Acetaminophen

Ball-and-stick Stick Space-filling

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20 atoms, 20 bonds.

IUPAC name: N-(4-hydroxyphenyl)acetamide
Molar mass: 151.165(21) g/mol
Atoms: 20
SMILES: CC(=O)NC1=CC=C(C=C1)O
InChIKey: RZVAJINKPMORJF-UHFFFAOYSA-N
PubChem CID: 1983

Made of

Structural formula of acetaminophen. Each unlabelled corner is a carbon atom, and the four hydrogens on carbon are not drawn. It shows which atoms are joined to which, not the shape. The model above shows the shape.

Pharmacy labels and chemical registers disagree about the name. The US Food and Drug Administration and PubChem use acetaminophen, while the European Chemicals Agency and the World Health Organization’s drug codes use paracetamol. Its IUPAC name, N-(4-hydroxyphenyl)acetamide, works as a map. A ring of six carbon atoms carries a hydroxyl group, an oxygen holding a hydrogen, on one carbon. On the carbon directly opposite sits an acetamide group, where a nitrogen links the ring to a carbonyl carbon and a methyl group. The carbonyl carbon is double-bonded to an oxygen; the methyl is a carbon carrying three hydrogens.

The pure solid is a white, odourless crystal with a bitter taste, and it melts between 169 and 170.5 °C. Cold water takes up very little of it, about 14 g per litre at 25 °C. Boiling water dissolves much more, and alcohol dissolves it freely. A saturated solution in water is only mildly acidic, with a pH of 5.5 to 6.5.

Structure and bonding

The viewer holds 20 atoms, eight carbon, nine hydrogen, one nitrogen and two oxygen, joined by 20 bonds. Its ring is drawn with three double and three single bonds: one resonance form, one of several Lewis structures whose average is the real one. OpenStax describes a benzene ring’s six carbon–carbon bonds as equivalent, each intermediate between single and double, with the electrons delocalised around the ring. PubChem’s computed conformer agrees: all six ring bonds come out at 1.395 Å.

Seen edge-on in Ball-and-stick, the ring lies flat, as a benzene ring does, with the O–H at one end and the nitrogen at the other. Beyond the nitrogen, the carbonyl carbon is trigonal planar and the methyl carbon at the tip is tetrahedral. Stick leaves the C=O as the only doubled bond outside the ring, and Space-filling shows the methyl hydrogens bulging at the far end.

With Labels on, two of the nine H symbols sit on the phenol oxygen and the nitrogen. OpenStax explains the consequence: hydrogen bonded to oxygen or nitrogen is strongly attracted to similar groups on nearby molecules, which is hydrogen bonding. The carbonyl oxygen, left partly negative by its electronegativity, can accept such a bond.

Where it turns up

The Hazardous Substances Data Bank called it principally a medicine in 1976, and its consumption pattern splits demand as 75 per cent analgesic use and 25 per cent exports. The Toxin and Toxin Target Database, as quoted on PubChem, calls it an over-the-counter pain reliever and fever reducer. It is also a main ingredient of many remedies for colds and flu. The United States used 5,790,000 kg in 2002, 21 g per person, against 55 g in France in 2004.

A smaller trade uses it as a chemical: in azo dyes and photographic chemicals, and as a stabiliser for hydrogen peroxide. In the United States it is also registered for controlling brown tree snakes.

The body also makes it from two other drugs, phenacetin and acetanilid, whose major metabolite it is. On the Hazardous Substances Data Bank’s figures it ranked among England’s most heavily used medicines in 2002, and it has been detected in the environment.

Why it matters

How acetaminophen eases pain has not been fully established, DrugBank says. One theory has it inhibiting COX-1 and COX-2, two forms of cyclo-oxygenase, the enzyme that makes prostaglandins, which trigger pain sensations. Aspirin blocks the same enzyme irreversibly; acetaminophen acts on it only indirectly and leaves platelets working. On inflammation the accounts differ: DrugBank reports no effect in peripheral tissues, the Hazardous Substances Data Bank weak activity in some nonrheumatoid conditions.

Fever falls because the drug acts on the hypothalamus, the brain’s heat-regulating centre. Blood vessels widen, more blood reaches the skin, and heat escapes. A normal temperature rarely drops.

In the liver the drug takes three routes. Most is joined to glucuronic acid or, to a lesser extent, to sulfate. A small share is oxidised by cytochrome P450 enzymes, mainly CYP2E1, to NAPQI, a toxic metabolite. When the main pathways are saturated, more follows that route. NAPQI then uses up the liver’s glutathione, a small molecule whose sulfhydryl groups normally react with it, and liver tissue can die. Children have less capacity for glucuronidation than adults.

Properties

Properties of acetaminophen Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 1983.
Property	Value	Unit	Source
Molecular formula (Hill order)	C₈H₉NO₂
Molar mass	151.165(21) g/mol	g/mol	IUPAC/CIAAW 2024
Carbon atoms	8
Hydrogen atoms	9
Nitrogen atoms	1
Oxygen atoms	2
Bonds	20
Single bonds	16
Double bonds	4
PubChem molecular weight	151.16 g/mol	g/mol	PubChem

Safety

An everyday medicine, but not a harmless one. In the European Chemicals Agency’s notifications, 98.1% carry the statement “Harmful if swallowed”, and smaller shares add skin and eye irritation and long-lasting harm to aquatic life. An overdose can destroy liver tissue through the NAPQI route above. The PubChem Laboratory Chemical Safety Summary holds the full classification, and a pharmacist or doctor is the person to ask about use.

Questions

Is acetaminophen the same as paracetamol?

Yes. Both names point to one compound, PubChem CID 1983, with the formula C₈H₉NO₂ and the IUPAC name N-(4-hydroxyphenyl)acetamide. The European Chemicals Agency registers it as paracetamol, and so does the World Health Organization's drug code N02BE01. American references such as the Hazardous Substances Data Bank use acetaminophen and add the abbreviation APAP, for N-acetyl-p-aminophenol. Brand names vary again by country; Crocin is one listed for India.

What functional groups can you see in the acetaminophen model?

Two, one at each end of the ring. The oxygen bonded to both a ring carbon and a hydrogen is a phenol group. At the other end, a nitrogen joins the ring to a carbon that carries a double-bonded oxygen: that is an amide, the same carbonyl-to-nitrogen link OpenStax calls a peptide bond in proteins. The chemical safety records list acetaminophen's reactive groups under exactly these two classes, amides and phenols.

Does acetaminophen dissolve in water?

Only slightly in cold water: about 14 g per litre at 25 °C, on the Hazardous Substances Data Bank's figure, though boiling water takes up more. The same record lists it as soluble in methanol, ethanol, acetone and ethyl acetate, slightly soluble in ether, and practically insoluble in petroleum ether, pentane and benzene.

Is acetaminophen an opioid or addictive?

No. PubChem files it under the Medical Subject Headings class of non-narcotic analgesics, a class of pain relievers that, as a rule, neither binds opioid receptors nor causes addiction. Aspirin and acetaminophen both act on the cyclo-oxygenase enzyme, but in different ways. A lack of addiction is not a lack of hazard: an overdose can damage the liver, and the European Chemicals Agency classification carries the signal word Warning.

Made of the same elements

C₈H₁₁NO₂ Dopamine 22 atoms, 22 bonds.
C₉H₁₁NO₂ Phenylalanine 23 atoms, 23 bonds.
C₈H₁₀N₄O₂ Caffeine 24 atoms, 25 bonds.
C₉H₁₁NO₃ Tyrosine 24 atoms, 24 bonds.
C₅H₉NO₄ Glutamic acid 19 atoms, 18 bonds.
C₉H₁₃NO₃ Epinephrine 26 atoms, 26 bonds.
C₆H₁₃NO₂ Isoleucine 22 atoms, 21 bonds.
C₆H₁₃NO₂ Leucine 22 atoms, 21 bonds.

All 25 compounds made of carbon, hydrogen, nitrogen and oxygen

C₃H₇NO₂ Alanine 13 atoms, 12 bonds.
C₁₀H₁₂N₂O Serotonin 25 atoms, 26 bonds.
C₅H₆N₂O₂ Thymine 15 atoms, 15 bonds.
C₁₁H₁₂N₂O₂ Tryptophan 27 atoms, 28 bonds.
C₂H₅NO₂ Glycine 10 atoms, 9 bonds.
C₄H₄N₂O₂ Uracil 12 atoms, 12 bonds.
C₄H₅N₃O Cytosine 13 atoms, 13 bonds.
C₅H₅N₅O Guanine 16 atoms, 17 bonds.
C₅H₄N₄O₃ Uric acid 16 atoms, 17 bonds.
C₁₂H₁₇NO DEET 31 atoms, 31 bonds.
C₁₃H₁₆N₂O₂ Melatonin 33 atoms, 34 bonds.
CO(NH₂)₂ Urea 8 atoms, 7 bonds.
C₁₃H₂₁NO₃ Albuterol 38 atoms, 38 bonds.
C₁₄H₁₈N₂O₅ Aspartame 39 atoms, 39 bonds.
C₁₄H₂₂N₂O Lidocaine 39 atoms, 39 bonds.
C₁₇H₂₁NO Diphenhydramine 40 atoms, 41 bonds.
C₂₀H₂₄N₂O₂ Quinine 48 atoms, 51 bonds.