Collect. Czech. Chem. Commun. 1979, 44, 2536-2549

Synthesis of new dibenzo[b,e]thiepin derivatives related to the antidepressant agent prothiadene

Miroslav Rajšner, Václav Bártl, Karel Šindelář, Emil Svátek, Jiří Holubek, Jan Metyš and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


A reaction of dibenzo[b,e]thiepin-11(6H)-one with cyclopropylmagnesium bromide afforded the carbinol VII giving by treatment with hydrogen bromide the bromo derivative IV. Application of the Gabriel synthesis led to the primary amine III postulated earlier to be a metabolite of the antidepressant agent prothiadene (I). Demethylation of 2-methoxy-11-(3-dimethylaminopropylidene)-6,11-dihydrodibenzo[b,e]thiepin (X) with boron tribromide or hydrobromic acid gave mixtures of geometric isomers of the phenol IX from which either the trans- or cis-form could be isolated; trans-IX is another potential metabolite of prothiadene (I). Attempts at preparing prothiadene N-oxide yielded as the main product the nitrogen-free diene XI which was apparently formed by a Cope elimination. The analogous sulfone XII was obtained as a by-product of the preparation of prothiadene S,S-dioxide (XV). Treatment of dibenzo[b,e]thiepin-11(6H)-one with methoxymethylmagnesium chloride opened the access to the aldehyde XVI which was further used for the preparation of the nitrile XVIII, alcohol XIX, carboxylic acid XX and acrylic acid XXI.