Steric effects on the proton-transfer equilibria of ketones, sulfoxides, and phenols

The proton-transfer equilibrium of several bases and acids, including some sterically hindered ketones, sulfoxides and phenols, has been investigated through the determination of the thermodynamics of the equilibrium, NMR 13C relaxation measurements and quantum chemical calculations. The analysis of such data yields information on steric effects on basicity or acidity, and on the underlying reasons for the anomalous behavior of species having a sterically hindered basic or acidic site. Thus, it is demonstrated that the anomalously low basicity of two sterically hindered ketones (tBu2CO and PhCOtBu) is enthalpic in origin, and stems from steric hindrance to the solvation of their protonated forms. No such effect is found for analogous sulfoxides, whereas phenols display a more complex behavior.