SYNTHESIS OF ACETAMINOPHEN
Cautions for experiment:
Handle p-aminophenol carefully - wear gloves
Acetic anhydride is toxic, corrosive and a lachrymator (causes tears) and
a skin irritant.
Avoid contact with skin, eyes and clothing.
USE ACETIC ANHYDRIDE IN A FUMEHOOD WHENEVER POSSIBLE
Hydrochloric acid is a skin irritant.
EXPERIMENTAL PROCEDURE
Place 1.05 g of p-aminophenol and 20 mL of water in a 125-mL Erlenmeyer flask. Add 1.0 mL of
concentrated hydrochloric acid, and swirl the flask for a few minutes to ensure that the amine
dissolves completely. If some amine remains undissolved, warm the mixture on a steam bath
until all the material is in solution. Prepare a solution for use as a buffer (this prevents the
reaction pH from changing significantly) by dissolving 1.25 g of sodium acetate tri-hydrate
(CH3CO2Na.3H2O) in 3.0 mL of water. If required, clarify the solution by gravity filtration. Add
the sodium acetate buffering solution in one portion. Immediately add 1 mL of acetic anhydride
while swirling the solution. Continue swirling the solution vigorously for at least 10 minutes to
ensure mixing. If the solution is highly colored then it can be purified using charcoal: add a
spatula full of decolorizing charcoal to the solution, swirl the solution on a steam bath for a few
minutes, and remove the charcoal by gravity filtration, using a fluted filter. Cool the reaction
mixture by immersing the flask in an ice-water bath, and stir the mixture vigorously until the
crude acetaminophen crystallizes. It may be necessary to scratch the walls of the flask
vigorously in order to initiate crystallization. Allow the flask to remain in the ice bath for about
15 minutes. Collect the crystals in a Büchner funnel by vacuum filtration. Wash the crystals with
a small portion (20mL) of ice cold water. Leave the crystals on the filter paper in the Büchner
funnel under vacuum to dry. Once dry, weigh the acetaminophen crystals, calculate the
percentage yield and determine the melting point.