Cu-Catalyzed Synthesis Of Isoindolin-1-Ones Via Annulation Of 2-Bromobenzonitrile And Phenylacetylene

As an important organic molecular skeleton,isoindolin-1-one is widely found in drug molecules and organic dye.Highly efficient synthesis of isoindolin-1-ones has become an important topic in the fields of organic chemistry,medicine,and material chemistry.Accompanied by the development of transition metal catalysis,a number of methodologies to synthesize isoindoline-1-one have been reported.The simplest method is the intramolecular reaction,but such reactions require the prior synthesis of a reaction substrate,such as alkynylamine or nitrone,which limits the application of the process.How to optimize the reaction steps is a difficult problem in the synthesis of this compound.At this time,the tandem annulation is an effective method to build multiple chemical bonds in one step which is widely used to synthesize isoindoline-1-one,but there are several disadvantages such as high temperature,poor regioselectivity,using palladium and ligands.How to economically synthesize isoindoline-1-one is a problem.In this paper,a reaction method for the cyclization of isoindoline-1-one under the condition of copper catalyst with 2-bromobenzonitrile and phenylacetylene as raw materials was designed.Taking 2-bromobenzonitrile and phenylacetylene as model substrates,the effects of catalyst,base,solvent,temperature and reaction time on the reaction were investigated.The optimum reaction conditions were determined as follows:CuI（10 mol%）,H₂O（3.0 equiv）,KO^tBu（1.5 equiv）,1,4-dioxane（0.2 M）,and reacted at 100℃for 6 h.Under the optimal reaction conditions,a series of studies on different reaction substrates were carried out.It was found that the derivatives of 2-bromobenzonitrile and phenylacetylene can introduce different functional groups in the meta and para positions,respectively have good yields.The method can efficiently and greenly convert the readily available raw materials into isoindoline-1-one compounds;finally the reaction mechanism is explored.The corresponding products were characterized by ¹H-NMR,¹³C-NMR and HRMS.