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SYNTHESIS OF ASPIRIN

Silverio, A.1, Soriano, R. 1, Tan, J. 1, Tequillo, H. 1, Tolentino, M. 1 

University of Santo Tomas, Faculty of Pharmacy1 

ABSTRACT

The experiment is performed to explore the chemical process in the synthesis of a common organic product called

acetylsalicylic acid (aspirin) and to become familiar with the optimum conditions needed for successful yields.

Aspirin, produced from the acid catalyzed esterification of salicylic acid and acetic anhydride, is synthesized and

 purified by recrystallization. Ferric chloride test was performed to detect the presence of enol in the salicylic acid,

commercially available aspirin, prepared aspirin, benzoic acid, benzyl alcohol, and a control group, which is water.

The color of the resulting mixture, whether purple or yellow, determines the presence of enol. Salicylic acid and

 prepared aspirin produced a purple coloration and therefore tested positive (contains enol) while commercially

available aspirin, benzoic acid, benzyl alcohol and water produced a yellow coloration and tested negative (contains

no enol). Starch test was likewise performed to detect the presence of starch in prepared aspirin, commerciallyavailable aspirin, and a control group, which is water. A blue or blue-black color indicates the presence of starch.

The commercially available aspirin produced a yellow coloration, therefore testing positive while prepared aspirin

and water tested clear. Melting point determination was performed as the last confirmatory test with test values of

136-138oC and 137-139oC.

INTRODUCTION

Aspirin, also known as acetylsalicylic acid,

is a derivative of salicylic acid. It is the most widely

used medicine in the world. It has the ability to

reduce fever (antipyretic), reduce pain (analgesic),

relieve swelling and pain associated with rheumatismand arthritis (anti-inflammatory), enhance the

elimination of uric acid (uricosuric), and interfere

with the body’s production of prostaglandins and

their products (thromboxanes), which are associated

with headaches, platelet aggregation and

vasoconstriction. [1]

Aspirin is a part of a group of medications

called nonsteroidal anti-inflammatory drugs

(NSAIDs), but differs from most other NSAIDs in

the mechanism of action. Aspirin’s ability to suppress

the production of prostaglandins and thromboxanes isdue to its irreversible inactivation of the

cyclooxygenase (COX) enzyme. Aspirin acts as an

acetylating agent where an acetyl group is covalently

attached to a serine residue in the active site of the

COX enzyme. This makes aspirin different from

other NSAIDs (such as diclofenac and ibuprofen),

which are reversible inhibitors.

The main side effects of aspirin are

gastrointestinal ulcers, stomach bleeding, and ringing

in the ears, especially with higher doses. In children

and adolescents, aspirin is not recommended for flu-

like symptoms or viral illnesses, because of the riskof Reye’s syndrome.

The synthesis of aspirin is classified as an

esterification reaction. Salicylic acid is treated with

acetic anhydride, an acid derivative, causing a

chemical reaction that turns salicylic acid’s hydroxyl

group into an ester group. This process yields aspirin

and acetic acid, which is considered a byproduct of

this reaction. Small amounts of sulfuric acid are used

as acid catalysts. [2] 

Figure 1.  Esterification of salicylic acid and acetic

anhydride to produce acetylsalicylic acid and acetic

acid.

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EXPERIMENTAL

A.  Compounds Tested

Salicylic Acid is a monohydroxybenzoic acid, a type

of phenolic acid and a beta hydroxyl acid. This

colorless crystalline organic acid is widely used in

organic synthesis and functions as a plant hormone. It

is derived from the metabolism of salicin. It is

 probably best known as a key ingredient in topical

anti-acne products. [3]

Acetic anhydride  has a chemical formula

(CH3CO)2O. It is commonly abbreviated Ac2O.

Acetic anhydride is the simplest isolatable acid

anhydride and is a widely used reagent in organic

synthesis. It is a colorless liquid that smells strongly

of acetic acid. [4] 

Benzoic acid  has the chemical formula C7H6O2  (or

C6H5COOH), is a colorless crystalline solid and a

simple aromatic carboxylic acid. It occurs naturally

in many plants and it serves as an intermediate in the

 biosynthesis of many secondary metabolites. Salts of

 benzoic acid are used as food preservatives and

 benzoic acid is an important precursor for the

industrial synthesis of many other organic substances.[5] 

Figure 3. Structure of Benzoic Acid.

Benzyl alcohol  is an aromatic alcohol with the

formula C5H6CH2OH. It is a colorless liquid with a

mild pleasant aromatic odor. It is a useful solvent due

to its polarity, low toxicity, and low vapor pressure.[6]

Figure 4. Structure of Benzyl Alcohol.

B. 

Procedure

1.  Reaction of Salicylic Acid and Acetic

Anhydride

Weigh 2 grams of salicylic acid and transfer to a hard

glass test tube. Add exactly 5 mL of acetic anhydride.

Carefully add 5 drops of concentrated sulfuric acid

and stir until salicylic acid is completely dissolved.

Place on a water bath with a temperature of 70-80oC

for 20-30 minutes with occasional stirring. Add

dropwise of room temperature water until the

solution becomes cloudy. Remove the solution from

water bath. Scratch the inner wall of the test tube and

rinse with ice cold water. Place the rinsings on a

 beaker. Add 20 mL of ice cold water to the beaker

and stir. Place the beaker on an ice bath for 10

minutes to allow aspirin to crystallize. Filter the

solution in a pre-weighed filter paper and allow to

dry. Weigh the aspirin.

2. 

Ferric Chloride Test for Salicylic Acid

Place 1 mL of water in 6 test tubes and add the

following: a) salicylic acid, b) commercially

available aspirin, c) prepared aspirin, d) benzoic acid,

e) benzyl alcohol, and f) control group, which is

water. Shake and add 1 drop of 2% aqueous ferric

chloride. Observe the color.

3.  Starch Test

Place 2mL of water in 3 test tubes and add the

following: a) prepared aspirin, b) commercially

available aspirin, and c) control group, which is

water. Add 1 drop of iodine. Observe the color.

4.  Melting Point Determination

Push the open end of a capillary tube into the

 prepared aspirin. Move the powder to the closed end

of the capillary tube by tapping it on the table until

the aspirin occupies 1-2 mm of the capillary tube end.

Seal the opposite end of the filled capillary tube.

Attach the capillary tube to a thermometer using

rubber bands by aligning the bulb of the thermometerto the closed end of the capillary tube. Make an oil

 bath by half filling a 100 mL beaker with warm

cooking oil. Heat the oil bath. Place the thermometer/

capillary tube assembly in an oil bath. The surface

level of the aspirin must be beneath the surface level

of the oil bath. Place the beaker on a hot plate and

frequently stir the oil to distribute heat uniformly.

 Not the temperature at which the aspirin melts.

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Repeat the procedure twice and average the results.

Compare the experimental result with the accepted

value.

Figure 5. An illustration of the setup used in Melting

Point Determination.

RESULTS AND DISCUSSION

Synthesized aspirin is a white crystalline solid. It is

obtained by mixing premeasured amounts of salicylic

acid, acetic anhydride and sulfuric acid. The

crystalline acid was obtained by recrystallization

 process.

Ferric chloride test was performed to test for the

 presence of enol. Upon adding ferric chloride to each

designated test tube, either a purple or yellow

coloration is observed. A purple color indicates the presence of enol while a yellow color indicates the

absence of enol.

Test Tube Observation Inference

Salicylic Acid Clear purple

solution

With enol

Commercially

available

aspirin

Turbid purple

solution

With enol

Prepared

aspirin

Clear purple

solution

With enol

Benzoic acid Clear colorless

solution

Without enol

Benzyl alcohol Yellow

globules

Without enol

Control Clear colorless

solution

Without enol

Table 1. Results of Ferric Chloride Test.

In the results obtained, only salicylic acid,

commercially available aspirin and prepared aspirin

contained enol. The others did not.

Figure 6. Results of Ferric Chloride Test (L-R, T-B).

Salicylic acid, commercially available aspirin 1,

commercially available aspirin 2, prepared aspirin,

 benzoic acid, benzyl alcohol and control.

Starch test was performed to test for the presence of

starch. A blue or blue-black color is the expected

result, indicating the presence of starch.

Test Tube Observation Inference

Prepared

aspirin

Clear colorless

solution

 No starch

Commercially

available

aspirin

Turbid yellow

solution with

 brown

 precipitate

With starch

control Clear colorless

solution

 No starch

Table 2. Results of Starch Test

In the results obtained, only commercially available

aspirin contained starch. The others did not.

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Figure 7.  Results of Starch Test (L-R). Prepared

aspirin, commercially available aspirin 1,

commercially available aspirin 2, control.

Melting point determination determines the purity of

the synthesized compound by comparing the

experimental melting point to the theoretical melting

 point.

Trial Temperature

1 136-138oC

2 137-139oC

Table 3. Results of Melting Point Determination

The synthesized compound has a melting point close

if not exactly the theoretical one, which is 136oC.

Percentage Yield

Weight of Salicylic Acid 2.0300 g

Weight of Evaporating Dish 24.7255 gWeight of Evaporating Dish +

aspirin

26.1339 g

Weight of aspirin 1.4084 g

Table 4. Raw data collected during the experiment

Salicylic Acid

( ) (

) ( )

 

Acetic Anhydride

(

) (

) (

) (

)  

Salicylic Acid is the limiting reagent while acetic

anhydride is the excess reagent.

 

     

   

 

The percentage yield is 69.38%.

CONCLUSION

Aspirin is a white crystalline solid formed from the

esterification of salicylic acid and acetic anhydride in

the presence of an acid catalyst. It contains an enol

group and may contain starch when produced

commercially. It has a melting point of 136 oC. It is

most commonly used as an NSAID.

REFERENCES[1]Bayquen, A., et. al. (2009). Synthesis of

Acetylsalicylic Acid (Aspirin). In Laboratory

 Manual in Organic Chemistry (p. 141). Quezon City,

Philippines: C & E Publishing.[2]http://en.wikipedia.org/wiki/Aspirin [3]http://en.wikipedia.org/wiki/Salicylic_acid [4] http://en.wikipedia.org/wiki/Acetic_anhydride [5]http://en.wikipedia.org/wiki/Benzoic_acid [6]http://en.wikipedia.org/wiki/Benzyl_alcohol