Simple synthesis of new imidazopyridinone, pyridopyrimidinone, and thiazolopyridinone derivatives and optimization of reaction parameters using response surface methodology

The reaction between ketene animal/ketene N,S-acetals (derived from diamines/cysteamine hydrochloride and 1,1-bis(methylthio)-2-nitroethene) with aromatic aldehydes, and Meldrum's acid led to the title compounds. The reaction conditions were optimized using response surface methodology (RSM). The two independent variables (temperature and water content of aqueous ethanol), and the responses (yield of product and reaction time) were studied. The range of each parameter selected was: T = 25–100 °C and water = 0–100%. The optimal values were: T = 72 °C and water = 33%. This work offers significant advantages including use of a green solvent, experimental simplicity, absence of catalyst, a simple work-up and purification process, moderate to good yields, and preparation of potentially bioactive compounds.