EXPERIMENTAL NOTES
SALICYLIC ACID SYNTHESIS
A. Experimental Purpose
Studying the reaction of esters in alkaline solution through the synthesis
of salicylic acid using gandapura oil.
B. Basic theory
1. Salicylic acid
Salicylic Acid According to Murlistyarini, (2015) , salicylic acid
(salicylic acid) is a lipophilic acid agent formulated in ethanol. Salicylic acid
belongs to the aromatic carboxylic acid group, but has a hydroxy group in the
beta position, therefore salicylic acid is categorized in the BHA group. Salicylic
acid is a monohydroxybenzoic acid, a type of phenolic acid. This crystalline
organic acid is widely used in organic synthesis and functions as a plant
hormone. Salicylic acid is a compound that is chemically similar to aspirin but
not identical to the active component of aspirin, which is known to be used in
anti-acne treatments. Salts and esters of salicylic acid are known as salicylates
(Irwandi, 2014) .
Salicylic acid, known as 2-hydroxy-benzoic acid, has a chemical
structure of C 7 H 6 O 3 . The macroscopic form of salicylic acid is a white
crystalline powder with a sweet taste, odorless and stable in air. Salicylic acid
is difficult to dissolve in water and more soluble in fat (Sulistyaningrum et al.,
2012) . Salicylic acid forms colorless needles. This substance is easily soluble
in alcohol and ether (Svehla, 1979) . Salicylic acid has the molecular formula
C 6 H 4 COOHOH and a molecular weight of 138.123 g/mol with a melting
point of 156 o C and a density at 25 o C of 1.443 g/mL. Salicylic acid can
sublimate but decomposes easily into carbon dioxide and phenol when heated
rapidly at around 200 o C (Patil et al., 2015) .
According to Kirk & Othmer, (1979) , salicylic acid is used for:
a. Raw materials for making aspirin
b. Raw materials for the manufacture of salicylic esters/salicylic salts
c. Raw materials for the manufacture of phenol resins
d. Raw materials for making antiseptic, anti-fungal, anti-dandruff
drugs and various skin diseases
According to Annuryanti et al., (2013) , naturally, salicylic acid comes
from the metabolism of salicin isolated from willow bark and has been used as
medicine since the beginning of human civilization to suppress pain. In
addition, salicylic acid can also be obtained from the extraction of sweet birch
and spearmint. Synthetically, salicylic acid can be obtained through the Kolbe
process and the Kolbe-Schimitt process. According to Poliakoff, (1961) , the
Kolbe and Kolbe-Schimitt processes have long been used to produce salicylic
acid in large quantities. In the Kolbe process, salicylic acid can be obtained
quantitatively through the reaction of phenol and sodium hydroxide with a
yield of only 50% ( Poliakoff , 1961) . yield (yield) reached 95% (US Patent
No. 4,376,867, 1983).
2. Methylsalicylate
Methylsalicylic acid or 2-hydroxy benzoic acid methyl ester is an organic
compound that has an aromatic ring. This compound is a methyl ester
derivative of salicylic acid. Methylsalicylate can be produced through the
condensation reaction of salicylic acid and methanol. The molecular chemical
formula for methylsalicylate is C8H8O3. The molecular weight of
methylsalicylate is 152.15 g/mol with a percent composition of C = 63.15%, H
= 5.30%, O = 31.55% (Astuti et al., 2007) . According to Kirk & Othmer,
(1979) , the physical properties of methylsalicylate are as follows:
1) Molecular Formula: C8H8O3
2) Forms at 1 atm 25ºC: liquid, colorless
3) Molecular weight, (g/mol): 152
4) Boiling point (ºC): 220.5
5) Freezing point, (ºC): -8.3
6) Critical temperature (K): 701
7) Critical pressure (Bar): 40.9
8) Density (g/cm3): 1.183
Methylsalicylate is a derivative of salicylic acid which is yellow in color
with a pungent odor like an ointment. Its property 7 is insoluble in water but
soluble in alcohol and ether. Methylsalicylate is an ester compound that is often
used as a raw material for making ointments (lotions) that can treat muscle
pain. The chemical structure of methylsalicylate can be seen in Figure 1.
Figure 1. Chemical Structure of Methyl Salicylate ( Methyl salicylate - Wikipedia, the free encyclopedia , tt)
According to Turner, (1958) , methylsalicylate is used for:
a. Flavoring agent in the food and beverage industry
b. Raw material for toothpaste and mouthwash
c. Raw materials for rheumatic drugs, heat drugs and anti-irritants
d. Solvent for cellulose and its derivatives
e. Insecticidal mixture
f. Printing ink raw materials
g. Raw materials in the perfume industry
Methyl salicylate has been widely developed into other compounds, for
example salicylic acid and acetylsalicylic acid (aspirin). Methylsalicylic
derivatives other than acetylsalicylic acid, namely the synthesis of
salicylanilides (Zhang et al., 2015) . Synthetically, methylsalicylate can be
obtained through an esterification reaction between methanol and salicylic acid
with the help of a concentrated H2SO4 catalyst (Chua & Sunarti, 1999) .
Esterification reaction is the reaction of forming ester compounds from
carboxylic acids and alcohols with an acid catalyst. The resulting ester
compound has a specific aroma and is characteristic. Apart from going through
the esterification process, methylsalicylate can be found in gandapura oil
(wintergreen oil). Methylsalicylate is produced from the distillation of the
twigs of the gandapura plant (Yuliani, 2005) .
3. Gandapura oil
Yuliani & Satuhu, (2012) stated that there are 2 species of gandapura in
Indonesia, namely Gaultheria fragrantissima which has wide/large leaves and
the type G. Procumbens which has small leaves. In its natural habitat,
gandapura grows on steep and rocky cliffs. Gandapura (Gaultheria
fragantissima) can grow in the highlands, 1300-3300 meters above sea level.
Gandapura is spread and grows wild in mountainous areas including on Mount
Lawu, Tawangmangu and in Wonosobo, Dieng. Gandapura is one of the
essential oil-producing plants that is included in the List of Fostered
Commodities of the Directorate General of Plantations based on the Decree of
the Minister of Agriculture number 511/kpts/pd.310/9/2006. One of the
gandapura oil-producing industries in Indonesia is located in Wonosobo,
namely the Rukun Farmers Group located in Sikunang Village, Kejajar
District, Wonosobo Regency.
According to Yuliani & Satuhu, (2012) , gandapura oil in international
trade is known as wintergreen oil. Gandapura oil is obtained from the
distillation of the gandapura plant ( Gautheria fragrantissima Auct ). Most
parts of the plant contain flavonoid compounds, while the leaves contain
tannins and oil. The main component of gandapura oil is methylsalicylate with
levels reaching 98% (Fang et al., 2016) .
The main component of gandapura oil (Wintergreen oil) is a
methylsalicylic compound which is widely used in the pharmaceutical,
fragrance, and food and beverage industries. The content of methylsalicylate in
gandapura oil reaches 93-98% (Mao et al., 2014) , however, gandapura oil
produced by Farmers Groups in Indonesia only has 82.23% methyl salicylate
content (Mauludi, 2003) . Gandapura trade oil contains 90% methyl salicylate,
so that 1 ton can produce 900 kg of methylsalicylate. Gandapura oil is produced
from the leaves and stems of the gandapura plant ( Gautheria sp .) through a
distillation process.
4. Esther's reaction in alkaline conditions
An ester can undergo a hydrolysis reaction in alkaline conditions which
is called a saponification or saponification reaction. The ester saponification
reaction is not reversible, so it often produces carboxylic acids and alcohols
with better yields than acid hydrolysis. Since the reaction takes place in an
alkaline environment, a carboxylate salt is produced. In alkaline hydrolysis
reactions, the OH- used is a reagent instead of a catalyst, while in acid
hydrolysis, the H+ used is a catalyst (Fessenden & Fessenden, 1992) .
Saponification is basically a soap-making process that takes place by
reacting fatty acids, especially triglycerides, with an alkali to produce glycerol
and a carboxylic salt (a type of soap). Soap is a salt (sodium) which has a long
carbon chain (Partana, 2008) .
Figure 2. Reaction of methylsalicylate in alkaline conditions
5. Reflux and Crystallization
Reflux is a method for mixing two substances or compounds by heating
without any compound being lost. Reflux is carried out by boiling the liquid in
a container connected to the condenser so that the evaporated liquid condenses
back into the container (Laksmiani et al., tt) . In general, the reflux method is
used to synthesize volatile compounds. In this condition, if normal heating is
carried out, the solvent evaporates before the reaction runs to completion. The
principle of the reflux method is that the volatile solvent used evaporates at
high temperatures, but is cooled by the condenser so that the solvent in the form
of vapor condenses on the condenser and drops into the reaction vessel so that
the solvent remains during the reaction (Wilcox & Wilcox, 1995 ) .
Crystallization is a purification method by forming crystals so that the mixture
can be separated. A gas or liquid can cool or solidify and form crystals due to
the crystallization process. Crystals can form from solutions that are saturated
with certain solvents. The larger the crystal size, the better because the smaller
the impurities contained (Arsyad, 2001) , while recrystallization is the
separation of crystalline solids. Often the compounds obtained from the results
of a chemical synthesis have a purity that is not too high. To purify these
compounds, recrystallization is necessary (Kabra et al., 2015) .
C. Tools and materials
The tools used in the "Salicylic Acid Synthesis" lab are a reflux
apparatus (three neck flask), beaker glass, watch glass, measuring cup,
Erlenmeyer, Buchner filter, recrystallization tool set, melting point
determination tool, Bunsen spirit. While the materials needed are gandapura
oil, 5 M NaOH, 5 M sulfuric acid, cooking oil, tap water and distilled water.
D. Ways of working
As much as 2.85 grams of gandapura oil was put into a 250 ml three
neck flask which had been equipped with reverse cooling and added 25 ml of
5 M NaOH. The mixture was refluxed for 30 minutes then cooled to room
temperature then added 35 ml of 5 M sulfuric acid dropwise while stirred. The
precipitate formed is filtered with a Buchner filter and followed by
recrystallization using hot distilled water as a solvent. Next, dry the crystals
obtained and determine their melting point.
E. Observation data
No
Treatment
Observation
1
A total of 2.85 grams of gandapura
oil was put into a 250 ml three-
neck flask
Its mass is 2.854 grams of
gandapura oil
2
Add 25 ml of 5 M NaOH
A white precipitate formed
3
Reflux for 30 minutes then cool
Refluxed/heated for 41 minutes,
until there is no white precipitate
and is clear in color and the
temperature does not exceed 80oC
4
Add 35 ml of 5 M sulfuric acid
A white precipitate appears with a
color change from cloudy white,
then pink and ends white.
Meanwhile, white foam also
appeared.
5
The precipitate formed was
filtered using a Buchner filter
Filtered until white precipitate
crystals remain until no water
drips, and uses filter paper in the
filtering process.
6
Recrystallization
Separate between filtrate (liquid)
and impurities (crystals)
7
Drying
Evaporate the remaining water
8
Solubility test
-
9
Smell test
-
10
Melting point test
After being tested, salicylic acid
began to melt when heated at 159 o
C
11
Salicylic acid weight
0.0216 grams
F. Discussion
This experiment is entitled "Synthesis of Salicylic Acid", which aims to
study the reaction of esters in alkaline solution through the synthesis of salicylic
acid using gandapura oil. The preparation of salicylic acid in this experiment was
carried out by hydrolyzing methyl salicylate, namely gandapura oil with an
alkaline catalyst, namely NaOH. The working principle of this experiment is an
ester hydrolysis reaction using NaOH as a base catalyst. The methods used are
reflux, crystallization and recrystallization methods. Methyl salicylate from
gandapura oil will form sodium salicylate salt when reacted with NaOH which
will then form salicylic acid when reacted with H 2 SO 4 (sulfuric acid). The
salicylic acid obtained was white crystals with small and brittle crystal forms.
In the first treatment, 2.854 grams of gandapura oil was put into a 250 ml
three-neck flask, then 25 ml of 5 M NaOH was added . When gandapura oil was
added to 5M NaOH, the mixture immediately agglomerated into a white
precipitate. This reaction is called saponification or saponification. The
saponification reaction is an ester hydrolysis reaction in an alkaline medium
(Fessenden & Fessenden, 1992) , then refluxed for 41 minutes at a temperature
of less than 80 o C until the white precipitate dissolves or disappears and is clear
in color, in the heating process using a bath containing oil so that the heat does
not hit the three neck flask directly. Generally it is only refluxed for about 30
minutes, but because the white precipitate has not disappeared when it is still 30
minutes, and an error occurs in the reflux process, where the condenser which
should be cold does not feel cold due to obstruction of cold water entering
through the hose and the temperature had exceeded 80 o C.
The reflux process aims to obtain sodium salicylate salt from methyl
salicylate contained in gandapura oil. The use temperature is kept below 80 o C
is intended so that the salicylate salt does not react again with alcohol which
causes the formation of esters, and so that no damage occurs to the salicylate
salt. After refluxing, the salicylate salt was removed from the three neck flask
and then cooled to room temperature.
After refluxing and cooling, H2SO4 is added drop by drop until a white
precipitate forms again. The addition of sulfuric acid is intended to acidify the
salicylic salt into free salicylic acid .
The salicylate precipitate is then recrystallized in order to produce purer
salicylic acid, namely by dissolving the white precipitate with hot distilled
water in order to dissolve the impurities from the precipitate. The solution was
recrystallized using a hot filter that was running hot water and heated using
Bunsen spirit, then the resulting solution was cooled using an ice bath, in order
to speed up the process of crystal formation due to a significant temperature
change. In principle, this process refers to the difference in solubility between
the substance to be purified and the solubility of the mixing agent. The desired
substance solution is dissolved in a solvent and then recrystallized by saturating
it (Vicry & Fitriani, tt) .
The results of the recrystallization are then filtered again using a Buchner
filter to separate the crystals and liquid, then the crystals obtained are in the oven
to dry the salicylic acid crystal solids and evaporate the impurities.
The reaction that occurs;
The results of the treatment that there was a change in color from cloudy
white, then pink, then white. A precipitate also forms when sulfuric acid is added
and white foam indicates a saponification or saponification process.
Furthermore, the solution is filtered using a Buchner filter to speed up and
simplify the filtering process so that no water remains, then a white precipitate
of salicylic acid is produced.
In this experiment, the reaction mechanism was that the hydroxide ion acts
as a base which will attack the H atom, this results in the O atom being negatively
charged because the O atom is more electronegative than the H atom. The other
hydroxide ion acts as a nucleophile which attacks the C carbonyl atom.
The double bond of the carbonyl group is broken and 2 pairs of electrons
are given to the O atom because the electronegativity of the O atom is more
electronegative than the C atom.
The C atom in this state is sp3 hybridized which makes the molecular state
that is bound to the C atom bound to the methoxy group immediately released
and then to obtain the stability of the methoxy which is a base will attack the H
atom on the hydroxyl group which will make the O atom negatively charged.
The reaction of adding sulfuric acid or H 2 O 4 . A protonation reaction occurs
in the sodium salicylate salt, namely the H + ion from H 2 SO 4 which converts
the salicylate salt into salicylic acid.
The dried salicylic acid crystals were weighed and the weight and yield were
calculated. The mass of salicylic acid obtained was 0.0216 grams and the yield
was 0.6% with a theoretical mass of 2.5966 grams. The yield and mass obtained
are very small compared to the theoretical mass due to an error in the reflux
process, namely the blockage of cold water flowing in the hose so that the
condenser does not feel cold causing an imperfect reflux process, and there was
also an increase in temperature reaching 80oC so that There may be damage to
the salicylate salt. The salicylic acid obtained was then tested for its melting
point and a melting point of 159 oC was obtained .
G. Conclusion
Based on the observations from the experiments that have been carried out,
it was concluded that the production of salicylic acid can be carried out by the
mechanism of the saponification reaction, namely the hydrolysis of methyl
salicylate from gandapura oil, then the reaction of adding NaOH through the
reflux method and the acidification reaction with sulfuric acid or H2SO4 . This
experiment also purified the precipitate by recrystallization method. The mass
of salicylic acid obtained was 0.0216 grams and the rendition was 0.6%.
