Optimization of the synthesis of 4-nonafluorobutylacetophenone by metal catalysed cross-coupling reation

The synthesis of 4′-nonafluorobutylacetophenone by metal-assisted cross-coupling reaction of 1-iodo-perfluorobutane and 4′-bromoacetophenone is presented. The effect of metal (iron, copper) metal salt (copper(I) bromide, copper(II) chloride), ligand (2,2′-bipyridine, N,N,N′,N″,N‴,N‴-hexamethyltriethylenetetramine, N,N,N′,N″,N″-pentamethyldiethylenetriamine), and solvent (N,N-dimethylformamide, dimethylsulfoxide) was studied in order to elucidate their role in the optimization of the reaction conditions. The best conditions were found for the reaction carried out in presence of copper as catalyst, 2,2-bipyridine as ligand and in presence of N,N-dimethylformamide as solvent that led to 73% yield of the desired product (for a quantitative conversion of both 1-iodo-perfluorobutane and 4′-bromoacetophenone). The resulting product was characterized by nuclear magnetic resonance, IR, and mass spectroscopy.