Patent GB-521109-A (GB)
Title: Manufacture of carbonyl compounds of steroids
IPC: C07J5/00
Filed: 1938-11-08
Abstract: 521,109. Cyclopentanophenanthrene ketones. SOC. OF CHEMICAL INDUSTRY IN BASLE. Nov. 8, 1938, Nos. 32378 and 32379. Convention dates, Nov. 12, 1937, and Sept. 30, 1938. Samples furnished. [Class 2 (iii)] Carbonyl compounds of steroids are prepared by condensing a steroid compound which contains the group -CH 2 .CO- with a nitroso compound or a nitric acid ester and converting the product so obtained into a di-carbonyl compound containing the group -CO.CO-. Parent materials mentioned include steroid compounds which possess side chains of the constitution -CO.CH, ; -CH 2 .CHO; -CH 2 .CO.OR; -CO.CH 2 .CO-; and -CO.CH 2 .COOR where R is a hydrocarbon residue or hydrogen. The .CH 2 -CO- may also be situated in the cyclopentanopolyhydrophenanthrene nucleus, which may be saturated or unsaturated and may contain substituents. The compounds may belong to a class of sterols, bile acids or sex hormones. Nitroso compounds include nitrous acid which is the preferred agent together with compounds which form nitrous acid such as an alkali nitrite and an acid, an alkyl nitrite such as ethyl or amyl nitrite, especially in the presence of an alkali alcoholate or a mineral acid, nitrosyl chloride or nitrosyl sulphate. In addition also aromatic nitroso compounds such as nitrosobenzene, nitrosodimethyl-, and nitrosodiethyl-aniline. The condensation is preferably conducted in an organic solvent such as alcohol or ether, but an aqueous suspension may be used. Condensing agents such as alkali hydroxides, carbonates, bicarbonates or alcoholates may be added. The conversion of the condensation products derived from the treatment with the nitroso compounds namely the oximes and anils into the desired ketones may be effected by any method known to be suitable for this reaction. Processes specified include a hydrolytic scission by means of a mineral acid such as hydrochloric or sulphuric acid, or an oxidative scission by means of permanganate, nitric acid, ferric salts, amyl nitrite and nitrous acid. The last two agents may if used in excess lead directly to the formation of the required ketones from the parent materials. Aldehydes such as formaldehyde, and bisulphites, both in acid solution may be used to treat the intermediate compounds. In cases where the intermediate compound is an oxime it is also possible to reduce this to an amine and convert the amine by oxidation to the required ketone. Oxidizing agents specified for this latter process include, halogens, oxygen in the presence of copper powder, hydrogen peroxide, permanganate, ferric salts, copper salts, nitrous acids, or biochemical methods such as vinegar bacteria or yeast. In examples (1) Amyl nitrite is added to a solution of # <SP>5</SP>-pregnenol- (3)-one-(20) in alcoholic sodium ethylate, and the reaction mixture allowed to stand for some days. Sodium nitrite in glacial acetic acid is then added and the solution poured into water and extracted with ether to give # <SP>5</SP>-20:21- dioxo-pregnenol-3. Ethyl nitrite and an alkali metal in ether may be substituted for amyl nitrite and sodium ethylate, and ethyl nitrate may be substituted for the alkyl nitrite. (2) An alcoholic solution of # <SP>3</SP>-pregnenol-3- one-(20), paranitrosodimethylaniline and caustic soda is heated under reflux. The product is hydrolysed with alcoholic sulphuric acid to give # <SP>5</SP>-20:21-dioxo-pregnenol-3. Samples have been furnished under Sect. 2 (5) of : (1) 3-acetoxy-allo-pregnane-20-one- 21-acid methyl ester prepared by the action of gaseous nitrous acid in ethereal solution on 3 - acetoxy - allo - pregnane - 21 - acid methyl ester followed by evaporation and chromatographic separation; (2) # <SP>5</SP>-20:21-dioxo-pregnenol-3 prepared by the action of amyl nitrite on # <SP>5</SP>-pregnane-3-ol-21-al in sodium ethylate solution followed by the decomposition of the isonitroso solution as in example (1).