Most drugs are chemical compounds which
are described as "organic
because they are comprised primarily of the elements carbon, hydrogen
oxygen. The present experiment will be the synthesis of a
organic compound called aspirin. The common chemical name is acetylsalicylic
Aspirin, the most widely used drug in the
world, has an interesting
history. Nearly 2500 years ago, Greeks reported that extracts of willow
and poplar bark could be used to relieve pain and symptoms of illness.
There are reports that American Indians, before the time of Columbus,
special teas made from the bark of willow trees to reduce fever. In
the Reverend Edward Stone introduced these extracts and teas to the
and in the early 1800's the active ingredient in willow bark (and in
flowers of the meadow sweet plant which had similar therapeutic
characteristics) was isolated and identified as salicylic acid (from salix,
the Latin name for the willow tree).
Although salicylic acid could be
synthesized in the laboratory and
quantities became available for therapeutic use in the mid 1800s, the
acidic properties caused irritation in the moist membranes of the
throat and stomach. In 1875, the sodium salt was introduced and
although the salt was less sour to the taste (actually it had an
sweetish taste), it did not alleviate the gastric discomfort problems.
In 1893, Felix Hoffman Jr., a chemist
working for the Bayer
in Germany, discovered a practical route for synthesizing an ester
derivative of salicylic acid, acetylsalicylic acid ("aspirin"):
Acetylsalicylic acid, a weaker acid
salicylic acid, was found
have the medicinal properties of salicylic acid without having the
taste or producing the stomach problems. The acetyl group effectively
the acidity of the drug during its ingestion and after it passes into
small intestine, it is converted back to salicylic acid where it can
the bloodstream and do its pain relieving action. Bayer called its new
product "aspirin," the name being derived from "a" for acetyl, and the
"-spir", from the Latin name Spiraea ulmaria, the meadow sweet flower,
which salicylic acid had been isolated. It was patented by Bayer in
and in 1915 Bayer Aspirin tablets became commercially available as a
prescription drug. The trademark is still owned by the Bayer A.G.
Today, aspirin is one of the most widely
pharmaceutical drug in the world. Its properties make it a powerful
(pain reliever), antipyretic (fever reducer) and anti-inflammatory
swelling) drug. Aspirin is not without its faults. It still causes some
stomach irritation in some individuals, and it has been estimated that
about 1 mL of blood is lost from the stomach lining for each gram of
consumed. Aspirin is known to interfere with normal blood clotting
actually may be a benefit in preventing heart problems). Reyes syndrome,
a rare but serious illness has been associated with aspirin, and
and teenagers should not use aspirin for flu like symptoms before
Salicylic acid reacts with acetic
anhydride according to the
Notice that this reaction does not contain a single reaction arrow,
but a double arrow. Up to this point, we have assumed that all
reactants only produce products. However, as the reactants
are used up, their concentration goes down, while the concentration of
the products increases. It turns out that the products can then
react and produce the original reactants. Because of this, it
will be very difficult to obtain a 100% yield of the desired
product. This is known as an equilibrium
reaction and there are several things we can do to help increase the
yield of final product, but that will be the focus of most of our work
in Gen Chem II.
The above reaction is an example of an
organic synthesis called esterification.
Esterification is the acid catalyzed reaction of a carboxyl
group and an -OH group of an alcohol or phenol to form a
ester. In the synthesis of aspirin the -OH group is the phenolic -OH
group attached to ring of the salicylic acid. The acetyl group,
from acetic anhydride, and the reaction is catalyzed by phosphoric
Synthesis of Aspirin:
- This lab is very time intensive and you must 'multi task' if you
are going to finish. The actual reaction to produce the aspirin
only takes a minute or two, however, there is a lot of preparation
before you are ready to run the reaction. It is important to
study the procedure before coming to lab and not just 'cookbook' it.
- Add approximately 200 mL of distilled water to your 600 mL beaker
and heat it with your hot plate until it boils.
- Construct an ice bath by filling your 450 mL beaker half way with
ice and put in just enough distilled water to cover the ice. Now
put 50-75 mL of distilled water into a clean 150 mL beaker and place
that into the ice bath. This will cool the water so it will not
dissolve your aspirin when you quantitatively transfer it from the
Erlenmeyer flask to the Buchner filter.
- You will need to thoroughly clean a 125 mL Erlenmeyer flask and
your largest test tube with soap and water. Rinse them with distilled
water and use a paper
towel to remove all visible signs of water. Use your
Bunsen burner (outer blue cone) to flame dry the Erlenmeyer flask and
the test tube.. BE
CAREFUL NOT TO BURN YOURSELF. Be sure to let the flask
and the test tube cool to room temperature and record their mass to the
nearest 0.001 g.
- Weigh out approximately 1.5 g of salicylic acid (to the
0.001 g) directly into a 125 mL Erlenmeyer flask.
It is important that no solid remains on the sides of the flask, since
any solid that is not in solution does not react and will decrease your
- Take your Erlenmeyer flask to the hood and measure out 3 mL of
acetic anhydride (~0.027 mole) with one of the 5 mL
ACETIC ANHYDRIDE IS EXTREMELY
WEAR GLOVES WHEN POURING IT AND BE VERY SURE THAT IT DOES NOT GET ON
HANDS. IF ACETIC ANHYDRIDE SHOULD COME IN CONTACT WITH THE
WASH IMMEDIATELY WITH PLENTY OF WATER FOR AT LEAST 5 (FIVE)
MINUTES. DO NOT BREATHE THE VAPOR.
- Add the acetic anhydride to the salicylic acid in the Erlenmeyer
in such a way that any salicylic acid clinging to the inside of the
is rinsed down into the bottom. Swirl the flask gently.
- After all the acetic anhydride has been added, add 10 drops of concentrated phosphoric
acid (H3PO4 - serves as a catalyst) and gently
swirl the mixture.
- Place the flask
in the hot water bath for approximately 5 minutes, swirling
occasionally. All of the
acid should have reacted by this time, leaving a clear colorless
of the final product and any excess acetic anhydride.
- While the reaction mixture is still hot, add 3 mL of distilled
THE DECOMPOSITION OF THE EXCESS ACETIC
ANHYDRIDE IS EXOTHERMIC. HOT VAPOR COULD BE EVOLVED AND
MAY OCCUR. STAND BACK.
- When the decomposition is complete, add an additional 25 mL of
Use some of it to rinse down the inside of the flask. Swirl the
to achieve thorough mixing.
- Add a handful or two of ice to your 600 mL beaker that contains
the hot water. It is now an ice bath.
- Place the Erlenmeyer flask in this ice water bath
and swirl occasionally. Allow the flask to stand
the ice bath until crystallization is complete (about 15 minutes, you
may need to add more ice during this time).
- Filter the crude product using your Buchner filtration
apparatus and wash the aspirin three times with
portions of cold water (this will remove any impurities). After
washing, pull air through the product
to remove excess moisture. The longer you allow the product to
air dry with the suction on, the better your yield will be.
- While the aspirin is air drying, clean and dry your watch
glass. Put a distinguishing mark on it and weigh it (to the
nearest 0.001 g).
- Transfer your product to your weighed watch glass and place
oven (place it on one of the shelves, NOT on the bottom of the oven, at
less than 90°C) for 10-15 minutes. Remove your watch
glass from the oven and let it cool to room temperature. Weigh
watch glass and product. Carefully break up any clumps to
facilitate drying and put the
watch glass back in the oven for another 10
it, let it cool, and weigh again. If the two weights agree to
or less, then your product is dry. If the two weights to not
to 0.01g, then you will need to continue the heating, cooling, and
until two consecutive weights are within 0.01g.
- Once your product is
dry, quantitatively transfer it to the test tube you cleaned earlier
and use a cork to seal it.
- Create a label with the following information:: Your Name, Date,
Product Name, Actual Weight of Product in the test tube, Theoretical
and % Yield.
- Affix the label to the corked test tube and turn it in to your
instructor. You will be testing the purity of this product in
next week's lab.
Calculation of Yield:
At this point, you ought to be able to calculate the theoretical
yield of a reaction in your sleep! Start by converting your grams
of salicylic acid into moles using its molecular weight, then use the
stoichiometry of the balanced chemical reaction to covert your moles of
salicylic acid into moles of acetylsalicyclic acid, and then finally
use the molecular weight of acetylsalicyclic acid to convert the moles
to grams. This is the theoretical amount of aspirin you should
generate if everything went perfectly. Then the % yield is your
actual yield divided by the theoretical yield, times 100:
% yield = 100 x (actual yield in
yield in grams)
(Updated 3/20/13 by C.R.