1. Introduction

Drug molecules are organic or organometallic compounds designed to interact with biological systems to produce therapeutic effects. The synthesis of drugs is a major branch of medicinal and pharmaceutical chemistry. One of the classical examples of a commonly used drug is Aspirin (acetylsalicylic acid), a widely used analgesic, antipyretic, anti-inflammatory, and antiplatelet agent.

2. Structure of Aspirin

• IUPAC name: 2-acetoxybenzoic acid
• Functional groups: Ester group (–OCOCH₃) and Carboxylic acid group (–COOH)

3. Synthesis of Aspirin

(a) Starting Material

Salicylic acid (2-hydroxybenzoic acid), obtained from phenol through the Kolbe–Schmitt reaction: Phenol ? Sodium phenoxide ? Reaction with CO₂ (125–140 °C, pressure) ? Salicylic acid.

(b) Acetylation Reaction

Salicylic acid is treated with acetic anhydride (CH₃CO)₂O in the presence of H₂SO₄ (conc.) or H₃PO₄ as catalyst. The hydroxyl group (–OH) of salicylic acid is acetylated to form aspirin (acetylsalicylic acid).

Salicylic acid + Acetic anhydride → Aspirin + Acetic acid

C₆H₄(OH)(COOH) + (CH₃CO)₂O → C₆H₄(OCOCH₃)(COOH) + CH₃COOH

4. Mechanism of Acetylation

1. Protonation of acetic anhydride by acid catalyst.
2. Nucleophilic attack by –OH group of salicylic acid.
3. Elimination of acetic acid ? Formation of acetylsalicylic acid (aspirin).

5. Properties of Aspirin

• White crystalline solid.
• Slightly soluble in water; soluble in ethanol/ether.
• Hydrolyzes in moisture to salicylic acid and acetic acid (hence stored dry).

6. Pharmacological Uses of Aspirin

• Analgesic: Relieves pain.
• Antipyretic: Reduces fever.
• Anti-inflammatory: Treats arthritis, inflammation.
• Antiplatelet agent: Prevents clot formation; reduces heart attack & stroke risk.

7. Other Commonly Synthesized Drug Molecules

• Paracetamol (Acetaminophen): Synthesized from p-aminophenol by acetylation.
• Ibuprofen: Synthesized from isobutylbenzene via Friedel–Crafts acylation + rearrangement + carboxylation.
• Sulfa drugs (e.g., Sulfanilamide): Derived from sulfonation and amination of aromatic amines.
• Antibiotics (Penicillin derivatives): Semi-synthetic modifications of natural penicillin.

? Summary Table