Collect. Czech. Chem. Commun. 1980, 45, 491-503

Synthesis of 3-chloro-5-(4-methylpiperazino)-6,7-dihydro-5H-dibenzo[b,g]thiocin, an eight-membered ring homologue of the neuroleptic agent octoclothepin

Karel Šindelář, Jiří Holubek, Emil Svátek and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 00 Prague 3


Alkylation of diethyl malonate with 2-(4-chlorophenylthio)benzyl chloride, the following hydrolysis and decarboxylation gave 3-[2-(4-chlorophenylthio)phenyl]propionic acid (IV); its chloride was cyclized in low yield by treatment with aluminium chloride to 4-(4-chlorophenylthio)indanone (V). The corresponding methylpiperazine derivative VIII was prepared viaintermediates VI and VII. A reaction of 3-(2-mercaptophenyl)propionic acid with 5-chloro-2-iodobenzoic acid and the following esterification resulted in the diester XVI which was cyclized by a Dieckmann reaction using sodium hydride in toluene to give ethyl 3-chloro-5-hydroxy-7H-dibenzo[b,g]thiocin-6-carboxylate (XVII). The acid hydrolysis afforded the ketone XVIII which was transformed via the intermediates XX and XXI to the title compound II. The product has a mild central depressant activity but it lacks the character of a neuroleptic agent.