Expeditious Scalable Catalyst-Free One-Pot Synthesis of 4-Alkoxy-5-amino-3-methylthiophene-2-carbonitriles via Sequential Reactions­ of Lithiated Alkoxyallenes with Isothiocyanates and 2-Bromoacetonitrile

Abstract

A synthetically simple and convenient approach to tetrasubstituted thiophenes with rare combination of the alkoxy, amino, and cyano groups has been developed. The assembly of polyfunctionalized thiophene ring is implemented in one preparative step by sequential addition of isothiocyanate and 2-bromoacetonitrile to the lithiated (with n-BuLi) alkoxyallene. The reaction proceeds through in situ formation and intramolecular cyclization of cyanomethyl 2-alkoxy-N-buta-2,3-dienimidothioate (1-aza-1,3,4-triene).