Understanding the regio- and diastereoselective synthesis of a potent antinociceptive isoxazolidine from C-(pyridin-3-yl)-N-phenylnitrone in the light of molecular electron density theory

Nivedita Acharjee

Abstract


[3+2] cycloaddition reaction of C-(pyridin-3-yl)-N-phenylnitrone and 2-propen-1-ol yields stereochemically defined potent antinociceptive isoxazo­lidine derivative. Computational quantum calculations (CQC) are performed for this synthesis to predict the polar character, mechanism and selectivity within the framework of molecular electron density theory (MEDT). Topo­logical analysis of the electron localization function (ELF) classifies the nit­rone as a zwitter-ionic(zw-) type three atom component (TAC) showing abs­ence of any pseudoradical or carbenoid centre. Four reaction channels corres­ponding to the possible regio- and stereoselective pathways are studied at DFT/B3LYP/6-311G(d,p) level of theory. The reaction follows one-step mech­anism with asynchronous transition states and the computed activation energies agree well with experimental data. The reaction can be differentiated into nine ELF topological phases, with faster C–C bond formation. Global electron den­sity theory (GEDT) at the favoured transition state and conceptual density functional theory (CDFT) indices at the ground state of the reagents indicate non-polar character. Non-covalent interactions are predicted by atoms-in-mole­cules (AIM) analysis and non-covalent interaction (NCI) plots at the transition states.


Keywords


MEDT; transition state; electron localization function; NCI

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DOI: https://doi.org/10.2298/JSC190914136A

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