Mechanism

M,echanism The synthesis of aspirin is classified as an esterification reaction, where the alcohol group from the salicylic acid reacts with an acid derivative (acetic anhydride) to form an ester. Aspirin is commercially synthesized using a two-step process. First, phenol (generally extracted from coal tar) is treated with a sodium base which generates sodium phenolate, which is then reacted with carbon dioxide under high temperature and pressure to yield salicylate, which is acidified, yielding salicylic acid. This process is known as the Kolbe-Schmitt reaction. Salicylic acid is then acetylated using acetic anhydride, yielding aspirin and acetic acid as a byproduct. This generally tends to produce low yields due to the relative difficulty of its extraction from an aqueous state. A method of extracting higher yields is to acidify with phosphoric acid and heat the reagents under reflux with a boiling water bath for between 40 to 60 minutes. The original synthesis of aspirin from salicylic acid involved acetylation with acetyl chloride. The byproduct from this is hydrochloric acid, which is corrosive and environmentally hazardous. As described above, it was then later found that acetic anhydride was a better acylating agent, with the byproduct acetic acid formed, which does not have the unwanted properties of hydrochloric acid and can also be recycled. The salicylic acid/acetic anhydride method is commonly employed in undergraduate teaching labs. Formulations containing high concentrations of aspirin often smell like vinegar. This is because aspirin can undergo autocatalytic degradation to salicylic acid in moist conditions, yielding salicylic acid and acetic acid. The acid dissociation constant (pKa) for Acetylsalicylic acid is 3.5 at 25 °C. ASA, being a weak monoprotic acid, dissociates as shown by the following reaction equation: •

2 years ago