Computational Estimation of the Aqueous Acidities of Alcohols, Hydrates, and Enols

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2021-05, Vol.125 (17), p.3600-3605
• Main Authors: Baldasare, Corey A, Seybold, Paul G
• Format: Article
• Language: English
• Subjects: A: Structure, Spectroscopy, and Reactivity of Molecules and Clusters
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/acs.jpca.1c01330

Alcohols are ubiquitous chemical species, and their acid dissociation constants are critical properties in many applications. It is useful to have a reliable and convenient computational procedure for estimating these acidities. Here we describe a quantitative structure–activity relationship (QSAR) for the pK as of alcohols in aqueous solution employing density functional theory computations at the B3LYP/6-31+G­(d,p) level with the CPCM implicit solvent model for the aqueous solutions. For the pK as, the energy difference in solution between the parent compound and the anion, ΔE(H2O), was used as a single descriptor. High quality QSAR equations are obtained both for the gas-phase Gibbs energy changes (ΔG r 0s, R 2 = 0.9764) and the aqueous pK as (R 2 = 0.9594). It is shown that the aqueous equation can also be used to estimate the pK as of fluorinated alcohols, hydrates formed by carbonyl compounds in aqueous solution, and enols that appear as minor components in keto–enol equilibria.