Theoretical Studies of Solvent Effect on the Basicity of Substituted Pyridines

Abstract

Molecular orbital calculations have been carried out of the basicities of substituted pyridines in the gas phase at the HF/6-31G*, MP2/6-31G*, and B3LYP/6-31G* levels and in solution based on the isodensity surface-polarized continuum model (IPCM). The correlated gas-phase MO basicities, especially at the MP2 level, agree well with the experimental gas-phase results. The IPCM model with MP2/6-31G* and B3LYP/6-31G* geometries also reproduces well the solvation free energy difference, ΔG°s, between the pyridinium ion and neutral pyridine in water, although it leads to a somewhat greater negative slope for the pKa(aq) vs σ plot (ρaq = −8.6 and −9.0 at the MP2/6-31G* and B3LYP/6-31G* levels, respectively, in contrast to the experimental slope of ρaq = −5.8). The model predicts a linear correlation between the theoretical (IPCM) ρ values in solution and the Onsager dielectric function (ε − 1)/(2ε + 1). The estimate of ion solvation free energy for H+ in acetonitrile (G°s = −250.4 kcal mol-1) indicates that there is a constant pKa difference of ΔpKa (=pKa(AN) − pKa(W)) = 7.7. This is due solely to the H+ ion solvation free energy difference of 10.5 kcal mol-1 between acetonitrile and water with near unity (1.02) slope for the δpKa(AN) vs δpKa(W) plot. The π donor effect of strong para π acceptors (p-CN, p-NO2, etc.) on the pKa values of pyridinium ions was found in the gas phase as well as in solution.