Synthesis Of Phenoxazinones And Phenothiazines Based On The Oxidative Umpolung Strategy Of Phenolic Cycles

Phenoxazinones and phenothiazines are widely present in nature and have important applications in the fields of dyes,medicine,and new materials.The drug molecules based on such structures show excellent biological activities in antibacterial,anti-tumor,anti-psychotic,anti-tuberculosis and other aspects.Therefore,it is of great significance to develop new,efficient and green methodology to synthesize them.This paper is based on the oxidative umpolung strategy of phenolic cycles:molecular oxygen is used as oxidant,low-toxic natural organic molecule gallic acid(GA)is used as organocatalyst,and manganese acetate is used as co-catalyst.The catechol compounds are oxidized to the intermediate o-quinone compounds,which realize umpolung;it then takes oxidative cross-condensation and oxiadative cyclization reactions with o-aminophenol compounds for synthesize of Phenoxazinones.The oxidative cross-condensation and cyclization between catechol and o-aminophenol is regarded as a template reaction.The pH of the reaction,the usage of catalyst,and the separation and purification method of the product were studied.The optimal reaction conditions were as follows:1 mmol o-aminophenol la,1 mmol catechol 2a,0.25 mol%GA/Mn,pH=10,50 mL water,room temperature,0.3 MPa oxygen,30 mins.When the reaction is over,the mixture is acidified,centrifuged or filtered,and recrystallized to obtain the target product 2-Hydroxy-Phenoxazine-3-One 3a with a separation yield of 97%.Finally,27 kinds of 2-Hydroxy-Phenoxazin-3-Ones(including 25 new compounds)were obtained with moderate to high yields,and their structures were characterized by nuclear magnetic resonance,high-resolution mass spectrometry,and single crystal diffraction.The possible mechanism of the synthesis of Phenoxazinones was proposed.The reaction is considered to be a tandem process,which undergoes multiple aerobic oxidations,two Michael additions and proton transfer;among them,the first Michael reaction is the intermolecular aza-Micheal addition at 5C site of o-benzoquinone,and the second one is an intramolecular oxa-Micheal addition at 4C site.In addition,when 3-substitued 2-Hydroxylphenol was used,the product has good substituent-oriented regioselectivity.The three-step synthesis method of Phenothiazine based on the strategy of oxidative umpolung of phenolic cycles is preliminarily studied:① Firstly,the catechol is oxidized to o-benzoquinone;②Secondly,the intermediate 3-(2-aminophenyl)thiobenzene-1,2-diphenol is synthesized by electrophilic reaction from o-benzoquinone and o-mercaptoaniline;③Finally,GA/Mn catalyzes the oxidative cyclization.In this thesis,three synthetic intermediates and three Phenothiazine compounds were synthesized in this way,and they were characterized by nuclear magnetic resonance and high-resolution mass spectrometry.This paper has developed a new and simple method to gain 2-Hydroxy-Phenoxazine-3-Ones,which is green,economical,efficient with mild reaction conditions and simple way of separation.Secondly,this thesis developed a three-step synthesis method for novel Phenothiazine compounds.