Study On Efficient And Practical Immobilized Heterogeneous Cu(Ⅰ) Catalyst In CuAAC Reaction

In2001, Sharpless and co-workers first proposed the concept of “click”chemistry, and summarizes the general characteristics of the “click” reaction. Sofar, Cu（I） catalyzed azide-alkyne1,3-dipolar cycloaddition （CuAAC） is the“click” reaction which is the most reported in the literature and has the widestrange of applications. It has been the most powerful tool for the synthesis of1,4-disubstituted-1,2,3-triazoles which presence potential drug activity, and thestarting materials organic azides and terminal alkynes almost do not react withany other functional groups, and this is the so-called biological orthogonality. Ithelps CuAAC reaction open a green channel in the field of biomedicalapplications, and has been widely used in the development of the lead compoundlibrary and synthesis of protein analogs as well as other biologicalmacromolecules.Cu（I） as a heavy metal ions, infiltrated into water or soil likely to cause seriousenvironmental problems, its natural cytotoxicity does not compatible with thefield of bio-pharmaceutical. And most of the Cu ions and their complexes appearblue or green, which will bring some trouble to the separation and purification ofthe product in organic synthesis.Immobilizing Cu（I） on a solid supporter can solve this problem to some extent,and gains widespread attentions by researchers, supporter materials includeinorganic matrix and organic matrix. After the end of the reaction, heterogeneouscatalyst can be recycled and reused by a simple method, reducing the loss of theCu（I） species, and the costs. We prepared three different heterogeneous Cu（I）catalysts based on Fe₃O-4magnetic nanoparticles （MNPs）, oyster shell waste andthermomorphic C18alkyl modified ligand, respectively. They were characterizedby FT-IR, TEM, XRD, AAS and TGA. Heterogeneous Cu（I） catalysts were usedin “one pot” CuAAC reaction for the synthesis of1,4-disubstituted-1,2,3-triazolesunder microwave conditions, the structure of the products characterized by FT-IRand1H-NMR.We have observed some advantages in the course of the reaction:1) CuAACreactions of a wide range of sources of raw materials, the reaction operation is simple, fast and efficient, the products were easily purified and highly yielded;2)CuAAC reactions were carried out in water and aerobic conditions, not onlylowers the cost of solvent but also reduces the environmental pollution,microwave heating can greatly shortens the reaction times and leads a higherselectivity;3) the heterogeneous Cu（I） catalysts can be recovered for reuse severaltimes without significantly loss of activity;4) catalysts can also be used for thesynthesis of multi-grams of1,2,3-triazoles in high yields.