Overcoming Interfacial Kinetic Barriers in 5-Hydroxymethylfurfural Extraction Using Salt and Amphiphilic Modifiers in...

5-Hydroxymethylfurfural (HMF) is a biomass-derived platform chemical with significant potential in the sustainable production of fuels and value-added chemicals. However, its large-scale synthesis from glucose in aqueous media is limited by humin formation arising from HMF accumulation, as well as its instability under acidic reaction conditions. These challenges highlight the need for rapid in situ extraction strategies to stabilize HMF and suppress side reactions. Accordingly, the development of environmentally benign and economically viable catalytic systems that enable efficient HMF extraction while maintaining catalytic performance is critical. Herein, molecular dynamics (MD) and enhanced sampling simulations are employed to investigate water-supercritical CO2 (scCO2) biphasic systems, with a focus on how interfacial properties govern HMF partitioning under varying temperature, pressure, and salt concentrations. MD simulations reveal that salt concentration has a stronger influence than pressure in modulating interfacial structure and properties, including interface thickness and interfacial tension. Despite an increased affinity of HMF for the scCO2 phase at elevated salt concentrations and pressures, it preferentially accumulates at the interface due to kinetic barriers and weaker stabilization in scCO2, as revealed by free-energy calculations using enhanced sampling simulations. Building on these insights, a strategy employing amphiphilic modifiers is used to enhance HMF extraction by facilitating its transport across the interface and by stabilizing HMF in scCO2. This approach is validated through simulations with isopropanol, which show a significant increase in HMF density in the scCO2 phase.