Study On The Synthesis Of Acridones Via Copper-catalyzed C-C Bond Cleavage

Acridone and its derivatives are versatile heteroaromatic compounds that have beenwidely used in the field of medicinal chemistry, synthetic chemistry, materialchemistry, biochemistry and other fields. Therefore, the more convenient, moreeconomical, and more environmentally friendly synthesis methods have the potentialapplication value. Although there’re some methods of the synthesis of acridones, allthe reported methods generally require stringent reaction conditions and tediousexperimental procedures or demand of excess amounts of a base or acid. With theconcept of green chemistry, the strategy of synthesizing acridones through the C-Hbond activation occurred. In contrast, developing new methods for C-C bond cleavagesynthesis of acridones is full of challenge. The reason is that, with the C-H bond ratio,cut off the C-C bond need to overcome the large energy barrier. When there are C-Hbond or other weak bonds in the molecules in the presence of at the same time, it’sdifficult to achieve selectively cut and functionalization of C-C bond. While there’resome reports about C-C bond cleavage, most of them utilized expensive transitionmetal catalyst. Developing C-C bond cleavage reaction in the air/copper system canprovide new ideas of material transformation. This paper developed a new methodwhich was copper-catalyzed C-C bond cleavage under mild, neutral conditions.Through the mechanism probing experiments, a preliminary exploration of themechanism of the reaction was taken out.The research work of this paper includes the following parts:Firstly, a preliminary attempt to one-pot synthesis of acridones. Explorations ofsynthesis of acridones on the1-(2-aminophenyl)ethanone with iodobenzene in copperiodide/air catalytic conditions, the influence of material ratio, different ligands,catalyst were taken out. CuSO4·5H2O (20mol%), NaHCO3(0.6mmol), PPh3(40mol%) in DMSO (1.5mL) under air stirred at140oC for12h affored58%acridones.Secondly, study on copper catalyzed1-(2-(phenylamino)phenyl)ethanone synthesisof acridone through ethyl ketone carbonyl C-C bond cleavage. The effects of differentsolvents, catalyst, temperature, amount of catalyst and mixed solvent on the reactionwere researched. CuI (20mol%), in DMSO (1.6mL) under air stirred at140oC for48h affored90%acridone. Having taken the optimized conditions in hand, weobserved the substrate scope.Finally, preliminary exploration of copper catalyzed1-(2-(phenylamino)phenyl)ethanone synthesis of acridone through ethyl ketonecarbonyl C-C bond cleavage. GC-MS was detected in the reaction solution, and aseries of possible reaction intermediates were synthesized to test the reaction.According to the13C labeling experiments, most of the carbonyl carbon in the productoriginate from the carbonyl carbon of the substrate. Intermolecular kinetic isotopeeffects and intramolecular kinetic isotope effects indicate that aromatic C-H bondcleavage may be not turnover-limiting and does not occur via a chelation-assisted,SEAr or a free radical mechanism.