How do cyanothioacetamides react with dimethyl acetylenedicarboxylate (DMAD) to form thiophenes and thiazoles, and what factors influence the product distribution?

The study investigates the reaction of cyanothioacetamides with dimethyl acetylenedicarboxylate (DMAD) to synthesize functionalized thiophenes containing an exocyclic double bond. Thiophenes with exocyclic double bonds are of interest due to their potential applications as photochromic molecular switches and as models of D–π–A (donor–spacer–acceptor) systems. Previous methods for synthesizing such compounds include pathways from isothiocyanates or by oxidation of thiophenes.

The reaction of cyanothioacetamides with DMAD leads to the formation of either thiazoles or thiophenes, depending on the structure of the cyanothioacetamide and the solvent used. Specifically:
Thiazoles (4a-d): Formed as the major products when reactions are conducted in ethanol, especially with cyanothioacetamides having bulky substituents on nitrogen (e.g., cyclohexyl and isopropyl). The yields range from 30% to 63%.
Thiophenes (5c,d): Formed as major products when reactions are conducted in acetic acid. The presence of bulky substituents on nitrogen and the second thioamide group favors the formation of thiophenes. The yields range from 34% to 75%.
Influence of Solvent: Acetic acid promotes the formation of thiophenes due to the formation of an iminium intermediate, which is stabilized by intermolecular hydrogen bonds. In ethanol, thiazoles are favored.
Structural Stability: The thiophenes formed have a planar structure stabilized by intramolecular hydrogen bonds. The presence of a second thioamide group in the intermediates also influences the reaction pathway, directing the formation of specific products.