NUCLEOPHILIC ACYL SUBSTITUTION: THE SYNTHESIS OF

ESTERS

L. S. S. INFANTE1 AND E.N.D. ORILLOSA2

1
, DEPARTMENT OF PSYCHOLOGY, COLLEGE OF SOCIAL SCIENCES AND PHILOSOPHY
2
DEPARTMENT OF CHEMICAL ENGINEERING, COLLEGE OF ENGINEERING
UNIVERSITY OF THE PHILIPPINES, DILIMAN QUEZON CITY, PHILIPPINES
DATE PERFORMED: DECEMBER 8, 2009

ABSTRACT

Esters are most commonly known as substances with pleasant smells. They
have a lot more uses though. Benzyl acetate is used as a flavoring reminiscent of
peach. Polyesters are used for making plastics. Esters are derivatives of an oxoacid
and a hydroxyl compound(alcohol or phenol). The method used in the experiment,
an acid-catalyzed nucleophilic acyl substitution between a carboxylic acid and an
alcohol is called the Fischer esterification.
In this experiment, ethyl butanoate was synthesized by mixing 5.25mL of
0.09 mol ethanol with 8.28mL of 0.09 mol Butyric acid, followed by the addition of
boiling chips. Concentrated H2SO4 was then added and the mixture was allowed to
reflux for 45-60 minutes. It was then cooled and saturated NaCl solution was added
to hasten separation. Solid NaHCO3 was added to remove the acid, followed by
collection and drying of the organic layer with anhydrous Na2SO4.
The amount of ester produced was 8.3mL. The theoretical yield is 11.89mL.
This means that the percent yield is 69.8% and the percent error is 30.2%. Possible
errors could have been from improper handling, measuring and traces of water on
the glassware that reduced the amount of ester produced.

INTRODUCTION Esters are derivatives of an oxoacid

Esters are most commonly known as
substances with pleasant smells. They
are among the most common of all
naturally occurring compounds.
Volatile esters(e.g. carboxylate esters)
can be found in perfumes and
essential oils. Glycerides, esters
formed from glycerol and fatty acids
can be found in most vegetable oils
and animal fats. Also, polyesters are
used in the synthesis of plastics.
and a hydroxyl compound(alcohol or
phenol). The alkoxy group (-O-alkyl)
from the oxoacid replaces at least one
hydroxyl group (-OH) of either an
organic or inorganic acid.
(Streitwieser, 1976) Some of the
common acids that are esterified are
carboxylic acids, phosphoric acid and
sulfuric acid. The method used in the
experiment, an acid-catalyzed
nucleophilic acyl substitution between
a carboxylic acid and an alcohol is
called the Fischer esterification. Other
methods include alcoholysis of acyl
chlorides, anhydrides, and nitriles,
alkylation of carboxylate salts using
alkylating agents such as alkyl halides
or the famous methylating agent,
diazomethane, Mitsunobu Reaction
and Steglich esterification. (Carey,
2000)
Fischer esters are obtained by
refluxing the parent carboxylic acid
with the alcohol in the presence of an
acid catalyst. Because carboxylic acids
are not reactive enough for attacks by
alcohols, a strong acid such as
hydrochloric acid or sulfuric acid is
needed to increase their reactivity
significantly. The mineral acid
protonates the carbonyl-group oxygen
atom and thus gives the carboxylic
acid a positive charge making it more
reactive. The ester product is then
obtained by the subsequent loss of
water from the tetrahedral
intermediate.
The Fischer Esterification method is a
good method for producing esters.
However, it has the disadvantage of
being able to use only alcohol as a
solvent. Thus, this method is limited to
the synthesis of only methyl, ethyl,
propyl, and butyl esters. Limitations to
these reactions are also brought about
by steric hindrance in the carboxylic
acid or alcohol. Alcohol reactivity is as
follows: CH3OH > 1o > 2o > 3o (steric
effects). (Carey, 2000)
Ethyl butanoate C2H5OCOC3H7
(C6H5CH2OCOCH3) is the ester formed
by the condensation of ethyl alcohol
and Butyric acid in the presence of
sulfuric acid. It is used as artificial
pineapple flavoring in alcoholic
beverages. It is can also be found in
some orange juices because most
people associate its odor with that of
fresh orange juice. (Tseng, 1993)
METHODOLOGY
In this experiment, pineapple
flavor ester was synthesized. 5.53mL
(0.09mol) of ethanol and 8.28mL
(0.09mol) of Butyric acid was mixed in
a 25-ml round bottom flask wherein
boiling chips were added
subsequently.
2-3drops of concentrated H2SO4
were then added while gently swirling
the mixture. The solution was then
allowed to reflux for an hour. The
mixture was cooled before it was
transferred into a 30mL separatory
funnel. The flask was rinsed with cold
water and the washings were added
into the separatory funnel until the
aqueous layer was twice the organic
layer. The funnel was then shaken and
the layers were allowed to stratify.
Saturated NaCl solution was
added to hasten separation after
which solid NaHCO3 was added to
remove the acid completely
demonstrated by the halting og
effervescence.
The organic layer was collected
into an Erlenmeyer Flask and dried by
adding enough anhydrous Na2SO4.
Lastly, the ester is transferred to a
clean and dry vial.
RESULTS AND DISCUSSION
In the experiment which
involves the synthesis of esters, the
group had been assigned for Equation 1.1. Fischer
pineapple. Pineapple, a multiple-ovary Esterificatrion Process
type of fruit, bears the ester Allyl H2SO4
hexanoate, the distinctive smell or C3H7COOH + C2H5OH
odor and flavor of the said fruit. CH3CH2CH2COOH2CH3 + H2O
Because this compound is hard to
synthesize in the laboratory, an easier
compound was synthesized, ethyl
butanoate. Ethyl butanoate resembles Equation 1.2. Pictoral Fischer
some physical properties of allyl Esterification Process in the
hexanoate, such as its odor. Applying Experiment
the principles of Fischer Esterification
process, ethyl butanoate was Ethanol (0.09 mol) + Butyric Acid
synthesized from the reaction of (0.09 mol) Water + Ethyl
ethanol and butyric acid with the use butanoate
of a catalyst, sulfuric acid and with
application of heat. Esterification is a
reversible reaction. Therefore, there's
+
the need for the reaction to be driven
to completion according to Le
Chatelier's Principle. The principle
simply states that the equilibrium +
shifts in favor of a certain reaction.
This was carried out by heating to Figure 3. Mechanism of
reflux an acid in a primary/secondary Esterification Process.
alcohol in the presence of a catalyst The protonation of the carbonyl
(H2SO4) with water as the byproduct. It oxygen activates the carboxylic acid
is important to note that the sulfuric toward nucleophilic attack by an
acid was needed to be concentrated alcohol. This yields a tetrahedral
because the concentration affects the intermediate. The transfer of a proton
dehydrating agent. It absorbs the from one oxygen atom to another
water molecules that are found on one yields a second tetrahedral
side of the equation, changing the intermediate and converts the OH
direction of the reaction. The reaction group into a good leaving group. The
counteracts and counterbalances the loss of a proton and expulsion of water
change with the loss of water regenerates the acid catalyst and
molecules by producing more esters. gives the ester product.
Saturated sodium chloride was added
simply for the purpose of hastening
the separation of layers by removing
water and alcohols that did not
undergo any reaction.
Carboxylic acid attains a proton from
sulfuric acid.
Alcohol attacks the carbocation of the
acid.
Proton transfer occurs on oxygen
atoms; expulsion of water
Loss of a proton; ester is formed.
The reaction can be pushed to
either direction depending on the
choice of reaction conditions. To push
the reaction forward, water was
removed so that ester rather than
carboxylic acid will be formed. Ester
formation is favored when the excess
solvent is the alcohol, meaning it's the
one with the largest volume in the set-
up. When water was removed, the
alcohol became the solvent. On the
other hand, the presence of a large
amount of excess water would favor
carboxylic acid formation. Thus, pure
or absolute ethanol was used. Pure
ethanol is anhydrous alcohol or
purified alcohol with no more than 1%
water. Anhydrous Na2SO4 was also
added to help in eliminating the
excess water in the mixture.
Solid NaHCO3 was used to
neutralize the acid added. The
complete removal of the acid can be
confirmed when the solution stops
bubbling. The products of its reaction
with H2SO4 are easily removed since
CO2 merges with air. It is a relatively
weak base and it is also innocuous,
with no effect in the reaction if used in
excess. In contrast to this, when using
NaOH, CO2 is not produced. Therefore,
there is no indicator whether the acid
is already neutralized or not. Also,
sodium hydroxide is a strong base and
would hydrolyze the ester formed.
Soap will be formed. Using sodium
hydroxide will eliminate the purpose of
the experiment in forming esters.
RCOOR' + NaOH  RCOONa + R'OH
5.25mL of ethanol 8.28mL of Butyric
acid was used. Both have the same
mol of .09, only the molecular weight
of the ester affected the amount it
produced theoretically. The theoretical
amount of ethyl butanoate that will be
formed is 11.89mL. The actual yield is
8.3mL. This means that there the
percent yield is 69.8% and the percent
error is 30.2%. Possible sources if
error include improper handling,
cleaning and not drying of the
glasswares that could have reduced
the amount of the ester produced due
to additional water content of the wet
glasswares.
CONCLUSION AND
RECOMMENDATION
The final product of the
experiment was 8.3mL of a clear liquid
with a very distinct smell of pineapple.
This is 69.8% of the theoretical yield
from 5.25mL of ethanol 8.28mL of
Butyric acid. The smell of the
pineapple alone indicates the success
of the experiment in synthesizing
esters.
It is suggested that
measurements should be done more
carefully especially in the
measurement of alcohols and acids.
Also, the use of better and more
precise equipment can greatly
decrease the percent error of the
experiment. Lastly, making perfectly
sure that the glassware used are dry
should be done to reduce errors in the
experiment.
Lastly, it is recommended that
the experiment be done in two
meetings because not everthing can
be done in the span of 3hours alone. It
would be better if the ester obtained
was also distilled and its boiling point
determined.

REFERENCES

APPENDIX