Ullmann Type N-Arylation Reactions of Iodo Pyrazoles with Phenyl Boronic Acid in Cu2O Catalyst

Abstract

Ullmann type reactions are one of the most effective methods to carry out the N-arylation of the pyrazole using copper catalyst. The Ullmann reaction carried out by conventional methods occur under hard reaction conditions using copper reagents at stoichiometric ratio and at high temperatures. With the development of more efficient copper catalysts, studies in this field have been continued and very efficient copper/ligand systems have been developed under mild conditions. Although it is known that many of copper / ligand system reactions are carried out under relatively mild conditions to increase the efficiency of Ullmann type reactions, in recent years, studies have been made on simpler catalyst systems which are ligand free and "green" solvents or solvent free. In this study, in order to contribute to N-arylation of pyrazoles in mild conditions, 4-Iodo-1phenyl -1H-pyrazole (Ph-IPz) and 4-iodo-3,5-dimethyl-1-phenyl-1H-pyrazole (Ph-IDMPz) compounds were synthesized according to the methods adapted from literature with N-arylation reaction of 4-Iodo-1H-pyrazole (4-IP) or 4-iodo-3,5-dimethyl-1H-pyrazole (4-IDMPz) with phenyl boronic acid in the prences of Cu2O catalyst. N-Arylation reactions of 4-iodopyrazols with phenyl boronic acit were carried out the presence of Cu2O catalyst, at atmospheric conditions, at room temperature, in methyl alcohol and without the use of any base and ligand. In this way , the synthesis of Ph-IPz and Ph-IDMPz was carried out for the first time with Ullmann reaction under the milder conditions. Synthesized ligands Ph-IPz and Ph-IDMPz were characterized by FT-IR, NMR and GC-MS mass spectra. The NMR and FT-IR spectra of the compounds showed characteristic peaks of both the pyrazole and the phenyl group. The absence of N-H proton peaks in the 1 H-NMR spectra of the obtained Ph-IP 2 and Ph-IDMP 2 compounds indicates that the phenyl group is attached from the pyrazole NH. The shifts in the C4 carbon peaks which are determinant for 4substituted pyrazoles in the 13C-NMR spectra also confirm the structure of the compounds.