Synthesis and insecticidal activity of chlorantraniliprole analogs containing phenylalanine and 1H-inden-1-one

In order to develop new insecticidal compounds with chlorantraniliprole as the lead, 2-methyl-3-aminobenzoic acid was used as the starting material, which was halogenated to generate 5-chloro-3-methyl-2-aminobenzoic acid; and then it was condensed with 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid to give 2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-chloro-8-methyl-4H-benzod1,3oxazin-4-one; finally, a phenylalanine fragment was introduced and cyclized to synthesize two series of 23 new compounds ( 4 and 5 ), compound 4 was chlorantraniliprole analog containing phenylalanine, and compound 5 was chlorantraniliprole analog containing 1H-inden-1-one fragment cyclized by compound 4 . The structures of all compounds were characterized and confirmed by proton nuclear magnetic resonance spectroscopy (¹H NMR), carbon spectroscopy (¹³C NMR) and high resolution mass spectrometry (HRMS). The preliminary indoor insecticidal activity tests showed that most target compounds had high insecticidal activity against oriental armyworm, Mythinma separata, with 14 compounds had 100% mortalities against M. separata at 100 mg/L, and compound 5k (the substituent in the 1H-inden-1-one fragment was hydroxyl) had 90% and 70% mortalities at 4 mg/L and 0.8 mg/L, respectively. And its LC₅₀ value was 0.55 mg/L. In addition, molecular docking results showed that compound 5k also acted on ryanodine (RyR), just like chlorantraniliprole, but the amino acid residues bound to the target were different, which might be beneficial for research on drug resistance management of oriental armyworm.