0-Sulphonyl-5,5-Disubstituted-Hydantoins and process for preparation thereof

摘要

1,167,262. 1 - Sulphonyl - 5,5 - disubstituted hydantoins. DAINIPPON PHARMACEUTICAL CO. Ltd. 16 Feb., 1967 [17 Feb., 1966 (2)], No. 7417/67. Heading C2C. Novel 1-sulphonyl-5,5-disubstituted hydantoins of the formula wherein R 1 and R 2 each represent phenyl or alkyl having from 1 to 4 carbon atoms or may together form a 5- or 6-membered cycloaliphatic ring with the carbon atom at the 5-position of the hydantoin nucleus; R 3 represents alkyl having from 1 to 4 carbon atoms, phenyl or substituted phenyl, said substituent on the phenyl nucleus being alkyl having from 1 to 4 carbon atoms, nitro, halogen, amino, hydroxy, alkoxy having from 1 to 4 carbon atoms or phenylalkoxy in which the alkoxy moiety has 1 or 2 carbon atoms and R 4 represents hydrogen, alkyl having from 1 to 4 carbon atoms, alkanoyl having from 2 to 5 carbon atoms, benzoyl or alkoxycarbonyl having from 2 to 5 carbon atoms; and salts thereof with pharmaceutically acceptable bases are prepared either by (1) subjecting a 3-sulphonyl-5,5-disubstituted hydantoin of the formula wherein R1 3 represents alkyl having from 1 to 4 carbon atoms, phenyl or substituted phenyl, said substituent on the phenyl nucleus being alkyl having from 1 to 4 carbon atoms, nitro, halogen, alkoxy having from 1 to 4 carbon atoms or phenyl alkoxy in which the alkoxy moiety has 1 or 2 carbon atoms, to a temperature ranging from 15‹ to 200‹ C. in an inert solvent in the presence of an alkali metal hydride, hydroxide, amide or alcoholate; or (2) reacting a 1,3-disulphonyl-5,5-disubstituted hydantoin of the formula wherein R11 3 represents the same substituents as R1 3 and may be the same as or different from R1 3 , with an acid or base at a temperature within the range of 15‹ to 200‹ C.; followed in either case by isolation of the resulting free acid or salt and optional conversion to other hydantoins of the first formula above by methods known per se. 3 - Sulphonyl - and 1,3 - disulphonyl - 5,5- disubstituted hydantoins of the second and third formulµ above, respectively, are prepared by reacting a 5,5-disubstituted hydantoin of the formula in the form of an alkali metal salt thereof or in the presence of a dehydrohalogenation agent, with a sulphonyl halide of the formula XSO 2 R1 3 , wherein X is a halogen. Pharmaceutical compositions, having antiinflammatory, anti-pyretic and analgesic activity, comprise, as active ingredient, a 1-sulphonyl-5,5-disubstituted hydantoin of the first formula above or a salt thereof with a pharmaceutically acceptable base, in association with a pharmaceutically acceptable carrier or diluent, and may be administered orally.