Experiment Five
Synthesis and purification of the
analgesic agent, Acetaminophen
(Paracetamol)
Introduction:
 Acetaminophen is a non-steroidal anti-
inflammatory/analgesic agent, it has also anti-pyretic
properties. It is widely used in arthritic and
rheumatoid conditions involving musculoskeletal pain
and other disorders such as headache.
Mechanism of action
 Now, recent research (2) has shown the
presence of a new, previously unknown
cyclooxygenase enzyme COX-3, found in the
brain and spinal cord, which is selectively
inhibited by paracetamol, and is distinct from
the two already known cyclooxygenase
enzymes COX-1 and COX-2. It is now believed
that this selective inhibition of the enzyme
COX-3 in the brain and spinal cord explains
the effectiveness of paracetamol in relieving
pain and reducing fever without having
unwanted gastrointestinal side effects.
Chemical properties:
 White crystalline powder.
 Molecular weight = 151.17
g/mole.
 Melting point = 170 °C.
 Insoluble in water, very
soluble in ethanol.
Synthetic procedure:
 Suspend 2.2 g of P-aminophenol in 6 ml distilled water.
 Warm the mixture in a water bath until all solid dissolved.
 Add 2.5 ml acetic anhydride to the hot solution, and then
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heat the reaction in water bath for 10 minutes.
Filter while the solution is hot using Buchner filtration
unit.
Leave to cool down for 10 minutes.
Filter the solid precipitate, and then wash it with cold
water.
Re-dissolve in about 20 ml hot distilled water….filter while
hot…cool in ice bath to form crystals.
Collect the crystals by Buchner filtration, and then dry it in
the oven.
Crystals shape
Calculations
• Weigh and then calculate the % yield of the reaction.
• p-aminophenol,Mwt=109.13 g/mole
• Acetic acid anhydrous, d=1.082 g/ml,
Mwt=102.09 g/mole
• Molecular weight of paracetamol= 151.17 g/mole.
Purity Definition
 is the absence of impurity or contaminants in a
substance
Purification technique:
 Crystalization
 Extraction
 Chromatography
 Filtration
 distillation
Technique to measure purity
 mp
 HPLC
 TLC
 NMR
 Mass spectroscopy
Identification test
 Test 1:
 Dissolve 0.1 g paracetamol in 10 ml water
 Add 0.05 ml ferric chloride solution.
 Violet blue color is produced
 Test 2:
 Boil 0.1 g of paracetamol with 1 ml HCl for 3 min.
 Add 10 ml water & cool, no ppt produced.
 Add 0.05 ml 0.1N potassium dichromate.
 A violet colour slowly develops, which don’t
become red .
Assay is done usually by using:
 Spectrophotometric Method.
 HIGH-PERFORMANCE LIQUID
CHROMATOGRAPHY (HPLC).
 What is the class of Paracetamol ?
 What is the difference between Panadol, Panadol
extra, Panadol night , Panadol cold & flu ,Panadol
advance & Panadol joint?
 How to prepare acetaminophen from benzene?
 Why it is better to start with p-aminophenol to
synthesis acetaminophen?
 Why acetic anhydride must not be in excess?
 Why the percent yield could be very low?