Electrocatalytic Synthesis Of N-heterocycle Without Transition Metal C-H Activation

Nitrogen heterocycles have certain advantages due to their special structure,optical properties and biological activity,and have many applications in luminescent materials and drug molecules.Therefore,it is of great significance to study a simple and green synthetic route to construct heterocyclic molecules.The problem faced by the current C-H bond activation reaction is the need for equivalent oxidants,such as metal Cu salt,Ag salt,benzoquinone,peroxide H₂O₂,persulfide K₂S₂O₈,high-valent iodine,etc.Due to the high cost of metals and the pollution of organic waste,it is difficult to apply them to industrial production on a large scale.The essence of chemical reaction is the transfer and gain and loss of electrons.In theory,electrons can be directly used as a clean oxidant to replace the equivalent chemical oxidant to control chemical waste pollution from the source.Combining the advantages of C-H bond activation and electrons as a clean oxidant,if a method for synthesizing nitrogen heterocycles using electrons as an oxidant can be developed,a highly efficient,green and environmentally friendly synthetic route can be provided for drug molecules,which can better adapt to the requirements of industrial applications.The main research work of this paper:A simple,environmentally friendly electrochemical method for generating nitrogen-centered free radicals was developed.Using N-phenylaminopyridine as raw material,no additional transition metal catalyst and oxidant are needed,using potassium hexafluorophosphate as a supporting electrolyte,sodium acetate trihydrate as an additive,and H₂O as a reaction solvent,a benzimidazolopyridine heterocyclic compound was synthesized in a one-step constant current electrolysis in an undivided electrolytic cell.During the experiment,a lot of screening work was done,and the possible influencing factors in the electrochemical synthesis process were optimized,such as electrode materials,current density,solvent,temperature,etc.Under the optimized system,the universality of the substrate was investigated,a total of 32different products were synthesized,and the gram-level reaction was also carried out under the optimized reaction conditions,and still a 50%yield was obtained.The reaction mechanism was preliminarily explored through free radical trapping experiments,cyclic voltammetry and deuterium band dynamic isotope experiments.The fluorescence properties of products containing morpholine groups were explored,and potential cell imaging properties were revealed;a series of cytotoxicity experiments were studied.