Photoinduced [4+1] Cyclizations To Synthetise The 2-Perfluoroalkylbenzimidazoles

Benzimidazole and its derivatives have good biological activity and they are important drug molecules.The introduction of fluorine atoms on benzimidazole is one of the important strategies for the chemical transformation of pharmaceuticals.The introduction of a fluorine-containing group on a benzimidazole compound can enhance its antiviral activity and enhance the bioavailability of the drug;It can enhance the mutual binding ability of the drug to the target protein and other target proteins selectivity by changing the group of the compound.In this thesis,we described a photoinduced[4+1]cyclization reaction:o-phenylenediamine as a substrate react with perfluoroiodoalkanes to synthesize the 2-perfluoroalkylbenzimidazoles.We found that the optimal conditions for the cyclization reaction are:1.0 equiv of o-phenylenediamine as a substrate,1.1 equiv of perfluoroalkyl iodine,4.1 equiv of NaOH,ultra dry N,N-dimethylformamide as solvent,system concentration is 0.2 M,and a 36 W compact fluorescent lamp irradiates theReaction bottle.Stirring at 0°C for 2 h.The results showed that Perfluoroalkyl iodide of different alkyl chains with various substituents on the phenyl ring can afford the corresponding 2-perfluoroalky benzimidazoles in high yields.The structure of the products is identified by single crystal X-ray diffraction ¹H NMR,¹³C NMR and HRMS.Mechanistic study indicates that perfluoroalkyl iodide and o-phenylenediamine forms a halogen bond adduct,the halogen bond adduct undergoes single electron transfer under visible light irradiation with oxygen to forms N radical and C radical,by radical coupling,nucleophilic substitution,aromatization,formation of the target product.The protocol is mild,and provides a novel,green,and efficient access to synthsis 2-perfluoroalkylbenzimidazole.