Elucidating the selectivities and the mechanism of [3+2] cycloloaddition reaction between 9α-hydroxyparthenolide and 4-methylbenzene-nitrile-oxide

[Display omitted] •An exploration of conceptual DFT indices indicates that 4-methyl-Benzonitrile-N-oxide will engage in this reaction as a nucleophile, whereas 9α-hydroxyparthenolide (2) will pay as an electrophile.•The ELF examination divulges that this reaction follows a two-step reaction mechanism.•The 1,3-dipolar cycloaddition reaction in the treatment of mycrobacterial infections like tuberculosis and diseases like hepatitis.•The biological results allow us to validate the docking protocol. Utilizing the Molecular Electron Density Theory, to survey the [2 + 3] cycloaddition processes between 4-methyl-Benzonitrile-N-oxide (1) and 9α-hydroxyparthenolide (2), reaction, activation energies and the reactivity indices are determined. An examination of conceptual DFT indices, 9α-hydroxyparthenolide (2) will provide in this reaction as an eletrophile, whereas 4-methyl-Benzonitrile-N-oxide (1) will share as a nucleophile. The reaction and activation energies clearly demonstrate that this cyclization is regio- chemo and stereospecific, which is in perfect agreement with the outcomes of the experiment. The mechanism of this [2 + 3] cycloaddition follows two steps mechanism, as indicated by ELF analysis.