Synthesis Of 2-Quinoline And 2-Arylzoyl-Substituted Quinazoline-4(3H)-Ones Based On The Ring Expansion Reactions Of Isatin

Isatin is a nature occuring small molecule,its five membered ring contains ketone carbonyl andγ-lactam functional groups,which exhibits both electrophilicity and nucleophilicity.Due to its unique structural characteristics,isatin has a wide range of applications in organic transformations.The carbonyl group at the C–3 position of isatin is relatively active and easily attacked by various nucleophilic reagents,which can be used to construct indolenones.In addition,the C₂–N₁and C₂–C₃bonds of isatin are easily broken and decarbonylated under basic conditions or in the presence of radical initiators,and isatin has also been used as a building block for the synthesis of heterocyclic molecules such as quinoline and quinolone.In the first chapter,we reviewed the recent literature reports on the construction of hydroxyindole ketones,spiro compounds and benzo heterocycles based on isatin,and proposed the research idea for the construction of two different quinazoline-4（3H）-one derivatives based on the oxidative ring expansion reaction of isatin.In the second chapter,a one-pot three-component method for the synthesis of2-quinolyl-substituted quinazoline-4（3H）-one starting from isatin,ammonia and methylquinoline using tert-butanol peroxide as oxidant,iodine as the additive,potassium carbonate as base in dimethyl sulfoxide is established.Quinoline and quinazolinone are simultaneously introduced into the same molecule.The reaction mechanism is discussed by the controlled experiments,which indicates that the target product could be obtained by the sequential condensation/oxdiation of two important intermediates o-aminobenzamide and 2-formyl-quinoline.This method realizes the ring-opening oxidation rearrangement of indigo and the construction of a new benzoazo-heterocycle.Compared with the traditional method for the synthesis of2-aryl-substituted quinazoline-4（3H）ketones,this reaction has the advantages of wide range of substrates and simple operation.A total of twenty-seven target products were synthesized and classified in this chapter.All compounds are characterized by ¹H NMR,¹³C NMR,IR and MS.In the third chapter,we have successfully established a TBHP-promoted three-component annulation reaction of isatin,ammonia and benzoyl formaldehyde hydrate for the rapid synthesis of various 2-arylzoyl quinazoline-4（3H）-ones by using tert-butanol peroxide as oxidant,iodine as catalyst and potassium carbonate as base in dimethyl sulfoxide.The study of the mechanism indicates that 2-aminobenzamide may be a key intermediate.This reaction underwent Baeyer-Villiger oxidation rearrangement and condensation cyclization cascade process,which realized the ring expansion of isatin promoted by TBHP.Compared with the previously reported procedures,this reaction does not require the use of metal catalysts,and has a broad range of substrate scope and is easy to operate.A total of 28 target compounds were synthesized,and the structures of these products were characterized by ¹H NMR,¹³C NMR,IR and MS（Some of the new compounds were characterized by HRMS）.