Calculation of the relative acidities and oxidation potentials of para-substituted phenols. A model for α-tocopherol in solution

Abstract

Relative acidities (ΔpK_a) of phenols and oxidation potentials (ΔE_ox) of the phenoxide anions have been calculated for nine para-substituted phenols using density functional theory. Solvent effects were incorporated using the conductor-like polarisable continuum method. Using the calculated ΔpK_a and ΔE_ox values in a thermodynamic cycle, the ΔBDE (bond dissociation enthalpy) of the phenols were also determined with all values calculated to within 1.5 kcal mol⁻¹ of experiment. The ΔpK_a and ΔE_ox values were calculated for 6-hydroxy-2,2,5,7,8-pentamethylchroman (HPMC), a model for α-tocopherol for which there are no known experimental values. The acidity of this compound is raised by 2.4 pK_a units and lowered by −0.79 V relative to phenol with a calculated ΔBDE of −14.9 kcal mol⁻¹. There is a negative correlation (r² = 0.86) between the ΔpK_a and the ΔBDE values. A stronger and positive correlation is found between the ΔE_ox (r² = 0.98) and the ΔBDE values. Using these correlations it is uncovered that hydrogen abstraction of phenols, as measured by the ΔBDE, is driven by electron transfer rather than by proton transfer.