Studies On The Synthesis Of 3-aminoquinoxalin-2(1H)-ones Based On Copper-catalyzed Oxidative Amination Of Quinoxalin-2(1H)-ones With Amines

Heterocyclic quinoxalinone derivatives are found in natural products and used in medicinal chemistry, which have exhibited a variety range of significant biological activities including acting as anti-tumor agents, anticancer agents, antimicrobial(or antifungal) agents, glycogen phosphorylase inhibitors and so on. Quinoxalin-2(1H)-ones derivatives are multi-purpose kind of potential lead compounds. 3-Aminoquinoxalin-2(1H)-one compounds represent an important structural element as a new class of glycogen phosphorylase inhibitors, anti-microbial and anticancer agents. This important pharmacophore has appeared extensively in numerous bioactive compounds that have been used in various clinical trials. However, traditional synthetic methods such compounds often require pretreatment reactants, multi-step synthesis, harsh reaction conditions, more byproducts, low yield and other shortcomings, which seriously hampered the application and development of 3-aminoquinoxaline-2(1H)-one compounds.In recent years, with the transition-metal catalyzed functionalization of C-H bond has been widely used, the copper catalyst gradually attracted attention of chemists. Cu catalyst is inexpensive and easy to get relative to the novel catalyst, such as Pd and Ru. Compare to the traditional synthetic processes, using copper salt catalyzed amination C-H bond is characterized as a shortened synthetic steps, atom economy and low toxicity. Therefore, the great application of copper-catalyzed C-H functionalization reactions to synthesis of multi-functionalized organic compounds is emerged as a hot topic. In this work, we described a novel and convenient approach to 3-aminoquinoxalin-2(1H)-one compounds via copper-catalyzed oxidative amination of quinoxalin-2(1H)-ones with primary and secondary amines as the nitrogen group sources. This synthetic strategy features with atom economy, concise steps, easy operation, and mild reaction conditions. The catalyst, solvent, temperature and reaction atmosphere were screened to optimize the reaction conditions. The scope and generality of the present process was then explored and a plausible reaction mechanism for the transformation reaction is proposed. We have developed a kind of high efficient and practical synthetic method, which has a wide application prospect.