Patent GB-492725-A (GB)
Title: Process for the manufacture of ª‡.ª‰-unsaturated ketones of the cyclopentano-polyhydrophenanthrene series
IPC: C07J75/00
Filed: 1937-03-25
Abstract: b -g -Unsaturated ketones of the cyclopentanopolyhydrophenanthrene series of the general formula <FORM:0492725/IV/1> where X indicates O, <FORM:0492725/IV/2> , where Y is either a hydroxyl group or a group convertible into a hydroxyl group by hydrolysis, and R is any substituted or non-substituted hydrocarbon group, are converted into the corresponding a -b -unsaturated ketones by any of the following methods: (1) gently heating for a short time in acid or alkaline solution; (2) the addition of halogen hydride followed by treatment with an alkaline agent to remove it again; (3) the addition of halogen followed by treatment with a metal such as zinc to remove it again; (4) heating in the absence of a solvent to an elevated temperature; (5) warming with a finely divided metal catalyst such as nickel or platinum, or an oxide such as aluminium oxide.  The b -g -unsaturated ketones may be prepared as described in copending application 486,992.  In examples: (1) a methanol solution of D 5-cholestenone-(3) is acidified with sulphuric acid and warmed on the water bath for five minutes to give D 4-cholestenone-(3); (2) an ethanol solution of D 5-cholestenone-(3) is made alkaline with caustic soda and warmed on the water bath for five minutes to give D 4-cholestenone-(3); (3) a concentrated alcoholic solution of D 5-pregnendione is just acidified with sulphuric acid and warmed as above to give D 4-pregnendione in the form of the so called b -progesterone.  This can be converted into a -progesterone by dissolving in hot alcohol, spraying with hot water and seeding with a -progesterone; (4) pure D 5-pregnendione is heated for about eight minutes to 160 DEG  C. to yield a weak yellow coloured product, the specific rotation of which indicated the formation of some D 4-pregnendione; (5) a drop of hydrobromic acid is added to a solution of D 5-androstendione in glacial acetic acid, whereupon the product is heated for ten minutes on the water bath, sprayed with water and seeded with D 4-androstendione The bulk of the material then crystallizes in the form of D 4-androstendione; (6) an alcoholic solution of D 5-17-ethyl-androstenol-(17)-one-(3) is acidified with sulphuric acid and heated for five minutes on the water bath.  It is then sprayed with water and the product crystallized from petroleum ether to give D 4-ethyl-androstenol-(17)-one-(3); (7) a glacial acetic acid solution of D 5-cholestenone-(3) is treated with an equimolecular amount of bromine to form 5 : 6-dibromo-cholestenone-(3), which on being treated with zinc dust in methanol solution acidified with sulphuric acid yields D 4-cholestenone-(3); (8) an alcoholic solution of D 5-pregnendione acidified with sulphuric acid is allowed to stand for 10 minutes without heating.  The reaction solution is treated with water and extracted with ether to give D 4-pregnendione-(3 : 20).  A sample has been furnished under Sect. 2 (5) of testosterone acetate obtained by treating a methanol solution of D 5-androstenol-17-one-3-acetate with 5N hydrochloric acid, and then spraying the solution with water.