2-Amino-4,5-dihydrothiophene-3-carbonitriles: A New Synthesis, Quantum Chemical Studies, and Mannich-Type Reactions Leading to New Hexahydrothieno[2,3-d]pyrimidines

trans-2-Amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles were prepared either by the reaction of 3-aryl-2-cyanothioacrylamides with alpha-thiocyanatoacetophenone or by the Michael-type addition of cyanothioacetamide to alpha-bromochalcones followed by intramolecular cyclization. The mechanism of the first reaction was studied using high-level quantum chemical calculations. Density functional theory (DFT) studies were carried out to determine the mechanism of the first reaction. A new approach toward the construction of the thieno[2,3-d]pyrimidine core system was demonstrated by the reaction of the prepared dihydrothiophenes with HCHO and RNH2 under noncatalyzed Mannich conditions.

Automated summary

In this study, trans-2-amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles were prepared through two different reaction pathways, and the mechanism of the first reaction was investigated using high-level quantum chemical calculations. A new approach to constructing the thieno[2,3-d]pyrimidine core system was demonstrated by reacting the prepared dihydrothiophenes with HCHO and RNH2 under noncatalyzed Mannich conditions.