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E2/S<sub>N</sub>2 Selectivity Driven by Reaction Dynamics. Insight into Halogen Bonding

Siwei Zhao, Hongyi Wang, Gang Fu, Wenqing Zhen, Meiling Liu, Li Yang, Jiaxu Zhang

2023Precision Chemistry14 citationsDOIOpen Access PDF

Abstract

High Resolution Image Download MS PowerPoint Slide Ubiquitous competition of stereospecific E2 elimination versus S N 2 substitution is of central importance in chemical synthesis. Herein, we uncover how the nature of the leaving group affects the intrinsic competing dynamics that remains largely unknown as opposed to its role in reactivity. Results are presented for a prototype case of fluoride anion reacting with ethyl chloride, compared to reacting with ethyl iodide. Chemical dynamics simulations reproduce scattering signatures observed in experiments and reveal that the direct stripping/rebound mechanisms characterize the E2/S N 2 reactions, in line with their dynamic fingerprints identified. Quite similar structures and energetics are found for the Cl – and I – leaving halides, whereas the competing dynamics show markedly distinct features. A halogen-bonding attraction is found to be crucial that modifies the interaction potential in the entrance channel and essentially tunes the underlying atomistic behaviors causing a mechanistic shift. This work highlights the dynamical effects induced by a leaving group on the proceedings of base-induced elimination and nucleophilic substitution, providing a unique insight into the reaction selectivity for complex chemical networks and environments.

Topics & Concepts

ChemistrySN2 reactionHalogenLeaving groupMolecular dynamicsIodideNucleophileComputational chemistryReactivity (psychology)HalideNucleophilic substitutionSelectivityChemical reactionSteric effectsChemical physicsStereochemistryMedicinal chemistryOrganic chemistryCatalysisMedicinePathologyAlkylAlternative medicineCrystallography and molecular interactionsAdvanced Chemical Physics StudiesInorganic Fluorides and Related Compounds