Thermodynamic Estimate of pKa Values of the Carboxylic Acids in Aqueous Solution with the Density Functional Theory

Abstract

AbstractThe 96 pKa values of 85 carboxylic acids in aqueous solution were calculated with the density functional theory method at the level of B3LYP/6‐31+G(d,p) and the polarizable continuum model (PCM) was used to describe the solvent. In the calculations of pKa values, the dissociation Gibbs free energies were directly calculated using carboxylic acid dissociation reactions in aqueous solution, i. e., no thermodynamic cycle was employed, which is different from the previous literatures. A highly significant correlation of R2=0.95 with a standard deviation (SD) of 0.36 between the experimental pKa values and the calculated dissociation Gibbs free energies [ΔG(calc.)] was found. The slope of pKa vs. (G(calc.)/(20303RT) is only 47.6% of the theoretically expected value, which implies that the ΔG(calc.) value from the theoretical calculation is larger than the actual one for all 85 carboxylic acids studied. Thus, by adding the 0.476 scaling‐factor into the slope, we can derive a reliably procedure that can reproduce the experimental pKa values of carboxylic acids. The pKa values furnished by this procedure are in good agreement with the experimental results for carboxylic acids in aqueous solution.