Investigating the mechanism of formation of nitro-substituted nicotine analogue via the [3 + 2] cycloaddition reaction of (E)-substituted nitroethene derivatives and (Z)-C-(3-pyridyl)-N-aryl-nitrones: a density functional theory (DFT) study

The formation of nitro-substituted nicotine analogues via the (3 + 2) cycloaddition (32CA) reaction between (E)-substituted nitroethene derivatives and (Z)-C-(3-pyridyl)-N-aryl-nitrones have been investigated using Density functional theory (DFT) at the B3LYP-D3/6-311G (d, p) level of theory. The results reveal that the reaction leads to the formation of the 4-nitro substituted exo isoxazolidine nicotine analogue (P2A). The rate constant for the preferred pathway (formation of P2A) in the reaction of A1 and A2 is 2.21 × 10¹⁰ s⁻¹, which is about 1.66 × 10² faster than the competing pathway through TS1B yielding product P1B with a rate constant of 4.23 × 10⁹ s⁻¹. Substituents on both A1 and A2 influence the activation barriers, with electron-withdrawing groups increasing the reaction’s electrophilicity and electron-donating groups increasing nucleophilicity. The calculated global reactivity indices support these trends, with A1 acting as the electrophile and A2 as the nucleophile.