SYNTHESIS OF ACETYLSALICYLIC ACID

Chemicals that have the ability to relieve pain have been known for many years,
first as folk remedies, and then as specific compounds that were developed
through research (and sometimes through trial and error). The most commonly
used painkiller currently on the market is aspirin. The aspirin tablet that is sold
today is the result of research that started in the late 1700s and lasted into the
twentieth century. The original compound under investigation was a derivative of
willow bark. A number of modifications and additions were made to the original
compound to improve everything from its taste to its ability to dissolve in the
stomach.
The compound that we know as aspirin, acetylsalicylic acid, actually does more
than simply relieve pain. It also will reduce fever and will reduce inflammation.
The United States produces almost 40 million pounds of aspirin each year; a
definite indication of its popularity.
Aspirin can be synthesized in the laboratory through a simple reaction between
salicylic acid and acetic anhydride. This type of reaction actually has a specific
name, esterification. An esterification reaction usually combines an organic
alcohol and an organic acid. Organic functional groups are important because
they help to determine the behavior of the compounds to which they are attached.
For example, most acids have a sour taste (like citric acid in lemons) and many
esters have odors (like wintergreen or vanilla).
To synthesize aspirin, salicylic acid will be combined with acetic anhydride. The
salicylic acid molecule actually has two functional groups attached to it, an acid
and an alcohol. The alcohol functional group is the one that will be involved in
the reaction to produce aspirin. The acetic anhydride (which is actually two acetic
acid molecules with a water molecule removed) will act as the acid part of the
reaction. In addition, a small amount of phosphoric acid will be added to help the
reaction occur at a reasonable rate.
The reaction is fast. Once the reaction is complete, a small amount of cold water
is added to react with any acetic anhydride that has not reacted. Then additional
water is added to help the aspirin crystallize from solution. Although the product
will appear pure at this point, it would actually require a large amount of
purification before it could be used.
Safety Precautions:
Acetic Anhydride is the anhydride of acetic acid and will react violently with
water. It can act as an irritant with a corrosive effect on tissue, especially the eyes
and upper respiratory tract. Any contact with the skin can cause redness and

peelingso exposed areas should be washed immediately and thoroughly. USE

GLOVES
Salicylic Acid is a moderately toxic chemical. Ingestion of large amounts may
cause abdominal pain and vomiting, dizziness, and headache. Symptoms
disappear when exposure is stopped.
Phosphoric Acid is a strong acid. Contact with the body results in rapid
destruction of tissue and can cause severe burns. Inhalation of acid mists or
vapors can cause an inflammation of the upper respiratory tract. If spills occur,
wash the area immediately with large amounts of water. Gloves should be used to
prevent contact.
Acetylsalicylic Acid (aspirin) is toxic only when taken in large amounts.
Contact, inhalation, or ingestion can cause asthma, sneezing, and irritation of the
eyes and nose, especially in people who are allergic to aspirin and aspirin
products. Ingestion of large amounts can also cause abdominal pain.
Procedure:
In a 125 ml. Erlenmeyer flask, mix 0.05 moles (7.0 g) of salicylic acid, 0.15
moles (16.5 ml) of acetic anhydride, and 20 drops of 85 % phosphoric acid. Heat
the flask in a beaker of hot water (85-95 C) for 10 minutes (in the hood). Remove
the flask from the beaker and SLOWLY add 5 ml of de-ionized water. (Caution:
this decomposition of excess acetic anhydride to acetic acid releases heat). Add
an additional 30 ml of de-ionized water. Cool the flask in an ice-bath to allow
crystallization to finish. Filter the crystals and air dry. Weigh the crystals and
observe their color and texture.
Questions:
1. Write the actual reaction for the synthesis of aspirin.
2. Why is the reaction mixture heated?
3. Why is the solution cooled before the aspirin is filtered out?
4. What does aspirin do?
5. How does aspirin work?