Potential psychotropic and antihistamine agents: 1- and 3-alkyl-9-(3-dimethylaminopropylidene)-thioxanthenes and 3-alkyl-11-piperazino-10,11-dihydrodibenzo[b,f]thiepins

Abstract

Reactions of 3-methylthiophenol and 3-ethylthiophenol with 2-iodobenzoic acid and (2-iodophenyl)acetic acid in the presence of potassium hydroxide and copper gave the acids IVab and Xab. The acids IVab afforded by cyclization with sulfuric acid mixtures of 1- and 3-alkylthioxanthones (Va + VIa, Vb + VIb) which were separated by crystallization or chromatography and the individual compounds were identified by spectra. The slightly prevailing 3-alkyl derivatives Vab were reacted with 3-dimethylaminopropylmagnesium chloride to give the tertiary alcohols VIIab which were transformed by the acid catalyzed dehydration to the title compounds Iab. 1-Ethylthioxanthone (VIb) afforded similarly via the tertiary alcohol VIII the title compound IX. The acids Xab were cyclized with polyphosphoric acid unequivocally to the ketones XIab which were converted via the alcohols XIIab to the chloro derivatives XIIIab. Substitution reactions with 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine led to the title compounds IIab and IIIb. The compounds prepared (I-III) have antihistamine activity and are more or less central depressant. Compounds Ib, IIb and IIIb revealed a clear cataleptic activity and compound Ib showed also antireserpine activity. Compound IX is centrally depressant only in high doses but it has anticonvulsant effects and a significant antitussive effect.