Name________________________________

Date_________________________________

Class ________________________________

Overview
In this activity, you will make aspirin. The chemical compound known as acetylsalicylic acid (aspirin) will be synthesized from salicylic acid and acetic anhydride using sulfuric acid as a catalyst. Aspirin is not very soluble in water and will be crystallized by the addition of cold water to the reaction mixture followed by gravity filtration.

Objectives
By the end of this activity, you should be able to:

• Understand the functional drawing of a chemical compound.

• Identify basic functional groups and understand how they can replace each other in a chemical molecule.

• Realize that slight modifications in chemical structure can alter a substance's effect on an organism.

• Understand how compounds can be synthesized.

• Understand the versatility of aspirin in treatment.

• Discuss the traditional use of herbs and plants as medicines.

Aspirin is an example of a medicine that had its origin in herbal folk remedies. Centuries ago, Hippocrates made potions of the bark of willow trees to reduce fever and control pain in childbirth. In 1763, Reverend Edward Stone, an observant Englishman, noticed that dried willow bark had much the same taste as Peruvian bark from the cinchona tree (called "quina") which was used successfully to treat malaria by the Native Americans. Quinine, a medicine originally derived from that tree, is synthesized today to treat malaria. Since the willow trees were abundant in cool and humid climates where people often suffered sore and swollen joints, Stone used the willow bark to treat their swelling and pain.

The active ingredient in willow bark, salicin, was isolated in 1829 by a French pharmacist. Hermann Kolbe purified the precursor to aspirin, salicylic acid, thirty years later from the meadowwood plant. Salicylic acid was widely used for a wide variety of symptoms during the latter half of the 19th century, but had its drawbacks. It was very bitter tasting and caused irritation of the mouth and stomach lining, vomiting, and even respiratory failure at high doses.

Felix Hoffman was a German scientist working for Frederick Bayer and Company in the late 19th century. He found a way to reduce the unpleasant side effects of salicylic acid, while maintaining its medicinal benefits. By changing the chemical composition of the molecule through a simple chemical reaction, he combined salicylic acid with acetic acid to produce acetylsalicylic acid or aspirin as we know it today.

Look at the handout or overhead provided by your teacher and examine the reaction where acetylsalicylic acid is produced. Salicylic acid, the reactant, has two functional groups (common arrangements of atoms found in organic molecules.) The first, the -OH group, indicates that the substance is an alcohol. The second, the carboxyl group (-COOH) indicates that the substance is an organic acid. In salicylic acid, the acidic nature of the molecule irritates the lining of the stomach and gastrointestinal tract. When the salicylic acid molecule reacts with acetic anhydride, the -OH group of the salicylic acid molecule combines with the acetic anhydride molecule, forming the byproducts of water (H2O) and acetylsalicylic acid, or aspirin. The -OH group of the salicylic acid molecule has been replaced with the ester group, which results from the reaction of an alcohol (OH) and an acid (acetic anhydride). This ester group reduces the strength of the carboxylic acid and makes aspirin easier on the mouth and stomach.

Aspirin was first commercially produced by Frederick Bayer and Company in 1899. It was the first medicine to be produced in tablet form and remains the most widely taken medicine in the world. Each year, over 30 billion tablets are consumed and aspirin manufacturers spend over 100 million dollars in advertising in the U.S. alone. Americans spend over 2 billion dollars annually on aspirin products including tablets, capsules, gums, and creams.

One of the most interesting new uses of aspirin is in preventing heart attacks. Aspirin inhibits blood platelets from clumping together to form blood clots.

Aspirin thus reduces the chances of a blood clot in the coronary vessels which supply the heart with blood. The same action probably explains the benefits reported in other conditions involving blood, such as reducing risk of stroke or clotting after surgery. Aspirin is also used as an anti-inflammatory drug to treat diseases, such as rheumatoid arthritis. Aspirin's ability to relieve pain seems to be due to its capacity to block pain impulses passing over spinal nerves. It does not permit the impulses to reach the sensory area of the brain, and the individual does not interpret the pain.

Despite the chemical modification of salicylic acid, acetylsalicylic acid, or aspirin, can still cause stomach upsets or heartburn, although buffered or enteric-coated aspirins may prevent these side effects. This is due to its function in inhibiting prostaglandins, which slow the production of gastric acid. When given to children with chicken pox or flu, aspirin can lead to Reye's syndrome, a deadly but rare liver disorder. It is known to aggravate kidney disorders, and it may cause allergic reactions, such as rashes, swelling, and life-threatening asthmatic attacks.

Materials Needed (per team)
2.0 g salicylic acid
5 mL acetic anhydride
5 drops concentrated sulfuric acid
50 mL distilled water
filter paper (12.5-15 cm)
ring stand with funnel
400 mL beaker for hot water bath
400 mL beaker of ice
125 mL Erlenmeyer flask
buret or measuring pipet
10 and 50 mL graduated cylinder
fume hood, hot plate, and balance
glass rod
dropper
wash bottle
safety gloves, lab coat, and goggles

Procedures
Day 1

1. Prepare a hot water bath by heating a 400 mL beaker filled halfway with tap water to boiling on a hot plate (may be prepared in advance by your teacher). The hot water bath should be 80-90 degrees C.

2. Mass your filter paper. Record the mass and set the filter paper aside (you will need this information for day 2). Weigh 2.0 g salicylic acid on weighing paper or boat, and place in a 125 mL Erlenmeyer flask.

3. Using a fume hood, follow your teacher's instruction to add the following to the flask: 5 mL acetic anhydride from a measuring pipet or from the 50 mL buret. 5 drops concentrated sulfuric acid (CAUTION: Sulfuric acid is highly corrosive).

4. Stir the mixture with the glass rod, or by swirling, and place the flask in the boiling water bath for 10 minutes.

5. Remove the flask, place it under the fume hood, carefully add 2 mL of room temperature or cool distilled water from 10 mL graduated cylinder to the flask.

6. Swirl the mixture and let flask stand for 5 minutes.

7. Add an additional 40 mL of distilled water from a 50 mL graduated cylinder and stir the solution with the glass rod until small white crystals begin to form.

8. Using a 400 mL beaker, make an ice and water slurry; place the Erlenmeyer flask in the slurry and allow the mixture to cool another 10 minutes to complete crystallization. Agitate mixture every 2 minutes.

9. Moisten the filter paper (from step 2) with distilled water and set up a funnel filtration system using a funnel and ring stand. Pour the aspirin mixture into the filter paper, rinsing the flask with small aliquots of distilled water or with a wash bottle. Wash the crystals twice with 5 mL portions of distilled water.

10. Let the aspirin dry until the next day.

1. Mass the filter paper containing the aspirin and subtract the weight of the filter paper (from Day 1 step 2). This will be the final mass of the aspirin you synthesized. Record your results in the following table.
   
   

   Filter Paper & Aspirin	-	Filter Paper w/o aspirin (from day 1, step 2)	=	Aspirin Yield
   	-		=

2. Calculate the percent yield of your aspirin by taking the mass of your aspirin product and dividing it by the theoretical yield of 2.5 g and multiplying by 100. (2.5 g is based on moles of salicylic acid and acetic anhydride in the equation).
   
   

   mass of aspirin	x	100	=	% yield aspirin
   	x	100	=

1. Describe the aspirin crystals. Sketch them below.

2. What are the functional groups found in salicylic acid? What do these groups tell you about the substance and how it might react in the body?

3. What happened to the -OH group in the salicylic acid when acetic acid was introduced to the experiment? How does this affect the end product?

4. Why did the aspirin need to be washed with the distilled water? How does this affect the end product?

5. How do different temperatures affect the solubility of the aspirin? Explain why the procedure called for placing the aspirin solution in a hot water bath and then an ice slurry.

6. What was the purpose of the fume hood?