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
收稿日期: 2023-11-23
修回日期: 2023-12-27
网络出版日期: 2024-01-18
基金资助
国家自然科学基金(31672069); 国家自然科学基金(32172400)
Design, Synthesis and Nematicidal and Fungicidal Activities of 8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine Oxadiazole Thioether Derivatives
Received date: 2023-11-23
Revised date: 2023-12-27
Online published: 2024-01-18
Supported by
National Natural Science Foundation of China(31672069); National Natural Science Foundation of China(32172400)
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1H NMR, 13C NMR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Rhizoctonia solani表现出良好的抑制活性, 其EC50值为7.22 mg/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.
郭倩男 , 黄森 , 赵薇 , 赵伟 , 严越 , 王济海 , 徐志红 . 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[J]. 有机化学, 2024 , 44(5) : 1620 -1629 . DOI: 10.6023/cjoc202311024
In order to discover new compounds with high nematicidal and fungicidal activity, 22 8-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-fluoro- benzyl)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.
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