CHEMISTRY 4
HOMEWORK
THE CHEMISTRY OF ADVIL (IBUPROFEN)
Name: Alyssa Jan Marie G. Valdez
Introduction
Since its introduction by Boots Group in 1969
as an alternative to aspirin, ibuprofen has become
one of the most common painkillers in the world
(Mijin et al., 2003). The name “ibuprofen” was
coined from its systematic chemical name, (±)-2-(p-
isobutylphenyl)propionic acid having chemical
formula C13H8O2 [ CITATION Ame18 \l 1033 ].
Moreover, ibuprofen was the first member of
propionic acid derivatives as a better alternative to
aspirin (Bushra et al., 2010). The structure of
ibuprofen is shown below.
Figure 1. Structure of ibuprofen.
At low doses, ibuprofen, more commonly
known as Motrin, Advil or Nurofen, is an over-the-
counter drug that has an excellent safety profile
similar to paracetamol in many countries due to its
ability to treat pain, inflammation, and fever, and
alleviate the symptoms of a migraine, menstrual
cramps, and rheumatoid arthritis [ CITATION Rai09 \l
1033 \m Kri18]. This can be attributed to the ability
of ibuprofen to block the synthesis of cyclo-
oxygenase (COX) enzymes, which are involved in
the production of prostaglandins. Prostaglandin is
involved in production of pain, inflammation, and
fever (Bushra et al., 2010).
It is also worthwhile to know that ibuprofen has
two enantiomers with its stereocenter in the α-
position of proprionate moiety, which means that
mirror images of their structures are non-
superimposable. The two optical isomers of
ibuprofen are R- and S+. Each of these enantiomers
Section: 12-Andromeda Core: Chem A
has distinct biological effects and metabolism in the
body. The S+ form of ibuprofen is
pharmacologically active, which means it produces
the pain-killing effects of ibuprofen. The R- isomer,
on the other hand, does not have the same property
as the S+ isomer as it cannot inhibit the production
of COX because it does not have the ability to bond
to the active site of the COX. The pain-relieving
effect of active S+ ibuprofen is further discussed
below [ CITATION Ana18 \l 1033 \m BCA].
Figure 2. Structures of (R)-ibuprofen (left) and (S)-
ibuprofen (right).
The first synthesis of ibuprofen involved six
steps. Initially, isobutylbenzene was subjected to
Friedel-Crafts acylation. Darzen’s reaction was then
used to form α, β-epoxy ester, which was then
hydrolyzed and decarboxylated to the aldehyde. The
product was then reacted with hydroxylamine to
give an oxime, which can be converted to nitrile and
hydrolyzed to form the acid. Today, the synthesis of
ibuprofen is trimmed down to three-step process
[ CITATION Ana18 \l 1033 ]. Most ibuprofen on the
market are prepared in the form of (R)-ibuprofen
since it has an enzyme called the 2-arylpropionyl-
CoA epimerase that converts (R)-ibuprofen into the
active (S)-enantiomer, and making the (S)-
enantiomer form is more difficult and expensive
[ CITATION Ana18 \l 1033 ].
Working Principle
When ibuprofen is ingested, it is broken down
and absorbed into the blood through the walls of the
stomach, which is achieved after the ibuprofen is
1
dissolved in water. It then reacts with amino acid https://bcachemistry.wordpress.com/tag/ibuprof
lysine to form ibuprofen lysinate, which is soluble en/
in water due to its ionic nature and the presence of
polar amino and carboxyl groups. Ibuprofen then Bushra, R., & Aslam, N. (2010). An Overview of
reversibly inhibits the production of cyclo- Clinical Pharmacology of Ibuprofen. Oman
oxygenase (COX)-1 and COX-2 in blood [ CITATION Medical Journal, 25(3), 155-166.
Rai09 \l 1033 ]. Cyclo-oxygenase are enzymes,
Duda, K. (2018). Is There Any Difference Between
which means they speed up reactions. These COX
OTC Pain Relievers? Retrieved from VeryWell
enzymes convert arachidonic acid to prostaglandin,
Health: https://www.verywellhealth.com/what-
which is produced when cells are damaged.
is-the-difference-between-motrin-and-advil-
Prostaglandins make the body respond to pain,
which includes inflammation, redness, increased 770459
temperature, and lower pain threshold. Ibuprofen Mandal, A. (2018). Ibuprofen Chemistry. Retrieved
sticks to the active site of COX-1 and COX-2 from News Medical: https://www.news-
enzymes, which leads to the inhibition of synthesis medical.net/health/Ibuprofen-Chemistry.aspx
of prostaglandins. However, these enzymes then
reject ibuprofen and in effect, the effects of Mijin, D. Ž., Stanković, M., & Petrović, S. (2003).
ibuprofen wear off after a few hours [ CITATION Ibuprofen: Synthesis, production and properties.
BCA \l 1033 ]. Hemijska industrija, 57(5), 199-214.
NSAIDs are also frequently taken inappropriately. Rainsford, K. D. (2009). Ibuprofen: pharmacology,
Ibuprofen, for example, has few adverse effects efficacy and safety. Inflammopharmacology,
when taken. As aforementioned, ibuprofen reduces 17(6), 275-342.
the production of prostaglandins. The inhibition of
prostaglandin biosynthesis of ibuprofen can cause
side effects such as gastrointestinal bleeding,
hypertension, congestive heart failure,
hyperkalemia, and renal insufficiency. The side
effects of ibuprofen are more commonly related to
the conditions in stomach and blood clotting as
prostaglandins are responsible for protecting the
lining of the stomach and promoting the
constriction of the blood vessels and clotting of
platelets [ CITATION BCA \l 1033 ].

References
American Chemical Society. (2018). Ibuprofen.
Retrieved from American Chemical Society:
https://www.acs.org/content/acs/en/molecule-of-
the-week/archive/i/ibuprofen.html
BCA Chemistry. (n.d.). Ibuprofen. Retrieved from
Word Press: