Copper-catalyzed Synthesis Of Disubstituted Imidazolones

Nitrogen-containing compounds especially nitrogen heterocylces are abundant in nature, and they often exsit in natural products, medicinal compounds, particularly in a large number of bioactive compounds. Because of this they have been studied for many years to promote human cilivizaiton to develop. In this big group, imidazolones can be used as the chromophores of the fluorescent proteins, and they are also antagonists of many receptors.Only several approaches to 2,4-disubstituted imidazolones were reported till now, and the protocols used reactions of oxazolones with amines, coupling of imidates with amino acid esters. Oxazolones, imidates and amino acid esters all have special structures, which result that only few kinds of imidazolones can be produced in these ways. In this condition, a simple and economical method is required to syhthesize imidazolones.In recent years, copper-catalyzed Ullmann-coupling reaction for synthsis nitrogen-containing compounds have attracted much attention, and great progress has been made in this. Because Ullmann-coupling is a kind of simple, wild and inexpensive synthesis method, our researches focus on prepation of imidazolones in this way.We have developed a simple and efficient copper-catalyzed synthesis of 2,4-disubstituted imidazolones without additon of any ligand or additive under mild condition. During the optimization process of the system, the best condition is: 20 mol% Cu₂O as the catalyst, Cs₂CO₃ as the base and DMF as the solvent at 80 oC.The advantages of this method is shown as below:1) the meterials used are lowmammaliantoxicity;2) use Cu₂O as the catalyst, Cs₂CO₃ as the base without ligand, very economical;3) the reaction temperature is only 80℃, the system and the purification is simple; 4) the substituent groups of the meterials are variable;5) will be of wide application in organic chemistry and medicinal chemistry.