Synthesis And Fungicidal Activity Of Novel2,5-Disubstituted-1,3,4-oxadiazoles Containing Benzimidazole Ring

Heterocyclic compounds play a vital role in pesticide research both at homeand abroad, due to their good selectivity, high activity and low dosage. Innumerous developed heterocyclic compounds,1,3,4-oxadiazole derivativeshave received increasing interests in diverse potential biological activities suchas inseticidal, anticancer, antifungal and antiinflammatory activities. On theother hand, benzimidazoles are important bioactive substances, and they arewidely used in pesticides and pharmaceuticals because of the vital role inbiological fields such as anticancer, antimicrobial, and antiviral activities, sothe research for the synthesis and applications of benzimidazole derivativeshave always drawn much attention.A comprehensive overview was got about the biological activities andsynthetic methods of1,3,4-oxadiazole derivatives and benzimidazoles. In viewof good antifungal activity of these two rings, we introduced benzimidazoleinto1,3,4-oxadiazole by Bioisosterism Principles and Structure Link Way, andsynthesized eight kinds of2-(benzimidazol-2-yl)-5-substitutedphenyl-1,3,4- oxadiazoles (I) and eight kinds of2-(benzimidazol-2-yl)-5-substitutedphenylamino-1,3,4-oxadiazoles (II) from o-phenylenediamine,Glycolic acid, hydrazine hydrate, substituted phenyl isothiocyanate andbenzoic acid by multi-step reactions with the aim of searching for newheterocyclic compounds which have good antifungal activity. Structures oftarget compounds were characterized by IR,1H NMR spectra and elementalanalysis.Target compound I Target compound IIIn this paper, we have discussed the synthetic process of target compoundsand intermediates in detail and made some improvement. To save materials,we reduced the amount of glycolic acid in the synthesis of1H-benzimidazole-2-methanol, but the product yields keep invariant. In order to avoid by-products in nucleophilic substitution of1H-benzimidazole-2-carbonylhydrazide and substituted phenyl isothiocyanate, protonic solvent ethanol wassubstituted by aprotic solvent acetonitrile. The syntheses of the targetcompound I was carried out by microwave-irradiation, which exhibits many advantages such as safe and simple, higher yield, shorter reaction time whencompared with conventional methods. In addition, we analyzed and discussedthe spectral properties of target compounds, confirming the main absorptionpeaks of IR and1H NMR.In the article, the biological activities of the target compounds weredetermined by the mycelium growth rate method. The antifungal activities oftwo series compounds (I, II) against Botrytis cinereapers and Sclerotiasclerotium were respectively tested. The results indicated that the EC50valuesof Ie, Ih, IIfwere2.55,6.34,5.12μg/mL, which were all less than that ofcarbendazim (7.40μg/mL), so we can know that the activies are increasedwhen we introduced benzimidazole into the1,3,4-oxadiazole derivatives. Onthe other hand, the activity of compound I was higher than that of compoundII in general. The result demonstrated that the1,3,4-oxadiazole derivativeslinking a benzene ring directly possessed high antifungal activities.