Reminder: These notes are meant to supplement, not replace, the textbook and laboratory manual.

Synthesis of Aspirin
1. Here is a balanced equation for the synthesis of aspirin:
O
CO2 H CO2 H
O O ||
OH || || H3 PO 4 O—C—CH 3 O
+ CH3 —C—O—C—CH 3 ||
+ CH3 COH
acetic
salicylic anhydride aspirin acetic
acid acid
Functional groups involved: Salicylic acid is both a carboxylic acid and a phenol. Acetic
anhydride is an anhydride. Aspirin is a carboxylic acid and an ester. Acetic acid is a
carboxylic acid.

* The mechanism of this reaction is:

O O HO O
|| || || ||
H3 PO 4 + CH3 —C—O—C—CH 3 H2 PO 4 + CH3 —C—O—C—CH 3

OH O
CO2 H CO2 H
HO O | ||
OH || || O—C—O—C—CH 3
+ CH3 —C—O—C—CH 3 | |
H CH 3

OH O OH O
CO2 H CO2 H
| || | ||
O—C—O—C—CH 3 O—C—O—C—CH 3
| | | |
H CH 3 H3 C H

OH O OH O
CO2 H CO2 H
| || || ||
O—C—O—C—CH 3 O—C—CH 3 + CH3 COH
| |
H3 C H
OH O
CO2 H CO2 H
|| ||
O—C—CH 3 + H2 PO 4 O—C—CH 3 + H3 PO 4

2. You are required to calculate a percent yield for this experiment. For instructions and
examples on how to do this, see the sample problems with solutions on this web site.
3. The organic reactants salicylic acid and acetic anhydride and the organic products aspirin
(acetylsalicylic acid) and acetic acid are shown in the equation in #1 above. The wash
solvents ethanol and acetone are:
O
||
CH3 CH2 OH CH3 CCH3
ethanol acetone

4. Safety considerations for this experiment include:

Among the catalysts, sulfuric acid and phosphoric acid are highly corrosive.
Pyridine is toxic and has a horrible smell, and boron trifluoride etherate isn't good for you
either. Handle them with care, in the fume hood.
All of the organic compounds involved in this experiment are at least slightly toxic,
and the solvents (other than water) are highly flammable. Handle them with the usual
precautions.
You will be using a sand bath or a hot plate and a Mel-Temp apparatus during this
experiment. Portions of these become very hot during normal use. Handle them with care,
and don't touch the hot parts. They are also electrical; do not use water or other solvents
carelessly around them. If the wires on any electrical apparatus are frayed, the shock and
fire hazards are multiplied; do not use the apparatus.