Photo-induced Decarboxylation Of Pyridine N-oxides Using ?-oxocarboxylic Acids

Pyridine and quinoline N-oxides and their derivatives are important nitrogen-containing heterocyclic compounds and important structural units of many drug molecules.Because pyridine N-oxides are easy to prepare and have good regioselectivity,direct C2-H functionalization provides an effective and straightforward route for the preparation of 2-substituted pyridine derivatives.Particularly,2-arylacylpyridine N-oxides serve as important intermediates for the synthesis of many drug molecules,such as acrivastine,bepotastine and carbinoxamine.Therefore,the synthesis of 2-arylacylpyridine N-oxide has received more attention.Currently visible light catalysis is a popular research topic in synthetic chemistry and catalysis.However,because most organic molecules cannot absorb visible light,the photocatalytic transformations generally require the presence of a photosensitizer,such as the expensive ruthenium and iridium complexes or organic dyes.In recent years,studies have shown that fluorescein as an organic dye has excellent photocatalytic activity in many reactions,but the problem of fluorescein's sensitivity to p H and poor solubility in organic solvents limits its development.In order to solve the above problems,a new organic dye photocatalyst fluorescein dimethylammonium(FD)was designed and synthesized in this paper,FD could effectively maintain the p H of the reaction system,such that fluorescein mainly exists in the form of a dianion,and can improve the solubility of fluorescein in organic solvents.On this basis,a green synthesis strategy was developed under visible light induced by using organic dye FD as a photocatalyst to realize the decarboxylation acylation reaction of pyridine N-oxide and ?-oxocarboxylic acid at room temperature.By screening the photocatalyst,solvent,light source,reaction time and the equivalent of photocatalyst,the optimal reaction conditions were determined as follows: FD(5 mol %)as the photocatalyst,dichloroethane(DCE)as the reaction solvent and 10 W blue LED as the light source at room temperature for 24 hours.Under the optimal reaction conditions,the applicability of the reaction was explored,30 2-arylacylpyridine N-oxides were synthesized and their structures were characterized.Next,the decarboxylation acylation reaction system was used to synthesize an intermediate of acrivastine on a gram-scale,which proved the application potential of the reaction system.Finally,the mechanism of the reaction was verified by control experiments.The results of free radical trapping experiment and singlet oxygen quenching experiment proved that the reaction system was carried out through free radical reaction pathways,and proposed the mechanism of the reaction.