Tricyclic compounds containing two chalcogen atoms in the central seven-membered rings as potential drugs: Synthesis of 3-chloro-6-(1-methyl-4-piperidyl)-6H-dibenz[b,e]-1,4-oxathiepin and 6-oxodibenz[b,e]-1,4-oxathiepin-2-acetic acid

Abstract

2-(4-hloro-2-fluorophenylthio)benzaldehyde (IIa) was subjected to treatment with 1-methyl-4-piperidylmagnesium chloride and the resulting secondary alcohol IIIa was cyclized with sodium hydride to the title compound Ia. In this synthesis, two by-products were isolated and identified as compounds IV and VIa. Repeating the synthesis of compound Ib by a similar way led to isolation of Vb and VII. Reaction of thiosalicylic acid with (3-iodo-4-methoxyphenyl)acetic acid in boiling aqueous potassium hydroxide in the presence of copper gave the methoxy diacid IX which was demethylated with hydrogen bromide in acetic acid to the hydroxy diacid X. Heating with acetic anhydride afforded the title lactone acid VIII. Compound Ia is an almost noncataleptic neuroleptic with a rather low antidopaminergic activity in the test of influencing the dopamine turnover and metabolism in the rat brain striatum. The acid VIII showed some antiinflammatory activity in the test of carrageenan-induced edema of rat's paw.