Elucidating the Role of Solvents in Acid Catalyzed Dehydration of Biorenewable Hydroxy-Lactones

Owing to the low boiling point, Tetrahydrofuran (THF) forms an economical choice of solvent in biorenewable processing. Multifold acceleration in reaction rates is experimentally observed for Br{\o}nsted acid catalyzed reactions in THF, as compared to that of water. Herein, utilizing ab-initio Car-Parrinello Molecular Dynamics (CPMD), classical Molecular Dynamics (MD) and Density Functional Theory (DFT) simulations, a systematic theoretical framework is presented to explain the significant differences in the reactivity of Br{\o}nsted acid protons in THF as compared to that of water. The probe reaction of choice is the dehydration of 4-hydroxy-6-methyl lactone (HML) obtained from a biomass-derived substrate. Classical MD simulations are elucidating the hydrogen bonding networks formed around the hydroxyl group of the reactant HML in presence of explicit solvation environment of water and THF. Activation free energy barrier for the water removal step is calculated using CPMD metadynamics simulations. In THF, the free energy barrier is 107 kJ/mol, which is observed to be lower by 26 kJ/mol, as compared to that of water. This significant difference in activation free energies for the dehydration step explains the difference in reactivity. Static DFT simulations further elaborated the effect of first solvation shell, around the hydroxyl substituent in describing the activation barriers of the dehydration reaction. While the solvent environment in DFT simulations is kept implicit in nature, few explicit molecules of THF and water are allowed to interact with the hydroxyl group and $\beta$-carbon of HML. Activation energies for the dehydration of HML are calculated to be 103 kJ/mol in the pure water environment. Akin to the difference in free energy barriers obtained from CPMD calculations, the activation energy calculated from DFT is observed to be 25 kJ/mol lower in THF as compared to that of water.