Substituted 10,11-dihydrodibenzo(b,f)thiepin derivatives and preparation thereof

摘要

Compounds of the formula wherein R1 and R2 are identical or different and can be hydrogen or halogen, at least one of the said substituents being other than hydrogen; R3 represents hydrogen, alkyl or hydroxyalkyl with 1 to 6 carbon atoms and n is 2 or 3 and acid addition salts thereof by treating reactive ester, e.g. halides or alkane or arene sulphonates, derived from secondary alcohols of the formula wherein R1 and R2 have the above significance, with diamines of the formula wherein R3 has the above significance, optionally in the presence of an alkali condensing agent and/or an organic solvent. The compounds of the first general formula above have neurotropic, psychotropic, sedative, analgesic, anti-histamine, anti-serotonin, anti-cholinergic, anti-emetic and ganglioplegic activity and potentiate thiopental narcosis. 1-, 2-, 3-, 4-, 6-, 7- and 8-chloro-, 8-bromo-, 8-fluoro- and 2,8-dichloro-substituted 10-(4-methylpiperazino) - 10,11 - dihydrodibenzo(b,f)-thiepin derivatives are obtained from the corresponding halogen substituted 10-chloro-10,11-dihydrodibenzo(b,f)thiepin and 4-methylpiperzine. Halogen substituted 10-chloro-10,11-dihydrodibenz(b,f)thiepin derivatives are obtained by treating the corresponding secondary alcohol of the second general formula above with thionyl chloride or anhydrous hydrochloric acid. Halogen substituted 10 - hydroxy - 10,11 - di-hydrodibenz(b,f)thiepin derivatives are obtained by reducing the corresponding halogen substituted 10,11 - dihydrodibenz(b,f)thiepin-10-one with sodium borohydride reagent. Halogen substituted 10,11 - dihydrodibenz(b,f)thiepin-10-one derivatives are obtained by cyclizing the appropriate halogen substituted 2-(phenylthio)-phenylacetic acid by heating with polyphosphoric acid. Halogen substituted 2 - (phenylthio) - phenylacetic acid derivatives or the amides thereof are prepared by hydrolysing the corresponding halogen substituted 2-(phenylthio)-benzyl cyanide with ethanolic potassium hydroxide. Halogen substituted 2 - (phenylthio) - benzyl cyanide is prepared by treating the corresponding halogen substituted 2-(phenylthio)-benzyl chloride with ethanolic potassium cyanide. Halogen substituted 2 - (phenylthio) - benzyl chloride derivatives are obtained by treating the corresponding alcohol with thionyl chloride. Halogen substituted 2-(phenylthio)-benzyl alcohol derivatives are prepared by reducing the corresponding halogen substituted 2-(phenylthio-benzoic acid with lithium aluminium hydride reagent. 2 - (21 - Chlorophenylthio)-, 2 - (31 - chlorophenylthio)-, 2 - (41 - fluorophenylthio)- and 2 - (41 - bromophenylthio) - benzoic acid are prepared by reacting the corresponding halogen substituted thiophenol with 2-iodobenzoic acid. 2 - Phenylthio - 3 - chlorobenzoic acid is prepared from 2-phenylthio -3- aminobenzoic acid which is, in turn, obtained from 2-iodo-3-nitrobenzoic acid by way of 2-phenylthio-3-nitrobenzoic acid. 4-, 5- and 6- chloro-2-(phenylthio)-benzoic acid and 5-chloro-2-(41-chlorophenylthio)-benzoic acid are prepared from the corresponding chloro substituted 2-iodobenzoic acid. 4-, 5- and 6-chloro-2-iodobenzoic acid are obtained from the corresponding chloro-substituted anthranilic acids. 4-Chloro-anthranilic acid is obtained from 4-chloro-2-nitro-toluene by way of 4-chloro-2-nitro-benzoic acid.