ANALOGY PROCEDURE FOR THE PREPARATION OF ERYTHRO OR MESO FORMS OF 3,3'-DIFLUOR-4,4'-DIHYDROXYDIBENZYL DERIVATIVES

摘要

1280767 3,3SP1/SP - Dihalo - 4,4SP1/SP - dihydroxydibenzyls BIOREX LABORATORIES Ltd 19 April 1971 [16 March 1970] 12554/70 Heading C2C Novel 3,31 - dihalo - 4,4SP1/SP - dihydroxydibenzyls of the general formula wherein R is a hydrogen atom or a C 1-6 alkyl or benzyl group, R 1 and R 2 are each a C 1-6 alkyl group, with the proviso that they are not both a methyl or ethyl group, and X is a halogen atom, are prepared (a) when R is a C 1-6 alkyl group, by hydrogenation of a diphenylethylene of the general formula wherein RSP11/SP is a C 1-6 alkyl group; (b) when R is a hydrogen atom, by dealkylation of the corresponding compound in which R is an alkyl group; (c) when R is a C 1-6 alkyl group, by reaction of an ether of the general formula with a haloethanol of the general formula Hal-CH(R 1 )-CH(OH)R 2 , wherein Hal is a halogen atom; (d) when X is a chlorine or bromine atom and R is a hydrogen or C 1-6 alkyl group, by treatment of the corresponding compound in which X is a hydrogen atom with bromine, chlorine or sulphuryl chloride, as appropriate; (e) when R is a C 1-6 alkyl group, by reaction of a Grignard reagent and a benzyl halide of the resepctive general formulµ wherein R 3 is a C 3-6 alkyl group; (f) when R is a C 1-6 alkyl or benzyl group, by reaction of the corresponding compound in which R is a hydrogen atom with a C 1-6 alkyl or benzyl halide in the presence of an alkali metal hydroxide and an inert solvent; and (g) when R is a hydrogen atom, by hydrogenolysis of the corresponding compound in which R is a benzyl group. Diphenyl ethylenes of the second general formula above are prepared by reaction of an ether of the third general formula above with a ketone of the general formula 4,4SP1/SP-Dihydroxydibenzyls of the first general formula above wherein X is a hydrogen atom and R is a hydrogen atom or C 1-6 alkyl group are prepared by reaction of an ether of the general formula with a ketone of the seventh general formula above, hydrogenation of the resulting diphenylethylene of the second general formula above wherein X is a hydrogen atom and optional dealkylation of the resulting desired product in which R is a C 1-6 alkyl group. Benzyl halides of the sixth general formula above are prepared by reaction of an ether of the third general formula above with an acid halide of the general formula R 3 COHal, reduction of the resulting ketone of the general formula and halogenation of the resulting alcohol of the general formula Pharmaceutical compositions having oestrogenic activity comprise, as active ingredient, at least one 3, 3SP1/SP-dihalo-4,4SP1/SP-dihydroxydibenzyl of the first general formula above, together with a solid or liquid pharmaceutical diluent or carrier, and may be administered orally.