Core ConceptsIn this article, we will discuss the steps in synthesizing Aspirin (acetylsalicylic acid), its applications, and its reaction mechanism.IntroductionBayer chemist Felix Hoffmann synthesized aspirin for the first time in 1897. Originally an antipyretic and anti-inflammatory drug, aspirin became crucial in preventing cardiovascular and cerebrovascular diseases due to its antiplatelet properties. This drug inhibits the production of prostaglandins, potent hormones involved in regulating smooth muscle and triggering inflammation. Additionally, aspirin prevents the synthesis of thromboxanes, which cause blood vessels to constrict and encourage platelet aggregation, the initial step in blood clot formation. Many doctors recommend low-dose aspirin daily for high-risk patients to reduce the risk of blood clots, heart attacks, and strokes.Synthesis of Acetylsalicylic Acid from Raw MaterialsWe will start our synthesis with phenol. Starting from this raw material illustrates the transformation of a basic compound into a widely used medication, highlighting key organic chemistry concepts and industrial applications.The process begins with phenol, which is first converted into sodium phenoxide by reacting with sodium hydroxide.The sodium phenoxide is then subjected to high pressure and temperature with carbon dioxide in the Kolbe-Schmitt reaction. This reaction introduces a carboxyl group into the ortho position relative to the hydroxyl group on the benzene ring, forming sodium salicylate.The sodium salicylate is then acidified with a strong acid, such as hydrochloric acid (HCl) or sulfuric acid, to produce salicylic acid. Notice that phenol is deprotonated first to form phenoxide, and there is a reason for that. The phenoxide ion is more nucleophilic than neutral phenol. This enhanced nucleophilicity is necessary for the reaction to proceed efficiently. Without deprotonation, phenol would not have sufficient reactivity to attack the electrophilic carbon dioxide molecule, leading to a much less efficient reaction.We then acetylate the salicylic acid by reacting it with acetic anhydride. This reaction replaces the hydroxyl group’s hydrogen atom with an acetyl group, resulting in the formation of acetylsalicylic acid (aspirin) and acetic acid as a byproduct.We use acetic anhydride because it efficiently transfers an acetyl group to salicylic acid’s hydroxyl group. There are a couple of features that make acetic anhydride desirable. First, it contains a good leaving group that displaces during the reaction, facilitating the transfer of the acetyl group. Second, its strong electrophilicity due to the carbonyl group (C=O) makes it reactive enough to allow the reaction to proceed, but stable enough to handle and store. Finally, unlike other acylating agents, acetic anhydride avoids producing water as a byproduct, which could hydrolyze the ester bond in aspirin, further increasing its desirability as a reagent.Reaction MechanismLet’s look at the mechanism for this last portion of the synthesis and divide it into steps.