Synthesis of 3-(6,11-dihydrodibenzo[b,e]thiepin-11-ylidene)propanoic acid and related compounds

The alcohol XIa, obtained by reaction of dibenzo[b,e]thiepin-11(6H)-one with vinylmagnesium bromide, was transformed by treatment with hydrogen bromide in acetic acid to the bromo compound XIIa which was converted via the nitrile XIIIa to the title acid VIIIa. The pure (E)-isomer was prepared and correlated via the dimethylamide XVIIIa with (E)-prothiadene (Ia). Similar procedures in the 2-methyl-6,11-dihydrodibenzo[b,e]thiepin and 10,11-dihydrodibenzo[a,d]cycloheptene series afforded the acids VIIIb and IV. The acids VIIIab were oxidized with hydrogen peroxide to the sulfoxides IXab and to the sulfones Xab. The acid IV is the suggested metabolite of the antidepressant amitriptyline (II) and the acids VIIIab-Xab are potential metabolites of the antidepressant prothiadene (Ia) and the antihistamine agent methiadene (Ib). The amides VII and XVIab were prepared from the acids via the acid chlorides. The (Z)-isomer of prothiadene (XXII) was prepared from dibenzo[b,e]thiepin-11(6H)-one by the Wittig reaction. The acids IV, VIIIab and IXab showed some antiinflammatory activity.