Essay D1
Professor James Whitesell
CHEM 151
28 February 2014
Essay D1 Aspirin: The Pain Killer that Changed Medicine
Aspirin Introduction and Synthesis
Usually in people’s daily lives or occasionally, they will experience either some pain
in their head or in certain regions of their body. The solution to reduce and kill this pain is
none other than painkiller medication. The most common painkiller medication sold over
the counter in today’s world is Aspirin. The chemical formula of this molecule is C9H8O4.
The molar mass of the compound is 180.157 g/mol. Although it is called Aspirin as a
medication, it is also known as either Acetyl Salicylic Acid or by its IUPAC name, 2Acetoxybenzonic Acid. This essential compound used in everyday life is made from the
synthesis reaction of Salicylic Acid and Acetic Anhydride when in the presence of
phosphoric acid and a catalyst to speed up the reaction. Not only is the process of
synthesizing Aspirin a long and tedious one, but also the reaction is actually a three-step
process to ensure the effectiveness of the final product.
In order to ensure the product will be effective, the Aspirin must be isolated and then
purified. Since the Aspirin in insoluble in cold water, the chilled solution can then be
filtered and then isolated to continue with the purification process. The purpose of the
purification process is to remove any unreacted reagent and Acetic acid that may have
ended up in the solution in some way. Acidic anhydride is caused to decompose the
addition of water once the formation of aspirin is complete: (1)
The use of acetic acid and phosphoric acid is because these solutions are water-soluble
and can be removed by washing the isolated product with chilled water. The purification
process is finally completed once the product goes through recrystallization. The
impurified aspirin is then dissolved in ethanol, which is then cooled to isolate aspirin out of
the impurities. If the product synthesized has the same melting point as the actual product,
then it is as pure as possible (1). The more pure the product, the more effective it will be
when used as a form of medicine.
There is another method is used to make the material that is needed for the production
of Aspirin. As the reaction above has shown, the used of Salicylic Acid is a necessity to form
the purest product of Aspiring for use. Another reaction involves the use of the reactant
Phenol. Phenol is a reactant that is made up of a benzene ring that is attached to a hydroxyl
group on the Carbon-1 position of the ring. From this reaction, Phenol is reacted with
Sodium Hydroxide (NaOH) in order to create the products needed for the next mechanism
reaction. The hydrogen group is donated to the OH- group that is made through heterolytic
cleavage of the Sodium Hydroxide. From that reaction, the Na+ is then attached to the Oanion attached to the Phenol. The products of the reaction are then Sodium Phenate and
Water (6). The reaction of the process is shown below:
From this procedure, the Sodium Phenate is then reacted with the reagent Carbon Dioxide,
and through a long and tedious mechanism, one carbon and one oxygen attach to the ONa
group on the 1-carbon position. As for the other oxygen, it attaches to the hydrogen
donated from the water and then attached to the 2-carbon position. This produces Sodium
Salicylate, which is then taken through one more reaction to produce the Salicylic Acid that
is used to synthesize Aspirin (6). The reaction of this procedure is shown below:
The final step of producing the reagent necessary for Aspirin synthesis is the reaction of the
Sodium Salicylate in the presence of the sulfuric hydrogen. Through this reaction, the
Sodium found in the reagent is then replaced via substitution with the sulfuric hydrogen,
which then makes Sodium Salicylate into Salicylic Acid, which can then be used in the
overall reaction that creates Aspirin (6). The final reaction is shown below:
Aspirin has a very unique process to make it, but its uniqueness as a molecule and
compound goes back to when it was discovered.
History of Aspirin
Aspirin dates back to ancient times, specifically around 3000 B.C. in Mesopotamia.
According to an ancient Sumer stone tablet from the Third Dynasty of Ur of medical text,
the tablet mentioned willow-tree based remedies, but however, the tablet did not specify
what these remedies (5). This was the start of observations that would eventually lead to
Aspirin’s discovery. It was later in 1543 B.C. where the Ebers Papyrus, an ancient Egyptian
medical text, mentioned willow and myrtle being used for remedies to treat pain, fever, and
inflammation (5). All of these different observations eventually lead to the modern
discovery of the medicine, especially from ideas that date back many generations.
As many people might know, Aspirin’s main purpose is to relieve the pain and
inflammation in the body caused by a variety of factors. One of these people was the first to
record treatments, like aspirin, that would be effective in reducing or eliminating pain. This
person was Hippocrates, a scientist who lived between 460 B.C. and 377 B.C. who is often
regarded as the father of modern medicine. Many of his methods of healing headaches,
pains and fevers included making a powder that was made from the bark and leaves of the
willow tree. Eventually, in 1828, many scientists discovered that this compound was called
salicin, which was a compound found in willow plants that would give a person pain relief.
From that discovery, the active ingredient was first isolated by a man named Johann
Buchner, a pharmacy professor at the University of Muich. He was the first to isolate the
active ingredient and turn it into a form of salicin that was a bitter tasting yellow, needlelike crystal. Although two Italian scientists named Brugantelli and Fontana isolated the
compound in 1826, it was very impure, so they technically did not completely isolate the
purest form of Aspirin for medical uses. Eventually, the crystalline form was extracted
when in 1829, a man named Henri Leroux synthesized only 30 g of salicin from 1.5 kg of
willow bark. And then, in 1838, a man named Raffaele Piria split the salicin into a sugar and
aromatic component and converted into an acid of crystallized needles, which became
known as salicylic acid (2). As previously stated, this reactant is involved with the overall
procedure to synthesize Asprin.
The only implication with salicylic acid was that it was tough on the stomach; so a
scientist named Charles Frederic Gerhardt in 1853 neutralized this acid by buffering it with
sodium and acetyl chloride, which then created acetylsalicylic acid. This event later brought
on the work of Felix Hoffmann, a German chemist who in 1899 used the reaction to
produce the product and gave it to his father for pain relief. This lead to Aspirin being
patented in 1900 by the Bayer Company. Aspirin is derived from the A (acetyl chloride), the
“spir” in the name of the plant that derived salicylic acid, and the “in” as the familiar name
ending in medicines. Since that time, Aspirin has been a major part of dealing with pain
inside the body (2). But the question involved with this is how the Aspirin works inside the
body.
Aspirin and its Effect in the Human Body
Aspirin serves two main purposes when reacting inside the body to deal with pain.
The first action is acting as an anti-prostaglandin, otherwise known as acting as an antiinflammatory, a fever-reducer, and a pain reliever. The second acting is acting as a blood
thinner, or an anti-platelet agent. All of these actions are required in order for Aspirin to act
efficiently and as safe as possible, otherwise the side effects can lead to more pain or even
death. Prostaglandins are lipid compounds that are derived enzymatically from fatty acids
and other reactions that take place within the human body. Whenever the body is injured
in any way, inflammation occurs in that region of injury as part of the natural healing
process. Enzymes, mediators, and other cells like white blood cells facilitating that region
cause this inflammation. One major enzyme involved with this inflammation is one called
cyclo-oxygenase, other wise abbreviated as COX. This enzyme is the one responsible for the
formation of a group of inflammatory mediators known as prostaglandins (3). There are
the molecules that cause pain inside the human body, so what Aspirin does inside the body
is prevent the generation of these molecules to prevent pain. This is done by ingesting a
recommended dose of aspirin in the body and then the stomach digests the medicine, and
the active ingredient is then sped throughout the body through the body’s blood stream.
What Aspirin does inside the body is inhibit the COX enzyme, which then prevents swelling
of the inflamed region and thus prevents the production of prostaglandins (4).
Not only does the medication prevent this pain from occurring, but it has also been
discovered that it can actually lower the risk of heart attacks. As many people know, a heart
attack is caused when blood flow is impeded in the body by blood clots in arteries or veins.
With the COX enzyme, it plays a very important role in blood cessation. Blood clotting is a
result of different functions caused by a variety of cells, especially platelets that are found
within the blood stream. When blood vessels are damaged, these platelets clump together
over the hole or vessel tear to facilitate repair. The COX enzyme activates a chemical known
as thromboxane A2 that causes the platelets to stick together to “plug” over the damaged
area (3). The problem with this sometimes is that with the platelets clumping together, it
can cause these platelets to form huge clumps, and then is some cases, can cause blood
clots that can lead to heart attacks occurring. The thing about Aspirin is that it inhibits the
enzyme activity done by COX, which leads to a reduction in the ability for platelets to
aggregate. When this happens, the Aspirin is causing a process called ‘blood thinning’ or it’s
acting as an anti-platelet. The only downside of this is that bleeding still occurs, although
major bleeding is rare, but still, Aspirin can cause this to happen. But because of this
process, it not only lowers the chances of a heart attach, bit it also relates to reducing the
risk of having a stroke (3).
Conclusion
In today’s world of modern medicine and chemistry in general, Aspirin stands as a
prime example of advancement in medical treatments and as a prime example of chemical
synthesis, reactions, and as a compound and molecules overall. Even though there is so
much already discovered about Aspirin, there are still many medical procedures being
tested out, such as the idea that Aspirin might be able to fight cancer, or even significantly
lower the risk of cancer occurring. And beyond possibly being able to fight cancer, it might
even help with a multitude of different diseases in the future with further analysis and
testing of the medicine. Just the multitude of what this medical compound and molecule is
capable makes Aspirin one of the most interesting medicines ever discovered.
Bibliography
(1) http://wwwchem.csustan.edu/consumer/aspirincons/aspirincons.htm
(2) http://inventors.about.com/library/inventors/blaspirin.htm
(3) http://www.aspree.org/AUS/aspree-content/aspirin/how-aspirin-works.aspx
(4) http://www.aspirin.com/scripts/pages/en/pain/html_how_does_aspirin_work.php
(5) http://www.medicalnewstoday.com/articles/161255.php
(6) http://www.aspirin-foundation.com/what/reactions.html