QUANTIFICATION OF SOLVENT EFFECTS ON THE ACIDITIES OF Z-ESTER AND E-ESTER FROM FLUID SIMULATIONS

Solvents effects on the acidities of Z and E esters have been investigated using Monte Carlo simulations with statistical perturbation theory. The differences in free energies of hydration for (Z)- and (E)-methyl acetate and for the corresponding Z and E anions in both acetonitrile and water have been computed. Ab initio molecular orbital calculations with the 6-31+G(d) basis set were used to develop the necessary anion-water potential functions for the liquid simulations. The Monte Carlo simulations predict a preferential stabilization of the less stable E ester by 3.0 +/- 0.2 kcal/mol in water and by 2.7 +/- 0.1 kcal/mol in acetonitrile. The free energies of solvation of the E anion are also predicted to be more favorable than for the Z form by 2.3 +/- 0.2 kcal/mol in water and 1.5 +/- 0.2 kcal/mol in acetonitrile. The gas-phase rotational barriers between the Z and E isomers are computed to be 14.1 and 5.0 kcal/mol for the ester and anion. These results are compared to experimental observations on the unusual acidity of Meldrum's acid, and with the solvent effects on intramolecular Diels-Alder reactions involving ester tethers.