Ligand-free Copper Catalyzed N-Arylation Reaction Of O-Aminophenol

Arylamines often serve as substructures in many biological active natural products, pharmaceuticals,and materials.Although the Ullmann reaction is one of the traditional methods to assemble these compounds and significant achievements have been made during the last decade,the harsh reaction conditions limit its application both in laboratory and chemical industry.During exploring copper-catalyzed N-arylation,we found that without ligand copper catalyzed coupling of o-aminophenol with iodobenzene gives the o-hydroxyldiphenylamine and o-hydroxyl- triphenylamine in high yields.After screening the influence of copper salt,solvent,base and the ratio of materials, suitable routes for the selective formation of o-hydroxyldiphenylamine and o-hydroxyl-triphenylamine were found out.The reaction condition of synthesizing o-hydroxyldiphenylamine:o-aminophenol(2.0 mmol),Arylhalides(1.0 mmol),20 mol%CuI and 2 equiv.K₃PO₄ or Cs₂CO₃ in DMF at 60-110℃stirred for 16 h under N₂ atmosphere.The reaction condition of synthesizing o-hydroxyltriphenylamine:o-aminophenol(1.0 mmol),Arylhalides(3.0 mmol),20 mol%CuI and 2 equiv.Cs₂CO₃ in DMF at 110℃stirred for 24 h under N₂ atmosphere.With the optimized conditions in hand,we investigated more aryl halides to evaluate the tolerance of this system.Yields of o-hydroxyldiphenylamine derivatives ranged from 57 to 93%.A wide range of functional groups were compatible with this reaction such as -OCH₃, -NO₂ and-COCH₃.Even aryl halide with a free -OH or-NH₂ attached directly to the benzene ring provide a considerable yield.Yields of o-hydroxyltriphenylamine derivatives were 50～85%.The electronic and steric factors affected the diarylation of o-aminophenol observably.Arylhalides carded a donating-electron substituted make the yields reduced obviously.In summary,we have demonstrated a new simple and efficient method to selectively mono- or diarylated of o-arninophenol.