Universal Trends between Acid Dissociation Constants in Protic and Aprotic Solvents

pKa values in non-aqueous solvents are of critical importance in many areas of chemistry. Our knowledge is, despite their relevance, still limited to the most fundamental properties and few pKa values in the most common solvents. Taking advantage of a recently introduced computationally efficient procedure we computed the pKa values of 182 compounds in 21 solvents. This data set is used to establish for the first time universal trends between all solvents. Our computations indicate, that the total charge of the molecule and the charge of the acidic group combined with the Kamlet-Taft solvatochromic parameters are sufficient to predict pKa values with at least semi- quantitative accuracy. We find, that neutral acids such as alcohols are strongly affected by the solvent properties. This is contrasted by cationic acids like ammonium ions whose pKa is often almost completely independent from the choice of solvent.

Automated summary

pKa values in non-aqueous solvents are crucial in chemistry, and our understanding of them is still limited. Using computational methods, we have established universal trends between solvents and found that the total charge of the molecule and the charge of the acidic group, combined with solvatochromic parameters, can predict pKa values with reasonable accuracy. We also observe that neutral acids are significantly influenced by solvent properties, while cationic acids are often independent of solvent choice.