Synthesis of Aspirin:

Synthesis of Aspirin:
Wear goggles and carry out all operations in a fume hood.
O
O
H
O O
H
O O
O H +
H
+ O +
O
O
O
O H
Salicylic acid Acetic anhydride o-acetylsalicylic acid Acetic acid
Equipment:
250 mL round-bottom two necked flask, magnetic stirrer, internal thermometer, reflux
condenser, oil bath, 50 mL beaker, Büchner funnel, crystallization dish.
Chemicals:
Salicylic acid
Acetic anhydride
Conc. sulphuric acid
Ice water
6,9 g (0,05 mol)
4,7 mL (0,05 mol)
4 drops
10 mL
Experimental procedure:
HPLC:
At first the HPLC device has to be prepared. Therefore a machine-made RP column has to be
equilibrated with the mobile phase (detailed information about the mobile phase you will be
given in the lab).
Prepare stock solutions of salicylic acid (50mg/L) and o-acetylsalicylic (50mg/L) in methanol as
reference standards for the HPLC.

Synthesis:
6.9 g salicylic acid have to be weighed in a 250 mL round-botton two necked flask equipped
with magnetic stirring bar and reflux condenser. Add 4.7 mL acetic anhydride. The reaction
mixture should be stirred at 100°C. Bigger deviations from 100°C should be avoided. During
the reaction 50 µL of the solution should be taken off every 20 minutes and transferred into a
Eppendorfcup The cup has to be filled up with 950µL of water. 5µL of the sample have to be
injected into the HPLC to monitor the conversion.. After 1hour some drops of sulphuric acid
have to be a added to the reaction mixture.
Stop the reaction when no further formation of the acetylicsalicylic acid is observable. After
the course of contact time, the reaction mixture has to be transferred into a beaker containing
10 mL of ice water. The crude product precipitates. The beaker contents are removed by
filtration under vacuum.
Working up:
The crude product is purified by recrystallization. Therefore about 20 mL of water and 15 mL
ethanol are added to the crude product. The mixture is heated in a water bath to 70°C until the
crude product is totally dissolved. Afterwards the solution is cooled down by an ice bath. The
cristalline product is again removed by filtration/decantation, analysed in the HPLC and dried
by 50°C in a drying oven overnight. The weight of the dried product and the yield are
determined.
Characterization:
Melting Point Determination:
o-Acetylsalicylic acid (135°C)
Salicylic acid (159°C)
Dried product
HPLC:
Analyse salicylic acid and o-acetylsalicylic acid before and after recrystallization.
Monitor reaction kinetics.
Stationary Phase: Different reversed phases (machine-made)
Mobile Phase: depends on column (detailed instruction in the lab)

Fixed wavelength detection at 254nm
Flowrate: 1 mL/ min
Injectionvolume: 5µL
Questions/Assignments
1. Formulate the reaction mechanism.
2. Can you observe differences in the reaction rate after the addition of sulphuric acid
3. Why is the sulphuric acid added to the reaction mixture
4. Describe the mode of action of Aspirin in short terms.