Theoretical investigation of reactivities of amines in the N-nitrosation reactions by N2O3.

N-nitrosamine is a class of carcinogenic, mutagenic, and teratogenic compounds, which can be produced from N-nitrosation of amine by nitrosating agents. N-nitrosation of 19 amines (eight acyclic amines, five heterocyclic amines, and six amines with unsaturated groups) by N(2)O(3) was investigated at the CBS-QB3 level of theory. The results indicate that generally the heterocyclic amines have the highest reactivities among the three kinds of amines, whereas the reactivities of the amines with unsaturated and electron-withdrawing groups are relatively low. Frontier molecular orbital analysis indicates that the energy gap between the HOMO of an amine and the LUMO of N(2)O(3) has a close connection with the reactivity of an amine. A structure-reactivity relationship of amines in the N-nitrosation reactions by N(2)O(3) was established using the stepwise multivariate linear regression. The results indicate that the reactivity of an amine has a definite relationship (R (adj) (2) = 0.947) with the heterolytic bond dissociation energy of R(1)R(2)N-H bond, energy of HOMO, NBO occupancy of the natural lone pair orbital of N atom, the NBO charge of the N atom, and the pyramidalization angle of an amine. This work will be helpful to gain more insight into the N-nitrosation reactions.