Synthesis And Biological Activity Of Benzimidazo[1,2,d]triazine Compounds

Benzimidazole compounds contain an aromatic heterocycle with two N atoms,the special structure can form hydrogen bonds with the enzymes and receptors in organisms,which makes these compounds possess a wide range of biological activity,such as antifungal,herbicidal,anti-inflammatory,antiparasitic,anticancer,antiviral and analgesic activities.Researchers used benzimidazole ring as a molecular skeleton and developed a series of fungicides with high efficiency and low toxicity,such as carbendazim,benomyl,fuberidazole,thiabendazole and cypendazole,which remarkably improved crop yield and quality.Because benzimidazole fungicides were applied at high-dose for long,certain varieties have developed serious resistance,such as carbendazim.Thus,developing novel antifungal substances as the substitutes of benzimidazole fungicides is of important significance.In this paper,different substituted hydrazine were introducded to the benzimidazole structure firstly,then the intermediates were cyclized to synthesize a series of novel benzimidazo[1,2,d]triazine compounds.Additionally,the fungicidal activities of the target compounds were evaluated.And the preliminary structure-activity relationships(SARs)were also determined.o-Phenylenediamine was used as the starting material to prepare 2-(chloromethyl)benzimidazole and 2-(1-bromoethyl)benzimidazole by reacting with chloroacetic acid and 2-bromopropionic acid,respectively.Then this intermediate was reacted with different substituted phenylhydrazines to synthesize seven 2-(1-(1-phenylhydrazinyl)alkyl)benzimidazoles.These seven intermediates were cyclized with different chloroformates respectively to give forty-one 1-oxo-3-(substituted phenyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-d][1,2,4]triazine-2(1H)-carboxylates.The structures of the target compounds were confirmed by FT-IR,1H NMR,13C NMR,EI-MS and single crystal X-ray diffraction.The mycelium growth inhibition method was used to evaluate the fungicidal activities of the target compounds against four kinds of plant pathogen—Fusarium graminearum,Botrytis cinerea,Rhizoctonia solani and Colletotrichum capsici.At the concentration of 50μg/mL,most of the compounds showed certain fungicidal activity.The inhibition rates of 21 compounds against Botrytis cinerea were over 50%,and B1 and C2 were up to 70.5%and 76.7%,respectively.The inhibition rates of 23 compounds against Rhizoctonia solani were higher than 50%,and A2,A8,C7,D6,E1,E2,F1 and F2 were up to 60%,respectively.The inhibition rates of 12 compounds against Colletotrichum capsici was higher than 50%,and B1,D1-D3,F1 and F2 were up to 60%.The relationship between the structure of the target compounds and the fungicidal activity was preliminarily analyzed.It was found that the introduction of electron-withdrawing groups at the benzene ring of triazine ring,such as halogen groups,could help to improve the fungicidal activity of the target compounds.At the same time,the size of the alkyl group at the carboxylate group also has a certain influence on the fungicidal activity.When alkyl became smaller,such as methyl and ethyl,the biological activity showed higher.