Mapping Reactivity and Stereochemical Evolution of Benzothiazolium Salts in [3+2] Cycloadditions Using Molecular Electron Density Theory
DOI:
https://doi.org/10.29356/jmcs.v70i1.2572Keywords:
[3+2] cycloaddition reaction, Electron Localization Function, Molecular Electron Density Theory, Bond Evolution Theory, Non-Covalent InteractionsAbstract
The electronic structure of the benzothiazolium salt 1 (1-(cyanomethyl)-2,3-dihydro-1H-benzothiazol-1-ium) and its reactivity in [3+2] cycloaddition (32CA) reactions with dimethyl(Z)-2-butenedioate 2 have been investigated using Molecular Electron Density Theory (MEDT) combined with Density Functional Theory (DFT) calculations at the M06-2X/6-311+G(d,p) level. Topological analysis of the Electron Localization Function (ELF) reveals that 1 act as a carbenoid-type three-atom component (TAC), characterized by a carbenoid C3 center. Conceptual DFT reactivity indices identify this TAC as a moderate electrophile and a supernucleophile. The polar 32CA reaction proceeds via a one-step asynchronous mechanism, as revealed by the Bond Evolution Theory (BET), and involves the formation of two stable molecular complexes. The activation barriers are low for both the endo and exo pathways. DFT calculations indicate that the endo pathway is slightly both kinetically and thermodynamically preferred over the exo one, in agreement with experimental findings. Non-covalent interactions (NCIs) analysis attributes this endo selectivity to a combination of weaker attractive interactions and enhanced van der Waals and repulsive interactions in TS-endo, which alleviates steric strain and stabilizes the TS.
Resumen. La estructura electrónica de la sal de benzotiazolio 1 (1-(cianometil)-2,3-dihidro-1H-benzotiazol-1-io) y su reactividad en reacciones de cicloadición [3+2] (32CA) con el dimetil (Z)-2-butendioato 2 se investigaron utilizando la Teoría de la Densidad Electrónica Molecular (MEDT) en combinación con cálculos de la Teoría del Funcional de la Densidad (DFT) al nivel M06-2X/6-311+G(d,p). El análisis topológico de la Función de Localización Electrónica (ELF) revela que el compuesto 1 actúa como un componente de tres átomos (TAC) de tipo carbenoide, caracterizado por un centro carbenoide C3. Los índices de reactividad de la DFT conceptual identifican a este TAC como un electrófilo moderado y un supernucleófilo. La reacción polar de cicloadición 32CA transcurre mediante un mecanismo asincrónico de una sola etapa, tal como lo revela la Teoría de la Evolución del Enlace (BET), e implica la formación de dos complejos moleculares estables. Las barreras de activación son bajas tanto para las vías endo como exo. Los cálculos DFT indican que la vía endo está ligeramente favorecida, tanto desde el punto de vista cinético como termodinámico, con respecto a la vía exo, en concordancia con los resultados experimentales. El análisis de las interacciones no covalentes (NCI) atribuye esta selectividad endo a una combinación de interacciones atractivas más débiles y de interacciones de van der Waals y repulsivas más intensas en el estado de transición TS-endo, lo que reduce la tensión estérica y estabiliza dicho estado de transición.
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Copyright (c) 2026 Mohamed Chellegui, Raghad Mowafak Al‑Mokhtar , Raad Nasrullah Salih, Lakhdar Benhamed, Sofiane Benmetir, Jesus Vicente de Julián-Ortiz, Haydar A. Mohammad-Salim, Ali Ben Ahmed
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