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Tittle: Synthesis of Aspirin
I.INTRODUCTION
The process of creating a desired organic compound from commercially accessible components
is known as organic synthesis. Creating the most straightforward synthetic pathways to a
molecule is the aim of organic synthesis.
One of the most popular drugs for lowering fever and relieving pain is acetylsalicylic acid,
commonly referred to as aspirin. It is a salicylic acid acetyl derivative. It melts at 135°C and is
a white, crystalline, somewhat acidic material.
Aspirin is synthesized through the reaction of salicylic acid with acetyl anhydride which causes
a chemical reaction that turns salicylic acid's hydroxyl group into an acetyl group, (R—
OH → R—OCOCH3).
For the reaction to take place, an inorganic acid such as phosphoric acid is used as a catalyst.
II. OBJECTIVES
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At the end of the exercise, the student should be able to:
1.
be introduced to the concept of organic synthesis;
2.
synthesize acetylsalicylic acid from salicylic acid by nucleophilic acyl substitution; and
3.
differentiate acetylsalicylic acid from salicylic acid by simple chemical tests.
III. MATERIALS AND METHODS
Materials: The major reactant, salicylic acid (C₇H₆O₃), comprises a phenolic group that undergoes
a reaction to produce acetylsalicylic acid.
The acetylating agent that supplies the acetyl group (CH₃CO) required for esterification is acetic
anhydride (C₄H₆O₃).
OR Another substitute for acetic anhydride is acetyl chloride (C₂H₃OCl).
By making acetic anhydride more reactive, concentrated sulfuric acid (H₂SO₄) acts as a catalyst to
accelerate the esterification reaction.
Alternatively, phosphoric acid (H₃PO₄) can be employed as a catalyst.
Water or ethanol: To aid in the end product's purification (e.g., crystallization).
Ice (optional): To help aspirin crystallize by cooling the reaction mixture.
Equipment: Erlenmeyer flasks or beakers—used to conduct the reaction.
Optional reflux equipment is used to heat and maintain a regulated temperature
Methods:
1. About 2 grams of salicylic acid should be measured in a dry, clean Erlenmeyer flask or beaker.
2. Fill the flask with 4 millilitres of acetic anhydride.
3. As a catalyst, add one or two drops of concentrated sulfuric acid (H₂SO₄). Acetic anhydride and
salicylic acid react more quickly thanks to the catalytic activity of sulfuric acid
4. Stir the mixture gently to ensure even distribution of the reactants.
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The reaction between salicylic acid and acetic anhydride produces aspirin (acetylsalicylic acid)
and acetic acid (CH₃COOH):
The reaction can be performed at room temperature, or the flask can be gently heated (if
necessary) using a water bath or reflux setup for a few minutes to speed up the reaction.
Crystallization:
After the reaction is complete, pour the reaction mixture into a beaker containing cold water or
ice to hydrolyse any unreacted acetic anhydride and to cool the reaction mixture.
Aspirin (acetylsalicylic acid) will precipitate out as a solid.
Filter the solid product using a Buchner funnel or filter paper, then wash it with cold water to
remove impurities.
Purification:
The crude aspirin can be purified by recrystallization. To do this, dissolve the solid product in
a minimal amount of hot ethanol or acetone.
Allow the solution to cool slowly, and aspirin crystals will form as the solvent evaporates.
Filter and dry the purified aspirin crystals under reduced pressure or air (Rainsford 8-10).
The purity of the aspirin can be confirmed by:
Melting point determination: Pure aspirin has a melting point around 135°C.
Thin-layer chromatography (TLC).
Infrared (IR) spectroscopy to confirm the presence of functional groups (acetyl and carboxyl).
IV. RESULTS AND DISCUSSION
Acetylsalicylic Acid (aspirin) preparation was the initial step in the experiment. When
phosphoric acid (a catalyst), acetic anhydride, and salicylic acid were combined, a white,
milky liquid was produced. The reaction's mechanism is:
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A clear yellow liquid was produced by heating the mixture in the first section of the experiment.
In order for salicylic acid to melt and react with acetic anhydride, heating was used. However,
water was not introduced at the beginning of the experiment; rather, it was added after heating.
This is to avoid acetic anhydride and water reacting at the beginning of the experiment, which
would have prevented the formation of aspirin. Acetic anhydride was broken down in this way
following the synthesis of aspirin.
The liquid turned milky and hazy with white precipitates after 40 millilitres of ice-cold water
were added, allowed to settle to room temperature, and then placed in an ice bath. Since aspirin
is insoluble in cold water, adding cold water is crucial to the purification process and the
separation of the crystals from the liquid. Purification is required to get rid of the phosphoric
acid, the acetic acid product, and any salicylic acid and acetic anhydride that did not react.
Purification has not yet been finished in this section; it was carried out in the recrystallization
section. Suction filtering was used for isolation, and white crystals that resembled sugar were
produced.
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The crude/impure product was then weighed and it weighed 4.40g. This is quite far from the
theoretical yield because it still contains impurities. This data was used to calculate the percent
recovery on the latter part of the exercise.
Recrystallization was the experiment's second component. The second step in the purifying
process is this. Drop by drop, 95% ethanol was added to the crystals until they dissolved, and
then distilled water was added until the crystals became hazy or until they recrystallized.
Aspirin and other contaminants, including salicylic acid, were dissolved in ethanol.
Conversely, just aspirin is recrystallized using cold water, leaving all contaminants behind.
Aspirin should not be recrystallized from hot water since it is an ester and esters hydrolyse in
hot water. The mixture was suction filtered after cooling in an ice bath, which helps with
purification and recrystallization.
The weight of the recovered sample was 2.85g. The calculations for percent yield were shown.
The percent yield was 109.25%, meaning there was a slight error. Perhaps, the sample was not
weighed properly or it was weighed when still wet.  On the other hand, the calculated percent
recovery was 64.77%. Certainly, another error occurred. This could be due to handling
problems in suction filtration or drying, etcetera.
As for the melting point data, the range of the crude sample was 120-124˚C and the range of
the purified sample was 122-124˚C. (Actually, there could have been an error here since I
wasn’t able to observe it. A classmate just told me the MP range of purified sample, too bad, I
forgot to tell my groupmates!). Comparing the results to the literature value of 135˚C, both the
purified and crude had a precise value BUT since the purified sample has a narrower range, it
is logically more comparable to the literature value.
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In Table 8, the differentiation of synthesized acetylsalicylic acid from commercially available
aspirin was accounted for. The test used in this part was Iodine test, which is a test for the
presence of starch (since iodine can form a black complex with starch). After dissolving
synthesized aspirin in 2mL water and 1mL iodine solution, a mixture of red-orange liquid and
white precipitates was obtained while when commercially available aspirin was dissolved in
2mL water and 1mL iodine solution, a black precipitate in a dark brown to black solution was
formed. This shows that commercially available aspirin contains starch.
Since salicylic acid has a phenol group, it gave a positive result to FeCl3 Test and KMnO4
Test, both of which react with phenol. Acetic anhydride gave a positive result to water
solubility test to form acetic acid. The recrystallized aspirin, an ester, did not give any positive
result to the tests since esters do not react with FeCl3 Test, KMnO4 Test and Tollen’s Test.
Small esters are actually fairly soluble in water but solubility falls with chain length and
hydrophobic parts. Since aspirin has a hydrophobic aromatic ring, it did not dissolve in water.
Having these results, the recrystallized sample was then identified (or assumed) as
acetylsalicylic acid.
V. SUMMARY AND CONCLUSION
Acetic anhydride and salicylic acid reacted to produce aspirin. As a catalyst, phosphoric acid
was employed. Acetic acid was produced and subsequently removed when cold water was
added. Salicylic acid and other contaminants were eliminated during the recrystallization
process.
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The purified sample is logically "near" to the literature value due to its narrow range, according
to a comparison of the melting point ranges of the crude and purified samples with the value
found in the literature.
Using an iodine test, the recrystallized product was distinguished from commercial aspirin,
which was found to include starch. The initial ingredients, salicylic acid and acetic anhydride,
were distinguished from aspirin by additional tests, including the water solubility test, the
FeCl3 test, the KMnO4 test, and Tollen's test.
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Works Cited
http://en.wikipedia.org/wiki/Aspirin
http://wwwchem.csustan.edu/consumer/aspirincons/aspirincons.htm
Rainsford, K. D. (2004). Aspirin and Related Drugs. USA: Taylor & Francis Inc, no page (ebook).
Whitten, K. W., R. E. Davis, M. L. Peck, G. G. Stanley (2007). Chemistry. 8th ed. USA:
Thomson Brooks/Cole, p. 947.