traces of diene is separated only with much difficulty; the inferior products obtained in other halogenation methods are such mixtures. The reaction temperature is an important factor, as previous studies on replacement reactions would suggest,e and a t elevated temperatures undesirable mixtures of chloro and dienic compounds are obtained. At temperatures between 78 and 90' the substitution reaction proceeds a t a satisfactory rate, with little competition from the elimination reaction.Methyl 3P-chlorocholanate, methyl and ethyl 3/?-chloro-ll-cholenate, methyl 3P-chloro-9( 11)cholenate and methyl 3~-chloro-12a-hydroxycholanate have all been prepared by this method, which m7e are studying further with the view of its use as a general method of preparing halides.'(1) Paper I 1 of this series, THIS JOURNAL, 79, 2161 (1957).(2) This investigation was supported in p a r t by grants (CS-9053 and C-2249) from t h e .4rk. (-1) Numbered according t o t h e consecutive order in which t h e compounds are described in t h e Experimental sections of this (111) and t h e accompanying papei ( I V ) . ( 5 ) Paper I of this series, T H I S J O U R N A L , 76, 3213 (1954).(6) E. D. Hughes and C. K. Ingold, T Y~P I S . Favaday soc., 37, 657 (1941). (7) Organic halides have been obtained often as a result of reaction between alcohols and tosyl (and mesyl) chlorides in pyridine [e.g., C. R. Noller, C . A. Luchetti, E. M. Acton a n d R. A. Bernhard, THIS J O U R N A L , 75, 3831 (19.5311, b u t t h e use of pyridine base and pyridinium halide on a tosylate appears to be novel. F. Drahowzal and D.For the preparation of ethyl 3,f3-chloro-9(11)cholenate...
