Analysis of the pKas of Aliphatic Amines Using Quantum Chemical Descriptors

Previous theoretical studies (Gross and Seybold, Int J Quantum Chem 2000, 80, 1107; Gross et al., J Org Chem 2001, 66, 6919; Gross et al., Int J Quantum Chem 2002, 90, 445) demonstrated that variations in several quantum chemical charge and energy indices for substituted anilines were strongly correlated with the experimentally observed pKa variations of these compounds. The present study examines whether a similar analysis can be extended to the pKas of nonaromatic amines. A particular interest will lie in assessing the role of the aqueous solvent in influencing the pKas. It is found that, in general, the quantum chemical indices obtained for the isolated molecules in the aliphatic amines do not correlate strongly with the experimental pKas. However, addition of a solvent model (SM5.4A, Chambers et al., J Phys Chem 1996, 100, 16385) leads to good correlations between the experimental pKas and the energy differences ( Eaq) between the neutral amines and their cations. The calculations in this study were performed at both the semiempirical RM1 and density functional B3LYP/6-31G* levels. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem 108: