Experiment 9

ESTERIFICATION OF SALICYLIC ACID: PREPARATION AND

CHARACTERIZATION OF ASPIRIN AND OIL OF WINTERGREEN
Bacuyag, Florence Mae S.
Mendoza, Jillian Ela M.
Munoz, Abel Christopher
Valino, Angelica Faye
College of Science
University of the Philippines Baguio

Abstract
Esterification is the process of making an ester using carboxylic acid or its
derivatives and catalysed by an acid. This experiment aimed to prepare and
determine the percentage yield of the aspirin produced, characterize crude,
recrystallized, and commercial aspirin, and to synthesize and react methyl
salicylate with FeCl3. Preparation of aspirin involves esterification of salicylic
acid, catalysed by phosphoric acid. The crude and recrystallized aspirin had a
percentage yield of 54.8% and 78.2%, respectively. The melting point ranges
were also determined. The crude aspirin had a lower melting point than actual;
the recrystallized aspirin was considered pure since it is within the melting point
range; the commercial aspirin yielded 134C-145C melting point. Crude,
recrystallized, and commercial aspirin were soluble in water, toluene, and
NaHCO3, but only crude and commercial aspirin tested positive in the test for
phenolic group. Methyl salicylate was also synthesized using salicylic acid,
methanol, and concentrated H2SO4 as catalyst. The methyl salicylate produced
was reacted with FeCl3 and produced a violet solution.

INTRODUCTION
Carboxylic acid derivatives are compounds having an acyl group bonded to an electronegative
atom or substituent that acts as a leaving group in the nucleophilic acyl substitution reaction. (McMurry,
2012).

Equation1. Nucleophilic Acyl Substitution Reaction (McMurry, 2012)

One of these acid derivatives is ester. Esters are derived from carboxylic acids and their
derivatives. The hydrogen in the COOH group in carboxylic acid is being replaced by a hydrocarbon
group, which can be aryl or alkyl, in esters. Esters are synthesized by an acid catalyzed nucleophilic acyl
substitution reaction. This process is called esterification. The reaction involves alcohol and an acid
catalyst (Clark, 2003).

Equation2. Esterification Mechanism Using Carboxylic Acid

 Salicylic acid, (C7H6O3), also known as ortho-hydroxybenzoic acid is a white crystalline solid. It
was first prepared from salicylaldehyde but these days, it is already made of sodium phenolate and
carbon dioxide followed by a treatment with acid. It is used in preparation to combat warts, corns,
calluses, and various skin diseases. It also has its bad effects, it is irritating to the lining of the mouth,
esophagus, and stomach, and can cause hemorrhaging of the stomach lining. This is mainly because
salicylic acid is diprotic acid, when dissolves in water, it releases two hydronium ions and makes the
solution more acidic (Brown, n.d.). Acetyl salicylic acid, was trademarked by the Bayer as Aspirin. The
a in the name Aspirin comes from the root acetyl, spir from the Greek root spirea (willow plant), and
in is a common medical suffix to help ease of pronunciation. (Ali, 2014)
Salicylic acid has a carboxyl and a hydroxyl group both attached to a benzene ring. It is a
difunctional organic compound which can undergo esterification in two different ways, it can act as a
carboxylic acid and an alcohol.
Salicylic acid as an alcohol will react with acetic anhydride, (C 4H6O3), and sulfuric acid, (H2SO4),
as a catalyst forming acetyl salicylic acid, (C 9H8O4), or aspirin. The phenol group on the salicylic acid
forms an ester with the carboxyl group on the acetic anhydride.

+ H2SO4 +
salicylic acid acetic anhydride (catalyst) acetyl salicylic acid carboxylic acid

Equation3. Synthesis of Acetyl Salicylic Acid (Aspirin)

Aspirin is the most used medication globally. It is used to treat fever, pain, and can act as anti-
inflammatory agent. It is a nonsteroidal anti-inflammatory compound.
In preparation of acetyl salicylic acid, recrystallization is involved. This process is an easy and
effective way to purify solid organic compounds as long as the solvent satisfies the following criteria:
It should readily dissolve the solute at elevated temperatures and sparingly at lower
temperatures. It should dissolve the desired solute and not the impurities.
It should dissolve the desired solute and not the impurities.
It should be chemically inert to the solute.
It should allow the solute to give well-formed crystals upon cooling.
It should be highly volatile to permit easy removal from the purified crystals.

Recrystallization is necessary because aspirin is crystalline at a room temperature but a solution

at a higher temperature when synthesized. This process recrystallizes the aspirin while the solid
impurities will remain dissolved in the solution, thus, isolating it. It requires the formation of a few
introductory crystals at the beginning. Formation of crystals can either be induced through seeding or
scratching of the walls of the container. Seeding involves the addition of a pure solid compound with the
same composition as that of the compound to be crystallized. Solid aspirin is isolated through suction
filtration.
This experiment aims to compute the percentage yield of the crude and the recrystallized aspirin. The
percent of starting material that is converted to product in a chemical reaction is referred to as the percent
yield. Organic reactions typically do not give 100% yields, meaning not all of the starting material is
converted to the product. The percent yield can be calculated with the following information:

Weight of the starting material limiting reagent (usually in grams or milligrams)

Molecular weight of starting material (g/mol)
Weight of product (in grams)
Molecular weight of product (g/mol)
 This experiment also aims to determine some characterizations of crude, recrystallized, and
commercial aspirin such as their melting point, their solubility in water, (H 2O), sodium bicarbonate,
(NaHCO3), and toluene, (C6H5CH3). Also, test for phenolic group is included.

On the other hand, salicylic acid as carboxylic acid reacts with methanol, (CH 3OH), and with the
presence of acid catalyst sulfuric acid, it yields into methyl salicylate.

+ H3C-OH H2SO4 + H2O

salicylic acid methanol (catalyst) methyl salicylate water

Equation4. Synthesis of Methyl Salicylate (Oil of Wintergreen)

Methyl salicylate or oil of wintergreen is used as a flavoring agent such as in candies and foods
and is also used in perfumes. It is also used by athletes to soothe muscular aches and pains. It has a
sweet and fresh scent like mint, thus, it is also added in gums and toothpaste. This experiment includes
the testing of the reactivity of methyl salicytate to ferric chloride, (FeCl 3).

RESULTS AND DISCUSSION

A. Preparation of Crude Acetylsalicylic Acid
In this experiment, preparation of crude ASA required three grams of salicylic acid reacted with
7.5mL acetic anhydride and five drops of 85% phosphoric acid. The salicylic acid reacted with excess
acetic anhydride, where phosphoric acid acted as a catalyst (Arias, 2016). Heat was also required to be
able to form the acetylsalicylic acid (ASA) and acetic acid (CH 3COOH) (Eddy, n.d.). A sour smell given off
by the reaction is due to the presence of the acetic acid. This reaction is called an esterification reaction
since the hydroxyl group in the salicylic acid formed an ester in the ASA (Pavia, et.al., 2005).

Equation 5. Synthesis of Acetylsalicylic Acid (retrieved from http://www.lahc.edu/)

While cooling the solution, more crystals started to form. This is due to the decreasing solubility of
ASA, thus it is solidifying. Water decreases the solubility of ASA so ice water was added to maintain its
temperature and solubility (Pavia, et.al., 2005). To induce crystallization, the walls of the beaker were
scratched. Crystals formed are mainly ASA but some substances are also present. Water also mixes with
the excess acetic anhydride and some other impurities thus making the ASA impure.
B. Preparation of Recrystallized Acetylsalicylic Acid
2.15 grams of crude aspirin was transferred to a 125mL E-flask with a 10mL each of diethyl ether
and petroleum ether. The flask was then cooled and the crystals were collected through suction filtration.
The ASA acquired was purified by recrystallization (Eddy, n.d.). In recrystallization, the impure
substance was dissolved in a hot solvent and is cooled to induce crystallization (Smart, 2002). Adding
ether to the ASA crystals prevented the crystals to decompose. (Pavia, et.al., 2005).

C. Mass Calculation
Table1. Mass in grams of the samples used in the synthesis and recrystallization of aspirin.
Weighed Sample Mass (in grams)

Mass of filter paper 0.41

Mass of filter paper + crude aspirin 2.56

Mass of crude aspirin 2.15

Mass of filter paper 0.41
Mass of filter paper + recrystallized aspirin 1.7

Mass of recrystallized aspirin 1.29

Table2. Weight in grams and molecular weight of the starting material and product.
Weight of the starting material limiting reagent 3g
(salicylic acid, C7H6O3)
Molecular weight of starting material 138.121g/mol
(salicylic acid, C7H6O3)

Weight of product (aspirin, C9H8O4) 2.15g

Molecular weight of product (aspirin, C9H8O4) 180.159g/mol

In solving for the percentage yield of the crude aspirin, the quantity in grams of salicylic acid as
the limiting reagent was converted to moles:

1mol C9H8O4
3g C7H6O3 138.121g C9H8O4 = 0.02172mol C9H8O4

Theoretical yield was calculated (the number of grams of product that would form if every mole of limiting
reagent were converted 100% to product). 0.02172mol salicylic acid will yield to 0.02172mol aspirin.

180.159g C9H8O4
0.02172mol C9H8O4 1mol C9H8O4= 3.91305 g C9H8O4 (theoretical yield)

Percentage yield was computed by dividing the actual yield, 2.15g of aspirin, by the theoretical yield.

2.15 g C9H8O4
3.91305 g C9H8O4 100 = 54.8% (percentage yield)

In the recrystallization of aspirin, 1.65g of the crude aspirin was mixed with 15ml each of diethyl
ether and petroleum ether. Crystallization was completed and crystals were collected by suction filtration.
1.29g of recrystallized aspirin was collected. In computing for the percentage yield, the mass of the
recrystallized aspirin was divided by the mass of the crude aspirin.

1.29g
1.65g 100 = 78.2% (percentage yield)

Thus, the percentage yield for the synthesis of aspirin is 54.8% and the percentage yield for the
recrystallization of aspirin is 78.2%.

D. Characterization of Aspirin

The melting point of crude aspirin, recrystallized aspirin and commercial aspirin were determined
and compared. The three kinds of aspirin were pulverized on a watch glass with the end of a test tube
one at a time and separately. The pulverized samples were then mounded. Afterwards, the open end of
the melting point capillary tube was pressed into the samples against the surface of the watch glass. The
capillary tubes were lightly tapped on the sealed end of the tube on the tabletop until the samples filled
about two to four mm height. A 25mL of oil was placed in a 50mL beaker. A thermometer was then
inserted through a cork near the top of the thermometer. The capillary tubes were separately attached
with the samples by means of a rubber band. The oil bath was strong heated with constant stirring until
the temperature is 10-15C below aspirins melting point, 135C. Afterwards, a very low flame was utilized
so that the temperature of the bath rises at a rate of 3C per minute. The temperature was recorded as
soon as a droplet of liquid formed which is the start of melting; the second temperature reading was also
recorded as soon as the last trace of solid liquefied which is the end of melting.
The melting point of the compounds can provide valuable information that can help in the
identification of aspirin or to establish its purity. The melting point is the temperature at which the solid
melts. The intermolecular forces that hold the aspirin together like hydrogen bonding, dipole-dipole forces
and London dispersion forces have to be overcome for melting to occur. These forces hold the molecules
together in a crystal lattice. Pure, crystalline organic compounds usually have sharp and characteristic
melting points. Compounds with minimal or large amounts of impurities can have a lower melting point
than the pure aspirin and increase in the melting point range. (OLT, n.d.) The rate of heating should be
slow near the melting point (about 3C per minute) to guarantee that the increase rate of temperature is
not faster than the ability of the heat to be transferred to the sample. It is necessary that the thermometer
bulb and the sample in the capillary tube be at thermal equilibrium. (LACC, 2005)
The melting point of acetylsalicylic acid or aspirin is 135C. The melting point range of crude
aspirin is 103C-120C, which is significantly lower than the actual melting point and has a wide range of
melting point. This implies that the crude aspirin still contains some impurities since it melted in a long
time. Possible impurities are water, salicylic acid, acetic anhydride, and phosphoric acid. The
recrystallized aspirin has a melting point of 136C-138C. This implies that the recrystallized aspirin is
pure since the melting point range is near the actual melting point and the range is sharp. The melting
point range of commercial aspirin is 134C-145C since more than 4mm was applied in the capillary tube.
Since it has a wide range of melting point, this implies that the commercial aspirin has other ingredients
other than aspirin itself. Possible ingredients may be water, corn starch, fillers or diluents, and lubricants.
The solubility of crude aspirin, recrystallized aspirin, and commercial aspirin with water, sodium
bicarbonate, and toluene was also determined. The three compounds were pulverized and 0.1g of each
was separately put in the test tubes. Afterwards, 2.5mL of water, sodium bicarbonate and toluene,
respectively, was added.
Aspirin is an aromatic compound which contains both a carboxylic functional group and an ester
functional group. It is a weak acid. Since aspirin has a polar component in its carboxyl functional group
and water is polar, aspirin is partially soluble in water. The aromatic ring it contains prevents it from being
fully soluble to water. Crude aspirin and commercial aspirin are also slightly soluble in water.
Aspirin is soluble in NaHCO3. The process underwent an acid-base reaction, giving a sodium
carboxylate which is an ionic species of aspirin. The sodium carboxylate can make the aspirin more
soluble in water. The sodium bicarbonate deprotonated the aspirin. Hence, aspirin is soluble in NaHCO 3.
All three compounds are soluble in NaHCO3.
 C9H8O4 + NaHCO3 -----> C8H8O2COO-Na+ + CO2 + H2O
Equation 6. Reaction of Aspirin with Sodium Bicarbonate

Acetyl salicylic acid is soluble in toluene. Because both toluene and aspirin have a non-polar
aromatic ring, aspirin is soluble with toluene. All three compounds are soluble with toluene.

The three compounds were also tested for phenolic group. Few crystals from each compound
were separately dissolved in five mL of water. Afterwards, a drop of 1% FeCl3 solution was added the
color was noted.
Ferric chloride forms highly colored complexes from red to violet with phenolic compounds.
Solutions containing the phenolic group are dark purple and ones without are a yellow color. The ferric
chloride test was used to compare the commercial aspirin, crude aspirin and recrystallized aspirin and to
check the purity of the product. Upon the addition of ferric chloride to each compound, there was a
formation of violet solution in crude aspirin, yellow solution in recrystallized aspirin, and light violet solution
in commercialized aspirin. The violet solution indicates the presence of phenol. The crude aspirins
formation of violet solution implies that there is still a presence of phenol group, salicylic acid, making the
crude aspirin impure. The light violet solution of commercialized aspirin accounts for the possible phenol
group in the ingredients or components further added in the pure aspirin. The formation of the yellow
solution in the recrystallized aspirin indicates its purity. The yellow solution implies that there is no
phenolic group in the recrystallized aspirin and no excess salicylic acid in the compound. (Odinity, 2014)

E. Synthesis of Methyl salicylate

In a test tube, 1g of salicylic acid was placed. Afterwards, 5mL of methanol 3 drops of conc.
H2SO4 (serving as an acid catalyst) were added respectively. The mixture produced was transparent.

Equation 7. Reaction of Methy Salicylate with Methanol

This mixture is then heated for at least 15 minutes, having been activated; the mixture produced a
sweet scent similar of that to commercial products such as Efficascent oil and Casino alcohol which
indicates the formation of ester. This mixture was stored for a couple of minutes and it thus produced
crystals which were very much fine and condensed and had a web-like aesthetic. Ferric Chloride was
dropped into the solution, forming a violet complex due to the reaction of the phenolic (-OH) character of
the methyl salicylate.
When aspirin comes into contact with air moisture, the compound will have a backward reaction
and it will go back to its original form. The aspirin loses its strength when hydrogen atoms and reverts
back to its original composition, salicylic acid and acetic acid. Acetic acid is also the same component
found in vinegar, which accounts for the vinegar smell of aspirin. (Why, 2010)

CONCLUSION
Esters are derived from carboxylic acids and their derivatives. The hydrogen in the COOH group
in carboxylic acid is being replaced by a hydrocarbon group, which can be aryl or alkyl, in esters. Esters
are synthesized by an acid catalyzed nucleophilic acyl substitution reaction. This process is called
esterification. The reaction involves alcohol and an acid catalyst. Salicylic acid, (C 7H6O3), also known as
ortho-hydroxybenzoic acid is a white crystalline solid. It was first prepared from salicylaldehyde but these
days, it is already made of sodium phenolate and carbon dioxide followed by a treatment with acid. By
means, of suction filtration ASA was prepared, on the other hand, methanol was added to salicylic acid
with an acid catalyst (H 2SO4) and was heated to produce methyl salicylate. The physical characteristics of
the three types of aspirin were observed, in addition, the reaction of methyl salicylate with FeCl 3 yielded a
violet solution. The objectives were successfully achieved.
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