A facile and green synthesis of methyl 7-aryl-5-methyl-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate derivatives using hyamine in aqueous media at room temperature

This study presents a novel one-pot synthesis of methyl 7-aryl-5-methyl-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate derivatives by reacting equimolar amounts of aromatic aldehydes (5 mmol), methyl acetoacetate (5 mmol), and 3-amino-1,2,4-triazole (5 mmol) in water at room temperature, catalyzed by hyamine (benzethonium chloride). Products were isolated by filtration, purified by recrystallization, and characterized using infrared spectroscopy (IR),1H NMR, 13C NMR, and electrospray ionization mass spectrometry (ESI-MS). The total of 12 synthesized triazolo-fused pyrimidine derivatives were obtained in high yields (up to 95%) with reaction time ranging from 5 to 8 h. The use of hyamine as a cationic surfactant catalyst enhanced the reaction rates through micellar effects, promoting high local substrate concentrations and stabilizing transition states. The hyamine-catalyzed MCR provides a green, efficient, and high-yielding method to synthesize triazolo-fused pyrimidine derivatives using water as a green solvent at room temperature.