Patent GB-520898-A (GB)
Title: Manufacture of cyclopentanopolyhydrophenanthrene derivatives
IPC: C07J75/00
Filed: 1938-11-03
Abstract: 520,898. Sex hormones. SOC. OF CHEMICAL INDUSTRY IN BASLE. Nov. 3, 1938, Nos. 31852 and 31853. Convention dates, March 17, and Sept. 27. [Class 2 (iii)] Cyclopentanopolyhydrophenanthrene - carboxylic acid amides are prepared by treating a free or esterified α-oxynitrile of this series with acid agents of which are mentioned hydrogen halides, sulphuric acid, phosphoric acid, acid salts, inorganic acid anhydrides or strong organic acids such as formic acid. The parent materials are obtained by the action of hydrogen cyanide on carbonyl compounds of this series preferably in slightly alkaline media and may be converted before the process of the invention into the more stable α-acyloxy- or α-halogen derivatives. Derivatives of androstane, pregnane or oestrane or their stereoisomerides are used. The nitrile group or groups may be directly attached to the nucleus or may be separated from it by one or more carbon atoms. The process may be carried out in the presence of solvents such as alcohols, ethers, chlorinated hydrocarbons, acetic acid or hydrocarbons and may be carried out at increased or reduced temperature or pressure. The amides obtained by the action of acid agents may finally be treated with alkaline agents such as the hydroxide or carbonate of an alkali or alkaline earth metals in absolute or aqueous alcohol or a metal alcoholate, to convert them to the corresponding carboxylic acid. During the process reactive groups may be changed and in particular the α-hydroxy group may be reesterified, saponified or eliminated in the form of acid or water. The treatment with acid and alkaline agents may be conducted in stages, varying conditions being used. For instance, the gentle action of an alkaline agent will hydrolyse any unchanged oxynitrile to the fundamental carbonyl compound which may then be removed by usual methods. Energetic alkaline saponification will hydrolyse an α- acetoxycarboxylic acid amide to an α-oxycarboxylic acid amide and strong alkaline conditions will convert the amide into the carboxylic acid. Powerful acid agents will eliminate water or acid giving unsaturated amides. Thus there may be obtained α-acyloxy-, α- oxy, α-halogen-, or α#unsaturated carboxylic acids or amides of steroids. In the examples (1) trans-dehydro-androsterone -cyanohydrin - diacetate in chloroform is treated with alcoholic hydrochloric acid at room temperature for two days. The product is treated with methyl alcoholic potassium hydroxide and poured into water. The precipitated flocks are extracted with alkali. A <SP>5</SP>-3-trans-17-dioxy-aetiocholenic acid containing some 17-acetate is recovered from the filtrate and #<SP>5</SP>-3-trans-17-dioxyaetiocholenic acid amide of m.p. 295-296‹ C. from the residue. The latter may be converted into the 3-mono-acetate by acetic anhydride and pyridine. (2) Trans-dehydro-androsteronecyanohydrin-diacetate is heated in a sealed tube with alcoholic hydrochloric acid in ethylene chloride for three hours at 60‹ O. The product on heating with methyl alcoholic caustic soda yields #<SP>5</SP>-3-trans-17-dioxy-aetiocholenic acid amide of m.p. 294-296‹ C. On heating this with n-propyl alcoholic caustic soda, A <SP>5</SP>-3-trans- 17-dioxy-aetiocholenic acid of m.p. 267-268‹ C. is obtained. Crude dioxy acid compounds may be purified by way of the methyl ester and its monoacetate. (3) Trans-dehydro-androsteronecyanohydrin-diacetate is allowed to stand for ten days at room temperature with alcoholic hydrochloric acid and then heated to 70‹ C. The precipitate formed after treatment with methanolic caustic soda yields # <SP>5</SP>. <SP>6</SP>:<SP>1</SP> <SP>6</SP>.<SP>17</SP>-3- trans-oxy-aetiocholacliene acid amide.