1. The acetyl chloride and pyridine should only be dispensed in a hood.

2. Always wear appropriate eye protection and gloves while handling the
chemicals.
Procedure
Part A- Preparation of Aspirin
1. Place 150 mg (0.001 mol) of salicylic acid in a 10 mL test tube and add
0.1 mL of
pyridine (just sufficient to dissolve it) while the tube rests in a ice-cold
water bath.
Keep the test tube in a hood while you are doing this! Pyridine smells
very bad,
and you may want to wear latex gloves to avoid getting it on your skin.

2. For the next step, be sure that the open end of the tube is not pointing
toward you
or anybody else. Occasionally the reaction goes quickly and shoots
material out
of the tube! Add one-tenth milliliter of acetyl chloride (slight excess
over 0.001
mol )in one portion to the test tube. Again, keep the mixture in a hood!

3. The mixture becomes viscous at this stage. Let the mixture sit in a
beaker of cold
Water bath for 15 min. – it does not need to be in the hood. While
waiting, set up
a vacuum filter flask with a Büchner funnel and a piece of filter paper
which just
fits the bottom of the funnel, as shown in the figure below. Attach a
thick rubber
tube to an aspirator mounted on a water faucet

4. Now add 5 mL of cold water to the test tube and cap it with a rubber
stopper.
Shake the mixture. Do this cautiously at first until you are sure that no
violent
reaction is occurring.The mixture should turn cloudy. Shaking is
continued until a
white product appears (it may takes several minutes, be patient!)

5. Turn on the water faucet all the way and check to be sure you have
good suction.
Break the suction by disconnecting the tube from the flask (leave the
water
running). Pour the mixture into the funnel, trying to get as much of the
solid
 transferred as possible. Connect the hose and apply full suction for at
least 30
seconds. Wash the crystals with cold water. Break the suction. Do not
just turn off
the water; this may create a back-flow of the water into your filter flask.
Dry them
on the filter paper for about 5 min.

Part B- Recrystallization
6. Carefully scrape off most of your crystals into a 50 mL beaker. SAVE
THE
FILTER PAPER! Add about 3 mL of cold water and place the mixture on
a hot
plate in a hood. Heat until all of the crystals dissolve (check with the
instructor if
complete solution does not seem to be happening.) When the crystals
are
completely dissolved in the hot solution, remove the beaker and allow
it to cool.
You should see nice crystals of aspirin beginning to form! When the
recrystallization is complete, filter again, and dry. SAVE THE FILTER
PAPER for
the next step!

Part C- Oil of Wintergreen

1. Place 1.00 gram of salicylic acid in a test tube. (record the actual mass
used)
2. Add 5 ml of methyl alcohol and 3 drops of concentrated sulfuric acid.
3. Heat this mixture in a boiling water bath for 15 min.
4. Note the odor of the liquid in your tube, remember to WAFT.
Results
Calculate the theoretical yield of aspirin in grams. Use this to calculate the
% yield for this
experiment.
% yield = actual yield (grams) x 100
theoretical yield (grams)
 Experimental
Your team will need to split into two groups. One group should be responsible for synthesizing
the aspirin while the other group prepares the standard solutions and plots the curve you will
use to analyze your product’s purity using absorption spectrometry.
Part I: Preparation of aspirin
Fill a large 600-mL beaker with about 450-500 mL of water and begin heating this over a Bunsen
burner using a ring stand and wire gauze. You will need the water to be around 75°C.
Fill your squirt bottle with deionized water and place it inside a large beaker of ice water to chill.
Now weigh approximately 2.0 grams (record the exact mass) of salicylic acid into a 50 mL
Erlenmeyer flask. Measure out 5.0 mL of acetic anhydride in your graduated cylinder and pour it
into the flask in such a way as to wash any crystals on the walls down into the bottom. Add five
drops of 85% phosphoric acid to serve as a catalyst.

Caution: both the acetic anhydride and the 85% phosphoric acid can cause chemical burns. Be
sure to handle these substances with caution and wash your hands after use.

Once the temperature of the water bath reaches 75°C, clamp the flask in place inside the water
bath and heat for at least 15 minutes. Stir occasionally. Maintain the temperature of the water at
75°C throughout this process.

At the end of this time cautiously add about 2 mL of deionized water to the flask to decompose
any excess acetic anhydride. Caution: There may be some hot acetic acid vapors evolved as a
result of this decomposition.

When the liquid has stopped giving off vapors, remove the flask from the water bath and add 20
mL more of water. Let the flask cool on the bench for about 5 minutes, during which time you
should see crystals of aspirin beginning to form.

After 5 minutes, place the flask in a beaker of ice water to hasten the crystallization and increase
the yield of products. Allow the flask to cool in the ice water for an additional 5 – 10 minutes.
If crystals are slow to form it may help to gently scratch the inside of the flask with a glass
stirring rod.
Collect the aspirin crystals by filtering the cold liquid through a Buchner funnel using suction. Be
sure to weigh the dry filter paper first. Use the chilled water from your squirt bottle to wash any
remaining crystals from your flask into the funnel while filtering.
Rinse the crystals several times using the chilled water from your squirt bottle to help remove
any impurities. Finally, draw air through the filter for several minutes to help hasten drying of the
crystals.

Place the filter paper under a heat lamp to dry. Allow the crystals to dry for at least 30 minutes.
Weigh the product and then heat for an additional 10 minutes. The crystals are dry when
subsequent weighings remain the same (i.e. all the water has been evaporated). The dry crystals
should have a light flaky appearance. Clumpy crystals suggest that they are still wet and need
further drying. It may help speed drying to break up clumps of crystals using your stirring rod.

Part II: Testing the purity

Once the crystals are completely dry you may test the purity using the Mel-Temp apparatus.
Your instructor will demonstrate the proper use of this device.
You will also need to determine the purity of your crystals using absorption spectrometry. For
this you will need to make a set of five or more standard salicylic acid solutions in the range of
10-3 to 10-4 M. You will need to prepare these standards using dilutions in the same way the
standards were prepared in the Manganese lab (refer to the information below, the Manganese
lab on-line handout and the on-line prelab for this experiment for how to prepare these
solutions).

In this case the samples will be purple and so we will measure all the data at a wavelength of 525
nm.
For this experiment we will use 50.00 mL volumetric flasks. Obtain 2 from the stockroom.
Use a few mL of acetone (not water) to rinse the flasks if necessary.
Salicylic acid is not soluble in water, but salicylic acid dissolved in acetone is. Thus, to make
your stock solution you should first calculate how much salicylic acid you will need, weigh this
amount directly into 50.00 mL volumetric flask, and then completely dissolve the salicylic acid in
10 mL of acetone solution before adding acetone to the mark.

To make up the diluted standards, pipette your calculated quantity of stock solution into a second
50.00 mL volumetric flask. Add 10.00 ml of acetone using a 10-mL pipette to be sure the
salicylic acid remains in solution. Then add 10.00 mL of 0.025 M Fe(NO3)3 solution using the
pipette, and fill to the mark with deionized water.
Measure the absorbance of these standards (what should you use as a blank?) and create a Beer’s
Law plot.
 When testing the purity of your aspirin product you will need to weigh out approximately 0.10
grams (accurately record the exact mass) of your aspirin crystals into a clean 50-mL volumetric
flask. Then pipette 10.00 mL of acetone into the flask and completely dissolve the solid product
to be sure that everything goes into solution. Next add 10.00 mL of 0.025 M Fe(NO 3)3 solution
and fill to the mark with deionized water. Measure the absorbance of this solution. If the
absorbance is greater than 1.2 absorption units, you will need to repeat this procedure using a
smaller mass of your product.

You can now use your Beer’s law plot to determine the molarity of the salicylic acid impurity in
this solution, and from this the percent mass of salicylic acid impurity in your product. The percent
purity of your aspirin can be determined by subtracting the percentage of impurities from one
hundred.

PREPARATION OF ASPIRIN AND ACETAMINOPHEN

1996 by David A. Katz. All rights reserved.
Reproduction permitted for education purposes as long as original copyright is included.
OBJECT
To synthesize some common pain relievers: aspirin and acetaminophen.
To determine the purity of the aspirin or acetaminophen.
THEORY
Aspirin, acetylsalicylic acid, was first synthesized in 1893 by Felix Hofmann, a chemist for the German firm of
Bayer. This compound had the medicinal properties of salicylic acid, an extract of willow bark, without the
unpleasant taste or the high degree of irritation of the mucous membranes lining the mouth, gullet, and stomach.
Aspirin is both an organic ester and an organic acid. It is used extensively in medicine as a pain killer
(analgesic)
and as a fever-reducing drug (antipyretic). When ingested, acetylsalicylic acid remains intact in the acidic
stomach,
but in the basic medium of the upper intestinal tract, it hydrolyzes forming the salicylate and acetate ions.
However,
its additional physiological effects and biochemical reactions are still not thoroughly understood.
Aspirin (molar mass of 180.2 g/mol) is prepared by reacting salicylic acid (molar mass of 138.1 g/mol) with
acetic
anhydride (molar mass of 102.1 g/mol). Aspirin is a weak monoprotic acid.
Acetaminophen is an amide, a compound that is a derivative of ammonia that has been reacted with an acidic
substance, in this case, acetic acid. Acetaminophen acts as a fever reducer and pain reliever. It can be found in
several analgesic preparations, such as Tylenol, some of which may contain other ingredients such as caffeine
and
buffers.
Qualitatively, the purity of an aspirin or acetaminophen sample can be determined from its melting point. The
melting point of a substance is essentially independent of atmospheric pressure, but it is always lowered by the
presence of impurities (a colligative property of pure substances). The degree of lowering of the melting point
depends on the nature and the concentration of the impurities.
SAFETY PRECAUTIONS
Wear safety glasses or goggles at all times in the laboratory.
Acetic anhydride is corrosive and its vapor is irritating to the respiratory system. Avoid skin contact and
inhalation
of the vapors. In the event of skin contact, rinse well with cold water. If the vapors are inhaled, move to an area
where fresh air is available.
Sulfuric acid is corrosive. Avoid skin contact. In the event of skin contact, rinse well with cold water.
p-aminophenol is harmful by inhalation and by contact with the skin. In the event of skin contact, rinse well
with
cold water. If the vapors are inhaled, move to an area where fresh air is available.
PROCEDURE
OPTION 1: THE PREPARATION OF ASPIRIN
Materials Needed
Salicylic acid
Acetic anhydride
Sulfuric acid, concentrated
Ethanol
Dropper
Erlenmeyer flask, 125-mL
Beakers, 2 400-mL, 100-mL, 10 or 20-mL
Graduated cylinders, 10-mL, 25-mL
Watch glass
Stirring rod
Vial to hold aspirin sample
Ring stand
Clamp (to hold 125-mL Erlenmeyer flask)
Buchner funnel
Filter paper to fit Buchner funnel
Vacuum filtration flask
Rubber tubing for vacuum flask
Ice
Thermometer, 110°C
Melting point capillary tube
Melting point apparatus
dropper
Disposable IR card
Optional: rubber gloves
Procedure
Weigh out 2.0 g of salicylic acid. Place it in a 125-mL Erlenmeyer flask.
Add 5 mL of acetic anhydride. Swirl the flask to wet the salicylic acid crystals. Add 5 drops of concentrated
sulfuric acid, H2SO4 , to the mixture.
Gently heat the flask in a boiling water bath for about 10 minutes.
Remove the flask from the hot water bath and add 10 mL of deionized ice water to decompose any excess acetic
anhydride. Chill the solution in an ice bath until crystals of aspirin no longer form, stirring occasionally to
decompose residual acetic anhydride. If an "oil" appears instead of a solid, reheat the flask in the hot water bath
until the oil disappears and again cool.
Set up a vacuum filtration apparatus. Wet the filter paper in the Buchner funnel with 1-2 mL of distilled water.
Turn on the water aspirator. Decant the liquid onto the filter paper, minimizing any transfer of the solid aspirin.
If
some aspirin is inadvertently transferred to the filter, that will not cause any difficulty.
Add 15 mL of cold water to the flask, swirl, and chill again. Pour the liquid and the crystals of aspirin onto the
filter
paper. Repeat until the transfer of the crystals to the vacuum filter is complete. Wash the aspirin crystals on the
filter paper with 10 mL of ice water.
Maintain the vacuum to dry the crystals as best possible.
If aspirin forms in the filtrate in the vacuum flask, transfer the filtrate and aspirin to a beaker, chill in an ice
bath,
and vacuum filter as before, using a new piece of filter paper. Dispose of the filtrate in the sink.
Determine the mass of the crude aspirin crystals.

Recrystallization of the Aspirin.

The major impurity in aspirin is salicylic acid. It can be removed by a recrystallization.
Place the aspirin crystals in a 100-mL beaker. Add 8 mL of ethanol and 25 mL of water.
Warm the mixture in a 60°C water bath (no flame, use a hot plate or a hot water bath). Warm the mixture until
the
aspirin dissolves. (If the solid does not dissolve after heating, consult with your instructor.)
Cover the beaker with a watch glass, remove it from the heat, and set it aside to cool slowly. Set the beaker in
an ice
bath. Beautiful needle-like crystals of acetylsalicylic acid form.
Collect the aspirin by vacuum filtration. Wash the crystals with two 10-mL volumes of ice water. Maintain the
vacuum to air dry the aspirin. If time does not permit, place the filter paper and aspirin sample on a watch glass
and
allow them to air-dry. The time for air-drying the sample may require that it be left with your instructor until the
next laboratory period.
Transfer the dry aspirin crystals to a pre-weighed sample container or vial. Determine the mass of the aspirin
crystals.

Determine the Melting Point of the Aspirin Sample

Fill a capillary melting point tube to a depth of 0.2 cm with the recrystallized aspirin.
Place the capillary tube in the melting point apparatus. Determine its melting point. (Your instructor will
demonstrate the use of this apparatus.)
Pure aspirin melts at 135°C.
The aspirin sample should be labeled with your name, the mass of the aspirin, the percent yield, and its melting
point.