C-N Coupling Reaction Of Quinoline-N-Oxides With Aryl Sulfonamides

The presence of N-quinoline-sulfonamide structural motifs has been frequently found in the frameworks of various pharmacologically active compounds. N-Quinoline-sulfonamides are widely used as synthons in synthetic organic chemistry, biochemistry and pharmaceutical chemistry, and its structure is also encountered in a multitude of marketed drugs and countless drug candidates.In this paper, the C-N coupling reaction of quinoline-N-oxides with aryl sulfonamides was investigated. The main contents are shown as follows:The coupling reaction of quinoline-N-oxides and aryl sulfonamides in the presence of diethyl iodobenzene with triphenylphosphine was developed. The C-N coupling reaction of quinoline-N-oxide and4-methylbenzenesulfonamide was carried out as a model reaction to optimize the reaction conditions (such as λ3-Iodane promoters, additives, bases, solvents and temperature). It was found that the reaction was treated with quinoline-N-oxide:4-methylbenzenesulphonamide:diethyl iodobenzene:triphenylphosphine=2:1:2:2(the amount ratio of material) in CH3CN at80℃to afford the best result. Under the optimal conditions, the coupling reaction of4-methylbenzenesulfonamide with quinoline-N-oxide produced desired product in97%yield. The reaction was also found to be suitable for various functional group-substituted quinoline-N-oxides with benzenesulfonamides (including5-bromo-2-thiophenesulfonamide), and a variety of new N-quinoline-sulfonamides were synthesized by the present way.