Chloride-free indium(III)-catalyzed glucose-to-HMF conversion: Overcoming kinetic barriers via water-mediated direct dehydration

This study investigates the mechanism of glucose-to-HMF conversion catalyzed by indium(III) nitrate hydrate [In(NO3)3·14.4 H2O], achieving remarkable HMF selectivity (84.6 %) and yield (83.8 %). Unlike conventional pathways that involve glucose-to-fructose isomerization, our findings demonstrate a direct dehydration route with 2,5-anhydromannose as a key intermediate. Experimental and theoretical insights from ex-situ FT-IR spectroscopy, kinetic analyses, Gibbs free energy calculations, and molecular dynamics simulations reveal that In(NO3)3·14.4 H2O facilitates glucose activation via a water-mediated proton exchange mechanism. The coordinated water molecules lower energy barriers, enhancing catalytic efficiency. Comparative studies highlight the superior reactivity of nitrate-based systems over their chloride, sulfate, and phosphate analogs. Notably, In(NO3)3·14.4 H2O functions as a phase-reversible catalyst, combining the advantages of both homogeneous and heterogeneous catalysis, thereby enabling facile recyclability while maintaining catalytic performance over five cycles. This work provides key insights into designing halogen-free catalytic systems for efficient HMF production while overcoming thermodynamic and kinetic challenges, paving the way for sustainable bio-based chemical manufacturing.