Kinetics, thermodynamics, and optimization studies using response surface methodology in quinoxalines synthesis with efficient heterogeneous catalysts: environmental sustainability metrics assessment

Abstract

In this study, a Box–Behnken design was employed to optimize the synthesis of quinoxaline derivatives via the condensation of benzil or furyl with 1,2-diamines using zirconium phosphate (ZrP) as a heterogeneous catalyst and water as a green solvent. The effects of reaction temperature (40–50 °C), catalyst amount (0.02–0.04 g), and stirring time (5–15 min) were investigated. The model exhibited excellent predictive accuracy with an adjusted R² of 0.997, yielding 97.90% quinoxalines under optimal conditions: 0.03 g catalyst, 12 min reaction time, and 45 °C. Catalyst reusability was confirmed for up to five cycles, with a slight decrease in yield (~ 90% after five uses). Kinetic analysis revealed first-order reaction kinetics with an activation energy of 70.34 kJ/mol. Thermodynamic parameters, including ΔS, ΔH, and ΔG, were calculated using the Eyring-Polanyi equation. A sustainability assessment using green metrics, such as atom economy (AE), reaction mass efficiency (RME), and the E-factor, demonstrated the improved environmental profile of the process. This method offers a greener and efficient approach for quinoxaline synthesis, with potential applications in the pharmaceutical and fine chemical industries.

Graphical Abstract