CHEM 251

Author’s Name
Institute’s Name
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Introduction

Acetylsalicylic acid, more commonly known as aspirin, is a non-steroidal anti-inflammatory

drug commonly used as a pain reliever and antipyretic. Every year, 50000 million aspirin tablets

are consumed worldwide. For instance, in the UK, every person takes 70 tablets a year separately

or consumes it with caffeine or vitamin C or other painkillers. The history of the use of medicinal

compounds containing Salicylic acid goes back to ancient times. More than 3500 years ago, man

knew this powder.

Around two centuries ago, a German archaeologist researching in Egypt, found an interesting

fact regarding Egyptian medication. They used more than 877 types of medicines for various

uses in ancient Egypt, one of which was salicylic acid to relieve pain. Furthermore, Frederick

Bayer, the founder of Bayer Pharmaceuticals, was born in Germany in 1825. The factory started

working in the field of pharmacy for a while, employing a number of young chemists and

starting to became a huge pharmaceutical giant. One of the young chemists at the Bayer factory

was Felix Hoffman. To achieve a painkiller to treat his father's arthritis, he performed various

tests on chemical compounds and color lesions. One of these chemicals was acetylsalicylic acid.

In March 1899, Bayer officially registered its product, aspirin, followed by extensive research in

other countries around the world, so that at the time of Hoffman's retirement in 1928, aspirin was

known worldwide.

Aspirin can easily be prepared by acetylation of the OH agent in salicylic acid. This is possible in

different ways. One of these methods is the use of acetic anhydride in an acidic medium, which

is due to the catalytic role of the acid, usually proceeds in the presence of acetic acid or sulfuric

acid. The aspirin esterification reaction is as follows:

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Figure 1- Aspirin Synthesize reaction in brief

Method and Materials

This experiment that took place has to deal with how aspirin is created by using only certain

chemicals. This process took up to a week of class time to complete and finish. There were many

steps that needed to take place in order to make the aspirin. The first step that we did was

gathering a measurement of 0.300 grams of salicylic acid (SA) and placing it into a 10 ml dry

Erlenmeyer flask. We ended up getting as close of measurement as possible so we ended up at

0.300 grams. Once we gathered the salicylic acid we then added 0.700 ml of acetic anhydride to

the flask. In order to do this, we had use an automatic delivery pipette. After this step my partner

and I then proceeded to add three drops of 85% phosphoric acid. By this time not much had

happened to the mixture it was basically white and foggy.

Our next step was to place the mixture into a hot water bath for approximately ten

minutes and would stir the mixture frequently. Once the ten minutes were up we added ten drops

of distilled water into the mixture. Then we added another 2-3ml of water to the flask and let the

mixture cool down to room temperature before our next step. Once cooled the flask was placed

in an ice-water bath. At this point my partner and I were able to see things form during the ice
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bath. then we then used the suction filtration. By doing so we're able to see the aspirin form

during this process and could then allow it to dry for farther test.

Our next step was to crystallize the product again by first transferring the aspirin crystals

into a 10 ml beaker and add 1 ml of ethyl alcohol to dissolve the crystals. When done place the

mixture on a hot plate and swished the mixture around to dissolve and solids. While this mixture

was on the hot plate we also added 2 ml of water to help dissolve any leftover solids. The

substance at this point was a real white foggy liquid. After the substance was a liquid we placed

this beaker in an ice water bath. After about 5 minutes of cooling the substance we could see

crystals forming at the bottom of the beaker. When instructed to we filtered the substance once

again and were able to really see the crystals form as the suction filtration was able to get rid of

all the unnecessary water that was around the crystals. Once this was done we then needed to let

the product sit so the crystals could form even more.

Result and Discussion

The percent yield of synthesized aspirin was estimated to be 31%. The theoretical yield of the

chemical reaction was 0.71 g, though, only 0.161 g of synthesized aspirin was essential gathers.

The recovery percentage for the produced aspirin was 22.67%. It means around one-fourth of

produced aspirin was successfully collected.

Table 1- Quantities of starting material, amounts, theoretical and percentage yields.

Salicylic acid Acetic 85% Ethyl alcohol Theoretical Yield

anhydride phosphoric Yield Percentage
0.3 g 0.7 ml 3 droplets 1 ml 0.71 g 31%
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Melting Point

The literature extracted melting point of aspirin is between 134C -136C. The experimental

base evaluated range for the un-crystalized aspirin was meaningfully different from the literature

value, 125C -140C. The difference in melting point is result of contaminants within the un-

crystalized aspirin specimen. The main element within the impurities is the residue salicylic acid,

and since the melting point of SA is higher than aspirin due to intermolecular forces of salicylic

acid including hydrogen bonds, dipole-dipole forces, and van der Waals forces and by converting

OH group in SA to OCOCH3 in aspirin, intermolecular hydrogen bonds are removed and the

melting point is reduced.

Table 2- Melting point ranges

Literature Melting Point Experimental Melting Point

134C -136C 125C -140C

Iron (III) Chloride Test for Phenol Evaluation

The FeCl3 test was implemented in order to evaluate the existence of phenol in both the un-

crystallized and crystallized aspirin. SA and acetylsalicylic acid were carried out as references,

as salicylic acid contains a phenol group, but acetylsalicylic acid does not so addition of FeCl3

must generate a color alteration of purple in SA contained compounds. Unavoidably, the

existence of the phenol group triggered a color alteration when Iron (III) Chloride was blended

with salicylic acid. After addition of Iron (III) Chloride to commercial aspirin very pale

alteration in color was observed which indicated existence of phenol group or SA in commercial
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Aspirin’s structure. Also, the synthesized aspirin color changed to purple, but was much similar

to the SA. in this instance, the color alteration is most likely sign of unreacted reagents. Also

commercial acetylsalicylic acid was tested and no noticeable alteration in color was observed,

indicating the purity of the compound.

Table 2- 1% Fe3Cl solution outcomes

Specimen Color Alteration

Commercial Aspirin Very Pale Purple

Commercial acetylsalicylic No Noticeable change

acid

Synthesized Aspirin Pale Purple

Salicylic acid Purple

Thin Layer Chromatography

TLC examination was implemented as a second technique to evaluate the pureness. The static

phase was silica gel and the portable phase was isopropyl ether: acetic acid: in a 97:3 v/v ratio.

The exploration of the TLC plate points out the existence of 4 compounds as anticipated as 4

compounds were placed on the plate, see Figure 2. The total distance was 5.8 cm. The SA plated

on point A, move up the farthest and formed a nice round circle with no flashing with an Rf equal

to 0.68. Also, the industrial aspirin plated on point D also formed a nice round circle with a

corresponding Rf value of 0.55. Compared to the SA, the industrial aspirin moved up less

distance, with the lower part of the circle connected to the line. Moreover, both the un-

crystallized and crystallized acetylsalicylic acid moved up approximately a similar distance, each

having corresponding Rf values of 0.51 and 0.53. Also, the un-crystallized aspirin had a little
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very pale flashing upwards, ending just under the middle point of SA. This proposes that the un-

crystallized aspirin yet encompasses slight amounts of SA. The crystallized acetylsalicylic acid

likewise demonstrated pale flashing, but, the flashing ends near to the upper side of the industrial

aspirin. This proposes that the crystallized and industrial acetylsalicylic acid have alike

characteristics.

Table 3- Measured Rf from TLC examination

RfA RfB RfC RfD

4⁄ 3⁄ 3.1⁄ 3.2⁄
5.8 5.8 5.8 5.8

Figure 2. TLC plate under UV light

Conclusion

The synthesis of aspirin proved to be partly successful, due to the low recovery rate and the

existence of unreacted reagents (phenol group) in synthesized aspirin. Both the iron (III) chloride
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test and TLC plate provide evidence that there was residual salicylic acid remaining in the crude

aspirin sample.

Extra Question

Since methyl salicylate contains phenol group attributed to salicylic acid so adding FeCl3 turns

the color from colorless to purple. Furthermore, since methyl salicylate contains R–COOH

(carboxylic acid group) by the addition of sodium hydrogen carbonate, carbon dioxide would be

observed.