Synthesis Of N-(1,7-Dioxo-tetrahydro-pyrazolo[1,2-α]Pyrazol-2-yl)-benzamide Derivatives

Five-membered nitrogen-containing heterocycles have been found core structural elements usually appearing in biologically active molecules and widely used in medicine, pesticides and other aspects. These bicyclic heterocycles are proved to have other important and useful bioactivities, and they have been developed as herbicides and pesticides, antitumor agents, calcitonin agonists and potent drugs for treatment of cognitive dysfunctions such as Alzheimer’s disease. Because of its pharmaceutical properties, synthesis of N,N-bicyclic heterocyclic derivatives have attracted chemist’s interest. They found that1,3-dipolar cycloaddition reactions of azomethine imines with various olefins have been a powerful approach for synthesis of N,N-bicyclic heterocyclic compounds.In the past decades, catalytic asymmetric1,3-dipolar cycloaddition reaction have been developed for several1,3-dipoles, including nitrones, nitrile imines, nitrile oxides, diazoalkanes, carbonyl ylides and azomethine imines. But in recent years, azomethine imines were the main object of study in1,3-dipolar cycloaddition reaction and especially were widely used in the synthesis of natural products-1,3-Dipolar cycloaddition reaction of azomethine imines had achieved great development. But to date, the synthesis of N,N-bicyclic core is still a challenging task in organic chemistry.Here we found a novel approach to synthesize N,N-bicyclic heterocyclic core. In this study, we synthesized N-(1,7-dioxo-tetrahydro-pyrazolo[1,2-α]pyrazol-2-yl)-benzamide derivatives by1,3-cycloaddition of azomethine imines and azlactones. The reaction conditions were optimized for the cycloaddition, CH2Cl2,25℃and without catalyst as the optimal reaction conditions, were used to synthesize a series of novel N,N-bicyclic heterocycles. In addition, we also proposed a possible reaction mechanism.