Collect. Czech. Chem. Commun. 1979, 44, 2689-2701

6,11-Dihydrodibenzo[b,e]thiepin-11-thiol and 11-acetic acid derivatives; Some 2-methyl-6,11-dihydrodibenzo[b,e]thiepins; Synthesis and pharmacological screening

Vladimír Valenta, František Kvis, Jiří Němec and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 00 Prague 3


11-Chloro-6,11-dihydrodibenzo[b,e]thiepin was transformed via the isothiourea V to the thiol IV which was used for the synthesis of aminoalkyl sulfides VII and VIII and of the methylpiperazide X. The same starting compound was used for alkylating diethyl malonate and via the intermediates XIV and XV, 6,11-dihydrodibenzo[b,e]thiepin-11-acetic acid (XVI) was obtained, which was converted to the methylpiperazide XVIII. Oxime XIX and 2-diethylaminoethylimine XX were prepared from 2-methyldibenzo[b,e]thiepin-11(6H)-one (II). Reduction of the ketone II afforded 2-methyl-6,11-dihydrodibenzo[b,e]thiepin (XII) giving by treatment with sodium amide and 3-dimethylaminopropyl chloride the amine XXIII. In the reaction of 6,11-dihydrodibenzo[b,e]thiepin-11-ol with sodium amide and 3-dimethylaminopropyl chloride, C-alkylation took place in addition to the expected etherification resulting in the diamine XXII. Reaction of phthalide with 4-aminothiophenol gave the acid XXIV which was transformed to the 3-dimethylaminopropyl ester XXV and N-acetyl derivative XXVI. Compound XXVI was cyclized with zinc chloride to the ketone III. Some of the compounds prepared exhibit structurally less specific peripheral and vegetative neurotropic effects (local anaesthetic, spasmolytic) and cardiovascular activity (antiarrhytmic).