Aspirin is the most widely used over-the-counter drug in the world. The average tablet contains about 325 milligrams of the active ingredient acetylsalicylic acid combined with an inert binding material such as starch. Aspirin is used to relieve pain, reduce inflammation, and lower fever. Aspirin originally was derived by boiling the bark of the white willow tree. Although the salicin in willow bark has analgesic properties, purified salicylic acid was bitter and irritating when taken orally. Salicylic acid was neutralized with sodium to produce sodium salicylate, which was better-tasting but still irritated the stomach. Salicylic acid could be modified to produce phenylsalicylate, which was better tasting and less irritating, but released the toxic substance phenol when metabolized. Felix Hoffman and Arthur Eichengrün first synthesized the active ingredient in aspirin, acetylsalicylic acid, in 1893.01of 04
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In this laboratory exercise, you can prepare aspirin (acetylsalicylic acid) from salicylic acid and acetic anhydride using the following reaction:
salicylic acid (C7H6O3) + acetic anhydride (C4H6O3) → acetylsalicylic acid (C9H8O4) + acetic acid (C2H4O2)
First, gather the chemicals and equipment used to synthesize the aspirin.
Aspirin Synthesis Materials
- 3.0 g salicylic acid
- 6 mL acetic anhydride*
- 5-8 drops of 85% phosphoric acid or concentrated sulfuric acid*
- Distilled water (about 50 mL)
- 10 mL ethanol
- 1% iron III chloride (optional, to test purity)
*Use extreme caution when handling these chemicals. Phosphoric or sulfuric acid and acetic anhydride can cause severe burns.
- Filter paper (12.5 cm)
- Ring stand with funnel
- Two 400 mL beakers
- 125 mL Erlenmeyer flask
- 50 mL buret or measuring pipet
- 10 mL and 50 mL graduated cylinder
- Fume hood, hot plate, balance
- Stirring rod
- Ice bath
- Wash bottle
Let's synthesize aspirin!02of 04
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- Accurately weigh 3.00 grams of salicylic acid and transfer to a dry Erlenmeyer flask. If you will be calculating actual and theoretical yield, be sure to record how much salicylic acid you actually measured.
- Add 6 mL of acetic anhydride and 5-8 drops of 85% phosphoric acid to the flask.
- Gently swirl the flask to mix the solution. Place the flask in a beaker of warm water for ~15 minutes.
- Add 20 drops of cold water dropwise to the warm solution to destroy the excess acetic anhydride.
- Add 20 mL of water to the flask. Set the flask in an ice bath to cool the mixture and speed crystallization.
- When the crystallization process appears complete, pour the mixture through a Buckner funnel.
- Apply suction filtration through the funnel and wash the crystals with a few milliliters of ice cold water. Be sure the water is near freezing to minimize loss of product.
- Perform a recrystallization to purify the product. Transfer the crystals to a beaker. Add 10 mL of ethanol. Stir and warm the beaker to dissolve the crystals.
- After the crystals have dissolved, add 25 mL of warm water to the alcohol solution. Cover the beaker. Crystals will reform as the solution cools. Once crystallization has started, set the beaker in an ice bath to complete the recrystallization.
- Pour the contents of the beaker into a Buckner funnel and apply suction filtration.
- Remove the crystals to dry paper to remove excess water.
- Confirm you have acetylsalicylic acid by verifying a melting point of 135°C.
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Here are some examples of follow-up activities and questions which may be asked upon synthesizing aspirin:
- You can compare the actual and theoretical yield of acetylsalicylic acid based on the initial quantity of salicylic acid. Can you identify the limiting reactant in the synthesis?
- You can compare the quality of the synthesized aspirin with commercial aspirin and salicylic acid. Add one drop of 1% iron III chloride to separate test tubes containing a few crystals of each substance. Observe the color: Pure aspirin would show no color, while salicylic acid or traces of it in impure aspirin will show a purple color.
- Examine the aspirin crystals under a microscope. You should see white small-grained crystals with obvious repeating units.
- Can you identify the functional groups in salicylic acid? Can you predict how these groups affect the properties of the molecule and how the body reacts to it? Salicylic acid has an -OH group (an alcohol) and a carboxyl group -COOH (an organic acid). The acid portion of the molecule is one of the factors that cause irritation in the stomach. In addition to irritation caused by acidity, aspirin causes stomach irritation by inhibiting the production of prostaglandins, hormones responsible for slowing gastric acid production.
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Here are some additional questions relating to aspirin synthesis:
- Can you explain what happened to the -OH group in the salicylic acid when the acetic acid was added? The -OH group from the salicylic acid combined with the acetic acid, producing water and an ester group. Can you see what effect this had on the end product? This reduced the strength of the acid and made the aspirin easier to ingest.
- Why do you think the aspirin was washed with distilled water? How did this affect the end product? How did this affect the actual product yield? Washing the aspirin removed most of the unreacted salicylic acid and acetic anhydride to yield a purer product. Some product was dissolved and lost in the washing process. Cold water was used to minimize dissolving the product.
- How did the synthesis use different temperatures to affect the solubility of aspirin? At higher temperatures (warm water), molecules have more kinetic energy and collide with each other more often to interact with water molecules, increasing the solubility of the aspirin. The ice bath slowed the molecules, allowing them to more easily stick together and "fall out" of the solution or crystallize.