| Water is a safe,cheap,non-toxic,and pollution-free solvent for chemical reactions compared with traditional organic solvents.The use of water as the only supporting medium would obviate the requirement of organic solvents which has a lot of disadvantages including toxicity,flammability,and environmental hazards.Therefore,the study of organic reactions in aqueous solvents is an important research direction of green chemistry.Owing to their wide applications in the fields of natural products,synthetic drugs,and bioimaging,quinazolinones as important organic intermediates have attracted substantial attention among synthetic organic chemists.Whereas,conventional organic transformations can mainly be problematic due to harsh conditions such as toxic and expensive transition metal catalysts,strong oxidants,and the requirement of a large number of organic solvents.Therefore,a new approach for the environment friendly preparation of quinazolinone compounds is highly desirable.In this paper,a green and simple method for the synthesis of quinazoli-nones is proposed.This method offers a practical and environmentally friendly strategy for the rearrangement reaction of N-(2-(4,5-dihydrooxazol-2-yl)phenyl)amide mediated by water-soluble small molecular acid in water as the reaction medium at the room temperature,which enables a metal-and organic solvents-free access to the green synthesis of quinazolinones under mild conditions.Furthermore,on the basis of the control experiment and literature precedents,a plausible mechanism for this reaction is proposed.The substrate N-(2-(4,5-dihydrooxazol-2-yl)phenyl)amide adsorbs protons to form an electrondeficientcenter.After the nucleophilic addition of water,proton transfer occurs to open the oxazolyl ring forming a primary alcohol.Then the proton mediates the intramolecular amino group and carbonyl group to condense into a ring,and then dehydration leads to a carbon-nitrogen double bond.Finally,the proton is removed to complete the rearrangement resulting in 2-substituted-3-(2-hydroxy-ethyl)quinazolin-4(3H)-one.Last,under the optimal reaction conditions,13 kinds of aliphatic-substituted substrates and 5 kinds of aromatic-substituted substrates were investigated to examine the scope and generality of the method.It turns out that the substrates with little steric hindrance can obtain high yields.And a yield of 89% was obtained when the reaction was carried out on a gram scale.Which is evidence that the reaction has a good application prospect. |
