Synthesis of Aspirin from Salicylic Acid & Acetic Anhydride

[lha08]

Homework Statement

Write the complete mechanism for the acid-catalyzed formation of aspirin from salicylic acid and acetic anhydride

Homework Equations

The Attempt at a Solution

I basically know the reaction but I'm not sure how to start the mechanism...Like i know that it is a substitution reaction where the OH group and the CH3--C==O switch places but how does it start? Does the the H group from the OH group first leave, then the CH3--C==O group can attack the O?

 

[chemisttree]

Its a bit like Fisher Esterification.

 

[Blueshift5]

Or is it the other way around where the CH3--C==O group leaves first and then the H from the OH group attacks the O?

it is important to understand the mechanism of a reaction in order to fully comprehend the process and its potential outcomes. The synthesis of aspirin from salicylic acid and acetic anhydride is a classic example of an acid-catalyzed esterification reaction. The mechanism begins with the acid-catalyzed protonation of the carbonyl oxygen in acetic anhydride, making it more electrophilic. This allows for the attack of the hydroxyl group on salicylic acid, resulting in the formation of an intermediate tetrahedral hemiacetal.

Next, the protonated hydroxyl group is eliminated, resulting in the formation of an acylium ion. This ion then undergoes a nucleophilic attack by the carboxylate anion of the salicylic acid, resulting in the formation of an ester and regenerating the acid catalyst. The final step involves the deprotonation of the newly formed ester, resulting in the formation of aspirin and acetic acid.

Overall, the mechanism for the acid-catalyzed formation of aspirin from salicylic acid and acetic anhydride involves multiple steps including protonation, elimination, nucleophilic attack, and deprotonation. Understanding this mechanism is crucial for optimizing reaction conditions and ensuring the successful synthesis of aspirin.