A Car-Parrinello Molecular Dynamics Simulation Study of the Retro Diels-Alder Reaction for Partially Saturated 2-Pyrones in Water

2-Pyrones have been identified as potential platform molecules derived from biomass to produce high-value chemicals. Theoretical studies utilizing density functional theory (DFT) simulations have shown the partially saturated form of these molecules undergoing a retro Diels-Alder (rDA) reaction in both vapor and solvent conditions. Developing an understanding of the effect of solvent media is crucial to improve the processing of these biomass-derived compounds. In this context, DFT simulations had shown limited access due to either implicit solvent or static explicit solvent environment applied in the model, which did not account for the contribution from the dynamics. Herein, Car-Parrinello molecular dynamics (CPMD) simulations, in conjunction with metadynamics, were performed to understand the effect of dynamics of the solvent on the rDA reaction of partially saturated 2-pyrones. For this, compounds containing both electron-donating and-withdrawing groups as substituent were studied. It was observed that, in the vapor phase, the results from CPMD simulations were in agreement with our previous DFT results. However, in water, a relative lowering in calculated activation barriers (by similar to 10 kJ/mol) was observed, due to the dynamic behavior of solvent, differentially interacting with the reactant and the activated complex, along the minimum energy path. For hydroxyl substituted 2-pyrones, computed activation free energy of 63 +/- 7 kJ/mol was in agreement with the apparent activation energy measured experimentally (42 +/- 18 kJ/mol). CPMD-metadynamics simulations were further applied to study the reaction energetics of complex 2-pyrone molecule undergoing a similar rDA reaction.