GB790452A - Steroids and the preparation thereof - Google Patents

Abstract

A D 9(11)-steroid is obtained by contacting, under anhydrous conditions, a steroid 11-hypohalite having a hydrogen atom at each of carbon atoms 9 and 11 and wherein the halogen is chlorine, bromine or iodine, with anhydrous sulphur dioxide in the presence of a basic organic compound substantially unaffected by the hypohalite and sulphur dioxide. As basic organic compounds there may be used pyridine, picoline, lutidine, collidine, conyrine, parvuline, formamide, methylformamide and dimethylformamide. The 11-hypohalite is prepared by the reaction of an N-haloamide or N-haloimide under anhydrous conditions in the presence of a base with an 11-hydroxy steroid. As N-haloamide or N-haloimide there may be used N-chloracetamide, N-bromacetamide, N-chlorosuccimide, N-bromosuccimide, N-iodosuccinimide, N-bromophthalimide, 3-bromo-5,5-dimethyl hydantoin or 1,3-dibromo-5,5-dimethyl hydantoin. Examples describe the dehydration of hydrocortisone acetate to produce 17a -hydroxy - 21 - acetoxy - 4,9(11) - pregnadiene-3,20-dione using (1) pyridine, N-bromoacetamide and anhydrous sulphur dioxide; (2) 1,3-dibromo-5,5-dimethylhydantoin instead of N-bromoacetamide; (3) N-chloro-succimide instead of N-bromoacetamide; (4) N-iodo succinimide instead of N-bromoacetamide; (5) lutidine instead of pyridine; (6) sodium hyposulphite instead of SO2; (7) exposing the reaction to the light of a tungsten filament lamp; (8) dimethyl formamide instead of pyridine; (9) a reaction solvent comprising pyridine and acetone, ethyl acetate, ethylene dichloride, acetonitrile, benzene or nitrobenzene. Also described are the dehydration of 11a -hydroxyprogesterone, 11b -hydroxyprogesterone, 11a ,17a - dihydroxy - 21-acetoxy - 4 - pregnene - 3,20 - dione, 6b ,11a - dihydroxyprogesterone, 11a - hydroxy - 4-androstene - 3,17 - dione, 11b - hydroxy - 4-androstene - 3,7 - dione, 11b - hydroxy - 17a -acetoxy - 4 - androstene - 3 - one, 3b - acetoxy-11b - hydroxy - 5 - androstene - 17 - one, 3b -acetoxy - 11b - hydroxyandrostane - 17 - one, 11a and b - hydroxypregnane - 3,20 - dione, 3a - acetoxy - 11(a and b ) - hydroxy pregnane-20 - one, 11(a and b ), 17 - dihydroxyprogesterone, 11(a and b ), 21 - dihydroxyprogesterone, 11(a and b ) - hydroxy - 21 - acetoxyprogesterone, 2 - methyl - 11b ,17a - dihydroxy-21 - acetoxyprogesterone, 11b ,17a - dihydroxy-21 - acetoxy - 1,4 - pregnadiene - 3,20 - dione, 11a - hydroxystigmastadienone, 11a - hydroxysitostenone, 11a - hydroxyergosterol, 11a - hydroxycholestenone, 11a -hydroxybisnorcholanic acid, methyl 3 - keto - 11a - hydroxy - 4,17(20)-pregnadiene - 21 - oate and 11a - hydroxyetiocholenic acid.