Experiment (18):

Preparation of aspirin and oil of

wintergreen
A)Aspirin

OH
O

OH
+ HC
3
salicylic acid
SA
(o-hydroxybenzoic acid)

O
O

CH3

OH

O
O

H2SO4

CH3
+ CH3COOH

Esterification

acetic anhydride

acetic acid

acetyl salicylic acid

ASA

Salicylic acid is the active ingredient in aspirin, but it is an extremely

harsh analgesic that is irritating for the mucous membranes and stomach
due to its strongly acidic nature. An acetyl group is added to buffer the
effect of the acid.
Biological activity: Analgesic (pain killer)
Antipyretic (fever reducer)
Side effects: Gastric irritation and bleeding
Commercial aspirin tablets usually contain 300 to 400 mg of ASA (max
strength tablet is 500 mg), buffers and sometimes caffeine, hold together
with starch binder.
SA contains both acidic and phenolic functional groups and can be
esterified on both groups to give different products in each case.
O

OCH3
OH

mehtyl sallicylate

OH
OH H3C

CH3OH

salicylic acid

OH

CH3

O
O C
CH3

acetyl salicylic acid

Methyl salicylate is the major component in oil of wintergreen.

Formulations that contain high concentrations of aspirin often smells

like vinegar. This is because aspirin can hydrolyze in moist conditions
yielding salicylic and acetic acids.(reaction)

Mechanism of the reaction:

STEP (1) Protonation of acetic anhydride by the acidic catalyst

O
H O S O H
O
O
H3C

H3C

CH3
H3C

H3C

O H

O H

O H

CH3

O
O S O H
O

CH3

H3C

O H

CH3

CH3

STEP (2) Nucleophilic attack by the phenolic O on the partial

positive C atom

COOH

O H

OH
H3C

COOH

O
C

O
CH3

O H

CH3

CH3

HSO4
COOH
O

O H
C
H3C

O
H

COOH

O
C

O
CH3

O
C
CH3

O
+

HO
H

+ H2SO4
CH3

Identification:
The produced ASA can be differentiated from SA by phenol tests
COOH
OH

COOH O
O C
CH3

OH
+ FeCl3

red, blue,green or purple complex

ferric chloride

+ HNO2

blue color

nitrous acid

Procedure:
1. Mix 1 g of salicylic acid and 2 ml of acetic anhydride in a round
bottom flask. Be sure to do this in the hood and don't let the acetic
anhydride contact your skin or get vapors into your eyes.
2. Carefully add 2 ml of sulfuric acid (the catalyst) to the flask and swirl
the mixture.
3. Fit a reflux condenser to the flask and heat the mixture for about 10
minutes.
4. After heating, cautiously add 3-4 drops of water.
5. Transfer it to a beaker then add 4 ml of water and cool in ice bath. If
crystals did not appear, scratch the walls of the flask with a stirring
rod to induce crystallization.
6. Filter the solid aspirin. Wash it with 2 ml of chilled water.
7. Place the filter paper with the product on a watch glass and put it in
the oven at 100 oC until dry.

B)Oil of wintergreen

OH
OH
+

salicylic acid

CH3OH
methanol

H2SO4

OCH3
OH
+ H2O

methyl salicylate

Procedure:
1. Place 0.2 g of salicylic acid into a clean, dry test tube.
2. Add 6 drops of methanol and agitate the tube until the contents are
well mixed.
3. Then add 1 drop of concentrated sulfuric acid.
4. Agitate the tube contents and place the tube in a beaker of boiling
water for 3 minutes.
5. After heating is complete remove the tube from the bath and add 15
drops of water to it.
6. Cautiously note the odor of the products in the test tube. Record the
odor.