Understanding the substituent effect on the acidity of alcohols and para-substituted phenols

Abstract

We carried out Hartree–Fock (HF) and density functional theory calculations on the conjugated bases of phenols and alcohols for 23 compounds and analysed their acid–base behaviour using molecular orbital (MO) energies and their dependence on solvent effects. Despite the well-known correlation between highest-occupied MO (HOMO) energies and proton affinity (PA), we observed that HOMO energies are inadequate to describe the acid–base behaviour of these compounds. Therefore, we established a criterion to identify the best frontier MO for describing PA values and also to understand why the HOMO approach fails. The MO that fits our criterion provided very good correlations with PA values, much better than those obtained by the HOMO energies. Since the frontier MOs are those which drive the acid–base reactions in each compound, they were called frontier effective-for-reaction MOs, or FERMOs. By using the FERMO concept, the reactions that are HOMO driven, and those that are not, can be better explained, independent of the calculation method used, since both HF and Kohn-Sham methodologies lead to the same FERMO.