Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Synthesis of 11-(dimethylaminoalkyl) derivatives of 11H-dibenzo[b,e]-1,4-dioxepin and 11H-dibenzo[b,e]-1,4-dithiepin

Abstract

1-[2-(2-Fluorophenoxy)phenyl]-4-dimethylaminobutanol (XI) was synthesized from 2-(2-fluorophenoxy)benzoic acid (VIII) in three steps and cyclized with sodium hydride in dimethylformamide to the title compound V. Reaction of 5-chloro-2-(methylthio)thiophenol (XIV) with sodium and liquid ammonia afforded benzene-1,2-dithiol (XIII) which was treated with 2-bromobenzyl bromide and gave 11H-dibenzo[b,e]-1,4-dithiepin (II). An alternative synthesis of compound II consisted in the cyclization of 2-(2-bromophenylthiomethyl)thiophenol (XVIII) and was accompanied by the simultaneous formation of 6H, 12H-dibenzo[b,f]-1,5-dithiocin (XIX) and thianthrene (XX). Reaction of compound II with n-butyllithium and the following treatment with dimethylaminoalkyl chlorides or with carbon dioxide resulted on the one hand in two further title compounds VI and VII, and in the carboxylic acid XXI on the other. 2-Chloro-11H-dibenzo[b,e]-1,4-dithiepin (XXII) was obtained by a further synthesis alternative using in the first step the cyclization of 2-(4-chloro-2-chloromethylphenylthio)thiophenol (XXV). Compound VI and VII showed a high degree of activity in the test of antagonization of reserpine hypothermia in mice.