Aspirin

Aspirin, also known by its chemical name acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID). It works to lower pain, fever, and swelling, and it also helps prevent blood clots. Doctors prescribe it for inflammatory conditions such as Kawasaki disease, pericarditis, and rheumatic fever. For people at high risk, long-term use reduces the chances of a heart attack, ischemic stroke, or dangerous blood clots. When taken for pain or fever, effects usually start within half an hour. Like other NSAIDs, aspirin blocks certain body processes, but it also uniquely interferes with normal platelet function.

A common side effect is an upset stomach. More serious issues include stomach ulcers, stomach bleeding, and worsened asthma. The risk of bleeding goes up in older adults, those who drink alcohol, take other NSAIDs, or use additional blood thinners. Aspirin is not advised during the final part of pregnancy, and it is generally not given to children with viral infections due to the risk of Reye syndrome. Very high doses can cause ringing in the ears.

The story of aspirin begins with willow bark (genus *Salix*), which contains a precursor called salicin. In the human gut, salicin is converted into the active compound salicylic acid, and people have used it for health benefits for at least 2,400 years. Scientists wanted a synthetic version. In 1853, chemist Charles Frédéric Gerhardt first made acetylsalicylic acid by treating sodium salicylate with acetyl chloride. Over the next 50 years, other chemists—mostly from the German company Bayer—figured out its chemical structure and found better ways to produce it. In 1897, either Felix Hoffmann or Arthur Eichengrün of Bayer was the first to create a pure, stable form. By 1899, Bayer had named the drug "Aspirin" and was selling it worldwide.

Today, aspirin is available without a prescription in most places, both as a brand-name and generic drug. It is one of the most widely used medications on the planet, with an estimated 40,000 tonnes (44,000 tons)—roughly 50 to 120 billion pills—consumed each year. It appears on the World Health Organization's List of Essential Medicines. In 2023, it was the 46th most prescribed medication in the United States, with over 14 million prescriptions.

The name "Aspirin" is a blend: the prefix *a-* from acetyl, *spir* from *Spirsäure* (the German word for meadowsweet, the plant from which salicylic acid was first isolated), and *-in*, a common suffix for drugs at the end of the 19th century. Bayer originally held the trademark, but lost or sold those rights in many countries.

Chemically, aspirin is an acetyl derivative of salicylic acid. It is a white, crystalline, weakly acidic substance that melts at 136 °C (277 °F) and decomposes around 140 °C (284 °F). Its acid dissociation constant (pKa) is 3.5 at 25 °C (77 °F). Aspirin is stable in dry air but slowly breaks down in moisture, turning into acetic and salicylic acids—which is why high-concentration formulations sometimes smell like vinegar. It decomposes quickly in solutions of ammonium acetate, acetates, carbonates, citrates, or alkali metal hydroxides. In alkaline solutions, hydrolysis happens rapidly, leaving only acetate and salicylate.

Because aspirin powder can form an explosive mixture with air, factories that make aspirin tablets must control airborne dust levels, much like flour mills. The U.S. National Institute for Occupational Safety and Health (NIOSH) recommends a time-weighted average exposure limit of 5 mg/m³. In 1989, the Occupational Safety and Health Administration (OSHA) set a legal limit of 5 mg/m³, but that rule was overturned in 1993.

The synthesis of aspirin is an esterification reaction. Salicylic acid is treated with acetic anhydride, which turns the hydroxyl group into an ester group, producing aspirin and acetic acid as a byproduct. Small amounts of sulfuric or phosphoric acid are used as catalysts. This reaction is a common demonstration in undergraduate teaching labs. Using acetic acid instead of acetic anhydride is possible, but the reaction is reversible and water can cause hydrolysis, so an anhydrous reagent is preferred.

Aspirin can form different crystal structures, a property called polymorphism. Until 2005, only one form (form I) was proven to exist, though hints of another had been debated since the 1960s. A 1981 report noted weak extra peaks in the diffractogram when aspirin was crystallized with aspirin anhydride, but these were dismissed as impurities. In retrospect, they were form II. Form II was finally confirmed in 2005, discovered during an attempted co-crystallization of aspirin and levetiracetam from hot acetonitrile. Pure form II can be made by seeding the batch with aspirin anhydrate at 15% weight.