Computational calculation of absolute aqueous pKa values for phenols

A mixed implicit–explicit solvation approach has been used to calculate absolute aqueous pKa values for a range of phenols using the economical and ubiquitous B3LYP/6-31+G* model. Judicious positioning of two water molecules around the phenol OH group and around the phenoxide O− group, along with use of a simple PCM implicit solvation model gives a good agreement between calculated and experimental values for phenol acidity; this agreement is improved if a small (−1.40 kcal mol−1) correction factor is applied. This approach offers a simple, rapid, and cost-efficient means of estimating aqueous pKa values for phenols.