Comprehensive comparison between the gas-phase S_N2 reactions at carbon and at nitrogen

As one of the most important chemical reactions, S_N2 reactions play a central role in both synthetic chemistry and the development of mechanistic paradigms. Most of the previous attention has centered on substitution at carbon, whereas displacement at nitrogen is clearly less studied and less understood. The S_N2@N reactions have enormous synthetic potential, especially in heterocyclic chemistry, which is a cornerstone of medicinal chemistry, and has been receiving increasing attention, both experimentally and computationally. In this review, we outline the experimental and theoretical studies on the gas-phase S_N2 reactions at nitrogen in recent years, and make comprehensive comparisons between gasphase SN2 at carbon and at nitrogen. Some new structure-energy relationships have been proposed. Meanwhile, the similarities and differences of the α-Effect, which refer to the increased nucleophilicity relative to a given basicity for nucleophiles with one or more pairs of unshared electrons adjacent to the attacking atom, between the gas-phase S_N2@C and S_N2@N reactions are discussed.