Assembly strategy for thieno[3,2- <i>b</i> ]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

A versatile synthetic route to thieno[3,2-<i>b</i>]thiophenes was elaborated from dimethyl 3-nitrothiophene-2,5-dicarboxylate. Nucleophilic substitution of the nitro group with sulfur nucleophiles, including thioacetate or disulfide anions as well as thioacetamide, yielded bis(thiophen-3-yl)disulfide and sulfide derivatives. The disulfide served as a suitable precursor for the preparation of 3-alkylthio-substituted thiophene-2,5-dicarboxylates by its one-pot reduction-alkylation using NaBH₄ in DMF followed by an alkylating agent. Base-promoted cyclization of electron-deficient 3-alkylthio derivatives furnished 2-aryl-, 2-aroyl-, and 2-cyano-substituted thieno[3,2-<i>b</i>]thiophenes, bearing a 3-hydroxy group. This protocol broadens access to functionalized thieno[3,2-<i>b</i>]thiophenes with potential applications in pharmaceutical and materials chemistry.