Green And Efficient Synthesis Of Pyranoquinolines Derivatives

Green Chemistry, a new branch of science emerged in recent decades, has attracted much attention. It involves in organic synthesis, catalysis, analytical chemistry, biochemistry, polymer chemistry, materials chemistry and other fields. The term green chemistry is defined as:The invention, design and application of chemical products and processes to reduce or to eliminate the use and generation of hazardous substances.In recent years, the multicomponent reactions (MCR) have attracted remarkable attention because it is a cheaper and environmentally friendly strategy. This process consists of a number (≥2) of synthetic steps which are carried out in the same flask without isolation of any intermediate to a product containing the main parts of all starting materials, which has the inherent advantages such as reducing time, separation process, energy and raw materials. The multicomponent reactions are environmentally friendly.Pyranoquinolines are cores of some natural products. They possess broad medicinal properties and biological activities which include antiplatelet aggregation, antiallergic activity, insecticide, antifungal, antibacterial, analgesic, antimicrobial, antipyretic, cytotoxic and antihistaminic properties and so on. So it is important to develop the synthetic method of pyranoquinolines. There have been several methods to prepare 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one and derivatives by three-multicomponents of 4-hydroxyquinolin-2(1H)-one, malononitrile and various aldehydes in one-pot catalyzed by Et3N, KF-Al2O3, TEBA (benzyltriethylammonium chloride), piperidine and ammonium acetate. However, these methods have the limitations such as involving toxic reagents, large amounts of catalysts, tedious work-up procedures and low yields. Therefore, there is still urgent to develop a green, efficient strategy for the preparation of potential biologically active pyranoquinoline derivatives.In the dissertation, we have developed a green synthetic method of 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives. In the first chapter, medicinal properties, biological activities and synthetic method were completely introduced.In the second chapter, we reported the preparation of 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives catalyzed by glycine in water. We screened kinds of catalysts, the loading of catalyst, solvent, and the molar ratio of reactants. The optimum reaction conditions were 4-hydroxyquinolin-2-one (1.0 mmol), malononitrile (1.2 mmol), phenyl aldehyde (1.2 mmol),20mol% glycine in 2ml water at 100℃. The reactions were completed in 4 hours and gave yields up to 95%.In the third chapter, a green, catalyst-free and efficient method to prepare 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives in the mixed solvent of ethanol and water (1:1) was investigated. And 16 substrates were successfully extended. It was very clear that aromatic aldehydes containing electron-withdrawing groups or electron-donating groups or furfural could smoothly give the corresponding products in good to excellent yields.In the fourth chapter, the synthesis of 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives was reported catalyzed by potassium carbonate. This method has the advantages of short reaction time (in 30 minutes), good yields of the products (82-91%), simple operation, easy isolation and environmentally friendly.