Theoretical studies of solvent effect on the basicity of substituted pyridines

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, Delta G(s)degrees between the pyridinium ion and neutral pyridine in water, although it leads to a somewhat greater negative slope for the pK(a)(aq) vs sigma plot (rho(aq) = -8.6 and -9.0 at the MP2/6-31G* and B3LYP/6-31G* levels, respectively, in contrast to the experimental slope of rho(aq), = -5.8). The model predicts a linear correlation between the theoretical (IPCM) rho values in solution and the Onsager dielectric function (is an element of - 1)/(2 is an element of + 1). The estimate of ion solvation free energy for H+ in acetonitrile (G(s)degrees = -250.4 kcal mol(-1)) indicates that there is a constant pK(a), difference of Delta pK(a) (=pK(a)- (AN) - pK(a)(W)) = 7.7. This is due solely to the H+ ion salvation free energy difference of 10.5 kcal mol(-1) between acetonitrile and water with near unity (1.02) slope for the delta pK(a)(AN) vs delta pK(a)(W) plot. The pi donor effect of strong para pi accepters (p-CN, p-NO2, etc.) on the pK(a), values of pyridinium ions was found in the gas phase as well as in solution.