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

Abstract The 96 p K a 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 p K a 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 R 2 =0.95 with a standard deviation (SD) of 0.36 between the experimental p K a values and the calculated dissociation Gibbs free energies [Δ G (calc.)] was found. The slope of p K a vs. ( G (calc.)/(20303 RT ) is only 47.6% of the theoretically expected value, which implies that the Δ G (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 p K a values of carboxylic acids. The p K a values furnished by this procedure are in good agreement with the experimental results for carboxylic acids in aqueous solution.