The Monovalent Copper Catalyzed Azide?Alkyne Cycloaddition Reactions And Their MultiComponent Reactions

The monovalent copper catalyzed azide and alkyne cycloaddition,that is CuAAC reaction,has been widely used in biological research,materials science and drug molecular design,and the copper-catalyzed multicomponent reaction from azide and alkyne can effectively construct complex heterocyclic compounds.In addition,the product of CuAAC reaction,N-sulfonyltriazole,plays an important role in organic synthesis and can participate in many reactions to prepare novel compounds.Therefore,the copper-catalyzed azide-alkyne cycloaddition reactions and the multi-component reactions have been the focus of attention of chemists.In recent years,studies on CuAAC reactions and copper-catalyzed tandem reactions have been reported continuously.In particular,methods for the synthesis of triazole compounds have made great progress.However,there are still some limitations in literatures about synthesizing triazoles:too many additives to be used in the reaction;some catalyst systems are too complex to prepare;using organic reagents as solvents or limited substrate scope,etc.Therefore,it is still of scientific significance to find a simple,green,efficient and versatile catalytic method for the copper-catalyzed azide-alkyne cycloaddition reaction and multi-component reaction.In this paper,we carry out the following three parts of research with this goal:Part one:The optimal reaction condition for copper-catalyzed azide and alkyne cycloaddition reactions was explored.Using copper sulfate/substituted thiourea as the catalyst system,the cycloaddition reaction of organic azides and alkynes was performed in one-pot process to provide triazole compounds,the yield is up to 99%.This method avoids adding too many additives in the reaction,uses water as a solvent for the reaction conditions,has a wide range of substrates and has great industrial application potential.Part two:The cycloaddition reaction between the sulfonyl azide and the terminal alkyne was further studied,and the application scope of the copper sulfate/substituted thiourea catalytic system was extended.It was found that CuSO4·5H2O/substituted thiourea can be used as a highly efficient monovalent copper catalyst system to prepare the N-sulfonyltriazoles.Compared with the existing methods,the method has the following advantages:mild reaction conditions,green solvent,saving the amount of additives,low reaction cost,wide substrate scope and so on.Part three:The copper-catalyzed three-component reaction of azide,alkyne and 2-aminobenzaldehyde was explored.With the optimized conditions in hand,the reaction was highly efficient to yield the imino-1,2-dihydroquinoline compounds.This method has a high atomistic economic efficiency,and almost no by-products generates in the reaction,and the operation is simple and rapid,which is beneficial to the application in industrial production.