DISTRICT UNIVERSITY FRANCISCO JOSÉ DE CALDAS

FACULTY OF SCIENCE AND EDUCATION

DEGREE IN CHEMISTRY
ACETANILIDE SYNTHESIS

1
Camilo Andrés Carvajal Pinilla: 20151150007
2
Andrés Bernal Ballén
1
Student Organic Chemistry II, 2Teacher
1,2
District University Francisco José de Caldas

Bogotá D.C. November 7, 2017

Abstract:
The following report shows the results of the synthesis of acetanilide, where, first, the reduction of
nitrobenzene to aniline was carried out and subsequently acetanilide was synthesized. During the
practice there were some drawbacks that caused that the expected crystals were not formed, among
which were the incomplete reduction of all the nitrobenzene and the possibility of not achieving
alkalinization of the solution for the release of the aniline.

Key Words: Synthesis, substitution, reduction, aniline, infrared.

Introduction This compound is slightly soluble in hot water.

Organic synthesis is the planned construction
of organic molecules through chemical
reactions. Often, organic molecules can have
a greater degree of complexity compared to
purely inorganic compounds. Thus, the
synthesis of organic compounds has become
one of the most important areas of organic
chemistry. [1]
Acetanilide is a solid and odorless chemical
with the appearance of a leaf or flake. Also, it
is known as N-phenylacetamide and was
formerly known by the brand name antifebrin.
[1]
Acetanilide can be produced by reacting
phenylammonium chloride or aniline with
acetic anhydride. [1]
It has the capacity to the produce auto
inflammation if it reaches a temperature of
545°C, but otherwise it is stable under most
conditions. The pure crystals are white. It is
flammable. Acetanilide is used as an inhibitor
in hydrogen peroxide and to stabilize cellulose
ester varnishes. Uses have also been found in
intermediation as an accelerator of rubber
synthesis, dyes and intermediate synthesis of
dye and synthesis of camphor. Acetanilide
was used as a precursor in the synthesis of
penicillin and other drugs and their
intermediates. [1]
It is the mother drug of the para-aminophenol
derivatives (phenacetin, acetaminophen).
Acetanilide has analgesic and fever-reducing
properties; it is in the same class of drugs as
acetaminophen (paracetamol). Under the
name acetanilide formerly listed in the formula
of several specific drugs and over-the-counter
drugs. In 1948, Julius Axelrod and Bernard
Brodie discovered that acetanilide is much
more toxic in these applications than other
drugs, causing methemoglobinemia and
ultimately causing damage to the liver and
kidneys. That is why acetanilide has been
largely replaced by less toxic drugs, in
particular acetaminophen, which is a
metabolite of acetanilide and the use of which
Axelrod and Brodie suggested in the same
study. [1]
METHODOLOGY
ANALYSIS AND RESULTS
-Mechanism:
Equation 1. Protonation of one of the oxygens of the
nitro group
The first step corresponds to the breach of the
double bond between the nitrogen and
oxygen. Then one of the oxygens, attacks a
hydrogen to form an OH. [2]
Equation 2. Aniline formation
Next to this, the N-O bond is broken and a
double bond is formed between N = OH, this
leaves two free electron pairs to the nitrogen,
which attacks a hydrogen and forms the N-H
bond. Subsequently, the oxygen attacks
another hydrogen, breaks the bond with the
nitrogen and releases water, which causes the
nitrogen to carry out another attack and the
NH2 group is formed. [2]
The next step corresponds to the protonation
of the carbonyl group of acetic anhydride: [2]
Equation 3. Oxygen attack of the carbonyl group to
the hydrogen of the acid.
The above equation shows how an oxygen of
the carbonyl group attacks the hydrogen of the
OH of acetic acid, this causes the electronic
pair of the O-H bond to break and the oxygen
to remain with these electrons. The next step
corresponds to the addition of the protonated
anhydride. The attack is performed by the
nitrogen of the aniline, as shown in the
following equation: [2]

Equation 4. Attack of nitrogen from aniline to
protonated anhydride.
Subsequently, a series of electron movements
occur, which causes the break and the
formation of bonds, this results in the formation
of acetic acid and an intermediate, the
protonated acetanilide: [2]
Equation 5. Elimination of acetic acid and formation of
protonated acetanilide.
Subsequently, the deprotonation of the
protonated acetanilide occurs. This
deprotonation is possible, due to the attack of
the acetate ion that formed in the first step.
The acetate ion attacks the hydrogen bound to
the oxygen of the carbonyl group, which
causes the hydrogen to deliver the electrons to
the oxygen, with this, charges are neutralized,
the acetanilide is formed and the acetic acid is
again formed, which is the catalyst of the
reaction: [2]
Equation 6. Deprotonation of protonated acetanilide
for the formation of acetic acid and acetanilide.
During the synthesis, disadvantages were
experienced because the acetanilide crystals
were not formed as expected. This could have
occurred because all of the nitrobenzene did
not react for the formation of the aniline, also
because of the lack of assurance that the
solution would be alkaline when adding the
NaOH, since no indicator paper was used to
know the acid/base character of the solution.
These two moments during the practice, could
be the cause of not forming acetanilide
crystals. So, if not reduce all the nitrobenzene,
the amount of aniline produced would be very
little, so this would lead to that, by adding
sodium hydroxide, there would be no aniline to
be released and therefore, it would not reach
synthesize acetanilide.
-Spectrum IR:
First, there are bands of 3295.52 and
3260.80cm-1, which correspond to the NH
intermolecular bridge, the following bands of
1664.64 and 1648.24cm -1 correspond, the first
to stretch C=O in an amide (RC(O)-NR2), while
the second to the NH flex. The bands of
1599.06; 1557.59; 1500.68 and 1489.11cm -1,
are bands of sp2 carbon tensions, and C=C
conjugate voltage. The band of 1436.07cm -1
corresponds to the stretching of the C-N bond.
At 1369.52cm-1, there is the band that
characterizes the swinging umbrella of the
CH3. The 1264.39cm-1 band may correspond
to the balance in the plane of the aromatic
bonds by the presence of the NH-C(O)-CH3
substituent, which polarizes the molecule. The
last bands of 695.37 and 754.2cm -1, determine
the type of substitution that benzene has,
which for this case, indicates a
monosubstitution. [3, 4]

CONCLUSIONS

The first stage of the synthesis, corresponded

to a reduction reaction of nitrobenzene for the
formation of the aniline, where, the test was
not performed to check if there were no traces
of nitrobenzene. Nor was the solution
completely alkalized for the release of the
aniline, doing this not to form the acetanilide
later.

All the nitrobenzene must be reduced and the

solution strongly alkalized to favor the
production of aniline.

BIBLIOGRAPHY

[1] Barcia, A., Laboratory of Organic

Chemistry. Higher Polytechnic School of the
Litoral. Synthesis of Acetanilide. 2011.
[Online] Available in: https://docgo.org/lab-6-
sintesis-de-la-acetanilida (Last access,
November 6, 2017)
[2] Cruz, F., López, I., Haro, J., Barba, J.,
Laboratory practice manual. Organic
Chemistry II. Autonomous Metropolitan
University. Mexico City. Mexico. 2012. [Online]
Available at:
http://www.izt.uam.mx/ceu/publicaciones/MQ
O2/MANUAL_QUIMICA_ORGANICA_2.pdf
(Last access, November 6, 2017)
[3] Clavijo, A., Infrared Spectral Analysis.
[4] Calderón, C., Manual for the Interpretation
of Infrared Spectra. Department of Chemistry
Science Faculty. National university of
Colombia. 1985.