Phosphonohydrazine mediated synthesis of N phosphorylated 5 aminopyrazoles with structural characterization and antimicrobial activity

This study reports the synthesis and structural characterization of a novel series of N-phosphorylated 5-aminopyrazole derivatives prepared through the reaction of phosphonohydrazines with activated α,β-unsaturated nitriles under mild reaction conditions, affording the target compounds in good to excellent yields (64–83%). Their structures were confirmed by FT-IR, ¹H, ¹³C and ³¹P NMR spectroscopy, LC-MS/MS and elemental analysis. A plausible reaction mechanism, consistent with literature precedents, is proposed for the formation of the pyrazole scaffold. Among the ten synthesized compounds, four representative derivatives (3a, 3e, 4a and 4e) were selected for preliminary antimicrobial evaluation in order to investigate the influence of the phosphorus functionality (P = O versus P = S) and the C-3 substituent on biological activity. The tested compounds exhibited promising antibacterial activity, particularly against Escherichia coli , with inhibition zones reaching up to 22 mm at 200 µg/mL. These preliminary results indicate that N-phosphorylated 5-aminopyrazoles constitute promising phosphorus-containing heterocyclic scaffolds for further structural optimization and biological investigation as potential antimicrobial agents.