Catalytic Regulation of Reaction Networks in High-Concentration 5-Hydroxylmethylfurfural Oxidation

Abstract The selective oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) is a key catalytic transformation for the production of renewable polymers. Although near-quantitative FDCA yields can be achieved under dilute conditions, increasing substrate concentration fundamentally alters the reaction regime, where catalytic oxidation pathways become strongly coupled with oxygen transfer, intermediate accumulation, and catalyst stability. Under concentrated conditions, intensified side reactions, humin formation, and catalyst deactivation collectively disrupt selective oxidation and severely limit process scalability. In this review, we define a concentration greater than 1 wt % as high concentration and present a mechanism-oriented perspective on high-concentration HMF oxidation, focusing on how substrate concentration reshapes catalytic reaction networks and governs the competition between desired oxidation pathways and parasitic reactions. Rather than classifying catalysts by composition, we establish a unified conceptual framework linking catalytic oxygen activation, reaction kinetics, mass transport, and microenvironment effects. Recent advances in noble metal, non-noble metal, and carbon-based catalytic systems are critically re-evaluated through this framework, together with emerging solvent-regulation and dynamic protection–deprotection strategies. Particular emphasis is placed on how catalytic systems regulate reaction flux under concentrated conditions through oxygen activation, intermediate stabilization, and pathway selection. Finally, key challenges and future opportunities are discussed, highlighting reaction network regulation as a central strategy for scalable biomass oxidation.