N-取代苯基-1-(2,4-二氟苯基)-2-(1H-1,2,4-三唑-1-基)乙基氨基甲酸酯的合成及生物活性
doi: 10.16801/j.issn.1008-7303.2022.0016
Synthesis and biological activity of N-substituted phenyl-1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethylcarbamate
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摘要: 为了寻找高活性的三唑类苯基氨基甲酸酯衍生物,以 1,2,4-三氮唑、2-氯-2,4-二氟苯乙酮为原料,采用活性亚结构拼接的策略,设计并合成了18个未见文献报道的N-取代苯基-1-(2,4-二氟苯基)-2-(1H-1,2,4-三唑-1-基)乙基氨基甲酸酯衍生物 6a ~ 6r 。其结构均通过 1H NMR、13C NMR和高分辨质谱(HRMS)的确证。抑菌活性测定结果显示:在100 μmol/L下,化合物 6m 对6种供试真菌具有良好的抑制作用,抑制率均达到50%以上。化合物 6p 对油菜菌核病菌Sclerotinia sclerotiorum的EC50值为7.1 μmol/L,抑菌活性高于对照药剂烯唑醇(EC50值9.1 μmol/L)。杀螨活性测定结果显示,在150 μmol/L时,化合物 6h 、 6k 和 6o 在48 h时对朱砂叶螨Tetranychus cinnabarinus的致死率分别为67.7%、74.9%和57.5%,杀螨活性低于对照药剂阿维菌素B1a(致死率100%)。本研究所合成的化合物 6o 兼具一定杀菌和杀螨活性,可为新型三唑类杀菌杀螨化合物的设计与研究提供参考。Abstract: In order to find highly active triazole phenyl carbamate derivatives, 1,2,4-triazole and 2-chloro-2,4-difluoroacetophenone were used as raw materials, and the strategy of active substructure splicing was adopted, eighteen N-substituted phenyl-1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethyl carbamate derivatives 6a-6r were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR and high resolution mass spectrometry (HRMS). The results of fungicidal activity assay showed that compound 6m had a good inhibitory effect on the 6 tested fungi at 100 μmol/L with a inhibition rate of more than 50%. The EC50 value of compound 6p against Sclerotinia sclerotiorum was 7.1 μmol/L, the fungicidal activity was higher than that of the control compound diniconazole (EC50 value was 9.1 μmol/L). The results of acaricidal activity showed that at 150 μmol/L, the lethal rates of compounds 6h , 6k and 6o were 67.7%, 74.9% and 57.5% for Tetranychus cinnabarinus at 48 h, respectively, and the acaricidal activity was lower than that of the control compound abamectin B1a (100%). The compound 6o synthesized in this study has both fungicidal and acaricidal activities, which can provide a reference for the design and research of novel fungicidal and acaricidal triazole compounds.
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Key words:
- 1,2,4-tiazole /
- carbamate /
- fungicidal activity /
- acaricidal activity
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表 1 目标化合物对6种植物病原真菌的抑制作用
Table 1. Inhibition of target compounds against six pathogenic fungi in vitro
化合物
Compound抑制率
Inhibition rate/%水稻纹枯病菌
R. solani小麦赤霉病菌
F. graminearum番茄早疫病菌
A. solani油菜菌核病菌
S. sclerotiorum棉花枯萎病菌
F. oxysporium辣椒疫病菌
P. capsici6a 43.5 ± 1.7 19.9 ± 1.1 13.9 ± 0.6 7.8 ± 0.6 11.0 ± 1.1 0 6b 13.5 ± 0.9 0 4.4 ± 0.6 2.5 ± 0.6 11.0 ± 1.1 0 6c 13.0 ± 1.5 17.3 ± 0.5 8.2 ± 0.6 12.6 ± 1.1 5.7 ± 1.1 0 6d 40.0 ± 1.5 19.6 ± 0.9 18.4 ± 1.0 15.0 ± 0.6 12.4 ± 0.6 0 6e 45.5 ± 0.8 21.8 ± 1.4 32.0 ± 0.5 49.3 ± 1.1 13.1 ± 1.1 0 6f 43.5 ± 1.7 16.9 ± 0.9 28.2 ± 0.6 22.9 ± 1.8 12.0 ± 1.1 0 6g 44.5 ± 1.5 26.2 ± 0.5 19.6 ± 0.6 18.7 ± 1.1 20.8 ± 2.2 10.0 ± 0.1 6h 20.0 ± 1.7 20.2 ± 1.4 11.4 ± 0.6 17.3 ± 0.6 9.5 ± 1.6 11.0 ± 0.6 6i 38.0 ± 0.8 30.4 ± 0.9 22.8 ± 1.5 38.0 ± 0.6 14.8 ± 1.6 8.3 ± 0.6 6j 42.5 ± 1.7 25.3 ± 0.5 15.8 ± 1.5 12.7 ± 0.6 9.5 ± 1.2 6.2 ± 0.6 6k 56.0 ± 1.7 22.0 ± 1.4 29.8 ± 1.0 41.6 ± 0.6 13.8 ± 1.6 5.2 ± 0.6 6l 31.0 ± 0.1 20.2 ± 1.4 9.2 ± 0.6 6.7 ± 1.2 17.3 ± 1.1 6.2 ± 0.6 6m 51.0 ± 1.7 51.8 ± 1.4 53.5 ± 1.0 66.6 ± 1.6 50.3 ± 0.6 51.7 ± 0.6 6n 31.0 ± 1.5 10.8 ± 0.5 12.3 ± 0.5 6.7 ± 0.6 5.6 ± 1.1 0 6o 49.0 ± 1.5 28.3 ± 1.1 57.0 ± 2.4 67.4 ± 1.1 21.1 ± 1.6 21.0 ± 1.2 6p 44.5 ± 1.5 44.0 ± 1.6 48.7 ± 0.6 67.6 ± 1.6 21.2 ± 0.6 12.4 ± 1.2 6q 42.5 ± 0.8 28.6 ± 0.9 7.9 ± 0.1 20.8 ± 1.1 13.1 ± 1.1 16.9 ± 1.6 6r 35.5 ± 1.5 20.2 ± 0.5 15.8 ± 1.5 8.1 ± 1.1 13.8 ± 1.6 0 烯唑醇 diniconazole 86.0 ± 0.9 84.6 ± 0.9 97.8 ± 0.6 70.1 ± 1.6 79.9 ± 1.1 81.4 ± 1.1 注:化合物浓度为 100 μmol/L。每个处理重复 3 次(平均值 ± 标准差)。Note: The compound concentration was 100 μmol/L. Each treatment had three replicates (Mean ± SD). 表 2 部分化合物对油菜菌核病菌的EC50值
Table 2. The EC50 value of some compounds against S. sclerotiorum
化合物
Compound取代基
R回归方程
Regression equation相关系数
Correlation cofficient, rEC50/(μmol/L) 95% 置信限
95% Confidence limit/(μmol/L)6m 4-CH(CH3)2 y = 0.4931x + 5.9931 0.9959 9.7 8.4~11.1 6o 4-OCH3 y = 1.3279x + 6.6398 0.9967 58.2 51.7~65.6 6p 4-CH2CH3 y = 0.6884x + 6.4814 0.9964 7.1 6.0~8.2 烯唑醇
diniconazole— y = 0.9198x + 6.8791 0.9980 9.1 8.2~10.0 注:每个处理重复3次。Note: Each treatment had three replicates. 表 3 目标化合物对朱砂叶螨的杀螨活性
Table 3. Insecticidal activities of target compounds against T. cinnabarinu
化合物
Compound校正死亡率
Corrected mortality/%24 h 48 h 6a 22.9 ± 0.7 25.8 ± 1.1 6b 43.1 ± 1.4 45.4 ± 1.0 6c 4.8 ± 0.7 14.2 ± 0.3 6d 19.1 ± 0.9 23.4 ± 0.8 6e 18.3 ± 1.1 36.1 ± 0.9 6f 14.6 ± 0.5 40.2 ± 0.3 6g 7.7 ± 0.6 39.2 ± 1.5 6h 54.6 ± 1.3 67.7 ± 1.4 6i 20.3 ± 0.9 23.3 ± 1.3 6j 13.1 ± 1.0 27.8 ± 0.4 6k 58.0 ± 1.1 74.9 ± 0.9 6l 48.8 ± 1.4 50.5 ± 1.5 6m 6.5 ± 0.6 9.1 ± 0.9 6n 9.5 ± 0.4 16.3 ± 1.0 6o 46.7 ± 1.1 57.5 ± 1.5 6p 15.7 ± 0.6 23.2 ± 1.0 6q 6.9 ± 0.9 21.8 ± 0.6 6r 6.7 ± 0.2 7.9 ± 1.1 阿维菌素 B1a
Avermectin B1a100 100 注:每个处理重复3次,化合物浓度为150 μmol/L。Note: Each treatment had three replicates. Compound concentration of 150 μmol/L. -
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目标化合物的核磁共振氢谱、碳谱谱图和高分辨质谱图.pdf
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