Molecular Dynamics Simulations and Experimental Verification to Determine Mechanism of Cosolvents on Increased 5-Hydroxymethylfurfural Yield from Glucose

Commercializing production of 5-hydroxymethylfurfural (HMF) from glucose has been hindered by low conversion of glucose and moderate HMF yields and selectivity. While it is commonly known that solvents such as dimethyl sulfoxide (DMSO) and acetonitrile increase HMF yields, neither solvent has been investigated with the use of maleic acid and aluminum chloride (AlCl3) for HMF production. We present kinetic analysis of HMF production from glucose using maleic acid and AlCl3 in water/cosolvent mixtures. Notably, acetonitrile (40% v/v) improves glucose isomerization, while DMSO (20% v/v) doubles fructose dehydration while also inhibiting HMF degradation. Molecular dynamics simulations are used to demonstrate that acetonitrile likely increases glucose isomerization by reducing the average distance of water from glucose. Using a predictive model, we optimize reaction conditions for 30 wt % glucose. By reducing sugar concentration throughout the reaction, degradation of sugars to humins is reduced. We further show that HMF solubility at high concentrations drastically limit yields. This is partially overcome by combining acetonitrile and DMSO as cosolvents, resulting in over 30% molar HMF yield from 30 wt % glucose. This improved understanding of the conversion of glucose to HMF suggests that biphasic reaction systems with nonprotic cosolvents may result in more economic commercial production.