A Study On One-Pot Synthesis Of Quinazolin-4(3H)-ones Through Anodic Oxidation

As one of the most basic reactions in organic chemistry,oxidation reaction is widely used to construct organic natural products and molecular structures with different oxidation states.Conventional oxidation reactions often require stoichiometic or even excess oxidants,higher reaction temperature,metal ligand catalyst,etc.With electrons as the oxidizing agent,organic electrochemical oxidation not only avoids the use of excess oxidants,but also emit hydrogen gas as the sole byproduct.The reaction is generally carried out at room temperature.In addition,by controlling the reaction potential,selective oxidation of the substrates can be achieved.In sum,electrooxidation complies well with the criteria of efficient and green chemistry.Electrochemical dehydrogenation and cross-dehydrogenative coupling reactions have achieved prominent developments in recent years.In this paper,the synthesis of quinazolin-4(3H)-ones and quinoxalines was studied by means of anodic oxidation.1)The reactions of anthranilamide and aldehydes were investrigated.With catalytic amount of p-toluenesulfonic as acid catalyst,anthranilamide and aldehyde produce quinazolin-4(3H)-ones in excellent yield under direct electrooxidation.No oxidants,metal salt is required in this reaction,and different aldehydes could be well tolerated.At the same time,we proposed a possible reaction mechanism through control experiments.2)The reactions of anthranilamide and alcohols were investrigated.With catalytic amount of TEMPO as redox-mediator,alcohols can produce quantitatively corresponding aldehydes under indirect electrooxidation.Subsequently,the aldehydes and anthranilamide produce quinazolin-4(3H)-ones in excellent yield under acid-catalyzed / anodic oxidation cascade.Benzyl alcohol,allyl alcohol and propargyl alcohol can be well tolerated in the reaction.In the meantime,we verified the different reaction mechanisms of direct electrooxidation and indirect electrooxidation after adding TEMPO through a series of control experiments.3)Under the same condition with 1)and 2),the synthesis of quinoxaline derivatives with 1-(2-aminopheny)pyrrole(or indole)and various aldehydes or alcohols was explored.