(ASA or Aspirin)
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 will use the first reaction
in order to prepare aspirin.
Salicylic acid will not react significantly with acetic acid to produce
Acetic acid anhydride, however, is more reactive than acetic acid because
its acetate group (CH3CO2-1) is a much better leaving group than the HO-1
from the 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 will 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.
McMurry, J., Organic Chemistry, 8th Ed., pp 830 and 835 (7th Ed, pp 802 &
J. Beran, Lab Manual for Principles of General Chemistry, 9th and 8th Ed.,
Experiment 19, pg 231.
phenol, carboxylic acid, ester, acid anhydride, macromolecule
Compound, Reaction, and Yield Data
Provide systematic names for the reactant and product in the substance
Provide tabulated and experimental melting ranges for product. Report mass
and moles for the reactant and product, and calculate yield % on a molar
The mechanism is called nucleophilic acyl substitution.
It is similar, but not identical, to the hydrolysis on pg 830 in McMurry
The electrophile is an acid anhydride, not an acid chloride.
The entering nucleophile is salicylic acid (its phenol O), 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, rather than chloride.
No base is involved. Provide structures of all intermediates in your lab
2.0 g salicylic acid
5.0 mL acetic anhydride
5 drops concentrated H2SO4
25 ml saturated NaHCO3(aq)
3.5 mL concentrated HCl
one 125-mL Erlenmeyer flask
70-mm filter paper and Buchner funnel
250-mL or 500-ml vacuum flask
Part A: Synthesis
1. Weigh 2.0 g of salicylic acid crystals. Place in a 125-ml Erlenmeyer
2. In a hood, slowly add 5.0 ml of acetic anhydride and
5 drops of concentrated sulfuric acid to the flask
Caution – Concentrated H2SO4 solutions are corrosive and cause acid
Carboxylic acid anhydrides are corrosive and extremely
They will cause burns, and they have a strong vinegar-like odor.
Use gloves and avoid all contact with skin, eyes, and
Perform entire step in fume hood.
3. Swirl the flask gently until the salicylic acid has completely
If mixture solidifies completely, proceed to step 4.
4. Heat the flask in a boiling water bath (100 oC) for a minimum of 10
Clamp the flask to a stand so that it does not fall over into the water
5. Allow the flask to cool slightly, and then place in an ice bath to
acetylsalicylic acid. If necessary, gently scratch the bottom of the
flask with a glass rod (to initiate crystal formation on microscopic
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.
Also, place a beaker of DI water in the ice bath and cool to < 5 oC for
use in later steps.
7. Collect the product by vacuum filtration using a 70-mm filter paper and
Buchner funnel. 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 5 – 10 ml of 5 oC DI
Then, apply vacuum to the crystals for 30 seconds to remove all of the
Dispose of filtrate in the appropriately labeled waste jar.
Part B: Purification
1. Transfer the crude solid to a 150-ml beaker. Add 25 ml of saturated
NaHCO3(aq) solution. Stir until all signs of reaction have ceased.
(Listen to fizzing.)
2. Vacuum filter the solution to remove all solid polymeric by-product.
3. Retain the filtrate! It contains the product in solution.
Dispose of solid in the appropriately labeled waste jar, and discard the
4. Place 10 ml of DI water in a 150-ml beaker, and place the beaker in an
Slowly add 3.5 ml of concentrated hydrochloric acid.
Caution – Concentrated HCl solutions and vapors are corrosive and cause
Use gloves and avoid all contact with skin, eyes,
5. Carefully, and slowly, pour the filtrate into the acid mixture while
The aspirin should precipitate out of this solution.
If not, ensure that the solution is acidic with blue litmus or pH paper.
Cool the mixture in an ice bath to complete the crystallization.
6. Vacuum filter to collect the crystals using a weighed 70-mm filter paper
in a Buchner funnel. Rinse the beaker and the Buchner funnel with 5 – 10
ml of 5 oC DI water to maximize product yield. Dispose of filtrate in
the appropriately labeled waste jar.
7. Dry the product in the oven (60 oC for 15 minutes), then weigh the dried
Obtain the melting range as well as the decomposition range, which is
only slightly higher than the melting range.
Dispose of product in the appropriately labeled waste jar, and discard
the filter paper.
1. Salicylic acid can be used to create two different types of esters.
Using the balanced reactions in the background section, and Figure 21.4
in McMurry (pg 825 in 8e), explain what happens at each of salicylic
acid’s two functional groups.
2. Two salicylic acid molecules can bond together when the phenolic OH of
one molecule reacts with the carboxylic acid COOH of the other.
Repeated reactions can cause a polymer or large macromolecule to be
created. Provide balanced reactions that show how four or more molecules
can bond together in a single chain.
3. What does anhydride mean? What would happen to the acetic anhydride if
water was present in the reaction mixture? See reactions of acid
anhydrides in McMurry, section 21.5 (pg 835). How would this affect the
See paragraph 2 on page 1 of this handout.
4. Because water is polar, it dissolves ions very well, but not organic
compounds. As a result, the solid product dissolves in basic solution
and then recrystallizes in acid solution. Use structural formulas to
depict balanced acid-base reactions of the solid aspirin product with
HCO3-1 and of the dissolved anion with H+. Include all (s) and (aq)
5. What substance are you “listening” for when NaHCO3 is added in step B1?
Provide a balanced decomposition reaction for the HCO3- ion with H+.
Include phase subscripts: (aq), (liq), and (g).