Analysis of the p K a s 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 p K a variations of these compounds. The present study examines whether a similar analysis can be extended to the p K a s of nonaromatic amines. A particular interest will lie in assessing the role of the aqueous solvent in influencing the p K a s. 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 p K a s. However, addition of a solvent model (SM5.4A, Chambers et al., J Phys Chem 1996, 100, 16385) leads to good correlations between the experimental p K a s and the energy differences (Δ E aq ) 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, 2008