| 4H-3,1-Benzoxazin-4-ones represent an important skeleton that exist in a number of physiologically and pharmaceutically bioactive natural products.During the past decade,C–H activation has been widely used in forming C（sp2）–O bonds between an aldehyde carbon and an oxygen moiety.This novel strategy uses TBHP as oxidant and CoCl2 as catalyst,allowing for Co-catalyzed synthesis of the useful benzoxazin derivatives and is highlighted by features such as readily availability of the starting materials and mild reaction conditions.2-Amino benzaldehyde and its derivatives were used as raw material to prepare N-（2-formylphenyl）amides,via condensation with a series of substituted benzoic acid derivatives.We chose N-（2-formylphenyl）benzamide as a model substrate,preparing 4H-3,1-benzoxazin-4-one product by using TBHP as oxidant and CoCl2 as catalyst in MeCN under refluxing conditions after a series of conditions screening.To verify the substrate adaptability for this novel method,we also prepared a series of amides as substrates.Experimental results show that 18 amides substrates were converted to benzoxazin derivatives with potential pharmacological activity under optimal conditions.Both the substrates and products have been well characterized by 1H NMR,13 C NMR.In addition,they were also confirmed by HRMS.At the same time,we also put forward the possible mechanism for this newly developed oxidative cyclization reaction.Adding the TEMPO can inhibit the reaction,which proves the rationality of the radical mechanism.Initially,the bond dissociation of TBHP takes place to give the tert-butoxy and hydroxy radicals.The abstraction of a hydrogen from aldehyde by the tert-butoxy radical generates acyl radical,which undergoes a carbon-oxygen bond-forming reaction to give six-member ring intermediates.A second hydrogen abstraction from this intermediates by the hydroxy radical,leads to the title product along with the generation of one molecule of water. |
PDF Full Text Request