| Nitrogen-containing compounds are found in numerous natural products with biological and pharmacological activity.They are frequently used in many fields such as pharmaceuticals,cosmetics and fine chemicals,so their synthetic methods have always been a research focus.Among them,tetrahydroquinoline derivatives(THQs)and ?-aminoketones are two important kinds of nitrogen-containing compounds.The THQs have significant antiviral and antitumor activities and receive tremendous interests.As building blocks,?-aminoketones can be converted into a series of valuable derivatives,which shows great application potential in the field of drug synthesis.The tandem reaction can construct target molecules from a series of simple raw materials in a one-pot method,which has the advantages of simple operation,high efficiency and without intermediate isolation,etc.These evident advantages render it an important way for the synthesis of complex natural products,medicines,and other nitrogen-containing compounds.The reported catalysts for the synthesis of THQs and?-aminoketones by tandem reaction are generally classified into homogeneous catalysts and heterogeneous catalysts.Heterogeneous catalysts can be reused,but there are some deficiencies existed,such as catalytic efficiency is generally lower compared with homogeneous catalysts,structure cannot be precisely regulated according to substrate and reaction type.However,the inherent defects of homogeneous catalysts such as difficulty in recovery and tedious separation processes,limit their application in large-scale industrial process.Thus,the development of heterogeneous catalytic systems with high catalytic efficiency and excellent recycle stability has been the ultimate goal.Metal-Organic Frameworks(MOFs)have been gradually bridging the gap between homogeneous and heterogeneous catalysts because they possess large specific surface area,high porosity,excellent designability,diverse topological structure,and can be functionalized with different groups to meet with the demand for different catalytic applications.Based on these advantages,MIL-101(Cr)-SO3H with good stability and high density Br(?)nsted acid sites is constructed.The acidic sites are well-organized inside the pores of MIL-101(Cr)-SO3H and its high porosity facilitates the mass transfer.In addition,the open Cr metal sites in the structure can work as Lewis acid.The dual catalytic active sites of MIL-101(Cr)-SO3H can work synergistically in catalyzing the same reaction or multiple steps reaction,which endows it with great potential applications in the synthesis of natural products and drug molecules.In this thesis,sulfonic acid functionalized MIL-101(Cr)is used to catalyze various types of tandem reactions to prepare THQs and(3-aminoketones,which not only expands the application of MIL-101(Cr)-SO3H,but also provides a new avenue for the synthesis of natural products.1.The sulfonic acid functionalized MIL-101(Cr)is synthesized under hydrothermal reaction conditions by a pre-modification method,and the structure is confirmed by PXRD,SEM and FT-IR.A catalytic system with MIL-101(Cr)-SO3H as catalyst and hantzsch ester as the hydrogen source is developed.It is applicable to the synthesis of THQs through the transfer hydrogenation of a series of 2-substituted quinoline derivatives.The catalyst can be recycled many times.The results of PXRD and ICP-OES indicate that the catalyst has good stability under this reaction system.2.MIL-101(Cr)-SO3H is applied to the Povarov reaction of aromatic amines,aldehydes and electron-rich olefins.The system is suitable for different aromatic amines and aldehyde substrates,enabling the preparation of various THQs under mild conditions.The coexistence of Lewis acid and Br(?)nsted acid sites within the porous structure of MIL-101(Cr)-SO3H may explain its higher catalytic activity than p-toluenesulfonic acid,p-nitrobenzenesulfonic acid and sulfonated ion exchange resin Amberlyst-15.After being recycled many times,the catalytic activity and structure of the catalyst still remain unchanged.3.In the fourth chapter,MIL-101(Cr)-SO3H is successfully applied to catalyze the Mannich reaction of aromatic amine,aromatic aldehyde and cyclohexanone for the preparation of ?-aminoketones.The effects of catalyst amount,substrate ration and solvent on the reaction were investigated.Under the optimal reaction conditions,the catalytic system is suitable for different substrates.The catalyst can be recycled many times without changing the catalytic activity and crystal structure.The results provide heterogeneously catalyzed of the Mannich reaction route for the preparation of?-aminoketones. |
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