Synthesis of Aspirin: How to prepare Oil of Wintergreen.

Organic chemistry can be defined as chemical reactions between molecules that contain carbon in a large part of their structure. Often these organic molecules contain many covalent bonds, which are the type of bonds found between two non-metal atoms. If you look on the periodic table you will see that only a small portion of the elements are considered to be nonmetals, including C, N, O, S, Cl, and F. This small number of elements can be bonded together in different amounts, bonding types (single, double triple bonds), and structural patterns to form over 10 million known molecules! The billions of dollars generated by the pharmaceutical industry is a prime example of how important organic chemistry is to our modern day society. In this experiment you will perform an organic synthesis to make aspirin. Aspirin is thetrade name for the molecule acetylsalicylic acid (aren’t you glad we don’t have to use “that” name when you have a headache).

The earliest known use of this molecule has been traced back to the fifth century B.C. The Greek physician Hippocrates described an extract of willow tree bark, a bitter powder that could be used to reduce fevers. In 1829, Salicin was isolated from willow bark and used as a pain reliever. Unfortunately Salicin was not very popular since it was found to be very acidic and a stomach irritant. In 1897 a German chemist named Felix Hoffman was working for the Bayer chemical company. Hoffman was looking for a less acidic pain reliever that his father could take for his arthritis. His research led to the synthesis of acetylsalicylic acid (ASA) or aspirin. Bayer patented the name and commenced to market the product in 1899. It was a huge success and sales grew rapidly. In fact, the company set up by Friedrich Bayer & Company is generally reckoned to have been the first pharmaceutical company, and the production of aspirin is generally accepted to have laid the foundation of the modern pharmaceutical industry.

Interestingly enough it wasn’t until the 1970’s that scientists began to understand how aspirin actually worked as a pain reliever. Today 80 billion aspirin tablets are consumed every year across the globe to reduce fevers, relieve pain, and even help prevent heart attacks.

In commercial aspirin products, a small amount of ASA (300 to 400 mg) is bound together with a starch binder and sometimes caffeine and buffers to make an aspirin tablet. The basic conditions in the small intestine break down the ASA to yield salicylic acid, which is absorbed into the bloodstream. The addition of a buffer reduces the irritation caused by the carboxylic acid group of the aspirin molecule. Aspirin can be produced in a one step chemical process by reacting salicylic acid with acetyl chloride, according to the reaction:

Aspirin is a white solid that is almost completely insoluble in water. We will use this physical property of our product to separate it from the final solution.If time allows, we will synthesize methyl salicylate, which is another ester of salicylic acid. It occurs in a wide range of plants and is known as ‘oil of wintergreen’. It is still used in candies and in ointments for joint and muscle pains.

Thin layer chromatography (TLC) is used to separate and identify aspirin. Small amounts of the synthesized product, starting material (salicylic acid) and commercial aspirin are placed along one edge of a chromatography plate. The plate is then placed in a container with solvent. With the plate acting like a wick, the solvent flows up the chromatogram, carrying the samples with it. Molecules that are more soluble in the solvent will move higher on the paper; the molecules that are more attracted to the plate will remain closer to the original line. After removing the plate, the samples can be detected wit UV light.

Safety Notes

1. The acetyl chloride and pyridine should only be dispensed in a hood.

2. Always wear appropriate eye protection and gloves while handling the chemicals.


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 tube.

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 acidhas 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.

Oil of wintergreen is the active ingredient in all formulations made for Pain Relief like Relispray, Fast Relief, Wintogeno, Volini. etc.


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