C₉H₈O₄ — Acetylsalicylic Acid

Acetylsalicylic acid (ASA), better known as aspirin, is one of the most commonly used medications worldwide. It belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs) and possesses analgesic (pain-relieving), antipyretic (fever-reducing), and anti-inflammatory properties. Its chemical formula is \(C_9H_8O_4\). Aspirin is also used in low doses as an antiplatelet agent to prevent heart attacks and strokes by inhibiting blood clot formation.

Acetylsalicylic acid was first synthesized in 1897 by Felix Hoffmann, a chemist at Bayer, who improved upon earlier formulations of salicylic acid, which were too harsh on the stomach. Today, aspirin remains one of the most widely studied and utilized pharmaceuticals in both medical and laboratory applications.

The molecular structure of acetylsalicylic acid consists of a benzene ring substituted with two functional groups:

• An ester group (–COOCH₃) derived from acetic acid.
• A carboxylic acid group (–COOH).

These functional groups are connected to the benzene ring in the ortho position, making aspirin an aromatic compound. The presence of both an ester and a carboxylic group gives it amphiphilic character, allowing moderate solubility in polar solvents like ethanol and slightly in water. The ester linkage (formed between salicylic acid and acetic anhydride) is responsible for aspirin’s stability and slower hydrolysis in the stomach compared to salicylic acid, thus reducing gastric irritation.

The roots of acetylsalicylic acid trace back to ancient medicine, where extracts of willow bark were used for pain and fever relief. The active component, salicin, was identified and later converted to salicylic acid in the 19th century. However, due to salicylic acid’s acidic and irritating nature, chemists sought a milder derivative.

In 1897, Felix Hoffmann successfully synthesized acetylsalicylic acid at Bayer, marking a breakthrough in pharmaceutical chemistry. It was patented under the name “Aspirin”—derived from ‘a’ (acetyl) + ‘spir’ (from Spiraea ulmaria, the meadowsweet plant rich in salicylic acid).

Aspirin became commercially available in 1899 and quickly became a household medicine due to its effectiveness and accessibility. It also marked the first mass-produced synthetic drug, paving the way for the modern pharmaceutical industry.

Laboratory Synthesis:

Aspirin is synthesized by the esterification reaction of salicylic acid with acetic anhydride in the presence of an acid catalyst such as sulfuric acid or phosphoric acid:

Here, salicylic acid (C₇H₆O₃) reacts with acetic anhydride ((CH₃CO)₂O) to form acetylsalicylic acid (aspirin) and acetic acid as a by-product. The reaction mixture is cooled, and the product is purified through recrystallization using ethanol or water.

Industrial Production:

On an industrial scale, the same process is applied but optimized for large-scale yields, high purity, and minimal waste. Catalysts and solvents are chosen to ensure efficient reaction rates and environmentally friendly recovery.

Physical Properties:

• Appearance: White crystalline solid with faint acetic acid odor.
• Solubility: Slightly soluble in cold water, freely soluble in alcohol and ether.
• Stability: Stable under dry conditions but hydrolyzes in moist air to salicylic acid and acetic acid.
• Optical Activity: It is optically inactive as it has no chiral centers.

Chemical Properties:

• Hydrolysis: In the presence of moisture or base, aspirin hydrolyzes to yield salicylic acid and acetic acid:

\(C_9H_8O_4 + H_2O \rightarrow C_7H_6O_3 + CH_3COOH\)

• Reaction with Ferric Chloride: Aspirin gives no color change with FeCl₃ solution, while its hydrolysis product (salicylic acid) gives a violet color, confirming the absence of free phenolic group.
• Reaction with Sodium Bicarbonate: Being acidic, it reacts with NaHCO₃ releasing CO₂ gas:

\(C_9H_8O_4 + NaHCO_3 \rightarrow C_9H_7O_4Na + CO_2 + H_2O\)

Aspirin’s pharmacological action lies in its ability to inhibit the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid into prostaglandins and thromboxanes. These molecules are responsible for pain, fever, inflammation, and blood clotting. By acetylating the active site of COX enzymes, aspirin irreversibly inhibits prostaglandin synthesis, leading to:

• Reduced inflammation and pain.
• Lower body temperature (antipyretic effect).
• Prevention of platelet aggregation, reducing blood clot risk.

This makes aspirin not only an effective over-the-counter painkiller but also a crucial medication for cardiovascular protection in low doses.

• Medical Applications:
• Analgesic: Relieves mild to moderate pain, including headaches, toothaches, and muscle pain.
• Antipyretic: Reduces fever by acting on the hypothalamus.
• Anti-inflammatory: Effective in conditions like arthritis and rheumatism.
• Cardiovascular Protection: Low-dose aspirin prevents heart attacks and strokes by reducing platelet aggregation.
• Industrial and Laboratory Uses: Utilized in organic synthesis, pharmaceuticals, and as a standard for testing purity in analytical chemistry.
• Veterinary Medicine: Used for pain relief and inflammation control in animals under supervision.

Although aspirin is generally safe at recommended doses, overuse or sensitivity can cause side effects. Common adverse effects include gastrointestinal discomfort, ulcers, or bleeding due to its effect on stomach lining prostaglandins. Allergic reactions can occur in some individuals sensitive to salicylates. It should not be administered to children with viral infections, as it can lead to Reye’s syndrome, a rare but serious condition.

Environmentally, acetylsalicylic acid is biodegradable and poses minimal ecological risk when disposed of properly. It should be stored in airtight containers, away from moisture, to prevent hydrolysis.