SYNTHESIS OF ASPIRIN

(ACETYL SALICYLIC ACID)

INTRODUCTION
Aspirin (acetylsalicylic acid) is a synthetic
organic chemical derived from salicylic acid.
Salicylic acid is a natural product found in the
bark of the willow tree and was used by the
ancient Greeks and Native Americans, among
others, to counter fever and pain. Salicylic
acid, the active ingredient of Aspirin was first
isolated from the bark in 1763 by Edward
Stone in 1716.
However, salicylic acid is
bitter and irritates the stomach.
A German chemist named Felix Hoffman is
credited with being the first to synthesize
aspirin in 1897. It is on the WHO Model List
of Essential Medicines, the most important
medications needed in the basic health
system. The name given for Hoffman's new
compound was A-spirin. Apparently this
comes
from
acetylation
(A-),
together
with Spirin, part of the name for Meadowsweet (Spiraea ulmaria), a plant rich in
salicylates. Aspirin is classified under the
category of non-steroidal anti-inflammatory
drugs (NSAIDs), and indicated in conditions
including fever, pain, rheumatic fever, and
inflammatory diseases. Lower doses of
aspirin have also shown to reduce the risk of
death from heart attack or risk of stroke.
Friedrich Bayer, the employer of Hoffman,
patented the name and began marketing the
product in 1899. It was a huge success and

sales grew rapidly. Bayer's company set up

by himself, is generally reckoned to have
been the first pharmaceutical company, and
the production of aspirin is generally
accepted to have laid the foundation of the
modern pharmaceutical industry.

SYNTHESIS
The synthesis of aspirin is classified as an
esterification
reaction.
Salicylic
acid is
treated with acetic anhydride, an acid
derivative, causing a chemical reaction that
turns salicylic acid's hydroxyl group into
an ester group (R-OH R-OCOCH3). This
process yields aspirin and acetic acid, which
is considered a byproduct of this reaction.
Small
amounts
of
sulfuric
acid (and
occasionally phosphoric acid) are almost
always used as a catalyst.

REACTION MECHANISM

AIM
Synthesis of crude aspirin in lab scale using
salicylic acid and acetic anhydride using
concentrated sulphuric acid as a catalyst.

APPARATUS REQUIRED
Beaker, glass rod, conical flask, water, hot
water bath, cold water bath, Erlenmeyer flask
etc.

CHEMICALS REQUIRED
Salicylic acid, acetic anhydride, phosphoric
acid.

THEORY
In this experiment you will synthesize aspirin
(acetylsalicylic acid, C9H8O4), purify it, and
determine the percent yield. The purity of
the product will be confirmed by qualitative
analysis and by measuring its melting point
range.
The reaction that is used for the synthesis is
shown below. In this reaction, an excess of
acetic anhydride (C4H6O3) is added to a
measured mass of salicylic acid (C 7H6O3) in
the presence of a catalyst, sulfuric acid
(H2SO4). The mixture is heated to form the
acetylsalicylic acid (C9H8O4) and acetic acid
(C2H4O2). After the reaction takes place,

water is added to destroy the excess acetic

anhydride and
cause
the
product to
crystallize. The aspirin is then collected,
purified by re-crystallization, and its melting
temperature measured.

PROCEDURE
1.
Weigh 2 grams of salicylic acid using
an electronic balance and Record the
weight.
2.
Transfer the salicylic acid completely
to a clean, dry 125 mL Erlenmeyer flask.
3.
Measure and take 4.0 mL of acetic
anhydride into the 125 mL Erlenmeyer
flask using a 10 mL graduated cylinder.
4.
Now carefully add 5 drops of
concentrated sulfuric acid
to the
Erlenmeyer flask using the dropper. Be
careful not to let the sulfuric acid drop
anywhere other than into the flask. Swirl
the flask to help mix the contents. Do not

add the sulfuric acid before the acetic

anhydride.
5.
Add water to 500 ml beaker and heat
it to boiling temperature. Fix the
Erlenmeyer flask to the ring stand in such
a way that the reaction mixture in the
flask is placed in the beaker containing
boiling water for about 10 minutes. The
reaction mixture turns into a yellowish
brown solution.
6.
Add 10ml of cold water to the reaction
mixture and keep it in a cold chain and
allow it to get crystallized.
7.
Weigh a piece of filter paper on a
watch glass. Record the weight of the
paper + the Place the weighed Whatman
filter paper 1 in the Buchner funnel. Wet
the paper with a small amount of water
using your wash bottle to seal the paper
to the funnel surface.
8.
Turn on the aspirator. Swirl the flask
and pour its contents carefully onto the
center of the filter paper. Use a stirring
rod to assist in getting the entire solid
out of the flask.
9.
When the entire solid has been
captured on the filter paper and the liquid
has all been sucked through, wash the
product by slowly pouring a measured

amount of ice water, not to exceed 15 mL,

surface of the precipitate. Decrease the
aspirator flow and adjust it so the liquid is
removed at a very slow drop rate. This is
to wash the precipitate to remove any
remaining acetic acid.
10.
Transfer the crystals obtained (after
filtration) into an Erlenmeyer flask add
10ml of ethanol for recrystallization. Then
add 60ml of warm water and stir it
thoroughly to dissolve the crystals.
11.
Put it in cold chain for crystallization
and repeat the procedure as in steps 7-9.
12.
Collect and weigh the crystals of
acetyl salicylic acid formed. Take a very
small amount (50 mg) of the sample to
perform heat test.

PURITY TEST: HEATING TEST

Aspirin is known to be unstable in the
presence
of
moisture
at
elevated
temperatures. At those temperatures, aspirin
hydrolyzes (i.e., reacts with water) to
decompose into salicylic acid and acetic acid.
Acetic acid has a characteristic pungent
smell. The detection of this odor depends on
the assumption that all of the acetic acid
(which was both a product in the reaction
and produced from the hydrolysis of excess
acetic anhydride) was removed from the
sample in the final washing process. To

another clean small test tube, add a few

crystals (about 10 mg) of your product,
again, from the 50 mg sample on the watch
glass in step 12, above. Heat it gently to
melting. Remove from the heat and note the
odor of the escaping vapor by carefully
fanning the vapors with your hand toward
your nose. Comment on the odor and on the
implications on the purity of your product.

OBSERVATIONS
Grams of salicylic acid (C7H6O3) =
Moles of salicylic acid =
Theoretical yield of aspirin in grams (C 9H8O4)
=
Actual yield of aspirin in grams (C9H8O4) =
Percent yield aspirin (C9H8O4) =
C7H6O3 + C4H6O3 C9H8O4 + C2H4O2
Salicylic
Acetic
Acetyl salicylic
acid
acid
anhydride
acid

CALCULATIONS

Acetic

PRECAUTIONS
Wear goggles throughout this experiment.
This experiment uses salicylic acid, acetic
anhydride and phosphoric acid. The salicylic
acid and aspirin may cause irritation to your
skin or eyes, but are basically not
hazardous.
An excess of these can be disposed of in the
sink or, if packaged, in the trash.
If you spill some, wipe it up with a wet
paper towel and throw the towel in the
trash.
The acetic anhydride and sulfuric acid can
cause bad burns.
Wear gloves when using these chemicals.
Excess chemicals must be disposed of in the
plastic tub of water. This will convert the
acetic anhydride to vinegar and dilute
sulfuric acid.

CONCLUSION
The aspirin obtained is not pure as presence
of acetic acid is evident by the heat test. The
acetic acid in the mixture can be separated
industrially.