Design, Synthesis, and Pesticidal Activities of Pyrimidin-4-amine Derivatives Bearing a 5-(Trifluoromethyl)-1,2,4-oxadiazole Moiety.

It is important to discover new pesticides with new modes of action because of the increasing evolution of pesticide resistance. In this study, a series of novel pyrimidin-4-amine derivatives containing a 5-(trifluoromethyl)-1,2,4-oxadiazole moiety were designed and synthesized. Their structures were confirmed by H NMR, C NMR, and HRMS. Bioassays indicated that the 29 compounds synthesized possessed excellent insecticidal activity against , , and and fungicidal activity against . Among these pyrimidin-4-amine compounds, 5-chloro--(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl)pyrimidin-4-amine () and 5-bromo--(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl) pyrimidin-4-amine() had broad-spectrum insecticidal and fungicidal activity. The LC values were 3.57 ± 0.42, 4.22 ± 0.47, and 3.14 ± 0.73 mg/L for , , and flufenerim against , respectively. The EC values were 24.94 ± 2.13, 30.79 ± 2.21, and 3.18 ± 0.21 mg/L for , , and azoxystrobin against , respectively. The AChE enzymatic activity testing revealed that the enzyme activities of compounds , , and flufenerim are 0.215, 0.184, and 0.184 U/mg prot, respectively. The molecular docking results of compounds , , and flufenerim with the AChE model demonstrated the opposite docking mode between compound or and positive control flufenerim in the active site of AChE. The structure-activity relationships are also discussed. This work provided excellent pesticide for further optimization. Density functional theory analysis can potentially be used to design more active compounds.