Stability and acidity of salicylic acid rotamers in aqueous solution. A continuous model study

Abstract

The stability in solution of the 2,OH-benzoic acid conformers as described by the continuous model of the solvent at the 6–31G */SCF level is discussed, on the basis of the torsional map obtained by rotation of the groups about the two main torsional axes in the flexible rotor approximation, with the geometries fully optimized in vacuo. Its comparison with the in vacuo map shows that salicylic acid behaves somewhat differently in the two media: the most stable conformers in vacuo are the least stabilized by the solvent. Rotamers with the carboxyl H trans with respect to the carbonyl group behave similarly to the corresponding cis rotamers in solution, despite the fact that their structures do not always correspond to a local minimum in vacuo. The solvent stabilizing effect is especially marked (12.5–18 kcal/mol) when the phenolic H is exposed to the solvent (i.e., when it is not involved in an intramolecular H-bond), and it is reduced even by a factor of two when an intramolecular H-bond is formed. Rotamers unfavored in vacuo by as much as 10 kcal/mol present an energy gap in solution of only 3–4 kcal/mol. When both carbonyl O lone pairs are available to interact with the solvent a stabilization of only 4 kcal/mol is observed; an intermediate value is obtained owing to the cooperative effect of just one of these lone pairs and those from the carboxyl O. To the best of our knowledge experimental results are not available for comparison, while previous Monte Carlo simulations show an analogous trend: also there the ΔG of solvation is insufficient to reverse the stability order. The reaction field maps show the high acidity in solution of the phenolic H in contrast with the carboxylic H, in agreement with the finding that the gas-phase acidity of the o- and p- hydroxybenzoic acids is not due to the carboxy but to the hydroxy proton.