Solvent Effects on the Diels-Alder Reaction of Methyl Vinyl Ketone and Cyclopentadiene from Computer Simulations

Abstract

Free energy of solvation profiles for the Diels-Alder reaction of cyclopentadiene and methyl vinyl ketone have been obtained in liquid propane, methanol, and water at 25 °C. Four transition states were located for the gas-phase reaction from ab initio calculations with the 3–21G and 6–31G(d) basis sets. Calculations at the MP3/6–31G(d)//6–31G(d) level confirmed that the endo-cis transition state is lowest in energy. The gas-phase minimum energy reaction path was followed in periodic cells containing 260-500 solvent molecules in Monte Carlo simulations, which yielded the changes in free energies of solvation. Essentially no solvent effect was found in propane; however, hydration is computed to lower the free energy of activation by 4.2 ± 0.4 kcal/mol, similar to experimental observations. Intermediate effects are computed and observed for methanol. The rate accceleration in water is traced to both a hydrophobic effect and enhanced hydrogen bonding to the carbonyl group in the transition state.