Nonsteroidal Antiinflammatory Agents. III. Syntheses of Benzothienothiepin, Benzothienoxepin and Their Acetic Acid Derivatives

Abstract

In order to search for new antiinflammatory agents, several acetic acid derivatives of sulfur containing tricyclic compounds were prepared. Initially, 4, 10-dihydro-10-oxobenzo [b] thieno [2, 3-e] thiepin (3) and 4, 10-dihydro-4-oxobenzo [b] thieno [2, 3-e] thiepin (19) were prepared by cyclization of 3-(phenylthiomethyl) thiophene-2-carboxylic acid (2) and 2-(phenylthiomethyl) thiophene-3-carboxylic acid (18), respectively, with polyphosphoric acid (PPA). The oxepin (5) corresponding to 3 was prepared by cyclization of the acid chloride of 3-(phenoxymethyl) thiophene-2-carboxylic acid (4) with aluminum chloride. However, cyclization of 2-(phenoxymethyl) thiophene-3-carboxylic acid (20) did not give the oxepin (21) corresponding to 19 but the rearranged compound, 4, 10-dihydro-4-oxobenzo [b] thieno [2, 3-e] oxepin (22). A similar rearrangement took place in the reaction of 4 with PPA yielding 4, 10-dihydro-10-oxobenzo [b] thieno [3, 2-e] oxepin (7). Furthermore, the acetic acid derivatives of 3, 5 and 19 were prepared by methods similar to those used for the syntheses of unsubstituted tricyclic rings. These acetic acid derivatives exhibited good antiinflammatory activities, details of which will be reported elsewhere.