2800
CLiNiwx,
CLARKE,STONNER, M A X S O N , JEXSINGS, ASD PHILLIPS
VOL.
27
Steroidal Heterocycles. V1.l Formylation of A/B-cis 3-Ket0steroids.~ Preparation of 5p- Steroidal [3,2-c]pyrazoles R. 0. CLINTON, ROBERT L. CLARKE, F.W. STOSNER, A. J. ~ I A X S O K.XF. , JEXNINGS, A N D D. K. PHILLIPS Sterlzny- Winthrop Research Institute, Rensselaer, il'ew l-orlz
Received February 21, 1966 The forniylatiori of 3-ketosteroids of the il/B-cis series has been shown to yield predominantly 2-hydroxymethylene-3keto-5p-steroids rather than 4-hydroxymethylene derivatives. The structures of the formyl derivatives were proved by their conversion t o the corresponding 5P-steroidal[3,2-c]pyrazolesand direct comparison of these with authentic samples prepared by catalytic hydrogenation of A4-steroidal [3,2-c]pyrazoles. Only in the 5p-stigmast-22-en-3-one series was evidence found for the formation of a 4-hydroxymethylene derivative as the mirlor product of formylation.
The 2-hydroxymet8hy1enc-3-ketosteroidsobtained by the condensation of A/B-trans- and A4-3-ketosteroids with ethyl formate in the presence of base have been employed extensively in recent years as intermediates in the preparation of a variety of substituted steroid^.^ On the other hand, the preparation and use of hydroxymethylene derivatives of A 'B-cis 3-ketosteroids have been reported in detail only by Tsuda and I n work concerned with the methylation of 3ketosteroid^,^^ 5p-stigmast-22-en-3-one (I) was formylated with ethyl formate and sodium methoxide in benzene, the derivative was methylated, and the formyl group then cleaved with acid. The resulting product was assigned the 4p-methyl structure I1 on the basis of its non-identity with the 2pmethyl analog 111. The latter compound was prepared, in admixture with the da-isomer, by catalytic hydrogenation of 2a-methylstigmasta-4,22-dien-3one in the presence of base. Since both methyl (1) Paper V, R . 0. Clinton, A . ,J. Manson, F. W ,Stonner, R . L. Clarke, K. F. Jennings, and P. E. Shaw, J . Org. Chem., 27, 1148 11962). (2) I'or the preliminary communication see R . 0. Clinton, R . L. Clarka, F. W. Stonner, D. K. Phillips, K. F. Jennings, and A. J . Manson, C h e m . Ind. (London), 2099 (1961). (3) E.0. (a) H . J. Ringold, E. Batres, 0. Halpern, and E. Necoechea, J . A m . Chem. Soc., 81, 427 (1959); (b) R. 0. Clinton, A . .J. Manson, F. W. Stonner, A. L. Beyler, G. 0. Potts, and A. Arnold. i b i d . , 81, 1513 (1959); ( c ) F. L. Weisenborn a n d H . E. Applegate, ibid., 81, 1960 (1959); (d) J. Edwards a n d H. J. Ringold. ibid., 81, 5262 (1959); (e) I
