Paracetamol
Properties
| State | Solid (white crystalline powder) |
| Color | White |
| Solubility | Slightly soluble in water (14 g/L at 25 °C); freely soluble in ethanol |
| Melting Point | 169 °C |
| Boiling Point | Decomposes above melting point |
About Paracetamol
Paracetamol (acetaminophen in the United States) is the over-the-counter analgesic and antipyretic in Tylenol, Panadol, Calpol, and roughly two-thirds of the cold-and-flu combination products on pharmacy shelves. The molecule is N-acetyl-para-aminophenol, formula C8H9NO2, molar mass 151.163 g/mol — a phenol ring with an acetamide para to the hydroxyl. It was first synthesized in 1877, but it took until 1955 for McNeil to launch it as Tylenol Elixir for children, marketed as a safer alternative to phenacetin (which caused analgesic nephropathy) and aspirin (which caused gastric bleeding and Reye syndrome in kids). The mechanism still isn't fully nailed down. Unlike NSAIDs, paracetamol barely inhibits peripheral COX-1 or COX-2 — which is why it has minimal anti-inflammatory action and minimal GI toxicity — but it does inhibit a CNS COX variant (COX-3 in dogs, less clearly in humans) and modulates the endocannabinoid system through its metabolite AM404. Toxicology is the dramatic story: about 5 percent of an ingested dose gets oxidized by CYP2E1 to NAPQI (N-acetyl-p-benzoquinone imine), an electrophilic quinone imine that glutathione normally mops up. In overdose, glutathione is depleted, NAPQI binds covalently to hepatocyte proteins, and centrilobular liver necrosis follows within 24-48 hours. N-acetylcysteine is the antidote because it replenishes glutathione. The synthesis from 4-aminophenol and acetic anhydride is still the cleanest selective N-acetylation in undergraduate organic lab.
Where you'll encounter it
If you've ever taken Tylenol for a hangover, dosed your kid with Calpol for a fever, or run an undergraduate orgo lab synthesizing the compound from 4-aminophenol and acetic anhydride, you've worked with paracetamol. The undergraduate synthesis is a textbook selective N-acetylation: the amine is more nucleophilic than the phenol, so it acetylates first under mild conditions, and you crystallize the white needles from hot water with about 70 percent yield. Hospital pharmacies and emergency departments treat paracetamol overdose as one of the most common poisonings worldwide — the Rumack-Matthew nomogram plots serum APAP concentration against time post-ingestion to decide whether to start IV N-acetylcysteine, and the antidote works essentially completely if started within 8 hours. Industrial synthesis runs by the kilotonne from 4-nitrochlorobenzene, the global market is around 145,000 tonnes per year, and most of that comes from a handful of bulk plants in India and China.
Common Uses
- First-line oral analgesic for mild-to-moderate pain (headache, back pain, post-surgical pain)
- Antipyretic for fever in children and adults, especially when NSAIDs are contraindicated
- Component of combination cold-and-flu products with caffeine, pseudoephedrine, or codeine
- IV formulation (Ofirmev) for post-operative pain control as an opioid-sparing analgesic
- Standard substrate in undergraduate organic chemistry teaching the selective N-acetylation of 4-aminophenol
Safety Information
Acute overdose causes severe centrilobular hepatic necrosis through the toxic CYP2E1 metabolite NAPQI, which depletes glutathione and binds covalently to hepatocyte proteins. Paracetamol is the leading cause of drug-induced acute liver failure in the US and UK. The antidote is N-acetylcysteine (IV or oral), most effective within 8 hours of ingestion, dosed by the Rumack-Matthew nomogram. Adult hepatotoxic threshold is roughly 7.5-10 g acute ingestion. GHS: H302 (harmful if swallowed), H315 (skin irritation), H319 (eye irritation). Chronic alcohol users and people on isoniazid have lower toxicity thresholds because of CYP2E1 induction.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.