Patent GB-516828-A (GB)
Title: Manufacture of ª‡-substituted side chain ketones of the cyclopentanopolyhydrophenanthrene series
IPC: C07J5/00
Filed: 1938-07-11
Abstract: 516,828. Cyclopentanophenanthrene ketones. SOC. OF CHEMICAL INDUSTRY IN BASLE. July 11, 1938, Nos. 20489 and 20490. Convention dates, July 9, 1937 and June 14, 1938. [Class 2 (iii)] Alpha-substituted side chain ketones of the cyclopentanopolyhydrophenanthrene series are prepared by causing a carboxylic acid halide of this series containing a nuclear keto group or an esterified or etherified enolised nuclear keto group to react with an aliphatic diazo compound. The parent carboxylic acid halides may contain in addition other substituents and one or more unsaturated linkages. The reaction of the diazo compound on the carboxylic halide may be conducted in such a manner that the diazo compound is maintained permanently in excess, in which case a diazo ketone is formed as the reaction product. This reaction occurs particularly when a diazo compound containing a keto group such as a diazo fatty acid derivative is used. On the other hand alpha-halogen ketones are obtained directly when the diazo compound is added slowly to the acid halide. If the parent materials contain hydroxyl or amino groups, these may be alkylated as a side reaction. Parent materials mentioned include halides of #<4>.<5> - 3-keto-aetio-cholenic acid, 3:11-diketoaetiocholanic acid, 3-keto-11-oxyaetiocholanic acid, #<4>.<5>-3-keto-11-oxy-aetio-cholanic acid, also halides of the ketoaetioallocholane-17-acetic acids, of keto-bisnorcholenic acids, 3-cadoxy aetio-allocholanones-17, and 3-carboxy-11-ketoaetio cholenic acids. Aliphatic diazo compounds mentioned include diazomethane unsubstituted or substituted particularly with radicals containing carbon such as diazoethane,' diazobutane, diazopropylenephenyld iazomethane, diazoacetophenone, and diazo-carboxylic acid derivatives such as diazo-acetic acid esters, amides and nitriles. The diazo compounds produced according to the invention may be hydrolyzed to oxypolyketones. Hydrolyzing agents mentioned include boiling water or dilute mineral acid, or an organic sulphonic acid such as toluene sulphonic acid or methane sulphonic acid, or converted into ethers-COÀCHÀ OR by the action of an alcohol or a phenol such as methanol, ethanol, cyclohexanol, triphenylcarbinol, or cresol, or into esters-COÀ#CH- | OOC.R by the action of an organic acid such as acetic, propionic, butyric, crotonic, palmitic, benzoic or phenylacetic acid, or into esters of inorganic ,acids -CO-CH.X, by the action of an inorganic acid such as hydrochloric, hydrobromic, iodic, boric or phosphoric acid. In examples (1) a benzene solution of #<4>.<5>-3- keto-aetiocholenic acid is dropped slowly into an ether solution of diazomethane to give 21- diazo-progesterone. By shaking with sulphuric acid at a mixed temperature there is obtained #<4>.<5>-21 oxypregnenedione-3:20. These may be. used as starting material compounds substituted in the nucleus. by hydroxyl or substituted hydroxyl groups. (2) An ether solution of diazomethane is added to the chloride of #<3>:<4-># <5-6>-3-acetoxy-aetio-choladienic acid. Dry hydrogen chloride is added to the remaining benzene solution to give the 3-enol acetates of 21-chloro-progesterone.