Patent GB-1093910-A (GB)
Title: Substituted 10,11-dihydrodibenzo(b,f)thiepin derivatives and preparation thereof
IPC: C07D337/14
Filed: 1965-12-31
Abstract: Compounds of the formula <FORM:1093910/C2/1> 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 <FORM:1093910/C2/2> wherein R1 and R2 have the above significance, with diamines of the formula <FORM:1093910/C2/3> 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.