Formal Report- Aspirin

SYNTHESIS OF ASPIRIN Authors: Meneses, Eunice Rae M., Pacheco, Meah G., P alma, Paola Louise R., Perez, Fleur Jeizl, Refuerzo, Maria Godesa University of Santo Tomas, Faculty of Pharmacy Abstract: Acetylsalicylic acid is synthesized through the esterification process of the salicylic acid and the acetic anhydride, an acid catalyst. Test for impurities such as the Ferric Chloride Test, Starch Test and Melting Point Determination were performed. It was concluded that impurities were present in the crude sample of Acetylsalicylic acid. I.

soluble in hot liquids (solvents) than they are in

Background of Study

Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 136 °C (277 °F), and a boiling point of 140 °C (284 °F). [1] It is insoluble in cold water. It is a prototypical analgesic used in the treatment of mild to moderate pain. It has anti-

cold liquids. If a saturated hot solution is allowed to cool, the solute is no longer soluble in the solvent and forms crystals of pure compound. Impurities are excluded from the growing crystals and the pure solid crystals can be separated from the dissolved impurities by [5]

filtration.

inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Acetylsalicylic acid also inhibits platelet

aggregation

and

is

used

in

the

prevention of arterial and venous thrombosis.

[2]

Aspirin can be made by reacting salicylic acid with acetic acid in the presence of an acid catalyst. The phenol group on the salicylic acid forms an ester with the carboxyl group on the acetic acid. However, this reaction is slow and has a relatively low yield. Acetic anhydride is used instead of acetic acid for its reaction is much faster and it has a higher yield since acetic anhydride is much more reactive than acetic acid.

[3]

Crystallization

is

the

(natural

or

artificial) process of formation of solid crystals precipitating from a solution, melt or more rarely

deposited directly from a

gas.

Figure 1. The Aspirin Synthesis Reaction

[4]

Crystallization is based on the principles of solubility: compounds (solutes) tend to be more

II.

Materials and Methods:

The materials used in this experiment are: hard glass test tube, 10-mL graduated cylinder,

dropping

pipette,

beaker,

thermometer, stirring rod, filter paper, and funnel. The following reagents were were utilized: utilized: salicylic acid, acetic anhydride, concentrated sulphuric acid. After the preparation of the indicated materials and reagents, 2 grams of salicylic acid was weighed through the use of analytical balance. The sample weighed was transferred then into a hard glass test tube. With the aide of graduated cylinder, an exact amount of 5 mL acetic anhydride was added to the sample in the test tube. 5 drops of concentrated sulphuric

was added as well, stirring it until the salicylic

Weight of salicylic acid

2.0055 g

acid was completely dissolved to obtain a

Weight of Acetylsalicylic

1.8032 g

solution. It was placed later on into a water

acid

bath set up which has a temperature of 70 to 80 °C for 20-30 minutes with occasional stirring. A drop wise of water with a room temperature was added until the solution becomes cloudy. After which, the solution was removed from the

Table 1. Weight of Salicylic Acid and Acetylsalicylic Acid

The weight of the salicylic acid is 2.0055 g while the weight of the Acetylsalicylic acid which was synthesized by the former is 1.8032 g.

setup. The inner wall of the test tube was

Ferric Chloride Test

scratched and it was rinsed with cold water. The

The ferric chloride test is used to determine the

rinsing was transferred into a beaker and was

presence or absence of phenols in a given

then placed on an ice bath for 10 minutes to

sample.   It is used as a purity test in the

accumulate crystals. The solution was filter in a

synthesis of aspirin. The addition of ferric

pre-weighed filter paper and was dried. And

chloride to salicylic acid produces a specific

lastly, the aspirin was weighed again.

color caused by the reaction of salicylic acid

[6]

After the accumulation of crystals,

with aqueous ferric (Fe(H2O)6+3) ion. The

confirmatory tests were performed. First is the

oxygen atoms of the acid group  –COOH, and of

Ferric

were

the -OH group on the salicylic acid together can

prepared, containing 1 mL of water. The

form a complex with Fe(H2O)6+3. That complex

following was added into each corresponding

has an intense violet color. In aspirin, the  –OH

test tube: salicylic acid, commercially available

group of salicylic acid has been replaced by a O-

aspirin, prepared aspirin, benzoic acid, benzyl

COCH3 group which prevents the second bond

alcohol, and the controlled variable which is the

from being formed. The resulting complex with

water. Each solution was shake and 1 drop of

aspirin shows only a slight yellow color, not very

2% aqueous Ferric chloride was added. The

different from that of Fe(H2O)6+3 itself.

Chloride

Test.

6

test

tubes

[7]

second confirmatory test is the Starch Test. 3 test tubes, each containing 2 mL of water was

Test Tube

prepared and the following were added into a

a.

corresponding test tube: prepared aspirin,

b. Commercially

commercially

available

aspirin,

and

the

controlled variable- water. 1 drop of Iodine was then added into each test tube. The melting point of the aspirin was determined. A 40 mL beaker with oil was prepared. It was placed on hot plate and a thermometer was immersed

c.

Salicylic Acid

Color Noted Purple 1. Faint Purple tinge

available ASA

2. Yellow

Prepared ASA

Light Purple

d. Benzoic Acid

No color reaction

e. Benzyl Alcohol

No color reaction

f.

No color reaction

Control- H20

Table 2. Ferric Chloride Test Results

into the oil to check the temperature of the water. 2 capillary tubes, each ¼ filled with the

Result shows that salicylic acid has a

aspirin is banded into the thermometer. The

color reaction in the Ferric Chloride test. A

temperature in which it started to melt and

purple solution was noted. Two commercially

when it was completely dissolved was noted.

available ASA were tested. The first obtained a lavender solution while the second had a yellow

III.

Results:

solution. The prepared ASA had a color reaction

as well in which it had obtained a lavender

wider range of temperatures, usually greater

solution. On the other hand, Benzoic acid,

than 2 degrees.

Benzyl alcohol and the controlled variable

Two capillary tubes containing sample which is

which is water didn’t undergo color reaction.

the prepared ASA were tested to determine the melting point of ASA. Based from the result, the

Starch Test The Iodine test is used to test for the presence of   starch. Iodine solution — iodine dissolved in an aqueous solution of potassium iodide — reacts with the starch, producing a purple-black colour. However, the intensity of the colour decreases with increasing temperature and with the presence of water-miscible organic solvents, such as ethanol. Test Tube a.

Color Noted

Prepared ASA

No color reaction

b. Commercially

1. Blue Violet

available ASA

2. Yellow Green

c.

[9]

Control- H20

average temperature where in the sample started to melt was at 120 °C, while the temperature where in it was completely dissolved was at 130 °C. Percentage Yield: Acetylsalicylic acid: 2.0055g Salicylic Acid x 1 mol SA x 1 mol ASA x 138.12g SA 1 mol SA 180.157 g ASA = 2.6159 g ASA (Limiting Reactant) 1 mol ASA 5 mL Acetic Anhydride x 1.082 AA x 1 mol AA x 1 mL 102.09 g AA 1 mol ASA x 180.157 g ASA = 9.5470 g ASA 1 mol AA 1 mol ASA (Excess Reactant)

No color reaction Percentage Yield:

Table 3. Starch Test Results

Result shows that only the commercially available ASA undergo color reaction. The first ASA tested had a violet solution while the second had a yellow one.

Percentage Yield = 1.8032 g x 100 = 68.932% 2.6195 g IV.

Conclusion

Salicylic

Melting point determination

acid

is

positive

in

Ferric

Chloride Test, meaning it has a presence of

Temperature

Temperature

started to melt

dissolved

Trial 1

120 °C

135 °C

Trial 2

120 °C

125 °C

because of its’ light purple color. The impurity

Average

120 °C

130 °C

of the prepared acetylsalicylic acid is because of

melting

point

is

obtain a yellow color or a faint purple tinge. The prepared sample was proven to be impure

Table 4. Melting Point Range of Trial 1 and Trial 2

Experimentally,

phenol group. A pure acetylsalicylic acid would

actually

recorded as the range of temperatures in which the first crystal starts to melt until the temperature at which the last crystal just disappears. It indicates the level of purity of a sample. An impure compound melts over a

the presence of salicylic acid that was not completely dissolved during the water bath heating process. Starch is used as a binder in drug products. Manufacturers usually use it and in the experiment, only the first sample of commercially available acetylsalicylic acid had a positive result.

The melting point range of a pure aspirin is from 138 °C to 140 °C.

 [6]

http://www.chemistry.mtu.edu/~kmsm

The gathered

result is lower (120 °C to 140 °C), which means

ith/SYP/Student/Tuesday/Aspirin.pdf [8]

Vogel's

Textbook

of

Quantitative

Chemical Analysis. Retrieved August 13,

impurities are present in the sample.

2014 from V.

[1]

[2]

References:

Zorprin,

http://en.wikipedia.org/wiki/Iodine_tes

Bayer

Buffered

(aspirin)

dosing,

interactions,

adverse

indications, effects,

Retrieved August 13, 2014 from

2014 from

http://reference.medscape.com/drug/z

http://www.westminster.edu/acad/sim

orprin-bayer-buffered-aspirin-

/documents/SDeterminationofMeltingP

343279#showall

oints.pdf

Acetylsalicylic

acid.

Drug

Bank.

http://www.drugbank.ca/drugs/DB009 45 Synthesis of Aspirin. Retrieved August

fossum/files/2012/01/8-Synthesis-ofAspirin.pdf Tavare,

N.S.

(1995).

Industrial

Crystallization. Plenum Press, New York.

Retrieved

August

13,

2014

from

http://en.wikipedia.org/wiki/Crystallizat ion Crystallization. Organic Chemistry at CU Boulder. Retrieved August 13, 2014

from http://orgchem.colorado.edu/Techniqu e/Procedures/Crystallization/Crystalliza tion.html [6]

"Ferric Chloride —  Pyridine Test Page". Chemistry.ccsu.edu. Retrieved 2013-0911. Retrieved August 13, 2014 from http://en.wikipedia.org/wiki/Ferric_chl oride_test

[7]

Gannon University SIM and Auburn University SIM. Retrieved August 13,

http://www.laney.edu/wp/cheli-

[5]

Determination of Melting Points.

more". Medscape Reference. WebMD.

13, 2014 from

[4]

[9]

and

Retrieved August 13, 2014 from

[3]

t

Aspirin

Preparation

of

Acetylsalicylic

acid

(Aspirin).Retrieved August 13, 2014 from

[10]

lab manual