01 of 05
How to synthesize aspirin – Acetylsalicylic acid – Introduction and history:
Salicylic acid was neutralized with sodium to produce sodium salicylate, which tasted better but still irritated the stomach.
Salicylic acid could be modified to produce phenylsalicylate, which tasted better and was less irritating, but released the toxic phenol when metabolized.
Felix Hoffman and Arthur Eichengrün first synthesized the active ingredient in aspirin, acetylsalicylic acid, in 1893.
In this lab exercise, you can prepare aspirin (acetylsalicylic acid) from salicylic acid and acetic anhydride using the following reaction:
salicylic acid (C 7 H 6 O 3 ) + acetic anhydride (C 4 H 6 O 3 ) → acetylsalicylic acid (C 9 H 8 O 4 ) + acetic acid (C 2 H 4 O 2 )
02 of 05
How to Synthesize aspirin – Acetylsalicylic acid – Objectives and materials:
First, collect the chemicals and equipment used to synthesize aspirin:
Synthesis of aspirin materials required :
- 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 chloride III (optional, to test for purity)
* Be extremely careful when handling these chemicals. Phosphoric or sulfuric acid and acetic anhydride can cause severe burns.
Equipment for synthesis of aspirin :
- Filter paper (12.5 cm)
- Kickstand with funnel
- Two 400 mL beakers
- 125 ml in Erlenmeyer
- 50 ml burette or measuring pipette
- 10 mL and 50 mL graduated bottle
- Hood, hot plate, scale
- Stirring rod
- Ice bath
- Wash bottle
Let’s synthesize aspirin …
03 of 05
How to make aspirin – Acetylsalicylic acid – Procedure for synthesis of aspirin :
- Weigh accurately 3.00 grams of salicylic acid and transfer to a dry Erlenmeyer flask. If you are calculating the actual and theoretical yield , be sure to note how much salicylic acid you actually measured.
- Add 6 ml of acetic anhydride and 5-8 drops of 85% phosphoric acid to the flask.
- Shake the bottle gently to mix the solution. Place the flask in a beaker of hot water for ~ 15 minutes.
- Add 20 drops of cold water drop by drop to the hot solution to destroy the excess acetic anhydride.
- Add 20 ml of water to the flask. Put the flask in an ice bath to cool the mixture and speed up crystallization.
- When the crystallization process seems complete, pour the mixture into a Buckner funnel.
- Apply suction filtration through the funnel and wash the crystals with a few milliliters of ice water. Make sure the water is close to freezing to minimize product loss.
- Do 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.
- Once the crystals have dissolved, add 25 mL of hot water to the alcohol solution. Cover the beaker. The crystals will reform as the solution cools. Once crystallization has started, place 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 the paper to remove excess water.
- Confirm that you have acetylsalicylic acid by checking a melting point of 135 ° C.
04 of 05
How to make aspirin – Activities for synthesis of aspirin :
Here are some examples of follow-up activities and questions that can be asked when synthesizing aspirin:
- You can compare the actual and theoretical yield of acetylsalicylic acid based on the initial amount of salicylic acid. Can you identify the limiting reagent in the synthesis?
- You can compare the quality of synthesized aspirin with commercial aspirin and salicylic acid. Add a drop of 1% iron chloride III to separate the test tubes containing a few crystals of each substance. Observe the color: Pure aspirin would not show a color, while salicylic acid or traces of it in impure aspirin would show a purple color.
- Examine the aspirin crystals under a microscope. You should see small grain white crystals with obvious recurring 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? Salicylic acid has a group -OH (an alcohol) and a carboxyl group -COOH (an organic acid). The acid part of the molecule is one of the factors that causes stomach irritation. In addition to the irritation caused by acidity, aspirin causes stomach irritation by inhibiting the production of prostaglandins, hormones responsible for slowing the production of stomach acid.
Here are other follow-up questions …
05 of 05
How To Make Aspirin – Acetylsalicylic Acid – More Follow Up Questions:
Here are some additional questions about aspirin synthesis:
- Can you explain what happened to the -OH group in salicylic acid when acetic acid was added? The -OH group of salicylic acid combined with acetic acid, producing water and an ester group. Can you see what effect it had on the end product? This reduced the strength of the acid and made aspirin easier to ingest.
- Why do you think the aspirin was washed with distilled water? How did it affect the end product? How has this affected the actual performance of the product? Washing the aspirin removes most of the unreacted salicylic acid and acetic anhydride to give a purer product. A product was dissolved and lost in the washing process. Cold water was used to minimize dissolution of the product.
- How has synthesis used different temperatures to affect the solubility of aspirin? At higher temperatures (hot water), the molecules have more kinetic energy and collide with each other more often to interact with the water molecules, thereby increasing the solubility of aspirin. The ice bath slowed down the molecules, making it easier for them to stick together and “drop” from the solution or crystallize.