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

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of 4′-nonafluorobutylacetophenone by metal-assisted cross-coupling reaction of 1-iodo-perfluorobutane and 4′-bromoacetophenone. ► Optimization of the reaction from the effects of metal, metal salt, ligand, and solvent. ► All compounds were identified by 1H NMR and 19F NMR spectroscopy.