Experiment 9- Synthesis of Organic Compounds [Aspirin] Group 7, Chem 31.

1, AB2,

Atienza, Von Ervy; Alcantara, Mark Jun Sir Kevin Sison May 24, 2010

Abstract

Organic synthesis is a branch of chemical synthesis dealing with the production of organic compounds
by organic reactions. Aspirin is one of the most widely used analgesics since its invention in 1853. The main
objective of this experiment is to produce acetylsalicylic acid via esterification. Aspirin (wanted product) and
acetic acid (by product) were produced by reacting salicylic acid with acetic anhydride and catalyzed using
phosphoric acid. After the reaction, the products were recrystallized to enhance the purity of the resulting
compound. The product was then subjected to physical and chemical tests and the results obtained were
recorded. Several methods and information regarding organic reactions learned from previous experiments
were used.

Keywords: Synthesis, Acetylsalicylic acid, Salicylic acid, Esterification, Recrystallization, Suction Filtration

Introduction

Organic synthesis is a special branch of

chemical synthesis and is concerned with the
construction of organic compounds via organic
reactions. Organic molecules can often contain a
higher level of complexity compared to purely
inorganic compounds, so the synthesis of organic
compounds has developed into one of the most
important aspects of organic chemistry. In the Experimental
experiment product synthesized was acetylsalicylic
acid, known as aspirin.
Production of Aspirin

Acetylsalicylic acid, commonly known as Two grams of salicylic acid, 5 ml acetic

aspirin is used as an analgesic to relieve minor
aches and pains, as an antipyretic to reduce fever,
and as an anti-inflammatory medication. It is
structurally related to salicylic acid. As can be seen
from the figure in the below, salicylic acid is both a
phenol and an aromatic carboxylic acid. Comparing
the two compounds, it can be observed that aspirin
is an ester, formed between acetic acid and the
phenol hydroxyl group of salicylic acid. The
carboxylic acid group makes aspirin mildly acidic.
Its aromatic ring causes it to be quite insoluble in
water. Aspirin can be made soluble by forming its
sodium salt. Salicylic acid reacts with acetic
anhydride when phosphoric acid is present as a
catalyst. Once the aspirin is synthesized, it can be
collected by suction filtration while the more water
soluble unreacted starting materials are washed
away in the aqueous solvent. At this point the
product is already isolated. To purify your product
further, it is necessary to recrystallize the crude
aspirin.
anhydride and 5 drops of 85% phosphoric acid
were placed in a 125-mL Erlenmeyer flask and
stirred. The flask was heated in a boiling water bath
for 5 minutes. Then the flask was removed from the
bath and, while still hot, 2 ml of cold water was
cautiously added to it. After complete
decomposition, 40 ml of water was added to it, it is
then stirred until crystals have begun forming. The
mixture was cooled in an ice bath to complete
recrystallization. The product was collected by
suction filtration, washed with 5 ml of cold water
and then dried. The product was recrystallized from
35 ml of hot water and decolorized using activated
carbon (if the product was colored). It was then
dried and weighed.
Test for the Product
a. Physical Test: The appearance, texture,
color, and odor of the product were
recorded. Its melting point was also
determined.
 b. Chemical Test: A few crystals of the
product were dissolved in 1 ml of methanol
in a test tube. One drop of 1% ferric
chloride solution was added to the solution.
The procedure was repeated using salicylic
acid and results for both tests were
recorded.
Results
Physical test
 Appearance – crystalline
 Texture – fine
 Color – white
 Odor – vinegar-like
 Melting point – 135 °C (275 °F)
Chemical Test (Ferric chloride test)
 Reaction with aspirin – no reaction
 Reaction with salicylic acid – formed violet
solution
Discussion
Aspirin is produced as a product of an acid-
catalyzed or esterification reaction between salicylic
acid and acetic anhydride, where the alcohol group
from the salicylic acid reacts with an acetic
anhydride causing a chemical reaction that turns
salicylic acid's hydroxyl group into an acetyl group,
(R-OH → R-OCOCH3). This yields aspirin and
acetic acid as a byproduct. Small amounts of
phosphoric acid are often used as a catalyst. Acetic
anhydride was used since it can be easily
decomposed by the addition of water and it can
also be reused.
Reaction Pathway
Reaction Mechanism
Aspirin is made from a reaction or
esterification between salicylic acid with acetic
anhydride which is catalyzed by an acid. The
mechanism is as follows. The acid protonates
acetic anhydride. The proton from the acid attacks
the carboxyl oxygen which in turn pulls the two
electrons in one of the pi bonds. It delocalizes the
electrons and spreads them out between the two
oxygen atoms. Then, the delocalized electrons, in
the presence of the hydroxyl group, rearrange in
such a manner as to create temporary bonds
between the two reactants. The proton from the
hydroxyl group attacks the positively charged
carbon (C attached to new OH group) of the
anhydride. The oxygen of the -OH group of the
salicylic acid then becomes positively charged.
After that, the positive charge shifts to the oxygen
atom between the two carbon atoms of the
anhydride as the hydrogen atom of the –OH groups
makes a bond with the said oxygen of the
anhydride. The electrons of the –OH group of the
anhydride delocalizes since there is a positively
charged oxygen atom that must be neutralized. As
the electrons delocalizes, the bond between the
carbon and oxygen (in the center of the anhydride)
breaks, producing a protonated aspirin and an
acetic acid. Finally, the deprotonated acid, being
negatively charged, acts as a nucleophile and
abstract the hydrogen of the protonated aspirin.
This results to the synthesis of acetylsalicylic acid
and acetic acid. Phosphoric acid, a strong acid was
added to catalyze the reaction or to act as a
facilitator to the nucleophilic acetylation of the
salicylic acid. The H+ from phosphoric acid
protonates the carbonyl oxygen of acetic anhydride
to make the carbonyl groups more susceptible to
nucleophilic attack.
Also, the mixture was subjected to heat in a water
bath in which a temperature of no higher than 80°C
was maintained. This temperature is necessary to
control the aspirin crystal formation and its rate of
reaction. If the temperature is raised any further
beyond 80°C, the aspirin might get hydrolyzed and
go back to being a salicylic acid and acetic
anhydride. Finally, cold water was added to the
mixture to separate aspirin from the rest of the other
products. This was so to decompose excess acetic
anhydride and dissolve acetic acid and phosphoric
acid. The aspirin is insoluble in cold water, and can
be completely isolated by filtering the chilled
reaction solution. Cold water was added to the
solution and not hot for hot water will cause an
the acetic anhydride is removed, a purer solution of
acetylsalicylic acid should be formed.
Guide Questions and Answers:
1. What is the reaction involved in the
synthesis of Aspirin?
The reaction involved in the synthesis of aspirin is
reaction between salicylic acid and acetic
anhydride.

→Esterification - the general name for a

chemical reaction in which two reactants (typically
an alcohol and an acid) form an ester as the
reaction product. Esters are common in organic
chemistry and biological materials, and often have a
characteristic pleasant, fruity odor. This leads to
their extensive use in the fragrance and flavor
industry.
increase in the temperature of the solution thereby
2. Write the reaction pathway and mechanism
converting the crude product back to the reactants.
for the synthesis of Aspirin.
Crystal formation (white needle-like) was
Pathway –
observed after the mixture was allowed to cool in an
ice bath for further completion of the reaction.
(Note: if crystal formation was slow, reduce the
volume of the solution of scratch the surface of the
beaker. These scratches would act as site of crystal
formation.) After which, recrystallization was done
to separate aspirin from other crude products which
are considered impurities. Mechanism –

Ferric Chloride Test

Ferric chloride test was done to check the

purity of the product. Ferric chloride reacts with
phenol to form an iron-phenol complex which gives
the solution a purple color. Aspirin, when mixed with
ferric chloride solution, did not produce a violet
solution. However, impure acetyl salicylic acid and
salicylic acid reacts with ferric chloride solution to
produce a violet coloration. This is due to the
presence of the phenol group. Since salicylic acid
contains phenolic –OH, it is suspected to form a
violet solution since its –OH group will be reacting
with the ferric chloride solution. The impure aspirin
also gives a positive result for this test for the main
impurity in the reaction will be excess salicylic acid,
which co-precipitates with the aspirin if the
procedure is done too quickly.

In order to create a purer aspirin, more

acetic anhydride could be added to the reaction.
This would ensure that all of the salicylic acid will
react and that it was the limiting reactant. The
unreacted acetic anhydride can then be removed by
adding cold water forming an acidic solution. After
3. Explain why the recrystallization of Aspirin
in the water should not be heated above
80°C?
 Recrystallization of aspirin in water must not
exceed a temperature reading of 80°C in order to
prevent hydrolysis of the ester, yielding back to
carboxylic acid.
4. Explain the results obtained when Aspirin
and salicylic acid were treated with FeCl3.
Reaction of salicylic acid with FeCl3
Ferric chloride, or iron (III) chloride will not
react with aspirin. It will, however, react with
salicylic acid. Therefore, a positive result was
obtained from the reaction of salicylic acid with
ferric chloride since the phenolic OH of salicylic acid
will react with FeCl3 giving a purple color. A
sample of pure aspirin should not exhibit any color
change.
Adding an aqueous ferric chloride solution
to a sample of aspirin is a good way to see if there
is any unreacted salicylic acid.
Application
A. Another pharmaceutical product derived
from salicylic acid is salol (phenyl
salicylate), the phenyl ester of salicylic acid.
Since phenol cannot be esterified by direct
interaction with salicylic acid, some indirect
method must be used. Write equations for a
sequence that might be used to prepare
salol from phenol and salicylic acid.
 Phenyl salicylate, C6H4(OH)-C-02C6H5, or
salol, is obtained by heating salicylic acid,
phenol and phosphorus oxychloride to 120-
125° C by heating salicylic acid to 2 =0° C
or by heating salicyl metaphosphoric acid
and phenol to 140-150° C. It crystallizes in
rhombic plates which melt at 42° C. and
boil at 172° C.
A. Aspirin and salol are both acidic
substances. Which is the stronger acid?
Which should be more easily hydrolyzed in
an alkaline medium? Why?
 Aspirin is a stronger acid due to the
presence of carboxylic acid which has a
reciprocal hydrogen bonding and highly
positive hydrogen. Salol, on the other hand,
is less acidic because it has a phenyl group
that reduces acidity. Aspirin’s conjugate
base is also more stable compared to salol.
It is easily hydrolyzed in alkaline medium
because of high ionization constant derived
from its acidic properties. The H+ in aspirin
is easily ionized due to the presence of O
(highly electronegative) in the carboxyl
group.
References:
http://www.drcarman.info/kem220lb/01lab220.pdf
http://capital2.capital.edu/faculty/wbecktel/AsprinL.h
tm
http://www.scribd.com/doc/28982674/Synthesis-of-
Aspirin?secret_password=&autodown=pdf
http://www.scribd.com/doc/13771924/Aspirin-
Synthesis-Data-Compilation