Research On Direct Amidation Of 2-methylquinolines

Over the past decade, environmentally benign processes toward amide synthesis have attracted extensive interest, and great progresses have been made. Amides are one of the basic starting materials for the preparation of various useful organic compounds. Amide motifs are also present in natural products, pharmaceuticals and functional materials. Conventional amide bond formation utilizes carboxylic acid derivatives, organohalides, amides, alcohols or aldehydes as coupling partners and requires preactivation, prefunctionalization or a strong oxidant. These reactions are based on the functional group transformations with a drawback of low atom-economical efficiency. Obviously, the direct aerobic oxidative amidation of methyl groups with amines is the most economical and clean way for the amide synthesis. Therefore, we developed a novel Cu-catalyzed direct aerobic oxidative amidation of 2-methylquinolines with amines.Herein, we successfully report a copper-catalyzed efficient direct aerobic oxidative amidation of 2-methylquinolines with amines to provide various aromatic amides in mild reaction conditions. The method afforded an efficient approach for the synthesis of amides in high yields and wide scopes with a catalytic amount of CuI catalyst using molecular oxygen as a green oxidant. To understand the mechanism of the reaction, control experiments and ¹⁸O labeling experiments were set up. These experiments show that 2-methyl-quinoline would be oxidized into the corresponding quinolyl aldehyde which further reacts with amines to afford imines. Hydrolysis and oxidation of imines provided the final product.In summary, we have developed a novel direct aerobic oxidative amidation of 2-methylquinolines with amines in the presence of a catalytic amount of CuI using molecular oxygen as a green oxidant.