engleski

Reactivity of Amines with Hypochlorous Acid. Computational Study of Steric, Electronic, and Medium Effects.

N-chlorination reactions of alkyl-, cycloalkyl-, heterocyclic, and aromatic amines by HOCl have been investigated in the gas and aqueous phase. Density functional (B3LYP), double hybrid (B2PLYPD), and composite theoretical model (G3B3) have been used to assess steric, electronic and solvent effects on the reactivity toward HOCl of different families of amines. When the solvent effects are included in calculations by using CPCM/UAHF model, all computational methods predict the same order of reactivity within each group of amines. In agreement with experimental data heterocyclic amines are the most reactive with energy barriers for N-chlorination calculated between 160 – 225 kJ/mol (B2PLYPD/AUG-cc-pVTZ//B3LYP/6-31G(d) level), whereas substituted anilines are the least reactive species with energy barriers calculated as high as 300 kJ/mol. Two different reaction mechanisms of N-chlorination have been considered in the gas phase: the one, which includes the transition state TSa with cyclic arrangement of four atoms (N, Cl, O, H) involved in an intramolecular rearrangement, and the second in which the hydrogen-bridged structure TSb is characterized with the linear N-Cl-O moiety. The former is energetically more feasible (ca. 120 kJ/mol) for alkyl-, cycloalkyl-, and heterocyclic amines, while the latter is operative in the case of aromatic amines only. If two water molecules are explicitly included in calculations, the rate-determining transition state TSw was located for N-chlorination of all amines under study. It is characterized by eight-membered ring geometry in which water molecules assist the simultaneous transfer of the three hydrogen atoms coupled with the N-Cl bond formation. In order to reproduce the experimentally observed trends in reactivity of amines toward HOCl the inclusion of bulk and specific solvent effects is mandatory. Steric effects were found to govern the reactivity of alkylamines, i.e. more bulkier amines were found to react slower with HOCl. It was also found that electronic structure parameters (HOMO-LUMO gap, NBO occupancy and NPA charge on N atom) can be successfully used as descriptors for the reactivity of heterocyclic and aromatic amines. These results indicate the predictive power of our computational approach which can be applied to calculate nucleophilic reactivities of more complex structures of environmentally or biologically relevant amines.

N-chlorination; reaction mechanism; amines; HOCl; computational chemistry

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