Study On Synthesis Of 3-methylflavone-8-carboxylic Acid

3-mehylflavone-8-carboxylic acid is used in the treatment of coronary heart disease like angina pectoris and myocardial infarction, and it is widely used in the medicine industry as the intermediates of the M. cholinocertor blocking drugs.The total synthesis route of 3-mehylflavone-8-carboxylic acid was chosen in this paper, and improved on the technics. The salicylic acid, used as the raw material, was synthesized to the target product via methyl esterification, bromo-substitution, C-acylation(esterification and Fries rearragement),cyclization,catalytic hydrogenolysis-dehalogenation and hydrolysis.The stong acid cationic exchange resin was used as catalyst instead of sulphuric acid in methyl esterification, and the effects of various factors was investigated. The optimum technical conditions are: n(salicylic acid):n(methyl alcohol) = 1:7, wt.(the catalyst):wt.(the caid)=1% , t=2h, T=68~72℃.Thus the yield is 92.40%. The product was affirmed by IR.The bromine was recycled in bromo-substitution by adding chlorine and the cost was reduced. The optimum technical conditions are: n(mehyl salicylate):n(bromine)=1 :0.55, T= 0~5℃, t=2h, then the temperature was risen to refluence. The rate of chlorine was 0.15g/min, chloroform was used as the solvent.Thus the yield is 98.50%. The product was affirmed by GC-MS.Propionyl chloride was replaced with propionic anhydride in C-acylation, and esterfication and rearrangement were completed in one step. The optimum technical conditions are: esterfication: n(methyl 5-bromosalicylate):n(propionic anhydride) = 1:1, phosphoric acid as catalyst, reflux for 3h;Fries rearragement: n(anhydrous aluminum chloride):n(methyl 5-bromosalicylate)=2:1, reflux for 7h. Thus the yield is 81.60%, and the purity is over 98 % by GC analysis。The product was affirmed by GC-MS.Sodium ethylate was used as catalyst in Baker-Venkataraman of cyclization, and all factors were studied. The best technical conditions are: n(methyl 5-bromo-3-propionyl salicylate): n(benzoyl chloride):n(sodium ethylate)=1:1.5:1.2, T=95~100℃,t=7h.Thus the yield is 81.30 %。 The product was affirmed by GC-MS.The effects of various factors in catalytic hydrogenolysis-dehalogenation were studied and the optimum technical conditions are: 10%Pd/C as catalyst, ethanol as solvent, T=70℃ , t=6h.Thus the yield is 92.50 %. The product was affirmed by GC-MS.The opitimum technical conditions of hydrolysis are: n(mehyl 3-methylflavone -8-carboxylate):n(NaOH)=1:1, methanol as solvent, reflux for 5h, Thus the yield is 98.00 %. The product was affirmed by NMR.