Research On N-Arylation Of N-Containing Heterocycles Catalyzed By Copper

N-Arylheterocycles are key structural motifs in many natural compounds with physiological activities. Now, they are widely applied in pharmaceutical, pesticide, N-heterocyclic carbene chemistry, organic electroluminescence and photoelectric converting materials fields. Therefore, the simple methods to access them have attracted a lot of interest of the chemists. The copper-catalyzed C-N bond formation by Ullmann condensation constitutes a powerful strategy for their preparation. Herein, we summarize these methods within recent decade. This paper includes significant achievements of heterocycle N-arylation catalyzed by copper with various bases and solvents.An efficient and inexpensive catalytic system:CuI/NaH/DMSO was devoloped, and the reaction condition was optimized. Many containing-NH heterocycles, such as pyrazole, imidazole, indole, pyrrole, piperidine and so on, could couple with both aryl-iodides and-bromides, even the activated aryl-chloride with moderate to excellent yields (68-97%). According to the experiment and reported mechanism, the reaction mechanism of this catalytic system was speculated. This method is simple and convenient, and the catalyst can be reused.We have devoloped an environmentally friendly and inexpensive catalytic system:activated copper/LiOH/water with TBAB as PTC. With this new method, N-heterocycles could coupling with both aryl-iodides and-bromides in moderate to excellent yields (23-87%). The catalyst system is stable in air and can be reused for several times.We also have devoloped an environmentally friendly and inexpensive catalytic system:CuI/tetraethylenepentamine/water that could greatly promote the N-arylation of heterocycles with both aryl-iodides and-bromides in yields up to98%. The results showed that the tetraethylenepentamine and triethylenetetramine could facilitate the solubility of CuI in water. For many functional groups can exist in its weaker basicity condition, this versatility makes the protocol widely used in synthetic chemistry. This catalyst is stable in air and can be reused for several times.12Betti bases were prepared and their spectrum identification were confirmed. Their promotion abilities in N-arylation reaction were investigated and1-[(dimethylamino)-(pyridin-2-yl)methyl]naphthalen-2-ol (L7) was found to be the optimal ligand. N-arylation reaction of heterocycles with both aryl-iodides and-bromides proceeded smoothly under lower temperature with good to excellent yields. The monocrystal structure of Cu(OAc)2·L7prepared in mixed solvent of ethyl acetate and ethanol was confirmed by X-ray single crystal diffraction.