Synthesis And Antioxidant Activity In Vitro Of 2-amidoquinoline Derivatives

Quinoline derivatives are important nitric heterocyclic compounds,which are abundant in natural products and synthetic compounds.It has good biological and pharmacological properties and is widely used in food processing,agricultural protection,drug screening and other fields.N-quinolinamide is a kind of an important pharmacophore in medicinal plants,which have attracted great interest in the scientific community.In recent years,the construction of carbon-hetero bonds by C-H activation has become the main method for synthesizing N-quinolinamide in the field of organic synthesis.However,the C-H activation requires the toxic metals as catalyst that are pollutant for the environment and the humans.In addition,the position numeber 2 in quinoline serves as an important reaction site,and its antioxidant activity is greatly enhanced after the introduction of the amino group.Few studies have been reproted on the2-amidoquinolines.Therefore,it has practical significance to explore a new method for the green synthesis of 2-amidoquinoline by constructing C-N bond via C-H activation without metal participation.In the manuscript,A total of 28 compounds were synthesized.We have developed a novel strategy for the regioselective synthesis of N-(quinolin-2-yl)amides through TsOH-mediated N-amidation ofquinoline N-oxides with inexpensive and commercially available nitriles as the amidation reagents.The mechanistic exploration suggested that the reaction probably proceeds through an acid-assisted 1,3-dipolar cycloaddition and N�O bond cleavage followed by a dehydro-aromatiza--tion process.The N-oxide plays a dual role,acting as a traceless directing group as well as a source of oxygen atom.Characterization of a series of N-(quinolin-2-yl)amides compounds by NMR and HRMS.The antioxidant activity of the compounds was explored by deoxyribose degradation assay for hydroxyl radical-scavenging using reduced glutathione(GSH)as a control.Compared to previous reported studies,this methodology does not require large amounts of organic solvent and displays several advantages,such as high atom economy(Relative to quinoline N-oxide),simple reaction conditions and excellent yields.Additionally,this methodology can be performed on a large scale without any problems.We have selected fourteen different N-(quinolin-2-yl)amides,after the test of antioxidant activity,twelve substances were found to have a high clearance rate of hydroxyl radicals,and consider as to have potential value of antioxidant activity research.