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

## TL;DR

This paper presents a new method to synthesize thieno[3,2-b]thiophenes using a disulfide intermediate, offering a versatile route for pharmaceutical and materials chemistry.

## Contribution

A novel synthetic strategy for thieno[3,2-b]thiophenes using a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate.

## Key findings

- Bis(thiophen-3-yl)disulfide and sulfide derivatives were synthesized via nucleophilic substitution.
- 3-alkylthio-substituted thiophene-2,5-dicarboxylates were prepared using one-pot reduction–alkylation.
- Base-promoted cyclization produced 2-aryl-, 2-aroyl-, and 2-cyano-substituted thieno[3,2-b]thiophenes with a 3-hydroxy group.

## Abstract

A versatile synthetic route to thieno[3,2-b]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-b]thiophenes, bearing a 3-hydroxy group. This protocol broadens access to functionalized thieno[3,2-b]thiophenes with potential applications in pharmaceutical and materials chemistry.