Making Paracetamol

- Introduction
Acetaminophen or paracetamol is the only
aniline-based drug still used now, it is not
directly linked to cancer, hemolysis, or
methemoglobinemia but it can still severely
damage the liver. In low doses, less than 4g a
day it is supposed to be safe for the average
adult. However, higher doses sometimes not
even that much more than the recommended
amount can lead to liver failure.

It was first produced by in 1877 and it was tested clinically by Joseph

Von Mering in 1839. It is prescribed as an antipyretic and analgesic.
It can reduce fever and increase the threshold for painful stimuli.
Acetaminophen is a good choice for pain and fever relief with little
blood-thinning or gastric effect.

Harmon Northrop Morse

- Safety: Acetic anhydride is corrosive, causes burns, flammable, and the vapor will irritate
the eyes and the respiratory system. 4-aminophenol is an irritant.
- Procedure: Acetaminophen can be prepared by acetylation of p-aminophenol. 1g of p-
aminophenol is dissolved in 10mL of distilled water in a conical flask and stirred briskly
at room temperature, in order to suspend the solids in the water. 1.2g of acetic anhydride
is added to the conical flask dropwise and the solid p-aminophenol will dissolve after about
30 seconds. After about 15min of shaking, the precipitate will form. After that, the ppt will
be filtered and washed with cold water, and dried. The crude desired product can be
purified by recrystallization from the hot water of a 50:50 mix of alcohol and water.
- Instrumental Analysis:
1. IR Spectroscopy:
IR spectroscopy is used to identify the functional group in the compound using IR
radiation which causes vibrational transitions of the molecule. The vibrational peak for
O-H and CH3 stretching at 3326 and 3162-3035 cm-1, respectively. Vibrational peaks
at 1654 and 1610 cm-1 were assigned to C=O and C=C stretching, respectively. The
N-H amide II bending appeared at 1565 cm-1. Asymmetrical bending in the C-H bond
appeared at 1507 cm-1, and the C-C stretching peak appeared at 1443-1437 cm-1.

2. H1NMR:
Nuclear magnetic resonance detects the structure of the chemical compound using radio
frequency radiation which causes nuclear spin for the protons. The two doublets for
(H-2 and H-6) at 7.27 ppm and (H-3 and H-5) at 6.95 ppm and a singlet of the CH 3
group is found at 2 ppm. At 9 ppm there is the proton of the hydroxyl group while that
at 9.7 ppm for N-H.
3. Mass spectroscopy:
Mass spectroscopy is used to determine the Mwt and molecular formula of the
compound by fragmentation of it with an electron beam. From the Mwt of these
fragments, the Mwt and formula were detected.