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 of different families of amines toward HOCl. When solvent effects are included 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 have the highest reactivity, with energy barriers calculated between 160 and 225 kJ mol−1 (B2PLYPD/AUG-cc-pVTZ//B3LYP/6-31G(d) level). The substituted anilines are the least reactive species, with energy barriers calculated as high as 300 kJ mol−1. 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, and H) involved in an intramolecular rearrangement, and the second in which the hydrogen-bridged structure TSb is characterized with the linear NClO moiety. The former is energetically more feasible (ca. 120 kJ mol−1) for alkyl-, cycloalkyl-, and heterocyclic amines, whereas the latter is operative in the case of aromatic amines. If two water molecules are explicitly included in the calculations, the rate-determining transition state TSw has been 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 NCl bond formation. To reproduce the experimentally observed trends in reactivity of amines, the inclusion of bulk and specific solvent effects is mandatory. Steric effects have been found to govern the reactivity of alkylamines, that is, more bulkier amines react slower with HOCl. It has been found that electronic structure parameters (HOMO–LUMO gap, natural bond orbital 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. © 2012 Wiley Periodicals, Inc.