Exploring a Mechanistic Descriptor in the Design of Solvents for Acid-Catalyzed Transformation of Biorenewable Platform Chemicals

Brønsted acid-catalyzed reactions in solvents present a versatile approach for the liquid-phase processing of biomass into valuable products. In these reactions, the choice of solvent is as crucial as the choice of catalyst as it significantly influences the production of biorenewable chemicals. Mevalonolactone (MVL), featuring a cyclic ester and a hydroxyl group, is an ideal biomass-derived platform chemical for studying acid-catalyzed reactions in solvents. MVL is commonly used to produce isoprene, a precursor for synthetic rubber. To design effective solvents for MVL dehydration, a molecular-level reactivity descriptor was examined in the organic solvent tetrahydrofuran (THF), water, and their mixtures. This descriptor acts as a mechanistic switch in the MVL dehydration reaction. Replacing water with THF led to a notable decrease in the free energy barrier of the reaction, from 108 to 82 kJ/mol, as determined by ab initio molecular dynamics and metadynamics simulations. The mechanistic descriptor was quantified as the coordination number of water molecules having strong interactions with the cyclic ester functionality of the MVL across different THF/water ratios. This descriptor showed a significant correlation with both experimentally measured MVL conversion and theoretically estimated free energy barriers of the dehydration reaction, offering valuable insights into rational solvent design.