Pd-catalyzed Cascade Protocol Synthesis Of2H-1,4-benzoxazin-3-(4H)-ones

2H-1,4-benzoxazin-3-（4H）-ones is a kind of important heterocycliccompounds with biological activities. the heterocyclic compound and itsderivative appeared in the cores of complicated natural products andpharmaceuticals, which have biological activities of anticancer andantibiosis. Due to its good biological activities, the research of synthesisof2H-1,4-benzoxazin-3-（4H）-ones is very significant. Simultaneously,it’s a effective means to synthesis of this heterocyclic compound by usingPd-catalyzed coupled reaction, and it’s also the research hotspots in thelast few decades. In this thesis, we designed two simple and efficientroutes to synthesis of2H-1,4-benzoxazin-3-（4H）-ones successfully bycascade protocol of Pd-catalyzed N-arylation.In the second chapter, we designed a new method to synthesize2H-1,4-benzoxazin-3-（4H）-ones by cascade protocol of “N-arylation—being amide ring”. In this method, we use o-halogen phenol as rawmaterials to synthesize2-（2-halogen phenoxy）carboxylic esters throughthe oxygen alkylation reaction, then2-（2-halogen phenoxy）carboxylicesters reacted with amine to synthesize2H-1,4-benzoxazin-3-（4H）-ones. Finally, we synthesized27kinds of2H-1,4-benzoxazin-3-（4H）-onesefficiently through the optimization of conditions. The best conditions ofthe reaction include10mol%Pd（OAc）₂as catalyst,10mol%（±）BINAP asligand, Cs₂CO₃as base, toluene as solvent, the temperature control at90℃and the reaction last24hours under N₂. The best yield up to97%.We analysed and discussed the effect of the diversity of the reactionsubstrates to this reaction. Last, The structures of all new compoundswere using IR,¹H-NMR,¹³C-NMR, MS and elemental analysis methodfor structure characterization.In the third chapter, we designed a new method to synthesize2H-1,4-benzoxazin-3-（4H）-ones by a cascade protocol of “oxygenalkylation—N-arylation”. In this method, we used o-halogen phenol asraw materials, which reacted with α-chloroamide to get the products.Finally, we synthesized24kinds of2H-1,4-benzoxazin-3-（4H）-onesefficiently through the optimization of conditions. The best conditions ofthe reaction include10mol%Pd（OAc）₂as catalyst,10mol%（±）BINAP asligand, Cs₂CO₃as base, toluene as solvent, the temperature control at110℃and the reaction last24hours under N₂. The best yield up to99%.Last, we analysed and discussed the effect of the diversity of the reactionsubstrates to this reaction. The structures of all new compounds wereusing IR,¹H-NMR,¹³C-NMR, MS and elemental analysis method forstructure characterization. In general, we designed two new methods to synthesize2H-1,4-benzoxazin-3-（4H）-ones and achieved high yields. It’s verysignificant for the synthetic research of such heterocyclic compounds andits derivatives.