Ionic Liquid–Catalyzed Annulation of Biomass-Derived Alkyl Lactates: Time-Dependent Tunable Synthesis of Bioactive Dihydroquinoxalines and Quinoxalines

Abstract

Recyclable ionic liquid–catalyzed tandem annulation of alkyl lactates has been demonstrated, enabling divergent synthesis of dihydroquinoxalines and quinoxalines as a function of reaction time. Notably, dihydroquinoxalines could be furnished swiftly at room temperature with high yields. More significantly, the tunable synthesis is exemplified by repeatably stopping–restarting processes. Furthermore, biological studies indicate that dihydroquinoxalines with alkoxycarbonyl substitution at the C4 position are promising agrochemical candidates in terms of their antifungal activity. This method features the advantages of biomass utilization (RP > 75%), eco-benign manner (E-factor < 3), and the capacity for antileishmanial agent synthesis. Mechanistic studies established a kinetic preference for the formation of dihydroquinoxaline rather than quinoxaline through decarboxylation being thermodynamically favored. The current study reveals that reaction time could modulate the selective conversion of lactates and demonstrates the feasibility of the production of biologically valuable heterocycles from biomass.