Oganesyan, Chem-105
Synthesis of Acetaminophen1
Target Molecule: Acetaminophen
Introduction
Acetanilide, phenacetin, and acetaminophen are mild analgesics (relieve pain) and antipyretics (relieve fever).
Preparation of acetaminophen involves treating an amine with an acid anhydride to form an amide. In this case,
p-aminophenol, the amine, is treated with acetic anhydride to form an amide, acetaminophen.
Experimental
SAFETY PRECAUTIONS
• Wear safety glasses or goggles at all times in the laboratory.
• Acetic anhydride is corrosive and its vapor is irritating to the respiratory system. Avoid skin contact and
inhalation of the vapors. In the event of skin contact, rinse well with cold water. If the vapors are inhaled,
move to an area where fresh air is available.
• P-aminophenol is harmful by inhalation and by contact with the skin. In the event of skin contact, rinse
well with cold water. If the vapors are inhaled, move to an area where fresh air is available.
Techniques: please read the techniques from PLK and the notes at the end of the handout.
• Vacuum filtration
• Recrystallization
• Melting point determination
• Thin Layer Chromatography (TLC)
A. Synthesis of acetaminophen
1. Weigh ~ 1.5 g of purified p-aminophenol (MW = 109.1 g/mol) and place this in a 50 mL Erlenmeyer flask.
Using a graduated cylinder, add 1.7 mL of acetic anhydride (MW = 102.1 g/mol, d = 1.08 g/mL) and 4.5
mL of water.
2. Place a magnetic stir bar in the flask and heat the reaction mixture on a hot place. Monitor the temperature
of the reaction (keep it at ~100oC).
3. After the solid has dissolved (it may dissolve, precipitate and re-dissolve), heat the mixture for an
additional 10 minutes to complete the reaction.
4. Remove the flask from the hot plate, and allow it to cool to room temperature slowly. If crystallization
1 Adapted from Pavia’s Organic Laboratory Techniques, Saunders College Publishing, Philadelphia (1990).
