Synthesis Of Quinazolinones Through Copper-catalyzed S_NAr Reactions

The quinzaolinone structural motif has attracted considerable attention in organic synthesis because of its presence in many natural products and its incredible biological activities which had been used in the field of medicine and pesticide.Therefore,new,simple,economical method of quinazolinone synthesis is very important.A convenient and efficient method for the synthesis of quinazolinones from simple and readily available2-halobenzamides and nitriles is described in this work.Initially,the Cu-catalyzed reaction of 2-bromobenzamide with benzonitrile was selected as model reaction to optimize the reaction conditions.The reaction conditions,such as copper catalysts,bases,solvents,reaction time and temperature were examined.It was found that the best result was obtained by using Cu(OAc)2(10 mol%)as catalyst,tBuOK(3 equiv)as a base,tBuOH(3 m L)as a solvent at 100 °C under N2 for 16 h.Under the optimized condition,the nucleophilic addition of 2-bromobenzamide with benzonitrile proceeded smoothly and delivered the corresponding quinzaolinone product in 80% yield.The studied on the scope of substrates showed that while 2-idobenzamides also successfully reacted with nitriles,2-chlorobenzamides failed to give the corresponding products.On the other hand,both aromatic nitriles and aliphatic nitriles were tolerated and led to the quinazolinones in moderate to good yields.Moreover,It is found that electronic effect was not remarkable,the nitrile compounds with both electron withdrawing and electron-donating groups could proceed well,but the steric effects on aromatic nitrile compounds had an side effect on the yields.Nuclear magnetic resonance(NMR)are used to characterize desired products.