Biphasic dehydration of fructose to 5-hydroxymethylfurfural (HMF) has shown unprecedented increases in productivity, but a mechanistic understanding is lacking. Herein, we couple fast experimental reaction kinetics, multiscale modeling (phase behavior, classical molecular dynamics(MD), and quantum mechanics/molecular mechanics MD), in situ sampling, and IR and ¹³C-NMR spectroscopy to elucidate the complex effects of nonpolar extracting organic solvents on the kinetics of fructose dehydration. We show that these organic solvents can reach significant mutual solubility with water at reaction temperatures, enabling the partition of the sugar and catalyst into the extracting phase. In the organic-rich environment, the dehydration of fructose proceeds faster and more selectively than in water due to increased relative abundance of the reactive furanose isomer, enhanced water–catalyst–substrate interactions driven by nanophase separation, and higher product stability stemming from preferential solvation. We demonstrate that these solvent effects impact other critical biphasic reactions in biomass upgrading and provide qualitative principles for solvent selection.

中文翻译：

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意想不到的动力学溶剂效应增强双相系统的活性和选择性

果糖双相脱水生成 5-羟甲基糠醛 (HMF) 的生产率已显示出前所未有的提高，但缺乏机制理解。在这里，我们结合了快速实验反应动力学、多尺度建模（相行为、经典分子动力学 (MD) 和量子力学/分子力学 MD）、原位采样以及 IR 和¹³C-NMR 波谱阐明非极性萃取有机溶剂对果糖脱水动力学的复杂影响。我们表明，这些有机溶剂在反应温度下可以与水达到显着的互溶性，从而使糖和催化剂能够分配到萃取相中。在富含有机物的环境中，由于反应性呋喃糖异构体的相对丰度增加、纳米相分离驱动的水-催化剂-底物相互作用增强以及优先溶剂化带来的更高的产品稳定性，果糖的脱水比在水中进行得更快、更具选择性。我们证明这些溶剂效应会影响生物质升级中的其他关键双相反应，并为溶剂选择提供定性原则。