Organic Lab #4  Synthesis of a Drug              Return
History
In the manufacture of aspirin it is necessary to start with a basic component salicylic acid. This acid was first obtained naturally from the silver birch's bark which the native people of Canada introduced to the early explorers to cure their headaches. Salicylic acid by itself has medicinal values but is extremely corrosive to the upper intestinal tract and stomach. Continued use of pure salicylic acid leads to ulcers of the intestine.

The chief component you will be using is methyl salicylate, which is the chief ester in the flavour "Oil of wintergreen". It is used to a considerable extent in candies, perfumes and in rubbing liniments. It has a mild irritating action on the skin and therefore acts as a counter-irritant to sore muscles.


Hydrolysis of the ester may be catalyzed by acid or bases but the latter is preferred because the reaction is driven to completion when sodium salicylate is produced.

The product, salicylic acid is isolated by acidifying the cold reaction mixture and collecting salicylic acid by precipitation and filtration.

Aspirin itself can be made from salicylic acid. Aspirin is the acetyl ester of the phenolic hydroxyl group in the salicylic acid molecule. (hence the abbreviation A.S.A. for acetylsalicylic acid).


Aspirin, in all it's disguises, is the second most popular over-the-counter (OTC) medication in history. It can be bought plain or buffered (Bufferin), in effervescent tablets or powders, (Alka-Seltzer or Bromo-Seltzer), alone or in combination with other analgesics, antacids, antihistamines, and decongestants, and in countless "special" remedies highly touted for arthritis or rheumatism. Sales of analgesic products already run more than $800 million a year. An amount exceeded only by that spent for cold or cough items.

Although the number and quantity of inert ingredients used in the formation and manufacture of aspirin tablets may vary among pharmaceutical companies, for most people the only practical difference among the standard 5-grain brands of aspirin tablets, plain or buffered, is price.  Any brand of this widely used drug can be an effective remedy for symptomatic relief as an antipyretic and an analgesic in a variety of common ailments. It reduces fever and aches in common respiratory infections such as colds, grippe, influenza, and relieves tension headaches and joint and muscle aches, as well as mild menstrual cramps. For some people it even works as a mild sedative.

There are some side effects to aspirin. Really severe pain, such as that experienced by migraine sufferers, is usually not relieved by aspirin, either alone or in combination with othertic and an analgesic in a variety of common ailments. It reduces fever and aches in common respiratory infections such as colds, grippe, influenza, and relieves tension headaches and joint and muscle aches, as well as mild menstrual cramps. For some people it even works as a mild sedative.

There are some side effects to aspirin. Really severe pain, such as that experienced by migraine sufferers, is usually not relieved by aspirin, either alone or in combination with otheronic use will lead to iron-deficiency anemia which is a result of small amounts of blood being lost over a long period of time.

Condensed Version of this lab:
The salicylic acid is obtained by the hydrolysis of "Oil of Wintergreen".  Once purified and dried, it will be esterified by treatment with acetic anhydride in the presence of a catalytic quantity of concentrated sulphuric acid. The role of the acid catalyst is to protonate one of the carbonyl groups of the anhydride thus rendering it more susceptible to nucleophilic attack by the oxygen of the phenolic hydroxyl group.

This lab will be done in two parts.
Part 1: Hydrolysis of the "Oil of Wintergreen"
Part 2: Esterification of salicylic acid into aspirin

Part 1: Hydrolysis of "Oil of Wintergreen"
1. Make up a solution of 5 grams of sodium hydroxide in 25 mL of water.

2. Record the mass of methyl salicylate in the data section. In at least a 100 mL round-bottomed flask, mix 3.0 g of methyl salicylate (Oil of Wintergreen) with the solution of 5 grams of sodium hydroxide in 25 mL of water.

3. Heat the mixture until boiling, then gently boil for 15 minutes more.

The sodium salt of the phenolic ester will precipitate out initially but it will redissolve as soon as the mixture is warmed.

Caution: The solution is caustic (strongly basic). Treat it with the respect it is due.

4. Allow the mixture to cool partially and then pour it into a 250 mL beaker rinsing the flask with a small quantity of water.

5. Cool the mixture in an ice-bath and acidify by careful addition of 13 mL of concentrated hydrochloric acid.

6. When precipitation is complete, collect the precipitate by filtration. Wash the product with small quantities of cold distilled water.

7. Weight a piece of filter paper. Filter your sample and place it into the oven for drying overnight.

8. After drying, weight the product and record the mass in the data table.

PART 1 DATA
Mass of methyl salicylate used : __________ g

Mass of filter paper : __________ g

Mass of filter paper and dry Salicylic acid : __________ g

Mass of Salicylic acid produced : __________ g

Calculations

1. Calculate the number of moles of methyl salicylate used.

2. Calculate the number of moles of salicylic acid produced.

3. Write a balanced equation for the reaction

4. From the balanced equation determine the number of grams of salicylic acid you should theoretically have produced.

5. Calculate the percentage yield.

Part 2: Synthesis of Aspirin
DO NOT USE YOUR SALICYLIC ACID. Package your sample of salicylic acid in a baggy and turn it in with your lab report.

Procedure
1. Mix 2.0 g of salicylic acid with 4 mL of acetic anhydride in a dry 125 mL Erlenmeyer flask.

2. Add 3-4 drops of conc. sulphuric acid.

3. Stir the mixture noting any rise in temperature.

4. Heat the reaction mixture in a water bath for 5 minutes to complete the reaction.

WARNING: THE NEXT STEP CAUSE A VIGOROUS REACTION AND CONCENTRATED ACETIC ACID FUMES.

5. Remove the flask from the water bath and without allowing it to cool add 2 mL of water in one portion. The excess acetic anhydride will vigorously decompose into acetic acid and the flask will boil.

6. When the decomposition is complete, add 35 mL of water and allow the flask to stand at room temperature until crystallization starts.

7. When crystals begin to appear, chill the flask in an ice-bath until crystallization is complete.

8. Collect the product by filtration and wash the crystal with cold distilled water.

9. To purify by recrystallization, place your crude aspirin in a 50 mL Erlenmeyer flask and dissolve it in a minimum amount of boiling propanol (Do this in a water bath).

10. Remove the flask and add warm water dropwise until the solution becomes slightly cloudy.

11. Allow the solution to cool until crystallization starts then finish crystallizing in the ice-bath.

12. Collect your product by filtration, wash with small quantities of cold water. Place in the oven and complete its drying overnight.

Part 2 DATA

Amount of Salicylic acid used : __________ g

Mass of filter paper and final product : __________ g

Mass of filter paper alone : __________ g

Mass of aspirin produced : __________ g

Calculations
1. Determine the number of moles of salicylic acid you used.

2. Determine the number of moles of aspirin you synthesized.

3. Write a balanced equation for the reaction.

4. Determine the theoretical yield of aspirin from the balanced equation.

5. Determine the percentage yield of aspirin you obtained.

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