Study On The Synthesis And Fungicidal Activity Of N-benzyl-thaizole-5-carboxamide Derivatives

With the increasing grain production,the use of pesticides has become increasingly popular.Fungicides have been playing an indispensable role in pesticide application.Study on novel high-efficiency fungicide will be of great significance on the subsequent development of pesticide,and the increase in grain production.Based on the combination principle,18 new compounds were designed and synthesized by thiazole and substituted aniline,which have good biological activity.In order to obtain compounds with excellent fungicidal activity,primary activity screening was carried out against eight kinds of targets including five kinds of in vitro and three in vivo targets.Trifluoromethyl ethyl acetoacetate or ethyl acetoacetate was used as raw materials to obtain ethyl 2-amino-thiazole-5-carboxylate by nucleophilic substitution and cyclization reaction.The product was diazotized,hydrolysised and acyl chlorinated to get 2-bromothiazole-5-carbonyl chloride,which was reacted with substituted aniline to obtain 2-bromo-N-phenylthiazole-5-carboxamide,from which the N-phenylthiazole-5-carboxamide derivatives were obtained.The single factor optimization method was used to optimize the yield of diazo reaction and the acyl reaction.The final optimized conditions for diazotization is:n(thiazole ester):n(NaNO2)=1:1.1,NaNO2 added dropwise in temperature-10?-5?,reaction time 3 h,the yield was 80%.The final optimized conditions for acylation is:n(acyl chloride):n(aniline)=1:1.2,in xylene/N2 system,reflux for 1 h,the yield was 77%.The structures of synthesized compounds were confirmed by 1H NMR,13C NMR,GC-MS and IR.Fungicidal test results showed that the new compounds generally have a moderate to strong fungicidal activity.Compounds 1d,2b,3c,exhibited moderate fungicidal activity against sclerotinia sclerotiorum,with inhibition rates of 76%,79%,71%,respectively.Compounds lc,2c,4b,exhibited moderate fungicidal activity against blumeria graminis,with the inhibition rate of 70%,60%,80%,respectively.Besides,the general fungicidal activity of the compound is 3>2>1>4.Compounds 2a,3a,3b have excellent fungicidal activity against Rhizoctonia solani and Puccinia polysra:The EC50 values against Rhizoctonia solani were 1.58 mg/L,1.48 mg/L,1.11 mg/L respectively,better than the positive control validamycin(9.52 mg/L),and close to the thifluzamide(0.42 mg/L);The EC50 values against Puccinia polysra were 3.17 mg/L,3.03 mg/L,3.09 mg/L respectively,better than ketotriazole(7.85 mg/L),and close to the thifluzamide(2.07 mg/L).