A New Strategy For Synthesis Of Benzimidazole Derivatives

Heterocyclic compounds are an important class of biologically active natural products and are often used as key scaffolds in numerous pharmaceutical intermediates,pharmaceuticals,and agrochemicals.Benzimidazole as an important class of heterocyclic compounds is applied in the field of biomedicine as dystrophin,anti-HIV antibody,anti-fungal antibody,antiviral drug and so on.Recent studies have shown that 2-aryl benzimidazole conjugates can induce apoptosis of MCF-7 cells in human breast cancer via a caspase-independent pathway.Chemists are dedicated to the synthesis of benzimidazoles because of the wide used in different scientific and technical fields.This paper mainly focuses on new methods for the synthesis of benzimidazoles.A series of chemical methods for synthesizing benzimidazole derivatives were summarized,including chemical methods,electrochemical methods,photocatalysis,and nanocatalysis as auxiliary catalytic methods.The basic one is the condensation of o-phenylenediamine with aldehydes,amines or acids;the second is o-phenylenediamine and alcohol as raw materials;the third is based on o-nitroaniline and alcohol as starting materials.However,to the best of our knowledge,these organic synthesis methods above all suffer from narrow substrate ranges and high reaction temperatures,long reaction times and high pressure.As our interest in heterogeneous catalysis,the development of green and mild synthetic methods still has great need and research significance.This article also describes the progress of organic nano-catalysts in recent years,and demonstrates the activity of supported nano-catalysts in the reaction system.This further confirms the focus of this paper and replaces the above three traditional synthesis methods."The hydrogen strategy",a process for the synthesis of benzimidazole derivatives starting from N-substituted 2-nitroaniline and alcohols under supported palladium catalysis.In the entire reaction system,the benzyl alcohol is oxidized to hydrogen released by benzaldehyde so that the nitro group is reduced in situ in the presence of a Pd/C catalyst.Since alcohols and N-substituted 2-nitroanilines are inexpensive and stable chemical materials,this method provides a highly efficient and envionmentally friendly route for synthesizing benzimidazole derivatives.More importantly,as a green reusable catalyst system,supported nanocatalysts can be repeatedly cycled six times without changing the catalytic activity in the reactions designed in this paper.Therefore,in the methods proposed in the paper,both organic synthesis and industrial production have the meaning of development and supplementation both in the supported nanocatalyst and in the"hydrogen-donating strategy".This article is divided into three parts.The first part reviews the synthesis of benzimidazoles and the development of supported nanocatalysts.The second part studies the synthesis of benzimidazole derivatives by palladium-catalyzed hydrogen synthesis.The third part is the experimental part.