Verfahren zur Herstellung von Thioninderivaten

1,256,733. Thionine derivatives. EGYESULT GYOGYSZER ES TAPSZERGYAR. 5 Feb., 1969 [16 Feb., 1968], No. 6247/69. Heading C2C. Novel thionine derivatives of the general formula wherein X is a halogen atom or a hydroxyl group, R and R1 are each a hydrogen or halogen atom or a C 1-5 alkoxy group and Y# is a hydroxide ion or an anion of an organic or inorganic acid, are prepared (a) by oxidation of a phenylene diamine derivative of the general formula in an acidic medium in the presence of a substance serving as a source of reactive sulphur; (b) by oxidation of a mixture of a phenylenediamine derivative of the second general formula above and N,N-bis-(#-hydroxyethyl or #-dihaloethyl)-aniline in an acidic medium in the presence of a substance serving as a source of reactive sulphur; (c) by reaction of a phenothiazine derivative of the general formula with chlorine or bromine and an amine of the general formula XCH 2 CH 2 NBCH 2 CH 2 X, wherein B is a hydrogen or halogen atom; (d) by oxidation of a phenothiazine derivative of the general formula in an acidic medium; and (e) when each X is a halogen atom, by halogenation of the corresponding thionine derivative of the first general formula above wherein each X is a hydroxyl group; followed optionally by reaction of the product with a stronger acid than that corresponding to Y#, or, when in the product Y# is an anion of an acid, by conversion thereof into the corresponding compound wherein Y# is a hydroxide ion by reaction with an alkali metal hydroxide or carbonate, followed optionally by reaction of the product with another acid. Pharmaceutical compositions having antitumour activity comprise, as active ingredient, a thionine derivative of the first general formula above, in association with a pharmaceutical carrier or excipient.