Carboxylation of Phenols Aspirin and the Kolbe-Schmitt Reaction

The preference for O-acylation of phenols arises because these reactions are kineti-cally controlled. O-acylation is faster than C-acylation. The C-acyl isomers are more stable, however, and it is known that aluminum chloride is a very effective catalyst for the conversion of aryl esters to aryl ketones. This isomerization is called the Fries rearrangement. 

ring acylation of phenols is observed under Friedel-Crafts conditions because the presence of aluminum chloride causes that reaction to be subject to thermodynamic (equilibrium) control. 

Fischer esterification, in which a phenol and a carboxyhc acid condense in the presence of an acid catalyst, is not used to prepare aryl esters. 

10 Carboxylation of Phenols Aspirin and the Kolbe-Schmitt Reaction 

The best known aryl ester is 0-acetylsalicylic acid, better known as aspirin. It is prepared by acetylation of the phenolic hydroxyl group of salicyhc acid  

10 CARBOXYLATION OF PHENOLS ASPIRIN AND THE KOLBE-SCHMITT REACTION 

Aspirin possesses a number of properties that make it an often-recommended drug. It is an analgesic, effective in relieving headache pain. It is also an antiinflammatory agent, providing some relief from the swelling associated with arthritis and minor injuries. Aspirin is an antipyretic compound that is, it reduces fever. Each year, more than 40 million Ib of aspirin is produced in the United States, a rate equal to 300 tablets per year for every man, woman, and child. 

The key compound in the synthesis of aspirin, salicylic acid, is prepared from phenol by a process discovered in the nineteenth century by the German chemist Hermann Kolbe. In the Kolbe synthesis, also known as the Kolbe-Schmitt reaction, sodium phen-oxide is heated with carbon dioxide under pressure, and the reaction mixture is subsequently acidified to yield salicylic acid  

Although a hydroxyl group strongly activates an aromatic ring toward electrophilic attack, an oxyanion snbstituent is an even more powerful activator. Electron delocalization in phenoxide anion leads to increased electron density at the positions ortho and para to oxygen. 

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