Patent GB-508072-A (GB)
Title: Process for the manufacture of oxo compounds of the cyclopentano-polyhydrophenanthrene-series
IPC: C07J5/00
Filed: 1937-12-22
Abstract: 508,072. Oxo-compounds of the cyclopentanopolyhydrophenanthrene series. SCHERING AKT.-GES. Dec. 22, 1937, Nos. 35538 and 35539. Convention dates, Dec; 22, 1936 and Nov. 26, 1937. Samples furnished. [Class 2 (iii)] Oxo-compounds of the cyclopentanopolyhydrophenanthrene series are prepared by oxidizing compounds of the general formula where X indicates a cyclopentanopolyhydrophenanthrene residue R hydrogen or a hydrocarbon residue, R1 and R2 hydrogen and /or a hydrocarbon residue such as an alkyl, aryl, aralkyl or cycloalkyl residue. the oxidizing, agents used are those oxidizing agents which are the customary agents for the rupture of double bonds, as described in Houben-Weyl; Die Methoden der Organischen Chemie, 1922, Vol. 2, pages 127-131,- such as for example ozone, chromic acid;. hydrogen peroxide, per-acids, per-salts, osmium tetroxide, vanadium compounds and lead or manganese tetra-acetate. Nuclear double bonds are protected during the oxidation by the addition of halogen or halogen hydride. In this case and also when other parts of the molecule are susceptible to oxidation it is necessary to select the _milder of the specified oxidizing agents, such as ozone or consecutively osmium tetroxide and lead tetra-acetate. The starting materials for the present invention may be obtained by the action of unsaturated metal organic compounds according to the process of Specification 467,790 on compounds of the cyclopentanopolyhydrophenanthrene series containing keto groups. such as cholestanone, saturated or unsaturated androstanolones such as androsterone and dehydroandrosterone, and follicle hormones containing keto groups. If R in the above general formula-is hydrogen, aldehydes are formed by mild oxidation and carboxylic acids by more vigorous oxidation. Alternatively the aldehydes first produced may be further oxidized to carboxylic acids. The hydroxyl group present on the ring carbon atom to which the unsaturated side chain is attached may be split off in. the form of water, for example by heating with acid anhydrides or by vacuum distillation to form a carbon to carbon double bond which in turn may be saturated by hydrogenation. In examples: (1) Cholestanone is treated in ether solution with bromostyrene in the presence of lithium metal and the product treated with ozone to give a product with a strong aldehyde reaction. This is further treated with chromic acid to give the corresponding hydroxy carboxylic acid. (2) Oestrone acetate is treated with bromostyrene in ether solution in the presence of magnesium and the 17-styryl-oestradiol-3 : 17 so produced is ozonized in chloroform solution to give oestradiol 3 : 17-carboxylic acid-'17. Specification 488,814 is referred to. Samples . have been furnished under Sect. 2 (5) of (1) 3-oxo-17-hydroxy-17-aldehydroandrostene prepared by treating dehydroandrosterone in ether solution with bromo.- styrene in the presence of lithium metal and oxidizing the 3.:.17-dehydroxy-17-styryl androstene so produced with first ozone and then with aluminium isopropylate. (2) 3: 17-dihydroxy-androstene-17-carboxylic acid prepared by acetylation on carbon atom-3 of the 3 : 17- dihydroxy-17-styryl androstene , produced as described above followed by oxidation with ozone. The nuclear double bond is intermediately protected by bromine. (3) 3 : 17-dihydroxy - #<5> - aetiocholene - 17 carboxytic acid prepared froin dehydroandrdsterone acetate by treatment with bromostyrene in other solution in the presence of lithium metal, followed by oxidation of the 3: 17-dihydroxy-17-styryl- #<5>-androstene with ozone.