Competitive dynamics of elimination and substitution reactions modulated using nucleophiles and leaving groups

Abstract

The competition between base-induced elimination (E2) and bimolecular nucleophilic substitution (S_N2) reactions and their intrinsic reactivity are hot issues in organic chemistry research. To investigate the influence factors of E2/S_N2 channel selectivity, the HO⁻ + CH₃CH₂Br reaction was performed utilizing direct dynamics simulations to unravel how the nucleophile and leaving group modulate the microscopic mechanisms of the X⁻ (X = F and HO) + CH₃CH₂Y (Y = Cl and Br) reactions. Our simulations showed a significant increase in the direct mechanism branching ratio from 0.41 to 0.62 when the nucleophile was changed from F⁻ to HO⁻. This mechanism shift was driven by the entrance channel complex's geometric configuration and the ion-molecular intermediate's lifetime. The disappearance of hydrogen-bonded complexes suppressed prolonged interactions of the prereaction complex, with more than half of the trajectories separating into products directly after the first collision. When the leaving group was changed from Cl to Br, the anti-E2 channel still dominated for the HO⁻ + CH₃CH₂Br reaction, although its decreased proportion indicated that S_N2 was more competitive. This result was attributed to the decrease in the b_max value in the HO⁻ + CH₃CH₂Br reaction, which diminished the role of direct stripping mechanism at large collision parameters and ultimately decreased the probability of the anti-E2 reaction. This study underscores the impact of nucleophiles and leaving groups on the dynamics of E2/S_N2 competition and its microscopic mechanisms, providing valuable insights into reaction selectivity in complex chemical environments and systems.