Synthesis and purification of acetylsalicylic acid

Synthesis of Acetylsalicylic Acid

Background Salicylic acid is a phenol as well as a carboxylic acid. It can therefore undergo two different types of esterification reactions, creating an ester either with the hydroxyl or with the acid. In the presence of acetic anhydride, acetylsalicylic acid (aspirin or ASA) is formed. Correspondingly, an excess of methanol will form methyl salicylate, which is also an analgesic. In this experiment, we shall use the former reaction to prepare aspirin. Salicylic acid will not react significantly with acetic acid to produce aspirin.

Acetic acid anhydride, however, is more reactive than acetic acid because the acetoxy group (-O2CCH3) is a much better leaving group than the OH- of acetic acid. The reaction has one complication, however, in that an esterification can occur between the phenol and acid portion of adjacent salicylic acid molecules. Further, more molecules can bind to the remaining free substituents on these molecules to create a macromolecule, or polymer. The polymer is formed as a by-product. Acetylsalicylic acid will react with sodium bicarbonate to form a water-soluble sodium salt, whereas the polymer remains insoluble.

This difference can be used to purify the aspirin product. The most likely impurity in the final product is salicylic acid, which can be either unconsumed reactant, or the result of hydrolysis of the aspirin product. Salicylic acid is removed during the purification steps as well. Salicylic acid, like most phenols, forms a highly colored complex with ferric chloride, and is easily detected. Aspirin does not form the colored complex because the hydroxyl has been acetylated. [pic]

Procedure Synthesis

1. Weigh 2. 0 g of salicylic acid crystals, and place them in a 125-ml Erlenmeyer flask. (If mixture solidifies completely, proceed to step 2. )
2. Add 5 ml of acetic anhydride and 5 drops of concentrated sulfuric acid to the flask
3. Swirl the flask gently until the salicylic acid has completely dissolved.
4. Heat the flask in a boiling water bath (100oC) for at least 10 minutes.
5. Allow the flask to cool at room temperature, during which time the acetylsalicylic acid should begin to crystallize from the reaction mixture. If it does not, then scratch the bottom of the flask with a glass rod, and cool the mixture slightly in an ice bath.
6. After crystals have formed, add 50 ml of DI water, and cool the mixture in an ice bath. Do not add water until crystallization is complete.
7. Collect the product by vacuum filtration. The filtrate can be used to rinse the Erlenmeyer flask repeatedly until all of the crystals have been collected.
8. Rinse the crystals collected in the funnel with 5oC DI water. Use an ice bath to cool the DI water. Finally, draw air through the crystals using the vacuum to remove all of the liquid. Put the filtrate in the proper waste jar.

Purification

1. Transfer the crude solid to a 150-ml beaker and add 25 ml of a saturated aqueous bicarbonate solution. Stir until all signs of the reaction have ceased. (LISTEN! )
2. Vacuum filter the solution. Any polymeric by-product will be filtered out. Retain the filtrate; it contains the product in solution.
3. Rinse the beaker and the Buchner funnel with 5oC DI water.
4. Prepare a mixture of 3. 5 ml of concentrated hydrochloric acid and 10 ml of water in a 150-ml beaker.
5. Carefully, and slowly, pour the filtrate, a small amount at a time, into the acid mixture while stirring. The aspirin should precipitate out of this solution. Ensure that the solution is acidic with blue litmus or pH paper.
6. Cool the mixture in an ice bath, then vacuum filter to collect the crystals. Dry the product in the oven (60oC for 15 minutes). Put the filtrate in the waste beaker.
7. Weigh the product, and calculate the yield. Also, determine the melting point and compare it with tabulated data.

Background Reading J. Beran, Lab Manual for Principles of General Chemistry, 7th Ed. Experiment 28, pg 323. McMurry, J. , Organic Chemistry, 7th Ed, pp 802 & 806-7 (6th Ed, pg 784 & 788-9).  Data To Collect Provide systematic names for the reactant and product in the substance section. Provide tabulated and experimental MP’s for product. Report mass and moles for the reactant and product, and calculate yield % on a molar basis. Mechanism The mechanism is called nucleophilic acyl substitution. It is similar, but not identical, to the hydrolysis on pg 802. The entering nucleophile is salicylic acid, not water. On the resulting tetrahedral intermediate, the H from salicylic acid moves to the middle O on the anhydride. Finally, the leaving group is acetic acid, not chloride. No base is involved. Provide structures of all intermediates in your lab report.

Post-Lab Questions

1. How can salicylic acid be used to create two different types of esters? Provide balanced reactions.
2. How can salicylic acid’s two functional groups cause a polymer or large macromolecule to be created? Provide balanced reactions.
3. What would happen if water were in the synthesis mixture? How would it affect the acetic anhydride and the product?
4. How does the product dissolve in base and recrystallize in acid? Provide balanced reactions.
5. What substance are you “listening” for when NaHCO3 is added? Provide a balanced decomposition reaction for the HCO3- ion.