Research On The Synthesis Of 2-Methoxyphenothiazine

Phenothiazine and its derivatives are greatly pharmacology-active and bio-active,with wide application in the industry of polymerization inhibitor,antioxidants,pharma-ceuticals and dyes.In recent research,they have shown remarkable electronic properties in the preparation of Organic Light-Emitting Diode(OLED) and light-sensitive materials.2-methoxyphenothiazine is one of important members of phenothiazine family, whose usage has newly been discovered.My research refers to the synthesis of 2-methoxyphenothiazine,in which a novel and reasonable route has been presented, with each step in the procedure being carefully analyzed and optimized.The optimized conditions and experiment results proved to be precious guidance for the production of the title compound and its analogs.The three steps are detailed as follows: Resorcinol and aniline underwent dehydration,under the catalysis of PTSA series,to give the key intermediate 3-hydroxydiphenylamine.The optimized parameters were: temperature:190℃,m(PTSA)/m(resorcinol)=3%(weight ratio), n(aniline)/n(resorcinol)=1.2:1(molar ratio),reaction time:5 h.After the reaction, aniline was distilled in vacuum and the solid obtained was recrystallized in water before some red solid appeared with yield of 92.4%.Compared with traditional catalyst, our new catalytic system led to higher efficiency,lower amount and shorter time.In the synthesis of 3-methoxy-N-phenyl-benzenamine,key parameters such as temperature,molar ratio of raw materials,amount of alkali and the time span of addition of DMS(dimethyl sulfate) were investigated.The results indicated the best condition: temperature:50℃,n(NaOH)/n(3-hydroxydiphenylamine)=1.2:1, n(DMS)/n(3-hydroxydiphenylamine)=1.3:1,time of addition:1.5h.The yield of methylation step was 90.5%and the total yield of 3-methoxy-N-phenyl-benzenamine was 83.6%.A one-pot synthesis of 3-methoxy-N-phenyl-benzenamine was tried at the same condition with the yield of 84.1%,showing better results and simpler operation. A new solvent,liquid paraffin,was employed in the synthesis of 2-methoxyphenothiazine.With the introduction of this new solvent,higher yield was obtained in lower temperature.The procedure was easier to operate and suitable for industrial production.Responsible surface methodology was used to optimize the experimental parameters,in which a quadratic equation of the reaction was set up.The results showed the best conditions:temperature:162.5℃,m(I₂) /m(3-methoxy-N-phenyl-benzenamine)=1.1%(weight ratio), n(S)/n(3-methoxy-N-phenyl-benzenamine)=2.22:1(molar ratio).The yield of this step in such conditions was 88.2%and the total yield of 2-methoxyphenothiazine after 3 steps was 74.2%.The structures of each intermediates and final compounds were confirmed by melting point,GC,HPLC,GC-MS,FT-IR,¹H NMR and ¹³C NMR.Compared with methods previously reported,our procedure has higher yield,lower cost,milder conditions, easier operation and better purity.It is more eco-friendly and of good value for production.