(Woods)

Synthesis of Aspirin

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Discussion: In the synthesis of aspirin, salicylic acid behaves as an alcohol and reacts with acetic anhydride (with a small amount of sulfuric acid acting as a catalyst) to produce an ester (alcohol + carboxylic acid).
Salicylic Acid + Acetic Anhydride Aspirin + H2O

After the reaction has subsided, add 40 ml of d-H2O to the flask and remove it from the ring stand. Allow the solution to cool for about 10 minutes with periodic stirring. As crystals of aspirin begin to form, the solution will become cloudy. Complete the crystallization by cooling with occasional stirring. Weigh the dry filter paper. Collect the crude aspirin by vacuum filtration taking care to clamp the filter flask to a ring stand. Remember to first moisten the pre-weighed filter paper with water. Wash the crystals in the Buchner funnel with 5 ml of ice-cold d-H2O, and suction dry the crude product for 1 to 2 minutes. Remove a small portion of the Crude aspirin (about the size of a match head), label it accordingly, and set it aside. You will later compare the purity of the crude sample with the recrystallized product.

O O OH H 3C OH Salicylic Acid O CH 3 Acetic Anhydride O

Each molecule of acetic anhydride forms two molecules of acetic acid in its reaction with water. The acetic acid couples with the -OH group on the salicylic acid molecule in a dehydration reaction to produce Aspirin and water. The water produced reacts further with the acetic anhydride to perpetuate the reaction. Assume that salicylic acid is the limiting reagent and that the theoretical yield of aspirin depends on the amount of salicylic acid used. Aspirin has a low solubility in cold water, so excess reactants can be washed away with cold water, which leaves the Aspirin free of any excess acid. Acetic anhydride must be handled with considerable caution. It is very corrosive and has an extremely disagreeable odor. The stock bottle must be kept in the fume hood. If you should accidentally spill some on your skin or clothing, flush it with water and apply sodium bicarbonate. Salicylic acid is less hazardous. It is the active ingredient in such topical rubbing medicines as Absorbine Jr. Procedures: I) Synthesis Place a 400 ml beaker of water (about half full) on a hot plate and heat to a gentle boil. In a 125 ml Erlenmeyer flask, weigh (accurate to the nearest 0.01 g) between 1.8 and 2.2 g of salicylic acid. Remember to either: A) Weigh the empty beaker first and then get the total weight, or B) Tare the empty beaker and add the compound to the desired weight. Caution: Acetic Anhydride reacts vigorously with water and must be handled with care. Add 5 ml of acetic anhydride to the flask, and then add 5 drops of concentrated sulfuric acid (a catalyst). Swirl the flask to mix the reagents and then clamp it to a ring stand. Lower the flask carefully into the beaker of boiling water, and heat for 8-10 minutes. Turn off the hot plate, raise the flask out of the water and carefully add 2 ml of d-H2O to the flask. Water reacts with excess acetic anhydride, converting it into acetic acid.

II) Purification The crude aspirin contains salicylic acid as its principal impurity, and recrystallization gives us a convenient purification method. Transfer the aspirin to a 125 ml Erlenmeyer flask and add 6 ml of ethanol. Gently warm the flask on a hot plate until the aspirin completely dissolves. Remove the flask from the hot plate immediately when the compound dissolves. Separately, add 5 portions of 5 ml d-H2O (a total of 25 ml), swirling the flask briefly after each increment. The H2O should induce crystallization of the aspirin. Cool the mixture for 10 minutes in an ice bath with occasional stirring. Collect the purified aspirin by vacuum filtration Remember to weigh the dry filter. After pouring the aspirin solution into the filter, spray about 3 mL of ice-cold d-H2O on the sides of the empty flask to capture any remaining crystals. Swirl the solution and pour through the funnel. Repeat this with another 3 mL of ice-cold d-H2O. Allow the aspirin to suction dry for about 5 minutes. Place in a drying oven at a low setting to finish drying. Weigh the purified aspirin. Test the melting point of both the crude and recrystallized product; record. SAVE your aspirin for the next lab.
Adapted from the Pierce chemistry lab manual

Chem-131 Lab-05 09-4 Synthesis Of Aspirin

(Woods)

Synthesis of Aspirin

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Name: __________________________________________________ The stoichiometric equations below show you how to obtain the theoretical amount of product (using the correct mole to mole ratio for the two compounds), and how to obtain the % Error or % Yield.

( 000.0 g A ) x

1 mol A Y mol B 000.0 g x = 000.0 g B x 000.0 g X mol A 1 mol B

Theoretical - Experimental Theoretical Salicylic Acid

x 100 = % Error

Experimental x 100 = % Yield Theoretical

_______________ g _______________ g

Theoretical yield of Aspirin (Show calculations)

Actual Yield of Aspirin % Yield of Aspirin (Show calculations)

_______________ g _______________ %

Melting Point of Crude Product Melting Point of Final Product Melting Point of Aspirin from CRC Handbook

_______________ C _______________ C _______________ C

Write out the structural formula of Aspirin. Circle the ester functional group. Circle and label the other functional groups which are present.

Chem-131 Lab-05 09-4 Synthesis Of Aspirin