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Synthesis of Aspirin

Danessa Allison and Mackenzie Lines


Period 4
Assigned: 5/4/17
Due: 5/15/17

Abstract:
The purpose of this laboratory experiment is to synthesize aspirin and to determine a
percent yield of aspirin. This can be done by reacting salicylic acid with acetic anhydride using a
phosphoric acid catalyst. This will be heated, then cooled to the point of crystallization. These
crystals will be placed in a vacuum filtration apparatus, and the result of this will be a sample of
solid aspirin. The purity of the aspirin that is synthesized will be found by determining the
melting point of the created compound and by the use of a salicylic acid indicator. The indicator
will turn a solution created from the synthesized aspirin and methanol purple when drops of 0.02
M FeCl3 are added. In this experiment, our absolute error was 9℃, and our percent error was
7%, based off of the actual melting point of aspirin, which is 135℃. Our percent yield of aspirin
was 56.420%. Only one drop of the indicator was added to our solution before it turned purple,
demonstrating high levels of salicylic acid impurities in our synthesized aspirin.

Discussion:
Aspirin is a synthetic compound, also known as acetylsalicylic acid. It is used as an over
the counter blood thinner, pain reliever, fever reducer, and as an anti-inflammatory medication.
The salicylic acid that is used to create aspirin was first discovered as early as 3000 BC by the
ancient egyptians in the naturally occurring forms of willow bark and myrtle. Hippocrates noted
its usefulness in relieving pain around 400 BC. In 30 AD, Greek and Roman doctors used this to
stop inflammation. Aspirin was first successfully synthesized by the Bayer affiliated chemist,
Felix Hoffman in the early 1890’s to be mass produced by Bayer in the late 1890’s. This form of
aspirin was more pure, stable, and palatable than any of its predecessors. In 1939, the drug
was approved by the FDA (Food and Drug Administration). In the 1970’s, doctors began to
recommend aspirin more consistently. Today, aspirin is known as the most successful non-
prescription medicine of all time and is a standard painkiller worldwide.
The chemical equation C7H6O3 + C4H6O3 → C9H8O4 + CH3COOH exemplifies the
reaction of salicylic acid and acetic acid that forms aspirin as well as acetic acid. This is done
with the use of a phosphoric acid catalyst, as shown below.

Esterification is the reaction between a carboxylic acid and an alcohol, usually with a
sulfuric or phosphoric acid catalyst. In this experiment, the salicylic acid contains the needed
carboxyl group and the acetic anhydride contains the needed hydroxyl group. The H3PO4 is the
acid catalyst used. This process creates an ester, which is a hydrocarbon that contains an ether
linkage next to a carbonyl group. This is fulfilled by the structure of the acetylsalicylic acid, or
aspirin. The ether is the oxygen in the chain, and the carbonyl is the double bond to the oxygen
just to the right of it in the chain. The mechanism for the synthesis of aspirin is depicted below. It
is based upon the aforementioned chemical equation and esterification process.
Crystallization is a process that is used to purify solid compounds. During this process a
solvent is used to completely dissolve a compound. Then the resulting solution is heated and
cooled. The higher temperature allows the solution to become saturated, resulting in a higher
concentration, and a greater amount of formed crystals. During the cooling process, the solvent
can no longer hold the solute’s molecules and crystals begin to form. The more slowly the
crystallization occurs, the less likely it is that the crystals will contain a higher level of impurities.
If solidification is too fast, impurities will be trapped inside the crystal structures. This is a source
of error for this laboratory experiment. In this particular lab, solid salicylic acid will be dissolved
into the solvent acetic anhydride. This will be heated in a flask with the catalyst, which will be
placed inside a beaker of water over a hot plate. This will be heated from 70℃ to 80℃ for ten
minutes. Then the solution in the flask will be cooled slowly by adding drops of distilled water to
the flask, and finally, the flask will be placed in an ice bath to cool it more quickly, allowing the
crystallization necessary for the rest of the procedure to take place.
After the crystals are formed, they can be transferred from the flask to the vacuum
filtration apparatus. A piece of 9.0 cm filter paper can be placed inside of a Buchner funnel,
which is inserted into the suction Erlenmeyer flask. A vacuum effect will be created by attaching
a rubber hose to the connector on the flask and an aspirator attached to the nozzle of a
laboratory sink. When it is connected to the side, the water will flow through the bottom of the
aspirator, creating the vacuum needed to evaporate any of the original solvent left over in the
crystals. The solid on the filter paper can then be removed and set on a watch glass to dry
further. Then the sample of synthesized aspirin can be tested for impurities.
Two purity tests will be used to see how pure the resulting aspirin is after the synthesis is
complete. First, salicylic acid impurities can be discovered by creating a solution containing the
experimental aspirin sample and methanol. An indicator, 0.02 M FeCl3, will be added to this
solution drop by drop until it turns purple. The more drops it takes to turn the solution’s color
purple, the more pure the aspirin sample is. Another test to determine the aspirin’s purity will be
its melting point. Since melting points are constant for every solid for which they are determined,
any variation in aspirin’s melting point, which is 135℃, will show some level of impurity or error.
To do this test, a sample of the synthesized aspirin will be placed in a melting point apparatus.
The temperature at which the sample begins to melt and is completely melted will be recorded
each time this is done. To determine an average melting point, both temperatures for each trial
should be averaged, and then all of the trials can be averaged together. In this experiment, this
calculation will result in the information needed to complete error calculations.
Sources:
● http://www.aspree.org/usa/participants/about-aspirin/
● https://www.britannica.com/science/separation-and-purification/Exclusion-and-clathration
● https://www.dartmouth.edu/~chemlab/techniques/vfiltration.html
● http://www.chemguide.co.uk/organicprops/alcohols/esterification.html
● http://www.drcarman.info/kem220lb/01lab220.pdf

Objectives:
In this lab, you will…
1. synthesize aspirin through crystallization.
2. calculate the percent yield of aspirin.
3. assess the purity of the aspirin using melting point, a salicylic acid indicator, and
thin layer chromatography.

Materials:
● Analytical Balance ● 250 mL Florence flask
● 10 mL graduated cylinder ● 100.0 mL graduated cylinder
● Hot plate ● Thermometer
● 600 mL beaker ● Stirring rod
● Buchner funnel ● 9.0 cm filter paper
● 1- hole rubber stopper ● Aspirator
● Suction Erlenmeyer ● Watch glass
● Rubber Hose ● Test Tube Rack
● Small Test Tube ● Melting Point Apparatus

Chemicals:
● Salicylic acid ● Ice
● Acetic anhydride ● Methanol
● Phosphoric acid ● 0.02 M FeCl3
● Distilled water

Safety:
Salicylic acid and aspirin may cause skin and eye irritation, but are basically non
hazardous.
Acetic anhydride and phosphoric acid can cause bad burns. Handle these chemicals
with care, avoid breathing their vapors, and always wear safety goggles.

Procedure:
1. Using the analytic balance, measure 3.00 g of salicylic acid and place it into a 250 mL
Florence flask.
2. Measure 6.00 mL of acetic anhydride and add this to your flask.
3. Carefully add 5 to 10 drops of 85% phosphoric acid (the catalyst) to the flask and swirl
gently for a few minutes to mix the components thoroughly.
4. Add ~200 mL of tap water to the 600 mL beaker. Place the reaction flask into the water,
and heat it on a hot plate at 70℃ to 80℃ for 10 minutes.
5. After heating, remove the flask from the beaker and cautiously add 20 drops of distilled
water.
6. Add 20.0 mL of distilled water and cool the reaction flask in an ice bath (600 mL beaker
with ice water). If crystals do not appear, you can scratch the walls of the flask with a
stirring rod to induce crystallization.
7. Assemble a vacuum filtration apparatus.
8. Mass a piece of 9.0 cm filter paper. Place the filter paper in the Buchner funnel, center it,
and dampen it with distilled water. Turn on the water flow for the apparatus.
9. Transfer the aspirin crystals onto the filter paper using a rubber policeman. Try to get the
crystals in the middle of the filter paper. Wash the crystals with 2-3 mL of chilled water.
Allow air to be drawn through the solid and filter paper for 15 minutes. The liquid in the
bottom of the flask is mostly water and can be washed down the sink.
10. Record the mass of a watch glass. Place the filter paper with the product on a watch
glass. Place the watch glass on a piece of paper with you and your partner’s name on it.
Place the watch glass on the back counter, and cover it with a paper towel. Your product
will dry overnight.
11. After drying, mass the filter paper, aspirin, and watch glass.
12. Check for impurities by dissolving a small sample of aspirin (~0.01 g) in ~ 1 mL of
methanol. Then drop by drop add 0.02 M FeCl3. The appearance of a purple hue
indicates salicylic acid impurities in your aspirin. Record the number of drops needed to
turn it purple. Don't add more that 25 drops.
13. Assess the purity of your aspirin by measuring the melting point of the aspirin using the
melting point determination procedure.

Cleanup:
● Keep a small sample of your aspirin in a small labeled test tube for the next lab.
● Clean all glassware thoroughly. Put away any glassware you used.

Data:
This chart contains the temperatures that we recorded in order to determine the average melting
point of the aspirin, and therefore will be used to calculate our error.
Trial: Initial Melting Temperature Final Melting Temperature
(℃) (℃)

Rough Trial 121.2 --


Trial 1 119.8 131.6

Trial 2 120.1 132.7

Trial 3 120.7 132.2

This chart contains the masses that we recorded throughout this lab, and will be used in the
theoretical and experimental yields of aspirin.
Mass of Salicylic Acid (g) 3.0063

Mass of the Watch Glass (g) 19.1291

Mass of the Filter Paper (g) 0.5281

Final Mass of Watch Glass, Filter Paper, and Aspirin (g) 21.8696

Analysis/Calculations/Error:

Theoretical Yield of Aspirin:


3.0063 g C7H6O3 1 mol C7H6O3 1 mol C9H8O4 180.1574g C9H8O4 = 3.9213g
C9H8O4

138.1207g C7H6O3 1 mol C7H6O3 1 mol C9H8O4

Mass of Aspirin: (Experimental Yield of Aspirin)


(mass of watch glass, filter paper, and aspirin) - (mass of watch glass) - (mass of filter paper)
21.8696g - 19.1291g - 0.5281g = 2.2124g

Percent Yield of Aspirin:


Experimental yield/ theoretical yield x 100%
2.2124g / 3.9213g x 100% = 56.420%

Average Melting Point by Trial:


Trial 1: 119.8℃ + 131.6℃ = 251.4℃ / 2 = 125.7℃
Trial 2: 120.1℃ + 132.7℃ = 252.8℃ / 2 = 126.4℃
Trial 3: 120.7℃ + 132.2℃ = 252.9℃ / 2 = 126.5℃
Overall Melting Point Average:
125.7℃ + 126.4℃ + 126.5℃ = 378.6℃ / 3 = 126.2℃

Absolute Error: Ea = [ xe - xt ]
Ea = [ 126.2℃ - 135℃ ] = 9℃

Percent Error: E% = Ea / xt x 100%


E% = 9℃ / 135℃ x 100% = 7%
Conclusion:
In this laboratory exercise, we synthesized aspirin from the reactants of salicylic acid and
acetic anhydride, using a phosphoric acid catalyst. First, these reactants were placed in a flask
and heated over a hot plate for ten minutes. Then the flask was cooled and crystals began to
form inside the flask. These crystals were transferred to our vacuum filtration apparatus, and
then later to a watch glass to dry overnight. The resulting solid was our synthesized aspirin
sample. When comparing our average melting point of our synthesized aspirin sample to the
actual melting point of aspirin, we had an absolute error of 9℃, and a percent error of 7%. In the
testing of impurities, only one drop of the indicator was needed to turn the solution of aspirin and
methanol purple. This demonstrates a high level of salicylic acid impurities in our aspirin, as
does the low average melting point that we calculated. Our percent yield was 56.420%.
Our error in this experiment was most likely a personal error. Our percent yield was most
likely low due to a loss of product, which could have occurred in the transfer of the aspirin
sample on the filter paper from the vacuum filtration apparatus to the watch glass. Some of the
solid may have remained in the filter, therefore lowering the overall mass of the aspirin, and
mathematically creating a lower percent yield. The watch glass and filter paper masses
remained the same, while the final mass of the watch glass, filter paper, and solid aspirin was
actually low due to a loss of product. This would result in a low experimental mass of aspirin,
and when this is divided by the actual yield, would create a low percent yield. Some crystals
may have remained in the flask after the cooling which caused the crystallization as well, while
the majority was transferred to the filter paper in the vacuum filtration apparatus. This would
also result in a loss of product, and therefore mass, in the same way as mentioned above.
Impurities were also noted in our experiment as only one drop of 0.02 M FeCl3 was added to the
aspirin and methanol solution in order to make it turn the purple color indicating salicylic acid in
the synthesized aspirin sample. This may have been caused by the heating of the salicylic acid
and acetic anhydride with the phosphoric acid catalyst, as we did not heat the hot plate to the
accepted temperature before placing the flask containing these reactants on it to facilitate the
reaction to completeness. Mathematically, our melting points were consistently low, causing our
average to be low as well. The low temperatures were most likely caused by these same
impurities and resulted in our error calculation results.
We were pleased with our results of this lab because our error percentage was very low.
However, we wish the salicylic impurities, demonstrated by the purple aspirin solution after the
addition of one drop of 0.02 M FeCl3, would have been lower. To improve our results, we could
run this experiment again and make sure to consistently transfer all of the crystals and solid
aspirin to the vacuum filtration apparatus and the watch glass respectively. This would give us a
more accurate percent yield. We should also be sure to heat the hot plate to the range of 70℃ to
80℃, before placing the flask of reactants into the beaker of water on top.This would result in a
lesser amount of salicylic acid impurities in the synthesized aspirin. Furthermore, we could run
more trials of the melting point determination in order to obtain a more accurate and precise
temperature measurement. From this laboratory experience, we have learned how to synthesize
aspirin using a phosphoric acid catalyst, as well as how to assemble and use a vacuum filtration
apparatus. We also learned how to use an indicator to determine the impurity level of a
synthesized solid. This knowledge may help us to get better results in the running of future
laboratory experiments that may require similar techniques. In the real world, pharmaceutical
manufacturers must understand these synthesis techniques in order to produce stable and pure
medications, such as aspirin. Impurities could cause serious harm to any individual that may
take that medication, and therefore, they must understand how to eliminate these impurities so
that a medication can be distributed to those that need it. Pharmacists must also understand
synthesis to understand how a drug works and what it can be used for, as well as what side
effects it may cause.