GB468025A - Process for the manufacture of reduction products derived from dehydroandrosterone - Google Patents

Abstract

Pure dehydroandrosterone is subjected to a process to give a saturated reduction product which comprises the replacement of the hydroxyl group at position -3 by a halogen followed by a reduction treatment, whereupon the halogen atom is reconverted into the hydroxyl group. The preferred halogenating agent is thionyl chloride, and the preferred method of reduction is a catalytic reduction using a noble metal catalyst such as platinum or palladium. The reduction may be either allowed to proceed to its full extent so that 4 atoms of hydrogen are added to one molecule of the unsaturated halogen ketone with the formation of a saturated halogen alcohol, or the reduction may be stopped when 2 atoms of hydrogen have been taken up with the formation of the corresponding saturated ketone. Additional halogenating agents are hydrochloric acid and also the agents which are mentioned in Houben-Weyl Methods of Organic Chemistry, page 1115. The replacement of the halogen by hydroxyl may be carried out by causing the halogen to react with salts of carboxylic or sulphonic acids whereupon the esters so formed are hydrolyzed. The conversion may however take place directly, or other substituents may intermediately be introduced into the reduction product, such as the amino group. In examples: (1) Thionyl chloride is added to an ether solution of dehydroandrosterone in the presence of precipitated calcium carbonate to give the corresponding unsaturated chlorketone. This is hydrogenated in alcoholic or glacial acetic acid solution in the presence of a palladium catalyst such as palladium black, palladiumbarium sulphate or palladium-calcium carbonate. The hydrogenation may be interrupted after two atoms of hydrogen per mol. of chlorketone have been taken up to yield the corresponding saturated chlorketone which can be separated by means of its semi-carbazide, or the hydrogenation can proceed until 4 atoms of hydrogen have been taken up, in which case the corresponding saturated chlor-alcohol is formed. The chlorketone thus obtained is heated with potassium acetate and the ester saponified with methyl alcoholic potash to give androsterone; (2) Dehydroandrosterone is halogenated with hydrogen chloride in methyl alcoholic solution and the product separated from any unconverted starting material by means of digitonine. The pure chlorketone so obtained is hydrogenated and converted into the free hydroxy compound as in example (1).