Design, Synthesis and Insecticidal Activity of New Phenylpyrazole Derivatives

To enhance the discovery of phenylpyrazole-based insecticides and acaricides with superior biological activity, leveraging the insecticide and acaricide of Nicoflurole as a lead compound, 25 novel phenylpyrazole analogues were designed and synthesized through the design strategies of bioelectronic rearrangement and active substructures splicing. The target compounds were confirmed by 1H NMR, 13C NMR and HRMS. The insecticidal activities against Tetranychus cinnabarinus, Myzus persicae, and Plutella xylostella were preliminarily screened and rescreened to preliminarily explore structure-activity relationship. Among them, methyl 1-(2-chloro-5-(1-(2,6-dichloro-4-(perfluoropropan-2-yl)phenyl)-1H-pyrazol-4-yl)nicotin- amido)cyclopropane-1-carboxylate (8e) showed 100% mite killing efficacy against Tetranychus cinnabarinus at 2.5 mg/L. 5-(1-(2-Bromo-6-chloro-4-(perfluoropropan-2-yl)phenyl)-1H-pyrazol-4-yl)-2-chloro-N-cyclopropylnicotinamide (8i) exhibited an insecticidal efficacy of 100% against Myzus persicae at 5 mg/L. 2-Chloro-N-cyclopropyl-5-(1-(2,6-dichloro-4-(perfluoro-propan-2-yl)phenyl)-1H-pyrazol-4-yl)-N-methylbenzamide (8a), 2-chloro-N-cyclopropyl-5-(1-(2,6-dichloro-4-(perfluoropro- pan-2-yl)phenyl)-1H-pyrazol-4-yl)benzamide (8b), and 8i demonstrated an insecticidal efficacy of 100% against Plutella xylostella at 2.5 mg/L. Molecular docking studies indicated that the enhancement of 8e acaricidal activity may be due to the incorporation of ester groups leading to an increase in corresponding hydrogen bonding interactions. This study provides valuable insights for the continued optimization and development of novel phenylpyrazole insecticides and acaricides.