Study On The Cu-MOF-based Catalysts For C-N And C-C Bond Construction And Its Application To Synthesis Of Bioactive Molecules

Synthesis methods for forming C-N bonds by Ullmann-type cross-coupling reaction and C-C bonds by Sonogashira coupling reaction are widely used in the field of synthetic biomolecules,drug molecules and material chemistry.and has achieved good results.However,homogeneous catalytic systems are inevitably faced with problems such as the inability of the catalyst to be effectively separated from the reaction medium,the difficulty in removing metal residues during product separation and purification,resulting in excess product metal residues,and the catalyst being non-reusable.Metal-Organic Frameworks?MOFs?are highly crystalline and relatively structurally stable composites that include organic bridging ligands and metal centers with well-defined geometries.These structural features make it rapidly an excellent heterogeneous catalyst which has exhibited good catalytic properties in a variety of fields.However,it is worth noting that the current research on the catalytic coupling reaction of Cu-based metal frameworks?Cu-MOF?and its derivatives is still limited.Based on this,the paper carried out Cu-MOF-catalyzed Ullmann C-N coupling and Sonogashira coupling reaction,and the catalytic system established by it was used for the synthesis of bioactive molecules.The specific work includes the following two parts.In the first part,Cu-MOF-74 as catalyst precursor,an effective heterogeneous copper-based amorphous Metal-Organic Frameworks?amorphous MOF,aMOF?catalyst was developed for the C-N cross-coupling reaction of nitrogen-containing heterocycles with aryl iodides/bromos.The coupling reaction of iodoanisole and imidazole was carried out as a model reaction,and the optimal reaction conditions were obtained:DMSO?1.0 mL?,Cu-MOF-74?10 mol%?,NaOH?2.0 mmol?,reaction at 120°C for 24 h,product separation yield is 90%.The method can also be successfully applied to the synthesis of the drug molecule imidazole/benzimidazoqu-inazolinone?83%,68%?and 2-phenylbenzimidaz ole?74%?.respectively.Compared with the homogeneous system?CuI/L-histidine?reported in the literature,the heterogeneous catalytic system has higher catalytic activity than the literature method.The copper residue in the coupled product is only 13 ppm,which is much lower than that in the homogeneous system.Metal residue in the co-product?619 ppm?.The crystal structure Cu-MOF-74 can form aCu-MOF-74?As a practical catalyst,?in situ under strong alkali and certain temperature by confirming the XRD,FT-IR,SEM,TEM structure and various control reactions of the catalyst before and after the reaction,This provides a new way to prepare aMOFs.And the separation of the catalyst can be achieved by simple centrifugation,and the Cu overflow amount in the reaction solution is less than 0.55%of the total copper amount,and after 6 cycles of recycling,the catalytic cycle activity of the catalyst is not significantly lowered.In the second part,Three Cu/C porous materials were prepared by direct carbonization at three different temperatures?450°C,600°C,900°C?using Cu-MOF-74 as precursors,named Cu/C-450,Cu/C.-600 and Cu/C-900.Characterized by scanning electron microscopy?SEM?,and transmission electron microscopy?TEM?,the results show that we have successfully prepared a core-shell structure in which a metal copper is encapsulated in a carbon skeleton to form needle crystals.The XPS results indicate that the metal center is mainly zero-valent Cu,which is due to its unique core-shell structure avoiding its further oxidation to Cu₂O and CuO.Subsequently,we used three porous materials to catalyze the sonogashira coupling reaction of an aryl iodide with an aromatic/aliphatic terminal alkyne or acetylene acid.The coupling reaction of phenylacetylene and p-iodoanisole was selected as the model reaction.The results of the conditional screening showed that the optimal reaction conditions were:Cu/C-450?10 mol%?,DMF?1.0 mL?,K₂CO₃?1.0 mmol?,and reaction at 120°C for 12 h,the yield reached 92%.,Under these conditions,27coupling products containing different substituents were synthesized in a yield of between 60 and 96%.Cyclic experiments showed that the catalyst did not significantly decrease in catalytic activity after 4 cycles.In summary,two MOF-derived aMOF and Cu/C porous materials were prepared and successfully used in Ullmann-type C-N coupling and Sonogashira coupling reactions.This result not only expands the application range of MOF materials,but also develops and perfects the synthesis method of constructing C-N bonds and C-C bonds.