Study On The Synthesis Of 6-Substituted-4-Chromanone-2-Carboxylic Acids

6-substituted-4-chromanone-2-carboxylic acids especially 6-fluoro-4-chromanone -2-carboxylic acid have special physiological and pharmaceutical activities.It is very important to study on the synthesis of 6-substituted-4-chromanone-2-carboxylic acids. Based on the research before,we designed a new route,which started from phenols and maleic anhydride,via hydroxybenzene esterification,carboxyl esterification, Fries rearrangment,Michael addition,to get 6-substituted-4-chroman-one-2-carboxylic acids.The synthetic technique of 6-fluoro-4-chromanone-2-carboxylic acid was studied in this article emphatically.The effects of temperature,time,the ratio of reactants and other factors were investigated and improved,results as follows:(1) In hydroxybezene esterification reaction,the mole ratio of p-fluorophenol and maleic anhydride was 1.0:0.48,the reaction lasted 1 hour at room temperature,the yield was 70.0%.(2) In carboxyl esterification reaction,p-toluene sulfonic acid was used as catalyst,the mole ratio of acid,ethanol and p-toluene sulfonic acid was 1.0:4.0:0.2, benzene was used as solvent,the reaction lasted 8 hours at 90℃,the yield was 81.0%. (3)In Fries rearrangement reaction,the mole ratio of phenol ester and aluminium chloride was 1.0:2.0,nitrobenzene was used as solvent,the reaction lasted 6 hours at 110℃,the yield was 61.4%.(4) In Michael addition reaction,sodium bicarbonate was used as catalyst,the reaction refluxed at 90℃for 15 minutes.The mole ratio of acid and sodium bicarbonate was 1.0:5.0,the yield was 86.0%.In order to expand the areas of application in this route,other 6-substituted-4-chromanone-2-carboxylic acids were synthesized from phenol,p-chlorophenol, p-cresol,o-cresol,m-cresol,p-nitrophenol.In the similar reaction conditions,results showed that phenols with alkyl substituent have better reaction activity. All products were identified by IR and ~1HNMR.This route is much of industrial value in cheap and easily gained material,convenient operation,friendly environment.