Copper-Catalyzed Benzomidazole Two-Position C-H Bond Activation To Construct N-O Heterocycles

Benzoxazole and benzoxazinone,two important N-heterocyclic compounds,have good application prospects in the fields of materials and medicine.Benzoxazole can be widely used in the material field because of its good mechanical properties and heat resistance,and can be used as a material for organic electroluminescence;The benzoxazinone as an important parental structure for the treatment of neurodegenerative mental diseases has attracted much attention in the field of drug research.Therefore,how to efficiently construct such compounds has also become a hot topic of research.Traditional methods for synthesizing N-O heterocyclic compounds such as benzoxazole and benzoxazinone generally adopt multi-step synthesis,the yield is relatively low,the functional group is poorly tolerated,and it has no high efficiency,which does not comply with modern green chemistry request.C–H activation can efficiently construct a variety of complex chemical bonds,improve the utilization of atoms,and at the same time have a very good functional group tolerance,in line with the concept of modern green chemistry.It is particularly noteworthy that series C–H activation can create multiple new chemical bonds in one step,avoiding the synthesis and separation of intermediates during the reaction,thereby reducing the post-treatment steps of the reaction and favoring the increase of the reaction yield.Therefore,in this dissertation,benzimidazole was used as raw material,respectively,with o-bromophenol and salicylic acid under the condition of copper as a catalyst,which could obtain a benzoxazole ring and a benzoxazinone respectively through a series C–H activation reaction.A method for producing a cyclic compound,which can synthesize an N–O heterocyclic compound by one-step reaction of a sp~2 C–O bond.In the reaction system of benzimidazole and o-bromophenol,we can also use o-iodophenol and o-hydroxyphenyl boronic acid instead of o-bromophenol with benzimidazole to obtain the target compound.In the above reaction,copper was used as a catalyst to catalyze the reaction and the sp~2 C–O bond was successfully synthesized to synthesize benzoxazoles.In this reaction system,the reaction underwent N-arylation of intermolecular benzimidazole,sp~2C–H activation of benzimidazole two position and reaction of phenol with intramolecular sp~2 C–H activation/C–O cyclization.In this reaction,we added TEMPO which found that TEMPO can inhibit the reaction and did not detect our target compound in the system,indicating that the reaction is a free radical reaction.This method can synthesize 17 compounds containing benzoxazole ring structure,of which 10 new compounds were structurally verified by hydrogen spectroscopy,carbon spectroscopy,high resolution mass spectrometry and infrared spectroscopy.Compared to the free radical reaction of benzimidazole with o-bromophenol,the reaction of benzimidazole and salicylic acid is completely different,because in this reaction,TEMPO is required as an oxidant to promote the reaction rather than a radical trap inhibitor.The reaction underwent the reaction of intermolecular benzimidazole N-acylation,sp~2 C–H activation of benzimidazole two position and intramolecular C–O cyclization of phenol.This reaction does not involve free radical intermediates.This method can synthesize 21 compounds,of which 20 new compounds are structurally verified by hydrogen spectroscopy,carbon spectroscopy,high resolution mass spectrometry and infrared spectroscopy.Due to the presence of the 1,3-tautomerism of1H-benzimidazole,it is difficult to separate the isomer products from the derivatives of monosubstituents on the benzimidazole ring,but in this system we succeeded.Two isomeric products of the reaction of 5-chlorobenzimidazole with salicylic acid were isolated.