Nucleophilic Acyl Substitution: The Synthesis of Ethyl Butanoate

Ruther Harvey Idiong-Cabral

Institute of Biology, University of the Philippines, Diliman, Quezon City 1101
Philippines

Date Performed: 15 August 2013; Date Submitted: 3 September 2013

Esters are a class of compounds that are abundant in nature, most of which have very
fragrant odors. To synthesize such substances, a carboxylic acid and an alcohol must
react, in the presence of an acid catalyst, in a type of nucleophilic acyl substitution
called a Fischer esterification reaction. In this experiment, 7.2 mL of ethyl butanoate
was synthesized from ethanol and butyric acid with a 60.54% yield. To improve the
yield of the experiment, more accurate materials and better techniques were
recommended.

Introduction nucleophilic acyl substitution. This is called a

Fischer esterification, or simply esterification3.
When a nucleophile is added to a
carboxylic acid and its derivatives, the initially In this experiment, ethyl butanoate
formed alkoxide ion intermediate will was synthesized via esterification of ethanol
eliminate one of the previous substituents of and butyric acid (Figure 2).
the carbon, leading to a net substitution O O
reaction (Figure 1). This reaction is more + H3C OH
known as nucleophilic acyl substitution1. H3C OH H3C O CH3
Figure 2. The overall reaction between butyric
O
- acid and ethanol
O O
Nu

2 R Nu
R R 2 R Nu
R
Figure 1. General mechanism of nucleophilic
acyl substitution
Direct nucleophilic acyl substitution
of carboxylic acids is hard to do in the
laboratory since –OH is not a good leaving
group. It is usually necessary to enhance the
reactivity of the acid, but under right
circumstances, carboxylic acid derivatives can
be prepared from nucleophilic acyl
substitutions1.
One of the more useful applications of
nucleophilic acyl substitutions in carboxylic
acids is preparing esters1. Simple esters can be
observed to have very fragrant odors. Many,
but not all, characteristic odors of flowers and
fruits are due to the presence of an ester
group2. Esters can be prepared with a
carboxylic acid and an alcohol, via
Experimental Details
To synthesize ethyl butanoate, 8.28
mL of butyric acid and 5.28 mL of ethanol
was used and poured into a 25-mL round
bottom flask. A few drops of concentrated
sulfuric acid were also added into the mixture.
The solution was then heated using a reflux
set-up (Figure 3).
After refluxing, the mixture was
cooled to room temperature, and placed into a
30-mL separatory funnel. The reaction flask
from earlier was washed with cold water and
the washings were added into the separatory
funnel. This was done until the aqueous layer
was twice the volume of the organic layer. The
funnel was shaken, and the layers were then
allowed to stratify. Saturated NaCl was added
to hasten the separation, and solid NaHCO 3
was added to remove excess acid. The organic
layer was collected and dried using anhydrous
Na2SO4. The crude ester was transferred to a OH OH OH
vial and submitted to the instructor.
+
C + R OH R OH R OH
+
R OH R' OH R' O
Figure 5. Addition of R’OH and loss of H+
from the R’OH

The next step of the mechanism

protonates an OH group and yields a second
tetrahedral intermediate (Figure 6)1.

OH + OH
H
+
R OH R OH2

Figure 3. A reflux set-up
Results and Discussion
In the first part of the experiment,
ethanol and butyric acid react will each other
via Fischer esterification reaction, which was
named after the German chemist, Emil
Fischer4. The mechanism of an esterification
reaction presents a series of protonations and
deprotonations, along with an addition, then
an elimination step3.
The first step of the mechanism
includes protonating the carbonyl group of the
carboxylic acid. This resulting intermediate is
pretty stable due to the presence of resonance
structures (Figure 4)3.
+ carbon, or nucleophilic acyl substitutions,
O + OH OH
H involves an addition to the carbonyl group
+
C followed by an elimination4. It is also
R OH R OH R OH
Figure 4. Protonation of the carbonyl group,
with resonance structures
After the protonation, the alcohol
attacks the carbonyl carbon, since it is weakly
nucleophilic, deprotonating the alcohol in the
process3. This forms a tetrahedral intermediate
(Figure 5)1.
R' O R' O
Figure 6. Protonation of an OH group
The previous protonation makes the
OH group a better leaving group. In the final
step, the OH group leaves as water and
another deprotonation takes place. The final
product of the reaction will be the ester
(Figure 7).
OH O H + O
-H 2O -H
R OH2
+ +
R C
R' O R' O R OR'
Figure 7. Removal of water and deprotonation
The mechanism of esterification
illustrates the general pattern of other
substitution reactions of carboxylic acids. As
illustrated above, substitutions in the carbonyl
OH
+
H3C OH important to note that this reaction is
reversible1.
Esterification, however, is a very slow
process. An acid catalyst is used to increase
the rate of the reaction. The acid also supplies
the necessary proton to start the reaction, as
seen in Figure 4. Because of this, the reaction
is also often called as an acid-catalyzed
esterification5. In the experiment, concentrated
sulfuric acid (H2SO4) was used as the catalyst.
Esterification also needs heat to make the
reaction faster, thus in the experiment, the
mixture was heated5.
As mentioned earlier, the reaction is
reversible, and thus, the reaction must occur in
equilibrium. The equilibrium constant (K) of
the reaction can be expressed by the
concentration of the reactants and products3.
[ RC O2 R ' ] [ H 2 O ]
K=
[ RC O2 H ] [ R' OH ]
Figure 8. The equilibrium equation of a
Fischer esterification reaction
Because of this equilibrium, if the
molar ratio of alcohol to carboxylic acid is 1:1,
the highest possible yield of the ester is 67%.
If the objective of the experiment is to produce
esters, then it would seem impractical to
synthesize it and expecting a relatively
“smaller” yield3.
This problem can easily be solved by
shifting the equilibrium, as explained in Le
Chatelier’s principle. It is said that if we add
more reactants, the equilibrium will shift to
produce more products and vice versa 5. To
increase the yield of the ester, it is possible to
use one of the reactants (typically the cheaper
one) in excess. This will lead to production of
more of the product. It is also important that
the reactants, including ethanol, used should
be pure and void of water, since the presence
of more water will shift the equilibrium to
produce more reactants3. Another technique
that can be used to improve the yield of ester
includes removing water as it is formed by
azeotropic distillation. This technique also
includes recycling the solvent, making it more
efficient. However, a Dean-Stark trap is
needed by the technique6. In this experiment,
an excess of 0.3 mL of alcohol was used,
making the butyric acid the limiting reagent.
This excess will now favor the production of
more products.
As noted above, esterification needs
heat, but most of its reactants are highly
volatile and will likely escape in a typical
water bath. This will definitely shift the
equilibrium of the reaction. To avoid this, a
reflux setup (Figure 3) was used. The cooling
water in the condenser will condense any
escaping vapors, and thus keep the equilibrium
of the reaction 2.
After refluxing, the mixture will most
likely contain ethyl butanoate, unreacted
butyric acid, unreacted ethanol, sulfuric acid
and some unwanted by-products. To remove
the excess reactants and catalyst, the mixture
was poured in a separatory funnel and washed
with water. The ethanol will most likely
dissolve in water, due to H-bonding. Solid
NaHCO3 was added to react with the
unreacted acids, which will produce salts. The
salts will then dissolve in water. Addition of
NaHCO3 is also efficient in signalling the
presence of acids in the mixture, since its
reaction (Figure 9) with acids produces carbon
dioxide, a gas. Thus, if bubbles can still be
seen in the mixture, unreacted acids are still
present5.
2 NaHC O 3 +2 H 2 S O 4 → Na2 S O4 +3 H 2 O+ 2C O 2
Figure 9. Reaction of sodium bicarbonate with
sulfuric acid
After separation, the organic layer was
then dried using anhydrous Na2SO4. This
reagent removes any substance with an
unhindered O-atom, including water. This is
another way to purify the product5.
After drying, the amount of crude
ethyl butanoate was measured using a
graduated cylinder. The experiment yielded
7.2 mL of crude ethyl butanoate. After
calculations, this would lead to a 60.54%
yield. This, however, is not the actual yield,
since the product is still crude.
As with all experiments, errors may
have been present, which may have affected
the yield of the experiment. Water may have
been present in the reagents, which could have
shifted the equilibrium leading to a smaller
yield. There may have been unnecessary water
present in the instruments used in the
experiment, which also could have shifted the
equilibrium. The water used in the condenser
may not be cold enough to effectively
condense all vapor, which can also upset the
equilibrium of the reaction. It was also
observed that after drying the crude product,
the solution became light orange, which could
indicate the presence of dyes in the mixture.
Also, the instruments used in measuring the
reagents may not be as accurate as intended,
which also could lead in errors. The conditions
in which the experiment was done, including
temperature and humidity, may have affected
the outcome of the experiment.
Conclusion
Publishing Company, Inc.: Redwood
City, CA, 1995; pp. 946-949.
[5] Lehman, J.W. Operational Organic
Chemistry: A Laboratory Course, 2nd
ed.; Allyn and Bacon, Inc.: Needham
Heights, MA., 1988; pp. 348-354.
[6] Puterbaugh, W.H., Vanselow, C.H.,
Nelson, K., Shrawder, E.J.
Esterification for the Introductory
Organic Laboratory Course: A
Modified Dean-Stark Trap. Journal of
Chemical Education 40(7); 1963; pp.
349-350.

To conclude, the objectives of the

experiment were achieved. An ester, ethyl
butanoate was synthesized using ethanol and
butyric acid as the reactants. The principles
behind the experiment were also discussed.
Even though only 7.2 mL and 60.54% yield of
ethyl butanoate was produced, the experiment
can still be considered a success, since the
objectives were attained.

For future experiments, it is

recommended to use more accurate and
precise instruments. Other techniques can also
be explored, including the azeotropic
distillation, for use in the experiment. Other
reagents which can yield other esters may also
be used for the experiment.

References

[1] McMurry, J. Organic Chemistry, 8th

ed. ; Brooks/Cole: Belmont, CA,
2012; pp. 818-819; 824-825.
[2] Pavia, D.L. Introduction to Organic
Laboratory Techniques: A
Contemporary Approach; Saunders
College: Philadelphia, PA, 1982; pp.
83-85; 469-470.
[3] Fessenden, R.J., and Fessenden, J.S.
Techniques and Experiments for
Organic Chemistry; Willard Grant
Press: Boston, MA, 1983; pp. 294-
295.
[4] Loudon, G.M. Organic Chemistry, 3rd
ed.; The Benjamin/Cummings
CALCULATIONS

expected yield=0.09 mol butyric acid × ( 1 mol ethyl butanoate

1 mol butyric acid ) ×(
116.16 g ethyl butanoate
1mol ethyl butanoate ) ×(
1 mL ethyl but
0.879 g ethyl bu

7.2 mLethyl butanoate

percent yield=( 11.89 mL ethyl butanoate )
× 100≈ 60.54 % yiel d