1. EKC 107 ORGANIC CEMISTRY LAB EXPERIMENT 1
ORGANIC CHEMISTRY LAB
EKC 107
EXPERIMENT 1 :
SYNTHESIS OF ASPIRIN
OBJECTIVE :
After this experiment session, students should be able to :
i. Understand the process of aspirin preparation
ii. Identify the advantages of aspirin as pain reliever
iii. Learn the aspirin purification process
KEYWORDS
Aspirin, Acetylsalicylic acid, Salicylic acid, Acetic anhydrade, Purification Feric chloride
INTRODUCTION
Aspirin, one drug of the first drug to come into common usage, is still mostly the
widely used in the world – approximately 35,000 metric tones are produced and
consumed annually, enough to make over 100 billion standard aspirin tablets every year.
Aspirin, also known as ‘acetylsalicylic acid’, has a chemical formula of C9H8O4.
The chemical structure of aspirin :
COOH
OCOCH3
Aspirin
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2. EKC 107 ORGANIC CEMISTRY LAB EXPERIMENT 1
Aspirin, is analgesic, anti-inflammatory, antipyretic and is an inhibitor of platelet
aggregation. Aspirin is prepared by chemical synthesis from salicylic acid, by acetylation
with acetic anhydride.
The father of modern medicine was Hippocrates, who lived sometime between
460 B.C and 377 B.C. Hippocrates was left historical records of pain relief treatments,
including the use of powder made from the bark and leaves of the willow tree to help heal
headaches, pains and fevers.
By 1829, scientists discovered that it was the compound called salicin in willow
plants which gave you the pain relief. According to “From A Miracle Drug” written by
Sophie Jourdier for the Royal Society of Chemistry : “It was not long before the active
ingredient in willow bark was isolated; in 1828, Johann Buchner, professor of pharmacy
at the University of Munich, isolated a tiny amount of bitter tasting yellow, needle-like
crystals, which he called salicin. Two Italians, Brugnatelli and Fontana, had in fact
already obtained salicin in 1826, but in a highly impure form. By 1829, [French chemist]
Henri Leroux had improved the extraction procedure to obtain about 30g from 1.5kg of
bark. In 1838, Raffaele Piria [an Italian chemist] then working at the Sorbonne in Paris,
split salicin into a sugar and an aromatic component (salicylaldehyde) and converted the
latter, by hydrolysis and an oxidation, to an acid of crystallized colourless needles, which
he named salicylic acid.”
Henri Leroux had extracted salicin, in crystalline form for the first time, and
Raffaele Piria succeeded in obtaining the salicylic acid in its pure state.
The problem was that salicylic acid was tough on stomachs and a means of
‘buffering’ the component was searched for. The first person to do was a French chemist
named Charles Frederic Gerhardt. In 1853, Gerhardt neutralized salicylic acid by
buffering it with sodium(sodium salicylate) and acetyl chloride, creating acetylsalicylic
acid. Gerhardt’s product worked but he had no desire to market it and abandoned his
discovery.
In 1899, a German chemist named Felix Hoffmann, who worked for aGerman
company called Bayer, rediscovered Gerhardt’s formula. Felix Hoffmann made some of
the formula and gave it to his father who was suffering from the pain of arthritis. With
good results, Felix Hoffmann then convinced Bayer to market the new wonder drug.
Aspirin was patented on March 6,1889.
The folks at Bayer came up with the name Aspirin, it comes the ‘A’ in acetyl
chloride , the “spir” in spiraea ulmaria (the plant the derived the salicylic acid from) and
the ‘in’ was a then familiar name ending for medicines.
Aspirin was first as a powder. In 1915, the first Aspirin tablets were made.
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3. EKC 107 ORGANIC CEMISTRY LAB EXPERIMENT 1
THEORY
Aspirin is commercially synthesized using a two-step process. First, phenol
(generally extracted from coal tar) is treated with a sodium base generating sodium
phonoxide, which is then reacted with carbon dioxide under high temperature and
pressure to yield salicylate, which is acidified, yielding salicylic acid. The process is
known as the Kolbe-Schmitt reaction.
O ONa O OH
OH ONa OH
CO2 H2SO4
NaOH
Salicylic acid is then acetylated using acetic anhydride, yielding aspirin and acetic acid as
a byproduct. It is a common experiment performed in organic chemistry labs, and
generally tends to produce low yields due to the relative difficulty of its extraction from
an aqueous state. The trick to getting the reaction to work is to acidify with phosphoric
acid and heat the reagents under reflux with a boiling water bath for between 40 to 60
minutes.
The original synthesis of aspirin from salicylic acid involved acetylation with acetyl
chloride. Unfortunately, the byproduct from this is hydrochloric acid, which is corrosive
and environmentally hazardous. As described above, it was then later found that acetic
anhydride was a better acylating agent, with the byproduct acetic acid formed, which
does not have the unwanted properties of hydrochloric acid and can also be recycle.
O OH O OH
OH O O O O
+ +
O O OH
Formulations containing high concentrations of aspirin often smell of vinegar. This is
because aspirin can undergo autocatalytic degradation to salicylic acid in moist
conditions, yielding salicylic acid and acetic acid. Purification of the product by
recrystallization and characterize it by measuring its melting temperature. Pure aspirin
has a melting temperature around 135-136o
.
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4. EKC 107 ORGANIC CEMISTRY LAB EXPERIMENT 1
GLASSWARE AND CHEMICALS
Glassware :
Beaker 250ml, Thermometer, Filtering flask, Enlermayer Flask 250ml, Heater.
Chemicals :
Salicylic acid, Acetic anhydride, Phosphoric acid, Solution of 1% Ferric chloride, Ice.
EXPERIMENT
Experiment 1 : Preparation of aspirin
1. Prepare 100ml of hot water by using 250ml beaker and heater. Adjust the water
temperature at 50o
C.
2. Weight 0.210 ± 0.005 gram salicylic acid [MW = 138.1 g/mol] and transfer into
the Erlenmayer flask.
3. Add 0.5ml acetic anhydride in a flask containing salicylic acid, then add one drop
of phosphoric acid into the mixture.
WARNING :
Wear gloves and goggles and carry out all operations in a fume hood. Be careful
while dealing with phosphoric acid since it is very corrosive and can cause skin
irritation.
4. Immerse the flask containing the mixture into hot water [temperature 50o
C] and
agitate the mixture with agitator until the entire solid salicylic acid dissolved.
5. Heat the solution for about 4 minutes to go the complete reaction.
6. Remove the flask from hot water and leave it cooled to the room temperature. At
this moment, acetylsalicylic acid should have crystallized from the mixture. If the
crystal still not yet formed, scratch inside the flask using small spatula and cooled
the flask in ice water until crystallization formed.
7. After crystallization done, add 3.0ml water and agitate the mixture.
8. Prepare the filtrate unit. Wet the filter paper with small amount of water and filter
the mixture. After the entire crystals have filtered, add 1.0ml cold water [water
cooled with ice water] into erlenmayer flask. Transfer the remaining crystal in the
flask to a filter funnel.
9. After the entire crystals have transfer, pour the crystal with 0.5ml cold water
[water cooled with ice water] for about 3 times.
10. Transfer the crystal to a glass saucer and leave it to dry.
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5. EKC 107 ORGANIC CEMISTRY LAB EXPERIMENT 1
Experiment 2 : Purification test
This test conducted in order to determine the absence of salicylic acid in product reaction.
1. Add 0.5ml water in three test tubes.
2. Add small amount of salicylic acid in first test tube.
3. Add small quantity of crystal from first experiment in second test tube. [The wet
crystal also can be used for this test].
4. The third test tube containing only water and will be used as control tube.
5. Add 1 drop of 1% ferric chloride in each test tube.
6. Shake all the test tubes and record the formed color. Formation of complex ferum-
phenol will produce red-orange color, depends on the type of absence phenol.
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6. EKC 107 ORGANIC CEMISTRY LAB EXPERIMENT 1
UNIVERSITI SAINS MALAYSIA
SCHOOL OF CHEMICAL ENGINEERING
EKC 107 - ORGANIC CHEMISTRY
LABORATORY COURSE
Name of student :________________________________
Matrix Num :________________________
Name of partner : _________________________________
Instructor : ____________________________________
EXPERIMENT : SYNTHESIS OF ASPIRIN
Experiment 2 : Purification test
Test tube Observation/Explanation
Water + salicylic acid + ferric chloride
Water + product of experiment + ferric
chloride
Water + ferric chloride
QUESTION
1. The important material for preparation of aspirin is salicylic acid. Preparation
process of salicylic acid using phenol is known as Kolbe-Schmit Reaction.
Discuss this reaction process in details.
2. Salicylic acid is one of the phenol groups while acetylsalicylic acid is not a phenol
group. Explain this statement.
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7. EKC 107 ORGANIC CEMISTRY LAB EXPERIMENT 1
UNIVERSITI SAINS MALAYSIA
SCHOOL OF CHEMICAL ENGINEERING
EKC 107 - ORGANIC CHEMISTRY
LABORATORY COURSE
Name of student :________________________________
Matrix Num :________________________
Name of partner : _________________________________
Instructor : ____________________________________
EXPERIMENT : SYNTHESIS OF ASPIRIN
Experiment 2 : Purification test
Test tube Observation/Explanation
Water + salicylic acid + ferric chloride
Water + product of experiment + ferric
chloride
Water + ferric chloride
QUESTION
1. The important material for preparation of aspirin is salicylic acid. Preparation
process of salicylic acid using phenol is known as Kolbe-Schmit Reaction.
Discuss this reaction process in details.
2. Salicylic acid is one of the phenol groups while acetylsalicylic acid is not a phenol
group. Explain this statement.
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