Synthesizing Aspirin and Oil of Wintergreen
Purpose
In this experiment, you will synthesize acetylsalicylic acid, commonly known as aspirin, and methyl
salicylate, oil of wintergreen, from salicylic acid. You will be able to see how two very different organic
compounds can be made from the same common starting material.
Introduction
We now live in a society that uses drugs frequently, many different kinds of drugs. Drugs fight
infection, relieve pain and even help us get to sleep or stay awake. Even though our society is not the
first to use drugs, we certainly use more than any other society before us. Part of this reason is that in
prehistoric times, the variety of drugs was limited. Most drugs were found in nature; therefore, when a
particular resource was depleted, the drug was no long available. Now we can synthesize compounds
that mimic many of the drugs found in natural and synthesize them on a very big scale. Each year, new
drugs are being synthesized, tested, and introduced to our society.
Freedom from pain has always been our goal for survival. In early primitive societies, alcohol, opium,
cocaine and hemp (marijuana) were used for pain relief. Unfortunately there were also a lot of side
effects. Salicylic acid was isolated from willow bark in 1860. It was found to be a good analgesic (pain
reliever) and antipyretic (reduces fever). However, the taste of the salicylic acid was sour and irritating
to the stomach. Chemists tried to modify the structure of salicylic acid to remove the undesirable affects
while keeping the healing properties of this compound. After many attempts at modifying salicylic acid,
the compound acetylsalicylic acid, later called aspirin was introduced in 1899 by Friedrich Bayer & Co.
The reaction for the production of aspirin is a very simple one-step organic synthesis.
O
C
OH
CH3
O
O O
COOH
+
salicylic acid
H3CCOCCH3
acetic anhydride
COOH
H3PO4
aspirin (acetylsalicylic acid)
Of all the pain relievers on the market today, aspirin is the easiest to make. The rest of the pain relievers
require multiple steps in their organic synthesis.
Another derivative of salicylic acid that has healing properties and is also a simple one-step organic
synthesis is called methyl salicylate.
O
O
C OH
C OCH3
OH
+
salicylic acid
CH3OH
methanol
H2SO4
OH
+
methyl salicylate
H2O
Methyl salicylate (oil of wintergreen) is used as a flavoring agent and it is also used in rubbing
compounds, like Ben Gay. When methyl salicylate is applied to the skin, it causes a mild burning
sensation which serves as a counterirritant for sore muscles. You will synthesize both of these
compounds in this experiment and observe first hand how compounds can look so different physically
but be quite similar chemically.
In addition to the synthesis, you will analyze aspirin by a technique called infrared spectroscopy.
Infrared (IR) spectroscopy uses infrared light to vibrate the bonds in an organic molecule. Chemical
bonds in different environments will absorb varying intensities and at varying frequencies. Thus IR
spectroscopy involves collecting absorption information and analyzing it in the form of a spectrum. The
frequencies at which there are absorptions of IR radiation (peaks) can be correlated directly to bonds
within the compound. Although IR can seem complicated, it can be simplified with a familiar analogy.
Like a human fingerprint, each organic compound has a unique spectrum. The IR spectrum is essentially
a chemical fingerprint for molecules. Using a chemical database, you’ll be able to confirm the identity of
your newly synthesized drugs.
Procedure
Part I: Synthesis of Aspirin
1. Heat approximately 150 mL of water in a 250 mL beaker using a hot plate. (Set-up the hot plate
under the hood.)
2. To a large test tube, add 1 g of salicylic acid, a boiling chip, and 8 small drops of 85% phosphoric acid
(H3PO4.)
3. Add 2 mL of acetic anhydride. Use the acetic anhydride to wash the other reagents to the bottom of
the test tub.
4. Mix the reactants thoroughly with a glass stirring rod, and then heat the reaction tube in the beaker of
hot water at ~90°C for 5 min.
5. Cautiously add 1.5 mL of d H2O dropwise to the reaction mixture. This step will decompose excess
acetic anhydride and be exothermic (give off heat.)
6. When the reaction is over, add 2 mL more water and allow the tube to cool slowly to room
temperature. Allow the solution to sit for 10 min. If crystallization does not occur during the cooling
process, add a seed crystal or scratch the inside of the tube with a glass stirring rod.
7. Cool the tube in ice until crystallization is complete, and then remove the crystals using vacuum
filtration. Wash the crystals with a very small quantity of ice cold water.
8. Place the product onto a piece of filter paper and squeeze the crystals between sheets of filter paper
to absorb excess water. Allow to air dry while performing Part II of this experiment.
9. After you have completed Part II, weigh the crystals and record the weight.
10. With the help of the instructor, prepare and obtain an IR spectrum of your product.
Part II: Synthesis of Wintergreen
1. Weigh approximately 1g of salicylic acid and place in a test tube.
2. Add 10mL of methanol to the test tube and gently shake the test tube until all of the salicylic acid
has dissolved.
3. Carefully add 20 drops of concentrated sulfuric acid (H2SO4) to the test tube.
4. Stir the contents in the test tube with a stirring rod.
5. Place the test tube in the water bath for approximately two minutes.
6. Remove the test tube from the water bath and carefully sniff the contents. If you smell wintergreen
then you have made methyl salicylate.
Results
Mass of aspirin produced
_________
Identification of aspirin (rate: Excellent, good, fair, or poor match)
_________
Print out IR spectrum and attach to report
Questions:
1. Describe the smell of methyl salicylate.
2. Provide two practical applications for IR.