Synthesis Of Diaryl Ketones Via Palladium-Catalyzed Direct Oxidative Ortho-Acyla-Tion Of Anilides With Toluene Derivatives

Transition-metal-catalyzed cross-coupling reaction has attracted much attention, and some novel methods of transition-metal-catalyzed cross-coupling were discovered and reported to forming diaryl ketone compounds which are important building blocks found in pharmaceutical, natural products and organic functional materials. Currently, the cases using benzoyl halides, benzaldhyde and benzonitrile as carbonyl sources has been reported, but the study that toluene used as carbonyl precursor to form benzophenone was not reported.It is firstly reported case that toluene as benzoyl source reacted with acetanilide to synthesizing N-(2-benzoylphenyl)acetamide in the presence of palladium acetate. To optimize reaction conditions, some factors were studied and the results was as follows:the palladium salts had higher catalytic ability than inexpensive metal salts (such as copper salts, iron salts and cobalt salt), and Pd(OAc)2was the highest among them. The additions (such as acids, bases and organic ligands) were no help. Unfortunately, metallic oxides (silver carbonate and copper acetate), peroxide reagent (such as di-tert-butylperoxide, potassium persulfate and hydrogen peroxide) and oxygen were also ineffective oxidants. Changing solvent didn’t improve the reaction to increase the yield. Finally, the optimized reaction conditions were concluded as follows:with20%palladium acetate as catalyst and with16.0equiv of tert-butyl hydroperoxide as oxidant, acetanilide reacted with toluene at95℃for12h to form corresponding diaryl ketone, the yield is94%.The scope of substrates was further expanded and a broad range of diaryl ketones was obtained. Except for the anilides with ortho-position substituent groups, the good to excellent yields of desire products were isolated when the electron-donating groups were at the position of anilides or toluene derivatives; but the yield was low or no product in the reaction when either anilides or toluene derivatives with the electron-withdrawing group used as substrates. At last, the proposed mechanism was depicted in details. In the presence of palladium acetate, the acetanilide reacted with in situ forming benzaldehyde from toluene, and the corresponding benzo-phenone was obtained.