Base-promoted regioselective synthesis of alkyl (2-tosyl/4-ethylcarbonyl) thiazole-5-carboxylates employing dithioates and active methylene isocyanides†

Abstract

Herein, we report highly efficient and base-promoted approaches for the diversity-oriented synthesis of 2,5- and 4,5-disubstituted thiazoles using alkyl 2-(methylthio)-2-thioxoacetates as synthetic precursors. The transformation involves the regioselective cyclization reaction between dithioates and active methylene isocyanides, leading to the tosyl and ester-substituted thiazoles at the 2^nd and 4^th positions, respectively. Notably, the reactions occur rapidly at room temperature under metal-free mild conditions, highlighting the practical applicability of this protocol. The methodology exhibits broad functional group compatibility at the 5^th position of the thiazole, accompanied by excellent yields, providing a valuable alternative to existing synthetic routes. The regioselective cyclized products were characterized and confirmed through single-crystal X-ray diffraction studies. Furthermore, it enriches the DFT-mechanistic studies for selective cyclization.