Copper-catalyzed Synthesis Of Quinazolinone Derivatives

Quinazolinone derivatives are important nitrogen-containing compounds, theywidely exist in nature products, and have attracted much attention for their biologicaland pharmaceutical activity. According currnt paers, most of the way of synthesis ofquinazolinone derivatives have some disadvatages, for instance, expensive substrates,harsh conditions, difficult separation and low rate of production. In this paper, weovercome these disadvatages to some extent, many quinazolinone derivatives weresynthesized through copper-catalyzed Domino reactions, and some important resultswere obtaied as follows:A new copper-catalyzed domino method for synthesis of quinazolinone derivativeshas been developed via reactions of substituted2-haloaromatic amides with（aryl）methanamines. The protocol uses CuBr was used catalysts, K₂CO₃as base andDMSO and DMSO as solvent, and the reactions were performed at110-130oC under air.The results of research indicate: the substituted group of2-haloaromatic amides havelittle influence in the rate of production, but the electron-donating substituted group of（aryl）methanamines can improve the rate of production, the electron-withdrewingsubstituted group of （aryl）methanamines can reduce the rate of production. The dominoprocess underwent Ullmann-type N-arylation, aerobic oxidation and intramolecularaddition. The method has the following advantages:（a） higher yields （b） the simple andefficient catalyst system;（c） without need of ligand and additive;（d） environmentalfriendly air as the oxidant.A new copper-catalyzed domino method for synthesis of quinazolinones has beendeveloped via reactions of substituted2-halobenzamides and α-amino acids. Theprotocol uses CuBr was used catalysts, K₂CO₃as base and DMSO and HOCH₂CH₂OH（VDMSO：VHOCH2CH2OH=75:1） as solvent, and the reactions were performed at110-120oC under air. The results of research indicate: the substituted group of2-haloaromatic amides have little influence in the rate of production, but the complex side chains of α-amino acids can improve the rate of production, the simple side chainsof of α-amino acids can reduce the rate of production, and the difficulty of reaction isharder. The domino process underwent Ullmann-type N-arylation, aerobic oxidation,intramolecular addition and oxidative decarboxylation, or underwent N-arylation,oxidative decarboxylation, intramolecular addition and aerobic oxidation. The method issuitable for natural and unnatural α-amino acids, and it has the following advantages:（a）the simple and efficient catalyst system;（b） without need of ligand and additive;（c）environmental friendly air as the oxidant.Quinazolinone derivatives which have aromatic ring will be synthetized by the firstway, quinazolinone derivatives which have aliphatic chains and aromatic rings will besynthetized by the second way. The range of application of the second way is wider thanthe first, however, the atom economy and yield of the first way is higher than the secondway. So the two ways of synthesis of quinazolinone derivatives is well complementary,we can select one of them according to the specific structure of quinazolinones.