Study On The Hydrogen Peroxide-mediated Synthesis Of Quinazoline Derivatives And Fragmentation Pathways Of The Products

Quinazoline and its derivatives are important parts of nitrogen-containing heterocyclic compounds,which widely exist in nature products.Due to their potential pharmacological and biological activities,the synthesis of quinazoline and its derivatives has been a hot research topic in the field of organic synthesis.In recent years,methodologies for the synthesis of quinazoline and its derivatives are adequate.A classic preparation of substituted quinazolines has been achieved via condensation of o-aminobenzyl amines with carbonyl equivalents,such as alcohols,aldehydes,ketones,amines,nitriles,and others;the reaction of o-carbonyl anilines or halides with benzyl amines,oximes,amidines,and ammonia equivalents also is an alternative to access quinazoline.However,the existing methods have some shortcomings,such as high reaction temperatures,expensive catalysts,high catalyst loading,multi-step reactions and narrow scope of substrates,which cannot meet the needs of these kinds of compounds.Therefore,more efficient,convenient and environmental friendly synthesis routes of quinazoline derivatives need to be explored.Hydrogen peroxide has been considered as an ideal oxidant for liquid-phase green chemistry as it is non-toxic,environmentally benign,and atom efficient,producing only water as theoretical byproduct.In this thesis,we developed three new one-pot reaction methodologies for synthesis of substituted-quinazoline derivatives via cross-coupling reactions of 2aminobenzylamine with aldehyde or benzyl bromide or toluene mediated by hydrogen peroxide.The present methods have advantages of mild conditions and good compatibility with aryl,alkyl and heterocyclic functional groups.Through the optimization of solvent,temperature,oxidant and other conditions,three series of compounds were finally synthesized efficiently,and their structures were all identified by 1H-NMR、13C-NMR and HRMS.The possible reaction mechanism of synthesis quinazoline compounds with the participation of hydrogen peroxide is proposed.Moreover,the complete fragmentation mechanisms of substituted-quinazoline derivatives have been investigated under tandem mass spectrometry and identified by high-resolution mass spectrometry experiments.Two major fragmentation pathways for the protonated ions[M+H]+of substituted-quinazoline after collision induced dissociation were shown:fragmentation of substituents and fragmentation of quinazoline skeleton.And it was also found that the isomers of 2-phenyl quinazoline(the substituents was located on the C2-phenyl or quinazoline skeleton)could be preliminarily distinguished by tandem mass spectrometry.