8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶噁二唑硫醚类衍生物的设计、合成及其杀线虫和杀菌活性

Design,Synthesis and Nematicidal and Fungicidal Activities of 8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine Oxadiazole Thioether Derivatives

为了发现具有高杀线虫和杀菌活性的新化合物,设计合成了22个8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶噁二唑硫醚类衍生物,并通过1HNMR,13CNMR和高分辨质谱(HRMS)对所有目标化合物结构进行了确证.杀线虫活性测定结果显示,在浓度为100 mg/L时,所有目标化合物对秀丽隐杆线虫(二龄幼虫)均有一定的毒杀活性.其中2-[8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶-2-基]-5-((2-氟苄基)硫基)-1,3,4-噁二唑(6j)、2-[8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶-2-基]-5-(((2-氯苄基)硫基)-1,3,4-噁二唑(6m)、2-[8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶-2-基]-5-((2-氰基苄基)硫基)-1,3,4-噁二唑(6q)、2-[8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶-2-基]-5-((3-甲氧基苄基)硫基)-1,3,4-噁二唑(6s)和2-[8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶-2-基]-5-((4-甲氧基苄基)硫基)-1,3,4-噁二唑(6t)对秀丽隐杆线虫的LC50分别为48.10、34.94、52.87、48.32和37.62 mg/L,均优于对照药剂噻唑磷(79.28 mg/L).杀菌活性测定结果显示,2-[8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶-2-基]-5-((2-溴乙基)硫基)-1,3,4-噁二唑(6d)对水稻纹枯病菌Rhizoctoniasolani表现出良好的抑制活性,其EC50值为7.22mg/L,优于对照药剂氟吡菌酰胺(110.02 mg/L).在100和200 mg/L浓度下,化合物6d对水稻纹枯病菌的保护防效分别为85.5%和92.1%,治疗防效分别为59.2%和79.0%.此研究合成的目标化合物具有一定的杀线虫和杀菌活性,可为咪唑并[1,2-a]吡啶类衍生物的设计和合成提供新思路,对探究咪唑并[1,2-a]吡啶类衍生物的生物活性多样性具有参考意义.

In order to discover new compounds with high nematicidal and fungicidal activity,228-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine oxadiazole thioether derivatives were designed and synthesized,and the structures of all target compounds were confirmed by 1H NMR,13C NMR and high-resolution mass spectra(HRMS).The results of nematicidal activity test showed that all the target compounds possessed certain toxic activity against Caenorhabditis elegans(second-stage juveniles)at the concentration of 100 mg/L.The LC50 of 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-fluorobenzyl)thio)-1,3,4-oxadiazole(6j),2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-chlorobenzyl)thio)-1,3,4-oxadiazole(6m),2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-cyanobenzyl)thio)-1,3,4-oxadiazole(6q),2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((3-methoxybenzyl)thio)-1,3,4-oxadiazole(6s)and 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((4-methoxybenzyl)thio)-1,3,4-oxadiazole(6t)against C.elegans were 48.10,34.94,52.87,48.32 and 37.62 mg/L,respectively,which were superior than that of fosthiazate(79.28 mg/L).The results of fungicidal activity test showed that 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-bromoethyl)thio)-1,3,4-oxadiazole(6d)had good inhibitory activity against Rhizoctonia solani.The EC50 value of compound 6d was 7.22 mg/L,which was superior to that of fluopyram(110.02 mg/L).At the concentration of 100 and 200 mg/L,the protective effects of compound 6d against rice sheath blight were 85.5%and 92.1%,and the curative effects were 59.2%and 79.0%.The target compounds synthesized in this study have certain nematocidal and fungicidal activities,which can provide new ideas for the design and synthesis of imidazo[1,2-a]pyridine derivatives,and have reference significance for exploring the bioactivity diversity of imidazo[1,2-a]pyridine derivatives.