Synthesis and pesticidal activity of new 1,3,4-oxadiazole thioether compounds containing a trifluoromethylpyrazoyl moiety

Abstract

In order to find new lead compounds with high pesticidal activity, a series of 1,3,4-oxadiazole thioether compounds (5 series) were designed by using penthiopyrad as a synthon. They were synthesized easily via five steps by using ethyl 4,4,4-trifluoro-3-oxobutanoate and triethyl orthoformate as starting materials. The synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS. The compound 2-(benzylthio)-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazole (5a) was further determined by X-ray single-crystal diffraction. It crystallized in the monoclinic system, space group P21/c, Z = 4. All the 1,3,4-oxadiazole thioether derivatives were screened for fungicidal activity against ten fungi and herbicidal activity against two weeds. The bioassay results indicated that some of the synthesized 1,3,4-oxadiazole compounds exhibited good fungicidal activity (> 50% inhibition) against the plant pathogens Sclerotinia sclerotiorum and Rhizoctonia solani at 50 μg/mL. Some of them exhibited certain herbicidal activity, and compounds 2-((3-chlorobenzyl)thio)-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazole (5e) and 2-((4-bromobenzyl)thio)-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazole (5 g) had bleach effect. Molecular docking is to find the best fit orientation of the 2-((4-bromobenzyl)thio)-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazole (5 g) molecule with the SDH protein (PDB: 2FBW). The docking results indicate that the compound 5 g and the lead compound penthiopyrad have similar binding interactions with SDH and carbonyl is a key group for these compounds.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11164-022-04839-x.