Study On The Synthesis And Antifungal Activity Of Triazole Benzamine Compounds

In recent years,plant diseases,including wheat take-all disease,have become a major threat to crop quality and yield.However,there are few fungicides that can effectively control wheat take-all disease,wheat stem rot disease,rape sclerotia disease and others at the same time.In order to meet the needs of control of these crop diseases,two series of triazole benzoyl arylamine derivatives were designed and synthesized in this study,and their antifungical activities were evaluated,and a good progress was made.1.The structure design of triazole benzoyl arylamine derivatives.According to the obtained structure and activity relationship of the thiophene carboxamide derivatives,the structural characteristics of the 2-position hindered benzamide active compounds in the literature,and considering the role of the triazole unctional group in various active compounds,2-triazole benzoyl arylamine derivatives were designed in which 1,2,4-triazole as a large steric hindrance was introduced to the ortho-position of the amides and provided a new active site,and the amide nitrogen atom was aromatized.2.Synthesis and characterization of 2-triazole benzoyl arylamine derivatives.The intermediate 2-(1,2,4-triazole)-6-chlorobenzonitrile was obtained by 2,6-di chlorobenzonitrile reacting with 1,2,4-triazole in the presence of K2CO3.Then the intermediate 2-(1,2,4-triazole)-6-chlorobenzonitrile was converted to 2-(1,2,4-triazole)-6-chlorobenzoic acid by hydrolysis of cyanide,amide diazotization and acidification.Forty-one target compounds were synthesized by acylation and amination of 2-(1,2,4-triazole)-6-chlorobenzoic acid.The structures of the target compounds were characterized and confirmed by 1H,13C NMR and HRMS.3.The evaluation of antifungical activities of the designed compounds.Using the mycelial growth rate method,a total of 41 2-triazole benzamide derivatives were tested against Gaeumannomyces graminis var.tritici,Sclerotinia sclerotiorum and Fusarium graminearum in vitro.The EC50 values of compounds 6g,6d,6f and 6c against wheat take-all were 0.01 μg mL-1,0.02 μg mL-1,0.03 μg mL-1 and 0.04 μg mL-1,respectively.The EC50 values of compounds 6g,6f and 5x against Sclerotinia sclerotiorum were 0.19μg mL-1,0.27 μgmL-1 and 0.7 μg mL-1,respectively.The EC50 value of compound 6g against Fusarium graminearum was 0.12 μg mL-1.Compound 6g,in particular,had excellent inhibitory activities against all three pathogens.4.The analysis of the structure and activity relationship of 2-triazole benzoyl arylamine derivatives.The structure-activity relationship of 2-triazole benzoyl arylamine derivatives against the wheat take-all were analyzed.It was found that the activities of the compounds were poor when the substituent groups at the amide nitrogen atom were alkyls,but the activities increased when substituted groups were phenyls.When the substituted phenyls had an electron-withdrawing group at its para-position,the activities became better,especially when the electron-withdrawing groupe were the ester carbonyl groups.This structure and activity relationship could also be applied to Sclerotinia sclerotiorum and Fusarium graminearum roughly.The structure and activity relationship of 2-triazole benzoyl arylamine derivatives confirmed the design idea of the compounds.Several compounds with excellent inhibitory activities against plant pathogens including wheat take-all were developed by the structural design and activity study of triazole benzoyl arylamine derivatives.Among these compounds,6g had a potential as a lead compound.The study of the structure and activity relationship provided theoretical support for the design and discovery of new active compounds,and had a great scientific significance.