Efficient Copper-Catalyzed N-Arylations In Water

It is well known that N-aryl compounds play an essential role in many fields, such as biochemistry, pharmaceutical chemistry and material chemistry. Their biological and pharmaceutical activities and material characteristics are widely studied and applied.Since Ullmann reaction was found in 1901, it has been widely used and developed for the synthesis of the N-aryl compounds. During the past century, especially after transition metals such as palladium were applied into catalytic reaction, researchers found that Ullmann coupling reaction using palladium as catalyst could be carried out under mild conditions and were easy to purify. However, palladium was very expensive and the reactions always need unstable and toxic organic phosphorus ligand. For the purpose of overcoming these disadvantages, studies were focus on cheap, non-toxic and effective catalysts, and the copper catalyst was born.Nowdays, many researchers prefer to use economical and environmentally friendly copper-catalyst instead of expensive and toxic noble metals such as palladium in Ullmann coupling reactions, however, few can avoid using organic solvent in the research. In fact, the toxic solvent still make damages to our human-being and environment. Additionally, there are some other problems such as high reaction temperatures, stoichiometric amounts of copper reagents and low toleration of functional groups. Therefore,these are the problems that restrain the pace of industrialization of many academic achievements.In our research, we have developed a simple and efficient copper-catalyzed method. We used CuCl as the catalyst, (1E,2E)-oxalaldehyde dioxime (OADO) as the new ligand of copper-catalyst, water as the solvent, NaOH as the base, nBu4NBr as the additive, and the cross-couplings were performed well at 100°C for N-arylation of nitrogen-containing heterocycles and aliphatic amines. The method has the following advantages:⑴the catalyst CuCl is accessible and non-toxic, and only little needed;⑵as the new ligand of copper-catalyst, (1E,2E)-oxalaldehyde dioxime (OADO) is very simple and efficient;⑶the solvent water is very economical and environmentally friendly;⑷the cross-couplings are performed well at 100°C;⑸the method is of good tolerance towards various functional groups in the substrates;⑹the method can lead to good yields (most over 80%, even some over 90%).As a result, it will attract much attention in industrial and academic researches.