Computational Estimation of the Gas-Phase and Aqueous Acidities of Carbon Acids

Carbon acids are compounds which ionize by dissociating along carbon-hydrogen bonds. Although commonly noted for the extremely low acidities of some members of this class, these compounds in fact display a wide range of pK_as and upon proper substitution can even form strong acids. This study employs density functional theory to estimate the gas-phase acidities (ΔG°s) of these compounds and applies a quantitative structure-activity relationship (QSAR) method at the B3LYP/6-31+G** level with the CPCM aqueous solvent model to estimate their aqueous pK_as. For the latter study, the energy difference ΔE(H₂O) in water between the parent compounds and their dissociation products was used as a single parameter. Good quality QSAR regression equations were obtained for both the gas-phase (R² = 0.9905) and aqueous (R² = 0.9647) dissociations. These equations should be useful for the estimation of missing pK_as for compounds in this class. A general discussion of the features affecting the pK_as of these compounds is also given.