Design, Synthesis, Antibacterial Of New Benzimidazole Derivatives

High efficiency, low toxicity, green and pollution-free are the characterares ofthe modern pesticides required by people. The appearance of the oxime-ethercompounds is in line with the demands of people on the modern pesticides. When thefirst oxime ether fungicides were developed, the oxime-ether compounds haveattracted more and more attention in pesticide due to its advantages of good biologicalactivity, high efficiency, low toxicity and low residue. In recent years, a large numberof fungicides and herbicides have been developed, such as trifloxystrobin andorysastrobin. At present, oxime ether is developed rapidly. The molecular design,synthesis and biological activity of oxime ether compounds remain one of the focusesin new pesticide creation.Pesticide containing heteroaromatic ring gradually becomes the main trend ofdevelopment of the future pesticide because of its flexible and changeable structures,variety of substituents, higher bioactivities, and high security and suits the demand ofdevelopment of the future pesticide. It is reported by Krapping in1960that all kindsof2-aminobenzimidazole is a broad-spectrum fungicides with high activities and lowtoxicity. The developments of the benzimidazole and its derivatives, especially2-substituted benzimidazole, are regarded as a category with variety bioactivities ofheterocyclic. The emergence of these fungicides suggests the start of a new era ofbactericides. The appearance of new the systemic fungicides has epoch-makingsignificance in the history of fungicides.Morpholine is an important kind of heterocyclic compounds, often used in thepreparation of medicine and pesticides because of its high biological activity, such aspesticides, sterilization, weeding, antivirus, and anticancer and so on. At the sametime, because morpholine has the advantages of efficiency, low toxicity and specialmechanism, the reasearches on the molecular design, synthesis and biological activityof morpholine are still important in the study of modern heterocyclic compounds.In the progress of looking for the new fungicide, triazole compounds have beenpaid more and more attention because of its wide spread biological activities. Manytriazole compounds have been developed and applied as fungicides, insecticides, plantgrowth regulator and drugs. Triazole compounds with different structures havedifferent biological activity. Developing new type of triazole compounds becomes aresearch focus at present. As the most important part of pesticide, the triazole compounds are developed more quickly and have more wide varieties than otherpesticides because the triazole compounds have power aspiration, lower toxicities topeople and livestocks and longer residual effects. As an important part of triazolefungicides, triazolone compounds have been found, from their application in China,not only to be a broad-spectrum and highly effective fungicide, but also have goodcombating effect for kinds of microbicides in food crops and cash crops.In order to find highly active pesticide varieties, oxime ether and ester moietywere introduced into benzimidazole matrix structure according to the law ofbiological electron row principle and active sub-structure connection in this paper.Two series of fifteen compounds containing benzimidazole were synthesized. Themain work was summarized as follows:（1） Synthesis of oxime-ether Ⅰ: the target1-（2-（4-morpholinomethyl）-1H–benzoimidazol-1-yl） propan-2-one oxime-ether5a-j were prepared starting fromo-phenylenediamine and chloroacetic acid via the reaction of cyclization, nuclephilicsubstitution reaction of alkylation, N-alkylation, oximation and etherification with aseries of aryl halides and alkyl halides.（2） Synthesis of ester Ⅱ: the target1-（（2-triazolemethyl）-1H-benzoimidazol-1-yl）alkyl/aryl acetate8a-e were prepared starting fromo-phenylenediamine and1H-1,2,4-triazole-1-yl-acetic acid via the reaction ofcyclization, N-alkylation with a series of Chloroactic acid alkyl/aryl ester. Thestructures of target compounds are shown as follows:（3） All the target compounds were confirmed by1H NMR, IR, MS andelementary analysis. Some experimental processes were improved. Thepost-processing operation was simplified and the yield of target compounds wasimproved. The synthetic condition characteristic absorption peaks of the targetcompounds were analyzed and discussed in details.（4） In this paper, the antifungal activities of the series compounds Ⅰ against Botrytis cinerea, Beans sclerotia and Sclerotinia sclerotiorum were tested,respectively, by the mycelium growth rate method. Results showed that the EC₅₀values of the target compounds range from5.98to17.73μg/mL against Beanssclerotia, suggesting a moderate to high antifungal activities. However, the activitiesof these target compounds were lower than that of carbendazim (EC₅₀=3.67μg/mL).In addition, compounds5a,5c,5e,5g–i exhibited good antifungal activities againstBotrytis cinerea with EC₅₀values of0.16–8.69μg/mL. Especially,5a showedexcellent activity, which was significantly higher than that of carbendazim (EC₅₀=0.18μg/mL). On the other hand, many target compounds such as5a,5c,5e,5g and5i,displayed good activities against Sclerotinia sclerotiorum with EC₅₀values of1.18–49.30μg/mL, and the activities against Sclerotinia sclerotiorum of5a,5g and5iwere even significantly higher than that of carbendazim (EC₅₀=57.30μg/mL).