Aqueous-Phase Multicomponent Reaction Mechanism for the Synthesis of Pyrido[2,3‑]pyrimidines: A Theoretical Perspective.

A theoretical investigation of the reaction among benzaldehyde, Meldrum's acid, and 6-aminouracil in aqueous solution is presented in this study, incorporating the impact of temperature on both the thermodynamic and kinetic aspects of the reaction. Five free energy profiles are presented, concerning the Knoevenagel condensation, Michael addition, cyclization, propanone, and CO release. We have also performed a simple kinetic analysis and a detailed microkinetic analysis. According to our results, the carbon-carbon bond formation between benzaldehyde and Meldrum's acid is the rate-determining step. The temperature increases the reaction rate; however, it is still insufficient for the formation of pyrido-[2,3-]-pyrimidines beyond trace amounts, in good agreement with experimental results. This explanation provides a thorough understanding of the multicomponent reaction mechanism that leads to the formation of pyrido-[2,3-]-pyrimidines, thereby opening new possibilities for further exploration and optimization of the catalyzed process.