PKa prediction from an ab initio bond length: Part 3 - Benzoic acids and anilines

A. P. Harding, P. L A Popelier

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    The prediction of pKa from a single ab initio bond length has been extended to provide equations for benzoic acids and anilines. The HF/6-31G(d) level of theory is used for all geometry optimisations. Similarly to phenols (Part 2 of this series of publications), the meta-/para-substituted benzoic acids can be predicted from a single model constructed from one bond length. This model had an impressive RMSEP of 0.13 pKa units. The prediction of ortho-substituted benzoic acids required the identification of high-correlation subsets, where the compounds in the same subset have at least one of the same (e.g. halogens, hydroxy) ortho substituent. Two pKa equations are provided for o-halogen benzoic acids and o-hydroxybenzoic acids, where the RMSEP values are 0.19 and 0.15 pKa units, respectively. Interestingly, the bond length that provided the best model differed between these two high-correlation subsets. This demonstrates the importance of investigating the most predictive bond length, which is not necessarily the bond involving the acid hydrogen. Three high-correlation subsets were identified for the ortho-substituted anilines. These were o-halogen, o-nitro and o-alkyl-substituted aniline high-correlation subsets, where the RMSEP ranged from 0.23 to 0.44 pKa units. The RMSEP for the meta-/para-substituted aniline model was 0.54 pKa units. This value exceeded our threshold of 0.50 pKa units and was higher than both the m-/p-benzoic acids in this work and the m-/p-phenols (RMSEP = 0.43) of Part 2. Constructing two separate models for the meta- and para- substituted anilines, where RMSEP values of 0.63 and 0.33 pKa units were obtained respectively, revealed it was the meta-substituted anilines that caused the large RMSEP value. For unknown reasons the RMSEP value increased with the addition of a further twenty meta-substituted anilines to this model. The C-N bond always produced the best correlations with pKa for all the high-correlation subsets. A higher level of theory and an ammonia probe improved the statistics only marginally for the hydroxybenzoic acid high-correlation subsets. © the Owner Societies.
    Original languageEnglish
    Pages (from-to)11283-11293
    Number of pages10
    JournalPhysical Chemistry Chemical Physics
    Issue number23
    Publication statusPublished - 21 Jun 2011


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