Synthesis and structure–activity relationships of chlordimeform imine analogues against Chilo suppressalis

To address the high carcinogenicity of 4-chloro-2-methylaniline (a metabolite of traditional chlordimeform), thirty chlordimeform imine analogues were synthesized using chlordimeform as the lead compound, retaining the core amidine group (–N = CH–N(CH₃)₂) while modifying the benzene ring. The synthesized amidine structures were confirmed by ¹H/¹³C/¹⁹F NMR spectroscopy. Insecticidal activity against resistant Chilo suppressalis was evaluated via the soaked water-oat stem method. At a concentration of 50 μg/mL, compounds 4d, 4m, 9c, and 9d exhibited a corrected mortality rate of more than 38.67%, which was superior to chlordimeform (22.00%) but significantly lower than that of the commercial insecticide fipronil (88.00%). Preliminary SAR analysis: Retaining the benzene ring’s 2-methyl group and replacing the 4-chloro with fluorine, cyano, phenoxy, or benzyloxy enhanced the insecticidal activity; replacing benzene with heterocycles/fused heterocycles (except pyrazole-substituted 4m) reduced the insecticidal activity. This study provides theoretical insights and candidate compounds for novel amidine-based insecticides.