PRACTICAL REPORT

SYNTHESIS OF ORGANIC AND INORGANIC COMPOUNDS

EXPERIMENT 1
SYNTHESIS OF ASPIRIN (ACETYL SALICYLIC ACID)

NAME : ORRYZA M. ILLAHI PRACTICUM DATE : 04/11/2023

STUDENT NUMBER : 23923002 COLLECTION DATE : 05/11/2023

GROUP : 3 RECEIVED BY :

ASISSTANT : BILGIIS CORRECTED BY :

Yogyakarta, ___________________________2023

ASSESSMENT CRITERIA

Cover : (Maks.5) Assistant,

Purpose : (Maks.5)

Introduction : (Maks.10)

Tools and materials : (Maks.5)

Method : (Maks.5) (_____________________________________)

Result and discussion : (Maks.55) Lecturer,

Conclusion : (Maks: 5)

References : (Maks.5)

Attachment : (Maks.5) (Prof. Allwar, Ph.D.)

 ABSTRACT

An attempt has been made to synthesise aspirin or acetyl salicylic acid using the
recrystallisation method, which aims to synthesise acetyl salicylic acid based on the acetylation
reaction between salicylic acid and salicylic acid based on the acetylation reaction between
salicylic acid with anhydra acetate using a sulfuric acid (H2SO4) catalyst and conducting tests
with iron (III) chloride (FeCl3) and test the melting point of acetyl salicylic acid using melting
point. using melting point. Recrystallisation is the purification of solids which is done by
dissolving the solid with a certain solvent where the substance can dissolve when heated.
dissolve when heated. The synthesis of aspirin was carried out by dissolving salicylic acid
(HOC6H) in a solvent (HOC6H4COOH) with acetic anhydride ((CH3CO)2O) and concentrated
H2SO4. The mixture was shaken and heated then cooled in a container with ice cubes. The
crystals formed were filtered and air dried. Crystals are weighed until constant then calculate
the yield formed and tested with FeCl3. The results obtained is a constant weight of 0.7474
grams of white-coloured crystals with a yield of 59.3% and the FeCl3 test changed the colour of
the crystal to dark purple.

Keywords: Acetyl salicylic acid, salicylic acid and crystals

INTRODUCTION

Aspirin is a medicine to relieve pain, fever, and inflammation. The drug, also known as
acetisalicylic acid, is also used to prevent the formation of blood clots, thereby reducing the risk
of heart attack or stroke in people with cardiovascular disease. Aspirin is a non-steroidal anti-
inflammatory drug that works to prevent the formation of prostaglandins, which are substances
that trigger inflammation, pain, or fever, so that these conditions can subside. In low doses, it can
inhibit platelets from sticking together, preventing blood clots from forming. Therefore, aspirin
can also be used to prevent cardiovascular diseases caused by blood clots, such as stroke. Aspirin
trademarks: Acetylsalicylic Acid, Aptor, Ascardia, Aspilets, Astika, Bodrexin, Cardio Aspirin,
Cartylo, Contrexyn, Coplavix, Farmasal, Gramasal, Inzana, Miniaspi 80, Naspro, Nogren,
Nospirinal, Novosta, Remasal, Thrombo Aspilets.

Aspirin is made by esterification, where the active ingredient of aspirin, salicylic acid, is
reacted with anhydrous acetic acid or can also be reacted with glacial acetic acid if anhydrous
acetic acid is difficult to find. This anhydrous acetic acid can be replaced with glacial acetic acid
because glacial acetic acid is pure and does not contain water besides that anhydrous acetic acid
is also made of two galsial acetic acids so that in the reaction the volume is all doubled. In the
process of making this esterification reaction assisted by an acid catalyst to accelerate the
reaction. But the addition of this catalyst is not very effective so heating is done to accelerate the
reaction. In the manufacture of aspirin, water is also added to recrystallise quickly and a
precipitate will form. This precipitate is aspirin.

Chemical data of Aspirin

Chemical Formula : C9H8O4

Relative Molecular Mass : 180.157 g/mol
Physical Data of Aspirin

Density : 1.40 g/cm³

Melting point : 135 °C (275 °F)
Boiling point : 140 °C (284 °F) (decomposes)
Water solubility : 3 mg/mL (20 °C)

Crystallisation is a very important purification method important in every synthesis of

inorganic or organic compounds. Crystallisation is a separation and purification technique used
to produce a wide variety of materials. Visually crystallization is defined as a phase change
where a crystalline product is obtained from a solution (Febriyanto, 2019). The principle of
crystallisation is that the solid will dissolve easily in hot solvents when compared with colder
solvents. If a solution of the compound is saturated in a hot state and then cooled, the compound
will dissolve. then cooled, the solute will decrease its solubility and form a precipitate (Hart,
2003). This experiment was conducted to synthesise acetyl salicylic acid based on the acetylation
reaction between salicylic acid and acetic anhydride and conduct FeCl3 test and test its melting
point. FeCl3 and test its melting point. The principle of this experiment is using the
crystallisation method which produces a white precipitate of acetyl salicylic acid. The precipitate
can be converted into crystals which were determined to be pure through the FeCl3 test.
METHODOLOGY

Equipment and Materials

Equipment used in this experiment are ice tubs, pumpkin heater of 100 ml, bunsen, petri
dish, glass funnel, beaker of 100 ml, ice cubes, dropper pipette, 10 ml volume pipette, 50 ml
volumetric flask, and glass stirrer. Materials used in this experiment are distilled water (H2O),
acetic anhydride ((CH3CO)2O), dry salicylic acid (HOC6H4COOH), pure alcohol, sulfuric acid
(H2SO4) and iron (III) chloride (FeCl3).

Work Procedure

The equipment and materials to be used were prepared then salicylic acid is weighed on
filter paper as much as 1 grams. Pour in 1 grams of salicylic acid into a 100 mL flask, 7 ml of
acetic acid anhydride and 5 drops of concentrated sulfuric acid. Shake the mixture until it
perfectly dissolve. Then heat over a water heater (the temperature inside the flask is maintained
at 50°-60° C) while stirring for 15 minutes. Let it cool while still stirring, and add 150 mL of
water. Then strain it with the aid of suction.

The purification is done by recrystallization. The solvent used is a mixture of 30 mL of

96% alcohol and 75 mL of distilled water. Put in the crystal in a solvent and heat it until all
crystals dissolve, then cool it gradually. The mixture will result in gorgeous needle-like crystals.
The crystal is then tested with a reagent of iron (III) chloride. The crystals formed were then
calculated the yield.

Equipment Set

SALICYLIC ACID WEIGHING

HEATING DEVICE

FILTERED WITH A BUCHNER FILTER AND VACUUM PUMP

RECRYSTALLISATION COOLING ASPIRIN CRYSTALS

CRYSTAL TESTING WITH FECL3

RESULTS AND DISCUSSION

Discussion

Acetyl salicylic acid (acetosal) or better known as aspirin is a salicylate ester resulting
from synthesis of organic acids with substitution on the hydroxyl group, namely acetic acid and
salicylic acid. Acid acetyl salicylic acid is an acid with a pKa value of 3.5 so that at a low pH the
acid will ionise and contact directly with the gastric mucosa mucosa, causing damage directly.
Protection of acetyl salicylic acid from acid contact stomach using oral acetosal which is
developed as tablets or delayed release capsules (enteric coated) that are resistant to enteric
capsules) that are resistant to acid and may reduce gastrointestinal disorders. Acetyl salicylic acid
has a density of 1.4 g/ml and a molecular weight of 180.15 g/mol. molecular weight of 180.15
g/mol with boiling point 140 °C and melting point 128-137 °C (Wilmana & Sulistia, 2012).

Structure of Acetyl Acid Salicylate (Riswiyanto, 2009).

Acetylation reaction is the reaction of introducing an acetyl group (CH3CO-) into organic
molecules such as (-OH and -NH2). Reagents that are commonly used are acetic anhydride acetic
anhydride or ethanoyl chloride (CH3COCl). This acetylation reaction is an equilibrium reaction
by taking one direction of reaction towards the ester side, which high yields and conversions can
be obtained by removing the water formed. This experiment uses an acetylation reaction because
the materials used are salicylic acid salicylic acid and acetic anhydride, so that an acetylation
reaction can occur (Groggins, 1985).

The experiment began with preparing the equipment and materials that will be used then
salicylic acid was weighed on filter paper filter as much as 1 gram. Salicylic acid is an organic
acid in the form of white crystalline powder, odourless, sweet-tasting and exists in nature in
some plants. Used for the manufacture of aspirin, dyes and food preservatives. Salicylic acid is
used as a specimen containing alcohol so that it will react with acetic anhydride and there is an
acetylation reaction on its (Martin, 2012). Weighing is done to get the initial mass (theory)
salicylic acid so that it can be calculated the yield and the use of filter paper is as a container
when weighing (Martin, 2012).

Structure of Salicylic Acid (Martin, 2012)

Acetic anhydride is used as a solvent for which plays a role in the acetylation process to
form acetyl salicylic acid without being diluted first with distilled water (H2O) (Martin, 2012).
Acetic anhydride ((CH3CO)2O) is an organic anhydride in the form of a colourless liquid organic
which is used as a hydrating and acetylating agents. It smells like vinegar due to its reaction with
air moisture to form acetic acid (Martin, 2012).

Acetic Anhydride Structure (Martin, 2012)

The addition of sulphuric acid to the mixture is as a catalytic acid that can accelerate the
synthesis by lowering the activation energy so that the reaction runs faster and the energy
required in the reaction acetylation reaction is less. Sulfuric acid (H2SO4) is a colourless viscous
liquid inorganic acid, resembles oil and is hygroscopic. The next stage of the solution was
shaken until the salicylic acid dissolved. Shaking is done to mix the three ingredients perfectly
by accelerate the collision between particles that continue to occur and dissolving the salicylic
acid solids thus accelerating the acetyl acid formation reaction (Martin, 2012). The shaking
produced a white precipitate which did not dissolve. The solution was heated for 15 minutes and
cooled to room temperature, then put into a container filled with ice cubes. Heating is done to
remove impurities in the solution in order to produce crystals with high purity and to accelerate
the solubility of salicylic acid solids salicylic acid solids, where the occurrence of kinetic
movement between particles that are getting faster so that it can accelerate the reaction rate
(Martin, 2012).

Cooling at room temperature done so that the heat in the solution out into the
environment so that the temperature solution drops and forms white white in colour with a lattice
that still tenuous (Hart, 2003). Cooling using ice cubes is done to accelerate the process of the
formation of acetyl salicylic acid crystals acetyl salicylic acid crystals because a decrease in
temperature will induce rapid crystal formation which is based on the difference in freezing point
of the components (Hart, 2003; Martin, 2012). The next stage after crystals are formed, distilled
water is added as much as 75 ml and heated while stirring briefly. The addition of water aims to
form crystals in order to take place perfectly and to hydrolyse the excess acid in the crystals of
acetyl salicylic acid crystals that are formed. This can be seen when adding water to the crystals,
the solution has like oil which indicates sulfuric acid which is used as catalytic acid hydrolysed
by water (Martin, 2012).

The next stage the crystals collected and filtered using a funnel lined with filter paper that
previously weighed. Filtering is done to separating between solid substances which is in the form
of crystals with distilled water solvent, where the crystals here is the residue while distilled water
is the filtrate (Martin, 2012). The residue obtained was then air dried for 5 minutes on the oven.
Drying is done to reduce the water content in the crystalline acetyl salicylic acid so that the yield
obtained is more accurate.

The next stage is carried out test with FeCl3 and test the melting point melting point of
acetyl salicylic acid crystals. Testing using FeCl3 was done to determine purity of acetyl salicylic
acid crystals crystals and to find out if there are still presence or absence of salicylate compounds
from the crystals formed. Tests carried out produces a crystal that is purple colour, this is
because FeCl3 reacts with the phenol group of salicylic acid to form a purple complex. The
results obtained showed a negative reaction where acetyl salicylic acid crystals changed colour to
dark purple when dripped with FeCl3 which indicating the presence of salicylic acid compounds
in the crystals (Groggin, 1985).
Reaction Mechanism Formation Aspirin

Salicylic Acid Acetic Acid Anhydride Aspirin Acetic Acid

Reaction Mechanism Formation Aspirin (Nisyak & Hisbiyah, 2019)

The reaction mechanism that occurs is acetic anhydride attacking H+ so that protonation
occurs. Then acetic anhydride resonates and attacks the the phenol group of salicylic acid. H+ is
released from -OH and binds with the O atom of acetic anhydride. Acetic anhydride breaks off
into acetic acid and acetyl salicylic acid (Fessenden & Fessenden, 1994).
CONCLUSION

Based on the experiment conducted, it can be concluded that the synthesis of aspirin or
acetyl salicylic acid (acetosal) can be done by using the crystallisation method with an
acetylation reaction mechanism, where the reaction between salicylic acid and acetic anhydride
which is assisted by a catalytic acid in the form of sulphuric acid, thus obtaining white-coloured
aspirin crystal in white colour. The crystallisation process carried out produced a yield of aspirin
of 59.3 % with average constant mass gain of 0.7474 grams. The discrepancy between the acetyl
salicylic acid levels of experimental and theoretical due to the factor of errors in conducting
experiment such as less thorough in addition of ingredients, shaking and the crystals obtained
have low purity or there is still the presence of purity or the presence of impurities in the crystal

Crystal aspirin obtained were tested with FeCl3 solution. The results obtained are dark
purple coloured crystals which showed that there is still salicylic acid content in the crystals.

REFERENCE

https://www.alodokter.com/aspirin#:~:text=Aspirin%20adalah%20obat%20untuk%20meredakan
,stroke%20pada%20penderita%20penyakit%20kardiovaskular

https://id.wikipedia.org/wiki/Aspirin

Febriyanto, R., 2019, Analisis Konduktivitas Produksi Bioflokulan-DYT sebagai Pengganti

Flokulan Sintesis, Journal of Community Based Environmental Engineering and Management.,
3(2): 41-48. Fessenden, R. J., & Fessenden J. S., 1994, Kimia Organik Edisi Ketiga Jilid Dua,
Erlangga, Jakarta

Groggin, P. H., 1985, Unit Processes in Organic Synthesis, Mac Graw Hill Book Company Inc,
New York. Hart, H., 2003, Kimia Organik, Erlangga, Jakarta

Martin, E. A., 2012, Kamus Kimia, Pustaka Pelajar, Yogyakarta

Nisyak, K., & Hisbiyah, A., 2019, Percobaan V Sistematis Asam Asetilsalisilat, Qiara Media,
Pasuruan. Riswiyanto, 2009, Kimia Organik Edisi Kedua, Erlangga, Jakarta
 OBSERVATION DATA

TREATMENT OBSERVATION RESULTS

1. 1 gram salicylic acid + 7 mL acid A WHITE COLOURED COLLOIDAL
anhydrous acetate + 5 drops of SOLUTION IS FORMED
concentrated sulfuric acid, stir to make
it homogeneous
2. Heated and stirred for 15 minutes with PRECIPITATE IS COMPLETELY
the temperature maintained in a 100 mL DISSOLVED INTO A COLOURLESS
glass beaker in the range between 50°- HOMOGENEOUS SOLUTION
60° C
3. Added 75 mL of distilled water WHITE COLOURED PRECIPITATE
FORMED
4. Filtered with a buchner filter and pump WHITE PRECIPITATE OF COARSE
vacuum ASPIRIN IS FORMED
5. Recrystallisation using a mixture of A WHITE COLOURED COLLOIDAL
solvent 15 mL ethanol P.A and 37.5 SOLUTION IS FORMED
mL distilled water
6. Heated on the stove Electricity PRECIPITATE IS COMPLETELY
DISSOLVED INTO A COLOURLESS
HOMOGENEOUS SOLUTION
7. Cooled in an ice-filled bath WHITE CRYSTALS FORMED
8. Filtered with a buchner filter and pump NEEDLE-SHAPED WHITE CRYSTALS
vacuum ARE FORMED
9. Weighed:
- Weight of blank filter paper 0.6058 GR
- Weight of filter paper + aspirin 1.3532 GR
crystals
- Weight of pure aspirin crystal 0.7474 GR
- % Aspirin crystal yield
10. Tested with a FeCl3 solution THE CRYSTALS TURN A PURPLE
DATA ANALYSIS

Data of experiment :

0.6058gr

1.3532 gr

0.7474 gr

Calculating moles of salicylic acid and anhydrous acetic acid

- Mole of salicylic acid = mass : Mr = 1 gr : 138.12 gr/mol = 0.007 mol

- Mass of anhydrous acetic acid = ρ.V = 1.08 ml/gr × 7 ml = 7.56 gr

- Mole of anhydrous acetic acid = mass : Mr = 7.56 gr : 102.09 gr/mol = 0.074 mol

Reaction Mechanism Formation Aspirin

Salicylic Acid Acetic Acid Anhydride Aspirin Acetic Acid

At first 0.007 mol 0.0074 mol - -

Reacted 0.007 mol 0.007 mol 0.007 mol 0.007 mol

Remaining - 0.0067 mol 0.007 mol 0.007 mol

ht of aspirin:

Theoretical weight of aspirin = mole × Mr = 0.007 mol x 180.16 gr = 1.26 gr

% Yield × 100% = × 100% = 59.3%

Scheme of work