Correlation of the acidity of substituted phenols, anilines, and benzoic acids calculated by MNDO, AM1, and PM3 with Hammett‐type substituent constants

Abstract

Heats of formation and net atomic charges of some 120 structures involving substituted phenols, anilines, and benzoic acids and the corresponding anions were calculated by MNDO, AM1, and PM3 semiempirical methods. The gas phase acidities of substituted phenols and anilines and the net atomic charges on the anionic heteroatoms of the corresponding anions have been successfully correlated with u-constants. Moreover, good correlations with u were found for the charges on the acidic hydrogens of substituted phenols and anilines. In contrast, the gas phase acidities of substituted benzoic acids and the charges on the anionic oxygens of the corresponding anions are better correlated with Taft uo constants. Comparisons of these results with experimental data and ah initio theoretical calculations indicate that AM1 and PM3 methods are much better than MNDO in predicting the acidity of aromatic compounds.

Baker–Nathan effect, hyperconjugation and polarizability effects in isolated molecules

“…16 We will try here to substitute for them energies calculated at the semiempirical level (methods AM1 and PM3 17,18 ) which were proved recently to be satisfactory for similar problems. 3,5, 19 We shall not deal with the whole concept of hyperconjugation but restrict our considerations to the equilibrium processes of aromatic compounds, i.e. to substituted benzyl cations.…”

Hydroxyl stretching in substituted phenols: An AM1 study

“…This information adds to the limited data base for hydroxyl-stretching predictions using the AM 1 approach and indicates that phenols, in general, are well described using this Hamiltonian. The correlation between the hydroxyl stretching of monosubstituted phenol correlated strongly with Hammett sigma values, but this is not surprising due to the multiple correlations involved and the well-known ability of semiempirical techniques to recognize substituent effects [25][26][27].…”

Theoretical analysis of peptidyl α-ketoheterocyclic inhibitors of human neutrophil elastase: Insight into the mechanism of inhibition and the application of QM/MM calculations in structure-based drug design

“…We have employed the PM3 Hamiltonian for the bulk of the QM/MM calculations since it has previously been shown to be as effective as ab initio methods for describing intrinsic substituent effects on the acidity of a variety of systems. 37 As a similar substituent effect is expected to operate in this case to control the electrophilicity of these inhibitors, the PM3 method should give relative energetics of sufficient accuracy to differentiate between the two mechanisms. The QM/MM program, which couples the AMBER 38 and Gaussian94 39 programs together, has been described previously, 13 together with the way of 'linking' the QM and MM regions across a covalent junction.…”