Reactivity of pyrazole derivatives with halomethanes: A DFT theoretical study

The N-alkylation reaction of pyrazole derivatives with halomethanes was studied using density functional theory (DFT). The hybrid method B3LYP was employed, along with an ECP basis set such as LANL2DZ for halogen atoms (X = Cl, Br, I) and the 6-311 + G(d,p) basis set for all other atoms. In order to predict the specific site at which the pyrazole derivatives interact with halomethanes, local reactivity descriptors such as the Fukui functions were calculated. Detailed analysis of transition-state energies showed that alkylation occurred at the nitrogen atom N₂ in the pyrazole derivatives, in agreement with the chemical reactivity results. The reaction mechanisms were elucidated by performing intrinsic reaction coordinate (IRC) calculations that considered the effects of the solvent and the species of halogen in the halomethane.