SYNTHESIS OF ACETYLSALICYLIC ACID (ASPIRIN) Adolfo, Angela Nicole G., Alcaraz Frances Jillian F., Aliman, Stephanie T., Astor, Jashmin D., Bauzon, Franchesca D., Cabral, Danica Rose G.
Department of Pharmacy, Faculty of Pharmacy University of Santo Tomas
ABSTRACT Acetylsalicylic acid, or commonly known as Aspirin, is one of the most widely used drugs to reduce fever. It is under the drug classification of a Nonsteroidal Anti-Inflammatory Drug or NSAID in short, Anticoagulant, Antiplatelet, Non-Opioid Analgesic, Antipyretic & Fibrinolytic (Thrombolytic). Aspirin is formed through the combination of salicylic acid and acetic anhydride. Both salicylic acid and acetic anhydride are mixed to create a crude product. In this experiment Aspirin was studied of how it was produced and how the product would react to different reagents. A commercial aspirin went through a procedure producing a synthesized aspirin, making up different results from the reactants and products seeing the differences of the results from each.
INTRODUCTION Acetylsalicylic Acid commonly known as Aspirin is among the most widely used medicine. Aspirin is also among the oldest. It has the ability to reduce swelling, redness, and soreness, it also acts as an analgesic to reduce pain. The synthesis of aspirin is acquired from salicylic acid which can be extracted in willow trees. The boiling point of salicylic acid is 211°C, a melting point of 159°C and a density of 1.44 g/mol.
Structural Formula of Aspirin (Acetylsalicylic Acid)
Acetic
anhydride
is
an
organic
compound also known as a type of acetic anhydride. The molecular formula for acetic anhydride is C4H6O3. The synthesis of acetic anhydride is quite simple as long as you remember the term 'carboxylic acid.' A carboxylic acid is a functional group whose molecular formula is defined as RCOOH. Acetic anhydride is useful as a building block for other chemicals, such as the household staple item vinegar. This usefulness also carries into the pharmaceutical industry. Acetic anhydride is used to make aspirin. As we see in the equation below, when acetic anhydride reacts with salicylic acid, aspirin is produced.
Crystallization refers to the formation of solid crystals from a homogeneous solution. It is one of the most used purifying methods
inorganic
experiments.
The
substance to be purified is dependent to its solubility in change of temperature whether in a hot or cold solvent. It is the main factor that affects crystallization. The substance to be crystallized should show the ideal solubility. It is essentially a solid-liquid separation technique and a very important one at that. Organic compounds that are solid in room temperature are usually purified by crystallization. The desired substance will crystallize on cooling, but the impurities will not. The objectives of experiment are the following: (1) to explore the chemical process in the synthesis of aspirin; (2) to be able to calculate for the percentage yield of the synthesized aspirin.
Structural Formula of Acetic Anhydride METHODOLOGY The materials needed for this experiment are test tubes, beakers, glass rod, iron ring/tripod, plastic wash bottle, Bunsen burner, clamp, pipette, and watch glass. The samples and reagents needed are salicylic acid, Formation of Acetylsalicylic Acid
acetic
anhydride,
conc.
H2SO4,
commercial aspirin, benzoic acid, benzyl
alcohol, 2& FeCl3, iodine solution, and
mL of ice-cold water to the beaker, stir
methyl alcohol.
then pack the beaker in ice for 10
A. Reaction of Acetic Anhydride and Salicylic Acid Get exactly 2.00g of salicylic acid and place it in a clean, dry 20-cm test tube. Place exactly 5.00 mL of acetic anhydride and 5 drops of conc. H2SO4 into the same test tube. Stir it until the salicylic acid dissolves. Prepare
the
set-up
for
the
preparation of aspirin by bringing a 250mL beaker three-fourths full of tap water to a boil; support it in a ring stand. Fill the wash bottle with distilled water and pack it in ice contained in a large beaker. Once the water begins to boil, turn the burner off and place the test tube in a water bath; stir well for 1 minute. Let the reaction mixture to remain in the water bath for 20-30 minutes. Remove the test tube from the water bath, then cautiously pour the contents into 5 mL of water in a 150-mL beaker. Stir for 1 minute once the reaction in the beaker subsides. Slowly add water until a maximum of 40 drops until the solution becomes cloudy. If the solution returns to being clear, continue to add water. Rinse the test tube with ice-cold water once the crystals of aspirin appear in the beaker, adding the rinse to the solution in the 150-mL beaker. Place 20
minutes for the aspirin to crystallize. Filter the crystals using filter paper and allow to dry overnight, then measure the weight of dried aspirin and compute for percentage yield. B. Ferric Chloride Test for Salicylic Acid In a 6 clean 10-cm test tubes, place 1 mL of water each. Put a crystal of salicylic acid in the first test tube, powdered commercial aspirin in the second test tube, synthesized aspirin in the third, benzoic acid in the fourth, 1 mL of benzyl alcohol in the fifth, and don’t add anything in the last test tube because it will serve as the control. Shake the test tubes to dissolve the solid and place 2 drops of 2% ferric chloride. Observe the color changes. C. Starch Test In a three 10-cm test tubes, place 2 mL of water each. Put a small amount of synthesized aspirin in the first test tube, powdered commercial aspirin in the second, and don’t add anything in the third because this will serve as the control. Add 1 drop of iodine solution to each test tube. The presence of starch will be indicated by blue or blue-black color change.
D. Preparation of Methyl Salicylate Place exactly 1.00g of salicylic
Table 1 - Reaction of Acetic Anhydride and Salicylic Acid
acid in a 20-cm test tube. Place 5 mL of methyl alcohol and 3 drops of conc. H2SO4 in the same test tube. Stir to dissolve the salicylic acid in the alcohol. Place it in a water bath for 15 minutes. A mint aroma will indicate the presence of methyl salicylate.
The formation of Acetylsalicylic Acid RESULTS AND DISCUSSION
is seen through the figure (Figure 1) below,
The experiment performed has 4
which went through a reaction of Salicylic
portions of experiments performed. First of is
Acid and Acetic Anhydride. Also forming
the Reaction of Acetic Anhydride and
Acetic Acid along with ASA or Aspirin.
Salicylic Acid which was performed/finished the longest, wherein the second objective would be accomplished. Then there is there’s the Ferric Chloride Test for Salicylic Acid, Starch Test, and lastly Preparation of Methyl Salicylate where the first objective will take part. For the results of the first part of the experiment the group was instructed to
Figure 1. Formation of Acetylsalicylic Acid
collect 1g of Salicylic Acid. And to collect the right or exact amount, they used a watch glassed. Firstly, they calibrated the watch glass (93g) and they weighed an addition of 1g (94g) to achieve the specified amount. After that the members collected 5mL of Acetic Anhydride and 5 drops of conc. H2SO4 (Sulfuric Acid) with caution. Through these they have collected the reagents they needed to use for the experiment.
Limiting Reagent: Salicylic Acid (C7H6O3)
Acetic Anhydride:
Salicylic Acid:
Theoretical Yield:
Figure 2. Reaction of Acetic Anhydride with Alicylic Acid In
Percentage Yield:
the
second
portion
of
the
experiment, six chosen samples we’re tested. And out of all the samples only three had a reaction with Ferric Chloride. And those are Salicylic Acid, Commercial Aspirin, and Synthesized Aspirin. In conclusion that Ferric Chloride has a rapid reaction with In this part of the experiment, the members
witnessed
the
synthesize
Salicylic Acid knowing that all three consists
of
of the reagent. And comparing from the
aspirin, wherein the percentage yield was
results (seen from Table 2) Salicylic gave a
obtained from. Coming from the calculations
more rapid reaction with Ferric Chloride
(seen above) the amount of acetic anhydride
regarding the value or hue of
and salicylic acid used was calculated
samples. As for the other samples they gave
through Stoichiometric calculations. There
no reaction, as they maintained a colorless
we obtained the limiting reagent. And then
reaction.
computed for the limiting reagent.
the three
Table 2 – Ferric Chloride Test for Salicylic Acid
In the third part of the experiment the Starch Test was performed. Wherein only Commercial Aspirin was the only sample to give a reaction with iodine solution, creating a dark-green solution as seen from the results from Table 3. Table 3 – Starch Test
As seen from Figure 3 (below) only 5 samples
we’re
immediately
observed,
because of the reason that the Synthesized Aspirin was still being done by the other members. The experiment was completely achieved in the second meeting.
And as seen from Figure 4 the Synthesized Aspirin sample was still not tested. But later on gave a colorless solution as a result. And as seen from the figure, Commercial Aspirin still had a light hue for the color green. But after standing, the sample gave a dark-green solution
Figure 4. Starch Test (without Synthesized Figure 3. Ferric Chloride Test for Salicylic Acid (without Synthesized Aspirin)
Aspirin)
The last portion of the experiment performed
was
Preparation
of
thus eliminated. Recrystallization removed
Methyl
impurities from the formed aspirin, which
Salicylate which should give a minty aroma
involved salicylic acid. To test for purity, a
to say that the experiment was a success.
number of tests were conducted. One of
And from the given results, the sample did
which was the ferric chloride test. A complex
give a efficacent oli-like smell or a minty
with an intense violet color is formed when
aroma. But after a few moments, the smell
ferric chloride is added to salicylic acid.
could not be much perceived anymore as it
When ferric chloride is added to pure aspirin
was in the first moment when it was
however, no reaction will occur. Another test
accomplished.
is the starch test, which is used to detect the presence of starch in the samples: prepared aspirin, commercially available aspirin, and control.
Commercially
available
aspirin
should react to the iodine solution (it should turn blue-violet or purple) because most pharmaceutical companies add starch to their products for aesthetic appeal.
Methyl salicylate, commonly known as oil of wintergreen, is another ester of salicylic acid. It is synthesized in a manner similar to aspirin, but at a lower temperature. Similar to aspirin, it also contains compounds that have analgesic and antipyretic properties. It was Figure 5. Preparation of Methyl Salicylate
first isolated in 1843 by extraction from a plant (Gaultheria spp.) which is in the mint family, which explains the characteristic
CONCLUSION In the experiment, aspirin was prepared from the chemical reaction of salicylic acid and acetic anhydride. Upon the addition of cold water, acetic acid was formed and was
minty odor of methyl salicylate.
REFERENCES Website: The Synthesis of Organic Aspirin. (2008, February
28).
Retrieved
from
http://www.studymode.com/essays/LabReport-Synthesis-Organic-Aspirin-FirstYear-Chemistry-65188753.html Acetic anhydride. (2015, May 15). Retrieved from http://webbook.nist.gov/cgi/cbook.cgi?ID=C 108247&Mask=8
Books: Bathan, G.I., Bayquen, A.V., Crisostomo, A.B.C., Cruz, C.T., de Guia, R.M., Farrow, F.L., Peña G.T., Sarile, A.S., Torres, P.C.. (2014). Laboratory Manual in Organic Chemistry Revised Edition. Quezon City, Manila: C & E Publishing, Inc.
