SYNTHESIS OF ASPIRIN
I.
OBJECTIVES AND BACKGROUND
You will:
 synthesize acetylsalicylic acid (aspirin) by carrying out a simple organic reaction,
 separate your product from the reaction mixture by vacuum filtration,
 purify your product by recrystallization,
 perform a chemical test to identify the change in functional group from reactant to
product, and
 determine the success of your synthesis by calculating the percentage yield of your
product.
INTRODUCTION
Aspirin is one of the most widely used
medications in the world. It is employed as an
analgesic (pain relief), an anti-pyretic (fever
control) and an anti-inflammatory. More recently,
studies have indicated that daily intake of small
doses of aspirin can lower the risk of heart attack
and stroke in high-risk patients.
The history of aspirin and its precursor dates back to ancient times. Documents
attributed to Hippocrates, the father of modern medicine, from the 4th century B.C. refer to
the alleviation of pain by chewing on the bark of a willow tree or ingesting a powder made
from the bark and leaves of the willow. This remedy was passed on from generation to
generation.
Fast forward now to the 19th century, where the field of organic chemistry began to
experience tremendous growth. By 1838, chemists had managed to isolate, purify and
identify the component of willow bark that provided the analgesic benefit. The compound
was named salicylic acid, which was based on the genus name of the willow.
Efforts to market salicylic acid met with failure, due to an unfortunate side effect-prolonged ingestion of salicylic acid led to stomach pain, and in some cases, ulcers.
Inspection of the structure of salicylic acid molecule (see figure below) sheds some light on
the cause of this problem. Salicylic acid contains two functional groups, a carboxylic acid
(-COOH) and an alcohol (-OH). The carboxylic acid group, as the name implies, has a
tendency to generate H3O+ in aqueous solution. In addition, since the alcohol group is bound
to a benzene ring, it belongs to a special class of alcohols known as phenols. Phenols have
many unique properties, one of which being that they are substantially more acidic than
other types of alcohols. As a result, the two acidic functional groups serve to lower the pH of
the stomach, leading to the gastric distress described above.

Figure 29-1. Structures of aspirin and salicylic acid
Chemists sought to modify the salicylic acid molecule, reasoning that modification of one
of the functional groups could lower the acidity of the compound without affecting the
medical benefits. This was achieved by taking advantage of some fundamental organic
chemistry. When an alcohol is allowed to react with a carboxylic acid in the presence of an
acid catalyst, the functional groups combine in a condensation reaction to form an ester and
water:
By reacting the phenol group of salicylic acid with acetic acid, an ester group (which is
not acidic) is formed and the resulting compound was named acetylsalicylic acid.
Although this reaction was first achieved in the 1850's, it wasn't until 1899 that
scientists at the Bayer company in Germany identified acetylsalicylic acid as a
commercially viable compound. They gave it the brand name aspirin (derived from the
arcane genus name of meadowsweet, another natural source of salicylic acid). The drug was
in high demand almost immediately, and Bayer was soon on its way to becoming a
pharmaceutical giant.
Synthesis
In this experiment, aspirin will be produced by reacting salicylic acid with acetic
anhydride, a derivative of acetic acid that has similar chemicals properties to acetic acid,
but reacts more rapidly and efficiently. to form acetylsalicylic acid (aspirin). Note in
Equation (29-3) that the byproduct of the reaction is now acetic acid rather than water.
Recrystallization
A chemical reaction seldom occurs in such a manner that the desired product is obtained
in an absolutely pure state. The synthetic reaction in this experiment will be no exception.
The acetic anhydride will be added in excess, so unreacted acetic anhydride will be present
at the end of the reaction. In addition, sulfuric acid (added as a catalyst) and acetic acid
product will also contaminate the product. Failure to remove these acidic impurites would
defeat the purpose of the reaction, which is to lower the acidity of the product compared to
the salicylic acid starting material! Consequently, a purification procedure must be carried
out to separate the aspirin from such impurities as unused starting materials and the acetic
acid by-product.
Recrystallization is an extremely useful technique for purifying crystalline solids. The
impure product is dissolved in a minimum volume of hot solvent. The solvent is carefully
selected so that the product is much less soluble in cold solvent than hot, so that the
product will recrystallize when the solvent is cooled, leaving the soluble impurities behind
in the solvent. The pure product is then isolated by vacuum filtration.
Iron (III) Chloride Test for Phenols
A convenient test can be carried out to identify the change in functional group from
reactant to product. A comparison of the structural formulas of aspirin and salicylic acid
shows that the salicylic acid has a phenolic group while aspirin has none. A specific test for
a phenolic group will illustrate this change in functionality.
If a drop of iron (Ill) chloride (FeCl3) solution is added to an aqueous solution containing
traces of a phenolic group, a color change occurs. The color varies from reds to blues to
greens depending on the particular phenol molecule present.
Mole Relationships in a Chemical Reaction
The mole relationships in a balanced equation are used to make predictions about a
reaction before it is performed in the laboratory, predictions such as: what mass of a
product can be prepared from a known mass of a reactant?
The following example will illustrate how these predictions can be made for the reaction:
2 C2H6 + 7 O2
4 CO2 + 6 H2O
How many grams of carbon dioxide will form if 4.150 grams of ethane are oxidized?
The balanced equation must be inspected to find the mole ratio of carbon dioxide to
ethane: four moles of carbon dioxide are produced by two moles of ethane. The conversions
are as follows:
moles of ethane  4.150 g ethane 
1 mole ethane
 0.1380 mole ethane
30.08 g ethane
moles of CO2  0.1380 mole ethane 
mass of CO2  0.2760 mole CO2 
4 moles CO2
 0.2760 mole CO2
2 moles ethane
44.01 g CO2
 12.15 g CO2
1 mole CO2
The three steps needed to solve this problem were:
1) convert grams of ethane to moles of ethane,
2) convert moles of ethane to moles of carbon dioxide using the balanced equation,
3) convert moles of carbon dioxide to grams of carbon dioxide.
You will perform a calculation similar to this one; you will use the mole relationship in
the balanced equation for the synthesis of aspirin to predict the mass of purified aspirin you
should theoretically have obtained based on the mass of salicylic acid that you used as
starting material.
Percentage Yield of Product
The amount of product obtained in a chemical reaction (experimental mass) is almost
always less than what was expected (theoretical mass). This difference occurs because of
incomplete reaction of the reactants, side reactions (in which different products are formed),
and/or loss of product from careless experimental technique. The smaller the difference is
between the experimental and theoretical masses, the more successful is the synthesis. The
success is measured in terms of percentage yield, which is calculated using the formula:
 experimental mass 
percent yield  
  100%
 theoretical mass 
II. PROCEDURE
A. Equipment Set-Up: Ice Bath
1.
Partially fill a 600 mL beaker with ice. Add about 50 mL of distilled water to an Erlenmeyer
flask and place it into the ice bath to cool.
B. Aspirin Synthesis
1.
Measure out ~3 g of salicylic acid on an analytical balance, recording its mass to the nearest
0.001 g. Transfer the salicylic acid into a second 125-mL Erlenmeyer flask (not the one with the
water in it), and record the mass of the salicylic acid on your report sheet.
2.
Add about 6 mL of acetic anhydride and ~1/4 mL of concentrated (18 M) sulfuric acid (using
the mark on the barrel of the disposable plastic pipet) to the flask. Caution: acetic anhydride
and sulfuric acid are corrosive materials. Swirl the flask until the salicylic acid has dissolved.
Allow the mixture to sit at room temperature for 15 minutes with occasional swirling.
During this time, assemble the vacuum filtration apparatus.
C. Separation of Product from the Reaction Mixture
1.
Cool the reaction flask by placing it in the ice bath. Stir constantly; the mixture should
thicken to a solid or semi-solid sludge.
2.
Add slowly, with stirring, 35 mL of the cooled water. Continue stirring until the mixture is a
watery sludge. (Place the remaining cooled water back into the ice bath. It will be used during the
vacuum filtration.) Allow the mixture to continue cooling in the ice bath for 10 to 15 minutes.
During this time, determine and record the mass of your watchglass. Also, warm ~50 mL of distilled
water to 50-70 ºC on a hot plate.
3.
Vacuum filter the mixture. Use small portions of the cooled water to assist in rinsing the last
of the crystals from the flask.
4.
When filtration is complete, disconnect the vacuum tubing from the flask, then shut off the
aspirator. Discard the solution in the filter flask. If all of the cooled water has been used, place
another 20 mL of distilled water into the flask and return the flask to the ice bath. This water will
be needed for the second vacuum filtration.
D. Recrystallization of the Product
1. Transfer the impure aspirin from the Büchner funnel to a 150-mL beaker. Add 10 mL of 95%
ethanol.
2. Add about 25 mL of warm (50-70 °C) distilled water and stir to dissolve the impure aspirin. The
mixture can be heated gently until the solid completely dissolves, but do not allow the mixture
to boil. If some product will not dissolve, add ethanol a few drops at a time until all the solid has
dissolve. Do not add too much ethanol, or you will have trouble getting the aspirin to recrystallize.
3. Place the beaker in the ice bath to cool. Stir the mixture constantly for the first five minutes as
crystals begin forming. Stir frequently after that, until the beaker has been in the ice bath for a
total of about 15 minutes.
4. Set up the vacuum filtration apparatus with a new piece of filter paper and vacuum filter the
purified aspirin. Use small amounts of the cooled water to help rinse the last of the aspirin crystals
from the beaker. Keep the aspirator on and allow air to be drawn through the product to help dry it
as you perform Part E. Spreading the product out over the filter paper in the funnel will aid in the
drying process.
E. Iron (III) Chloride Test for Phenols
1. Place a match head-sized quantity of the pure aspirin into a medium test tube. Into a second
medium test tube place a match head-sized quantity of salicylic acid.
2. Add 5 mL of distilled water to the tubes containing the aspirin and the salicylic acid, and to an
empty tube. This third tube will be used as a control for color comparison. Agitate the tubes to
dissolve the solids as completely as possible. Add 2 to 3 drops of 0.2 M FeCl3 solution to each tube
and shake. An orange to purple color is indicative of the presence of the phenol group of salicylic
acid. Record your observations.
F. Yield of Purified Aspirin
1 Once your aspirin appears to be dry, transfer it to the watchglass. Determine and record the mass
of the watchglass and dried aspirin.
Report Sheet: Synthesis of Aspirin
Name
Partner's Name
Aspirin Synthesis
Mass of salicylic acid
Recrystallization of product
Mass of watchglass
Mass of watchglass and dried aspirin
Mass of dried aspirin
Results
Mass of aspirin expected
Calculation:
Percent yield of aspirin
Calculation:
Date
Instructor's Initials
Iron (III) Chloride Test for Phenols
Salicylic Acid
Observation:
Conclusion:
Purified Aspirin
Observation:
Conclusion:
Blank
Observation:
Conclusion: