Competing C and N as Reactive Centers for Microsolvated Ambident Nucleophiles CN(HO): A Theoretical Study of E2/S2 Reactions with CHCHX (X = Cl, Br, I).

As an ambident nucleophile, CN has both C and N atoms that can act as the reactive center to facilitate substitution reactions. We investigate in detail the potential energy profiles of CN(HO) with CHCHX (X = Cl, Br, I) to explore the influence of solvent molecules on competition between the different nucleophilic atoms C and N involving the S2 and E2 pathways. The energy barrier sequence for the transition states follows C@inv-S2 < N@inv-S2 < C@anti-E2 < N@anti-E2. When two different atoms act as nucleophilic atoms, the S2 reaction is always preferred over the E2 reaction, and this preference increases with microsolvation. For the ambident nucleophiles CN(HO), C as the reactive center always has stronger nucleophilicity and basicity than N acting as the reactive center. Regarding the leaving group, the height of the energy barrier is positively correlated with the acidity of the CHCHX substrate for the E2 pathway and with X-heterolysis for the S2 pathway. Furthermore, we found that in the gas phase, the energy barrier for different leaving group systems decreases gradually in the order Cl > Br > I, while in the SMD solution, the energy barrier and product energy increase slightly in the system from X = Cl to Br; this change may be due to the significantly weakened transition-state interaction for the X = Br system. Our activation strain, quantitative molecular orbital, and charge analyses reveal the physical mechanisms underlying the various computed trends. In addition, we also demonstrate the two points recently proposed by Vermeeren, P. . 2020, 26, 15538-15548.