Patent GB-517276-A (GB)
Title: Manufacture of ª‡-dicarbonyl compounds of the cyclopentanopolyhydrophenanthrene serie
IPC: C07J75/00
Filed: 1938-07-12
Abstract: 517,276. Cyclopentanophenanthrene diketones. SOC. OF CHEMICAL INDUSTRY IN BASLE. July 12, 1938, Nos. 20642 and 20643. Convention dates, July 13, 1937, and June 1, 1938. [Class 2 (iii)] Alpha-dicarbonyl compounds of the cyclopentano-polyhydrophenanthrene series are produced from compounds of this series containing in the 17-position a side chain of the structure -CO-C1##R1 where R1 represents hydrogen or a monovalent residue containing carbon and R2 represents two halogen atoms or a diazo group by methods generally known to be capable of replacing the group R 2 by oxygen. Treatments specified which are used to carry out the process of the present invention include in the case where R represents two halogen atoms treatment with a hydrolysing agent such as water either alone or in the presence of an acid or a basic reagent such as oxalic acid or a carbonate or a hydroxide of an alkali or an alkaline earth such as a carbonate or hydroxide of calcium magnesium, sodium or potassium or an oxide of a heavy metal such as lead oxide. In the case where R2 represents. a diazo group, treatments mentioned include direct oxidation such as by the action of atmospheric oxygen preferably with exposure to ultra-violet light, or by sulphur dioxide. There may also be used a reduction process to form the corresponding hydrazone followed by the action of a hydrolysing agent such as an acid. Reducing agents mentioned for this latter modification include hydrogen sulphide and catalytic reduction with hydrogen in the presence of a metal such as colloidal palladium. Other substituents present in the molecule may undergo change simultaneously with the process which constitutes the present invention, thus ester and ether groups may be hydrolysed and keto groups may be reduced. In examples (1) 21-Dibromo progesterone prepared by the action of bromine on the reaction product of #<4>.<5>-3-keto-aetio cholenic acid chloride with diazomethane is boiled with calcium carbonate for several hours in aqueous propyl alcohol solution. The product is diluted with water and extracted with ether to give #<4>.<5>-3:20:21-trioxo-pregnene. This compound is also obtained if 21-dibromoprogesterone-21-carboxylic acid ester is treated with calcium carbonate as above, and the product heated to cause decarboxylation. (2) An alcohol solution of #<5>.<6>-21-diazo-pregnenol-3. one-20 is reduced with hydrogen sulphide for several days with the occasional addition of ammonia. The product is filtered, extracted with ether and treated with sulphuric acid and glacial acetic acid to give A <5>.<6>-20-21-dioxopregnenol-(3). Instead of the free diazopregnenolone, an ester or ether thereof may be used. Alternatively direct oxidation by atmospheric oxygen accompanied by exposure to ultra-violet light may be used. Other starting materials specifically mentioned include #<5>.<6>- 21 - methyl - 21 - diazo-pregnenol-3-one-20 and #<3>.<4>-#<5>.<6>-3-acetoxy-11-oxy-21-diazo-pregnadiene-one-20. From this latter compound there is obtained #<4>.<5>-3:20:21-trioxo-pregnenol-11. Specification 512,954 is referred to. The Specification as open to inspection under Sect. 91 includes also the treatment of cyclopentanopolyhydrophenanthrene compounds with the above side chain attached to any position other than position-17, and in particular the 3-position is specifically mentioned. The group R1 in the general formula for the side chain is also specifically referred to as a cyano group. As parent materials there are also specifically mentioned compounds of the type of oestrone and hydro-oestrone. This subjectmatter does not appear in the Specification as accepted.