THE PRACTICUM OF ORGANIC CHEMISTRY

RECRYSTALLIZATION AND MANUFACTURE OF ASPIRIN

Group 2

By:

Mohammad Afifudin Armadani/18030194020/PKU 2018

Mariatul Qibtiyah/18030194051/PKU 2018

Era Melania/18030194085/PKU 2018

State University of Surabaya

Faculty of Mathematics and Science
Chemistry Department
Chemistry Education Study Program
2020
A. Title of the experiment: Recrystallization and Manufacture of Aspirin
B. Purpose of the experiment:
At the end of this experiment students are expected to be able to:
1. Do the recrystallization well
2. Determine the appropriate solvent for recrystallization
3. Remove impurities through recrystallization
4. Making aspirin by acetylation of the phenol group
5. Recrystallizing aspirin synthesis results well
C. Basic Theory
Methods of Recrystallization
Recrystallization is one of the most effective ways to purify organic
substances in solid form. Therefore this technique is routinely used for the
purification of compounds synthesized or the result of collation from natural
ingredients. before further analysis, for example by means of
spectrophotometry (UV, IR. NMR and MS). There are five steps to
recrystallizing substances, namely:
1. Choose a suitable solvent
Commonly used solvents if sorted according to their increase in polarity
are petroleum ether (n-hexane), toluene, chloroform, acetone, ethyl acetate,
ethanol, methanol and water. A solvent suitable for re-installing a sample
of a particular substance is a solvent that can dissolve it well in a hot state,
but slightly dissolves in a cold state. Usually polar compounds are
recrystallized in less polar solvents and vice versa. The combination of two
solvents is sometimes used in recrystallization, for example chlorofonn-
methanol, hexane-acetone, water methanol and others.
2. Dissolve the compound into the hot solvent as little as possible
Substances to be dissolved should be dissolved in a hot solvent with as
little volume as possible, so that it is estimated to be around the saturation
point. If the dissolution is too runny, steam the solvent so it's
saturated. When a combination of two solvents is used first the substance
is dissolved in a good solvent in a state of heat until dissolved, then add a
 bad solvent drop by drop until turbidity arises. Add a few drops of good
solvent so that the turbidity disappears, then filtered.
3. Filter the solution in hot conditions to remove insoluble impurities.
Filtering the solution in a hot state is intended to treat impurities
that do not dissolve or are suspended in solution, such as sand dust and
others. To make the filter run fast, Buchner's funnel is usually used. If the
solution contains impurities, then before filtering, add a little (± 2% by
weight) activated charcoal to adsorb the dyes. The addition of activated
charcoal should not be too much because it can adsorb the purified
compound.
4. Cooling the filtrate
The filtrate is cooled at room temperature until crystals
form. Sometimes this cooling is done in ice water. The addition of a seed
(seed) in the form of pure crystal into the solution or scratching the walls
of the container with a stirring rod can accelerate the crystallization
process.
5. Filter and dry the crystals
If the crystallization process has been complete, the crystals
obtained need to be filtered quickly using a Buchner funnel. Dry the
crystals obtained by the excitator. Aspirin (acetosal) is an ester of acetic
acid with salicylic acid (o-hydroxy benzoic acid). Therefore, this
compound can be made by reacting salicylic acid with acetic acid
anhydride using concentrated sulfuric acid as a catalyst.
The equation of reaction:

O O

C O H O C OH
O
H3C C
O C CH3
+ O ⇌

H3C C

Salicylic acid Acetic acid anhydride aspirin

 Aspirin is a colorless crystal with a melting point of 133.4°C. This
compound dissolves in both alcohol and ether but is slightly soluble in
water. In the medical field this substance is used as an antipyretic (decreasing
heat) and analgesic (pain reliever).

Salicylic acid
Salicylic acid has the formula C6H4COOHOH in the form of a small crystal
which has a molecular weight of 138,123 g/mol with a melting point of
156°C. Easily dissolves in cold conditions but can dissolve in hot
conditions. Salicylic acid can sublime but can easily decompose to carbon
dioxide and phenol when heated at 200°C. Salicylic acid is mostly used as an
ingredient of medicines and intermediates in drug factories and pharmaceutical
factories such as aspirin and some of its derivatives (Kristian, 2007).

Solvent characteristics for recrystallization:

1. High solubility for substances purified at elevated temperatures and low
solubility at laboratory temperatures / temperatures lower than laboratory.
2. Dissolve a little impuritis
3. Produces good crystalline form from purified compounds
4. Must be able to easily separate purified crystalline compounds, for example
they have relatively low boiling points. The reaction of phenolic salts with
carbon dioxide results in the occurrence of hydrogen substitutes in the ring
by the COOH group. This reaction is known as the Kolbe reaction, which is
an important reaction in the production of phenol to become hydro-
hydroxybenzoic acid or salicylic acid (Wahyudi, 2003)

D. TOOLS AND MATERIALS

Tool
1. Erlenmeyer
2. Glass stirrer
3. Corong Buchner
 4. Dropper drops
5. Burning spiritus
6. Thermometer
Material
1. Salicylic acid
2. Concentrated sulfuric acid
3. Aquadest
4. Ethanol 96%
5. Norit
6. FeCl3 Solution
7. Acetic acid anhydride

E. Procedure
a. Recrystallization
1 grams of salicylic acid

- Put into 125 mL erlenmeyer

- Added 5 mL of aquades
- Heated the mixture until homogeneous and shaken
- Added water in every 10 mL (±70 mL) slowly until the crystal right
dissolves
- Calculated the volume of aquades needed
- Added some drops of aquades until it is really homogeneous
- Added norit as much as 1-2% of salicylic acid's weight (if the
solution is colored)
- Boiled and shaken for a while
- Filtered when it still hot

Residue Filtrate

- Heated
- Cooled in a room temperature
- Filtered with Buchner funnel which is equipped with
vacuum pump
 Filtrate Residue

- Dried in the desicator

- Weighed the mass
- Tested the melting point and compared with
the melting point of the formerly substances

Result

b. The Making of Aspirin

2,5 grams of salicylic acid
- Put into 125 mL erlenmeyer
- Added 3,75 grams of CH3COOH anhydrous
- Put into waterbath (temperature of 55-60oC) and shaken
- Cooled in a room temperature
- Added 3 drops of concentrated H2SO4
- Added 37,5 mL aquades
- Heated until homogeneous
- Filtered with Buchner funnel which is equipped with vacuum pump

Filtrate Residue

- Added 7,5 mL of 96% ethanol and 25 mL aquades

- Heated
- Filtered with Buchner funnel which is equipped with
vacuum pump
- Dried

Filtrate Residue
 - Weighed the mass - Tested with FeCl3
- Tested the melting point

Result Result
F. Observation Result
G. Analysis And Discussion
The practicum titled recralization and making of aspirin has 2 experiments,
namely recrystallization and making aspirin.
1. Recrystallization

The first experiment was salicylic acid recrystallization. This

experiment aims to recrystallize well and determine the appropriate
solvent for recrystallization. The first step is to weigh 1 gram of salicylic
acid (white powder solids) in an analytical balance carefully and
thoroughly. Then put 1 gram of salicylic acid into a 125 mL erlenmeyer,
then add 5 ml of distilled water (colorless liquid). The resulting mixture is
a mixture that is not completely dissolved, this is because the water solvent
is only partially soluble because the solution is saturated because the ratio
between the solvent and the substance is not balanced.

Next heated mixture until homogeneous while shaken. Then added

slowly every 10 mL of water approximately 70 ml of water until the
crystals dissolve. Then calculate the volume of distilled water needed for
the right crystal to dissolve. Then add a few drops of distilled water until
the mixture is completely homogeneous. The purpose of this heating is that
the solubility process can be accelerated and carried out on insoluble
results. This is caused at high temperatures can increase the kinetic energy
of the particles so that collisions between particles often occur. Then added
1% -2% norit from salicylic acid. The function of adding norite is to bind
impurities that have been mixed with the keistal. Next boil while stirring a
few moments then filtered in a hot state. The filtrate obtained (colorless
solution) is then heated and cooled at room temperature. Cooling is
intended to form crystals. Because when the temperature is cold, the
aspirin molecules in the solution will move slowly and eventually
accumulate to form deposits. The solution is then filtered with a Buchner
funnel equipped with a vacuum pump. The residue from the filtering is
then dried in a desiccator. Then the mass is weighed and the melting point
is tested and compared with the melting point of the original substance.
 The residual mass obtained was 0.532 grams. Testing the melting point
by using a melting point, the crystals are inserted into the capillary tube
and the diameter of the capillary tube is very small. After the crystal has
been inserted into the capillary tube then inserted in the melting point tool.
The temperature used is a low temperature in order to facilitate
observation in determining the temperature of the melting point, the
temperature is observed until the crystals in the capillary tube melt into
liquid. The melting point obtained is 160℃.

Reactions that occur in this experiment:

From this experiment it can be concluded that 1 gram of salicylic

acid which is recrystallized can form a colorless elongated crystal.
salicylic acid of 0.532 grams is colorless with a melting point of 160℃
and% purity of 53.2%. Suitable solvents for recrystallization are those that
can dissolve substances well in hot conditions, but slightly dissolve
substances in cold conditions and are usually recrystallized in less polar
solvents and vice versa, solvents suitable for recrystallization of salicylic
acid are aquades. Impurity in salicylic acid compounds can be removed
through the process of recrystallization with distilled water.

2. Making Aspirin

This experiment aims to make aspirin by acetylation of a phenol group

and recrystallizing aspirin properly synthesized

The first thing to do is weigh 2.5 grams of salicylic acid (white powder
solids). Then the salicylic acid solids are put into a 125 mL erlenmeyer.
Then added 3.75 grams of CH2COOH anhydra (colorless solution) which
is weighed using a careful analytical balance. the mixture that is formed is
a mixture that is not completely dissolved and white. The excess acetic
acid is added so that the salicylic acid reacts completely. In addition, by
shifting the equilibrium toward the product, the resulting aspirin will be
more and more anhydrous acetate is used because to prevent the presence
of water, because if there is water the aspirin crystals will decompose back
into salicylic acid.

The next step is put into a water bath with a temperature of 55-60℃
while stirring. Warming is done to speed up the reaction, other than that
because salicylic acid and aspirin are slightly soluble in cold water. Then
cooled at room temperature. Cooling is intended to form crystals, because
when the temperature is low the aspirin molecules in the solution move
slowly and eventually accumulate to form deposits. After being put into
the bath and cooled formed imperfect white crystals Then add 3 drops of
concentrated H2SO4 (colorless solution) and a colorless solution is formed
and then formed imperfect white crystals the function of adding
concentrated sulfuric acid is as a catalyst that accelerates the reaction but
do not react. Subsequently added to 37.5 mL of distilled water and heated
to homogeneous. The aim of adding 37.5 mL of water is that
recrystallization takes place quickly and a precipitate will form. It also
dissolves salicylic acid as a raw material for the formation of aspirin
because of the hydrogen bonds formed between the -OH group with water,
as well as stopping the reaction because the water will hydrolyze the acetic
acid anhydride into two acetic acid molecules. This precipitate is aspirin
and then filtered with a buchner funnel that has been equipped with a
vacuum pump. The filtering process produces a colorless filtrate and a
white crystalline residue.

The aspirin crystals that have been obtained are then purified by
recrystallization which aims to obtain purer crystals. The first step is to
add 7.5 mL of 96% ethanol (colorless solution) and 25 mL of distilled
water. Crystallized crystals will dissolve easily and the crystals will
separate from water and obtain a purer crystal with a minimized amount of
impurities. Then the crystals are added with solvents made from ethanol
and water, the crystals are insoluble. Salicylic acid dissolves in the
addition of ethanol, ethyl acetate, and acetone. This happens because
salicylic acid is polar. While the distilled water solvent only partially
soluble because the solution is saturated because the ratio between the
solvent and the substance is not comparable. then heated. This heating
aims to accelerate the dissolution process and be carried out on non-marine
products. This is caused at high temperatures can increase the kinetic
energy of the particles so that collisions between particles often occur.
Then filtered again with a buchner funnel that has been equipped with a
vacuum pump and dried. After going through this screening process the
filtrate is obtained in the form of a colorless solution and a residue in the
form of a white aspirin crystal. The aspirin crystal is then weighed. The
mass of aspirin obtained was 1,520 grams.

The next step of the aspirin is tested its melting point and tested with
FeCl3. Aspirin is tested using a melting point, aspirin crystals are inserted
into the capillary tube and the diameter of the capillary tube is very small.
The temperature used is a low temperature in order to facilitate
observation in determining the melting point. Observe the temperature
until the aspirin crystals in the capillary tube. The melting point of aspirin
crystal obtained was 136℃. After melting point testing, aspirin crystals are
tested with ferric chloride solution and produce ferric chloride solution
which remains light yellow and white precipitate. This shows that the
aspirin obtained is pure because it does not contain -OH from salicylic
acid.

Reactions that occur in this experiment:

 From this second experiment it can be concluded that the making of
aspirin can be done by acetylation of phenol groups to form 1.520 grams
of colorless elongated crystals with a melting point of 136 ℃ which when
tested with FeCl3 solution produces a light yellow solution.
Recrystallization of aspirin synthesized in the form of colorless elongated
crystals.

H. Conclusion
According to the result of observation, we can conclude that:
1. One gram of salicylic acid that is recrystallized can form a colorless
elongated crystal. salicylic acid of 0.532 gram colorless with a melting
point of 160oC and percent purity of 53.2% (not in theory)
2. The suitable solvent for salicylic acid recrystallization is aquades
3. Impurities in salicylic acid compounds can be removed through the process
of recrystallization with aquades
4. Preparation of aspirin can do through acetylation of phenol groups
5. Recrystallization of synthesis result of aspirin is colorless elongated
crystals
I. References
Kristian, Rieko. 2007. Asam Salisilat dari Phenol. Skripsi Fakultas Teknik
Universitas Sultan Ageng Tirtayasa:Banten
 Tim Dosen Kimia Organik. 2017. Buku Petunjuk Praktikum Kimia Organik.
Surabaya: Universitas Negeri Surabaya Fakultas Matematika dan Ilmu
Pengetahuan Alam Jurusan Kimia
Wahyudi, Iskandar, S.M. and Parlan. 2003. Common Text Book Kimia Organik
II. Malang: JICA

J. Attachment
1. Answer Of The Question
1) Recrystallization
Known:
 Initial mass of salicylic acid = 1 grams
 Final mass of salicylic acid = 0,532 grams
Asked: % purity of crystallization ....?
Answer:

% purity = x 100%

= x 100%

= 53,2%
2) The Making of Aspirin
Known:
 Mass of salicylic acid = 2,5 gram
 Molar mass of salicylic acid = 138 gr/mol
 Mass of acetic acid anhydrous = 3,75 gram
 Molar mass of acetic acid anhydrous = 102 gr/mol
 Result mass of aspirin = 1,520 gram
 Molar mass of aspirin = 180 gr/mol
Asked: % rendement....?
Answer:
 Mol of salicylic acid = 2,5 gram : 138 gr/mol = 0,018 mol
 Mol of acetic acid anhydrous = 3,75 gram : 102 gr/mol = 0,036
mol
 C7H6O3 + (CH3CO)2O  C9H8O4 + CH3COOH
M = 0,018 0,036 - -
R = 0,018 0,018 0,018 0,018
S = 0 0,018 0,018 0,018

Theoritic mol of aspirin = 0,018 mol

Theoritic mass of aspirin = mol x molar mass = 0,018 mol x 180 gr/mol
= 3,24 gram

% Rendement = x 100%

= x 100%

= 46,91%
2. Documentation