Theoretical Investigation of the Gas-Phase S2 Reactions of Anionic and Neutral Nucleophiles with Chloramines.

The S2 reactions at nitrogen center (S2@N) play a significant role in organic synthesis, carcinogenesis, and the formation of some environmentally toxic compounds. However, the S2@N reactions specifically for neutral compounds as nucleophiles are less known. In this work, reactions of dimethylamine (DMA) and F with NHCl were investigated as model reactions to validate an accurate functional from 24 DFT functionals by comparing with the CCSD(T) reference data. M06-2X functional was found to perform best and applied to systematically explore the trends in reactivity for halides (F and Cl) and simple amines toward the substrates NHCl and NHCl (S2@N) as well as CHCl and CHCl (S2@C). The computational results show that the backside inversion channel dominates most the S2@N reactions except for the case of F + NHCl, which reacts preferentially via proton transfer. The overall activation free energies (Δ G) of the inversion channel for the S2 reactions of F and Cl with chloramines are negative, whereas those for amines as nucleophiles are around 30-44 kcal/mol. The S2@N reactions for all the nucleophiles investigated here are faster than the corresponding S2@C. Moreover, amines react faster when they have a higher extent of methyl substitution. Additionally, the energy gap between the HOMO of nucleophile and LUMO of substrate generally correlates well with Δ G of the corresponding S2 reactions, which is consistent with previous results.