A One-pot Synthesis Of Benzimidazoles Via Alcohol/amine Catalyzed By Ionic Liquid

Benzimidazoles are important intermediates in organic synthesis.A variety of biologically active compounds with a benzimidazole moiety can be used to treat a variety of diseases.Benzimidazoles can be used as catalyst carrier or ionic liquid in chemical industry,and also found utilities in materials chemistry and fuel cells.Therefore,it is important to develop a simple and effective method for the synthesis of benzimidazoles.First,two sulfonic acid internal salts were prepared by the reaction of 1,3-propane with N-methylimidazole and pyridine,respectively.Then eight Br（?）nsted acidic ionic liquids were prepared by the reaction of the two sulfonic acid internal salts with equal molar ratio of four inorganic acids,respectively,and as catalysts applied in the synthesis of benzimidazoles from condensation of o-phenylenediamine with various alcohols or amines.Eight IL/TEMPO/Na NO₂ as catalyst systems were applied in the synthesis of benzimidazoles from various alcohols and o-phenylenediamines,respectively,and their catalytic properties were investigated systematically.It was found all the catalytic systems from the eight ionic liquids were efficient in the aerobic oxidation of the benzyl alcohol to benzaldehyde.Meanwhile,[MIMPs]Cl showed best catalytic perfomance in the condensation of benzaldehyde,generated in situ,with o-phenylenediamine to give2-phenylbenzimidazole.The reaction of benzyl alcohol with o-phenylenediamine to give2-phenylbenzimidazole was used as a model reaction to optimize the reaction conditions.From the systematic experiments the optimal reaction conditions were obtained,which are as follows:CH₃CN/H₂O（10:1）as the solvent,a molar ratio of benzyl alcohol to o-phenylenediamine of 1:1.1,the loadings of[MIMPs]Cl,TEMPO and Na NO₂ of 20 mol%,5 mol%and 8 mol%,a reaction temperature and time in the first step of 45°C and 5 hours,and a reaction temperature and time in the second step of 55°C and 5 hours.Under these conditions,the yield of 2-phenylbenzimidazole was 94.8%.The substrate scope investigation showed that the system had a wide range of substrate tolerance,being suitable for the reaction of o-phenylenediamine with aromatic/heteroaryl/alicyclic alcohols or long-chain allyl alcohols.The eight ionic liquids were applied to the respective condensation of benzylamines with o-phenylenediamines to give benzimidazoles,and[MIMPs]Cl was the best among the ionic liquids.The aerobic oxidative condensation of benzylamine with o-phenylenediamine to give 2-phenylbenzimidazole was used as a model reaction to optimized the reaction conditions.The optimal reaction conditions are as follows:N,N-dimethylformamide as the solvent,a molar ratio of benzylamine to o-phenylenediamine of 1:2.5,the amout of[MIMPs]Cl of 25 mol%,reaction temperature 100°C,reaction time 20 hours.Under these conditions,the yield of 2-phenylbenzimidazole was 91.3%.The substrate scope investigation showed that the protocol colud be applicable to condensation of various benzylamines with o-phenylenediamines to their corresponding benzimidazoles.