Estimating the pKa of phenols, carboxylic acids and alcohols from semi-empirical quantum chemical methods

Quantitative structure property relationships (QSPR) for the pK(a) of phenols, carboxylic acids and alcohols were developed from descriptors derived from semi-empirical molecular orbital theory quantum chemical calculations. A training set of compounds were used to refine the models and a validation set of appropriate chemicals were chosen to test the models. Correlation coefficients for the estimated versus observed pK(a) values were 0.96 for phenols, 0.84 for non-aromatic carboxylic acids, 0.89 for benzoic acids and 0.89 for alcohols. The results obtained by the quantum chemical method are compared to results obtained from linear free energy relationships (LFER) and the merits of each approach are discussed., (C)1998 Elsevier Science Ltd. All rights reserved.