Synthesis Of N,O-Bidentate Coordinated Copper Complexes Derived From Quinoline And Catalytic Chan-lam Coupling Reactions

Copper complexes are a class of compounds with variable coordination structures.Depending on the ligands,mononuclear or polynuclear copper complexes with various structures can be synthesized.Copper complexes with different ligand usually exhibit good properties and have a special applications in biology,medicine,materials and catalysis.For example,the active sites of many metalloenzymes and metalloproteins contain binuclear copper structural units,and certain copper complexes with novel topological structures are important for exploring and studying the mechanism of action of antibacterial and antitumor drug molecules.Therefore,the design and synthesis of copper complexes with novel structures has always been an important research in the field of organic synthesis.On the other hand,the copper-catalyzed Chan-Lam coupling reaction is one of the powerful methods to construct carbon-hetero bonds such as C-N and C-O etc.However,the catalyst was mainly concentrated on copper salt and few studies on copper complexes as catalyst for Chan-Lam reactions were reported.The research work in this thesis focused on the design synthesis of quinoline skeleton-derived N,O-bidentate ligands and their copper complexes,which were used as catalyst for Chan-Lam coupling reaction.The specific work and important conclusions are as follows:1.The synthesis of 2-bromomethylquinoline was carried out by NBS bromination of 2-methylquinoline as a raw material,which was then reacted with tetrahydropyrrole,morpholine and 4-methylpiperidine followed by oxidation to provide the ligands L¹-L³ respectively.The ligands reacted with anhydrous copper chloride or copper acetate to produce complexes I-III and IV-VI.These compounds were characterised by modern analystic methods such as NMR,X-ray diffraction and IR spectroscopy.The optimum reaction conditions were determined by examining the effects of the structure of copper complexes,temperature and solvent on the reaction of 1H-benzimidazole(1a)with phenylboronic acid(2a)as model substrates.They are listed as follows:copper complex II(8 mol%),1a:2a=1:3,CH₃OH(1 m L),50°C,12 h.Under the standard conditions,a range of substrates for the reaction was investigated and eighteen coupling products were obtained to determine the effect of substituent groups and steric hindrance on the reaction.The results showed that arylboronic acids containing electron-withdrawing groups were more reactive than the electron-donating groups.The mild reaction conditions,wide range of substrates and high yields provide a new approach for the synthesis of imidazole derivatives.2.According to similar procedure,the ligands L⁴-L⁶ were synthesized by NBS bromination of 8-methylquinoline,the reaction of 8-bromomethylquinoline with nitrogen heterocycles(tetrahydropyrrole,morpholine and 4-methylpiperidine)followed by oxidation.Copper complexes VII-IX and X-XII were prepared by the reaction of L⁴-L⁶ with anhydrous copper chloride or copper acetate respectively.The structures of these compounds were determined by NMR,X-ray diffraction and IR spectroscopy.The complexes VII-XII were applied to the coupling reaction of phenol(1a)and p-methylbenzene boronic acid(2a).By examining the effects of catalyst,temperature,solvent and base on the template reaction,the optimum reaction conditions were determined:X(8 mol%)as catalyst,1a:2a=1:2,K₂CO₃as base and CH₂Cl₂(1 m L)as solvent,0°C,10 h.Under the optimum conditions,the coupling reactions of arylboronic acids containing different substituents with phenol derivatives were performed and sixteen coupling products were obtained in moderate to good yields.The results indicated that both the electronic effects of the groups and the spatial site resistance had different influence on the reaction activity.The reaction provides a new route for copper-catalyzed the formation of C-O bonds.