DEPARTMENT OF PURE AND APPLIED CHEMISTRY

Visayas State University, Baybay, Leyte

CHEM126 Organic Chemistry II
Laboratory Report

Name
Course/Yr
Group No

: Mark Ryan R. Tripole

: BS Chemistry II
: 2

Date Performed
Date Submitted
Score

: 01/20/2015
: 01/29/2015

Experiment No. 8
The Preparation of Acetanilide

I. Introduction
Acetanilide, a compound also known by its IUPAC name as either N-phenylacetamide or Nphenylethanamide, is an odorless solid chemical that has either a leaf or a flake like appearance.
The crystals of acetanilide are white in color and it is only sparingly soluble in water, but more or
less soluble in other solvents like diethyl ether, ethanol, benzene and acetone. Looking at the
past applications in the compound, acetanilide was considered to be the first aniline derivative
that was found to possess analgesic as well as anti-inflammatory properties and because of this
was included as a stable in medical practice under the trade name Antifebrin. But then it was
found to cause a condition known as cyanosis (characterized by the purple coloration of the skin
due to the tissues near the surface having low oxygen saturation) and was discontinued and less
favored over much less toxic aniline derivatives such as phenacetin (which was also eventually
found to be potentially carcinogenic). In its own right, acetanilide is not an analgesic, but is
rather metabolized in the body into acetaminophen, also well known as Paracetamol. Acetanilide
also found its way into photography in its experimental use as photographic developers.
Eventually, the commercial usage of acetanilide has died down and most of its usage is involved
with organic synthesis, being a precursor in the synthesis of penicillin and a host of other
pharmaceuticals. Its closest use in todays commercial spectrum is as an inhibitor that slows the
decomposition of drug-store hydrogen peroxide solutions.
The synthesis of acetanilide comes about by the acylation of aniline with carboxylic acids
or their derivatives to give an amide product. Though there are quite a number of methods into
the synthesis of the compound, the most common laboratory procedure that is popularly used in
introductory organic chemistry courses is through the acylation of aniline with acetic anhydride.
The objective of the experiment was to gain familiarization of the laboratory process in the
synthesis of acetanilide, as well as gain familiarization of the mechanisms behind the process of
acylation (defined as the process of adding an acyl group to a compound). Another objective of
this experiment would be to obtain adequate knowledge into the basic ideas and concepts behind
each particular portion of the experiment and why certain steps are involved.

II. Results
Shown in the succeeding pages are the results based on the experiment, the data obtained
through the performance of the procedure and related calculations.

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Calculation of number of moles of acetanilide produced to determine limiting reagent:

Aniline
No. of moles of acetanilide =20 grams aniline x

1 mol aniline
x
93.12 grams aniline

1 mol acetanilide
1 mol aniline

No. of moles of acetanilide = 0.214 moles

Acetic Anhydride
No. of moles of acetanilide = 26 grams acetic x
anhydride

1 mol acetic
anhydride
102.09 g acetic
anhydride

1 mol acetanilide
1 mol acetic
anhydride

No. of moles of acetanilide = 0.253 moles

Since it is the aniline that produces the smaller amount of the acetanilide, then it is the limiting
reagent that will determine the amount of the final product.

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Calculation for theoretical yield for acetanilide:

Theoretical yield = 0.214 mol acetanilide

135.16 grams acetanilide

1 mol acetanilide

Theoretical yield = 28.92 grams acetanilide

Calculation of percentage yield based on actual yield:
Actual yield = 4.5 grams
Percentage yield =

Actual yield
Theoretical yield

100%

Percentage yield =

4.5 grams
28.92 grams

100%

Percentage yield =

15.15 %

Further elaboration on the results shall be given in the next section of this laboratory report.

III. Discussion
Shown below is a simple schematic diagram of the experimental procedure performed.

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The reaction as shown in the procedure is characteristic of an addition of an acyl group to

a compound. For this particular reaction, the acylating group is the acetic anhydride and the
aniline is the compound to be added to. The general equation for the reaction is shown below:

As shown in the general equation above, an acyl group from the acetic anhydride is added
to the aniline, while the other component goes on to form acetic acid in solution. This reaction
first goes through a series of steps before arriving at the final products.
The first step of the procedure was to prepare a solution of aniline in water and
hydrochloric acid. Because of the fact that aniline is only sparingly soluble in water, adding it
without an acid will not facilitate the acylation reaction as it is supposed to happen in the later
step because the aniline is not adequately dissolved. The hydrochloric acid helps in this step by
making the aniline more water soluble through the protonation of the amino group. A simple
mechanism of this protonation is shown below:

This mixture of aniline hydrochloride was then heated up to 60C on a hot plate basically
to allow for a complete reaction and the acetanilide product to remain dissolved in solution. The
next step of the procedure was to take the reaction beaker off the heat, then the addition of the
acetic anhydride to the aniline hydrochloride solution, which was then followed by the addition
of a solution of sodium acetate. The first part of the mechanism would be the deprotonation of
the aniline hydrochloride back to its original aniline form. The mechanism for deprotonation is
shown below:

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Once the aniline has been reformed in this step, the amino group then goes on to initiate
a nucleophilic attack on the reactive sites of the acetic anhydride, which is at one of the partially
positive carbonyl carbons. The mechanism for this part of the reaction is shown below:

As shown in the mechanism above, the first step in the mechanism comes in the form of a
nucleophilic attack. What essentially forms in this step is a tetrahedral intermediate that is
pretty unstable and thus results in the reformation of the carbon to oxygen double bond and the
expulsion of the other acetate group. It would be wise to take note in this portion of the
mechanism that there are counter ions that balance out these charges on the intermediates. The
more important is that the protonated acetanilide intermediate is balanced out by the chloride
ions in solution. This brings in the next step of the mechanism, which is the deprotonation of the
protonated intermediate. In its protonated form, the compound is more or less a hydrochloride
salt which is soluble in water. This is the main reason why the precipitation of product does not
happen immediately. The sodium acetate solution is added to provide excess acetate ions that
will facilitate the deprotonation of this intermediate, releasing it from its hydrochloride salt form
and allowing the acetanilide final product to precipitate out of solution. The mechanism for this
final step of the reaction is shown in the next page.

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After the addition of the sodium acetate solution, the precipitation of the acetanilide out
of solution came almost immediately. The reaction beaker was then cooled in an ice bath and the
product allowed to further crystallize with the aid of vigorous stirring. The product was then
collected through vacuum filtration and left to dry for two days, after which the product was
then weighed and its melting point determined using a Thomas Hoover Apparatus.
POSSIBLE SIDE REACTIONS
The only side reaction of particular note for this reaction would be the hydrolysis of the
acetic anhydride in the presence of the excess of water. It itself, acetic anhydride is already
pretty unstable a compound and readily reactions. A simple diagram of this is shown below:
0

But considering its usage as the acylating agent in this procedure, acetic anhydride is
found to have a relatively low rate of hydrolysis, low enough to allow for the acetylation of
amines to be carried out in aqueous solutions.

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THE YIELD
For the experiment the group had obtained a final yield of 4.5 grams which amounted to
around a percentage yield of 15%, way off mark from the expected 14-16 grams that could be
obtained based on the proportions of the chemicals used. One can only speculate as to the reason
behind this, but the most probable one could be the quality of the chemicals used. Looking back
at the experiment, the aniline and the acetic anhydride were obviously old stock and may have
already lost their efficiency as chemicals. And for one thing, the procedure didnt exactly call for
extremely specific conditions, which is why this is the only reason I can think of for the extremely
low yield. Moreoever, we had not exactly applied the usage of decolorizing charcoal for this
experiment, which is an explanation for the off white or close to tan color of the acetanilide
product in the end. This may be of minor importance, but another possible factor could have
been that the crystals were not allowed to fully form in solution and was put through vacuum
filtration quite soon. A much higher yield could have possible been obtained if more time was
allowed for the acetanilide to precipitate out of solution. The possibility of side reactions is quite
low, considering the only one of prime importance would be the hydrolysis of the acetic
anhydride (which as already explained before has a low rate of hydrolysis in water).

IV. Conclusion

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V. Answers to Questions
1. Although ethyl phenylacetate reacts readily with ammonia and with methylamine to
yield the corresponding amide, the reaction of ethyl phenylacetate with t-butylamine is
so slow and the yield so small that it is essentially useless in the laboratory. Suggest a
reason for the failure of the aminolysis with t-butylamine. (Hint: What is the mechanism
of aminolysis?)

One reason that seems pretty obvious at first glance would essentially be the issue of sterics,
meaning that the t-butyl group on the amine is a relatively bulky group and making it
essentially add to a big molecule like the ethyl phenylacetate would result in an extremely
slow reaction with little to no yield. (NOT SURE ABOUT THIS ANSWER PA MGA KATOKAYO)
2. Write equations for the synthesis of the following amides (a) benzanilide (b) N-tbutylphenylacetamide (c) succinimide.
A. BENZANILIDE

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B. N-T-BUTYLPHENYLACETAMIDE

C. SUCCINIMIDE

3. What is the function of the sodium acetate used in the preparation of acetanilide
according to the procedure given? Write the equation for the preparation of acetanilide
as you have actually performed through the experiment (not the equation on the report
form). Include all reactants and indicate the role of sodium acetate.
The main function of the sodium acetate in the mechanism is to be a source of and excess of
the basic acetate ions that will help in deprotonating the water soluble hydrochloride salt of
the acetanilide. Initially, the acetanilide product is protonated and remains dissolved in the
solution. Once the product is deprotonated by the acetate ions and is no longer a
hydrochloride salt, its solubility in water is essentially decreased and it crystallized out of
solution. The reaction equation including all the reactants is shown in the succeeding page.

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Page 10 of 12

4. Acetyl chloride and ketones may be used to acetylate aniline but both reagents offer
certain disadvantages. Suggest possible disadvantages to the use of each. Do these
reagents offer any obvious advantages?
In reference to the acetyl chloride, the one disadvantage that would be fairly obvious would
be its reactivity. In general acyl chlorides are very reactive compounds and they react
vigorously. So there might be somewhat of a relative danger in handling them, especially due
to the fact that they react readily with water. As for the ketones, Im guessing that the
reaction would more or less favor the nucleophilic addition of the aniline to the carbonyl
ketone forming an imine. As for the advantages, one could possible be that the reactions with
aniline and acetyl chloride would be non-reversible with a good yield, overall more efficient
in a sense. And given the reactivity of the compounds, the reactions could very well happen
at room temperature, no heating required.
5. For persons sensitive to aspirin, 4-hydrocetanilide is often prescribed as an analgesic.
Suggest a synthesis leading to the preparation of this pharmaceutical product beginning
with phenol.
STEP 1 Nitration of Phenol

STEP 2 Reduction of nitro group to an amine

STEP 3 Formation of amide (4-hydroxyacetanilide or Paracetamol)

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VI. References

Acetanilide
http://www.chemistrylearner.com/acetanilide.html
Acetanilide
http://en.wikipedia.org/wiki/Acetanilide
Acetanilide
http://www.britannica.com/EBchecked/topic/3210/acetanilide
Succinic Acid
http://en.wikipedia.org/wiki/Succinic_acid
562 - Organic Synthesis
www.orgsyn.org/demo.aspx?prep=cv2p0562
The preparation of acetanilide from aniline.
wwwchem.uwimona.edu.jm/lab_manuals/c10expt23.html
Synthesis of acetanilide
http://fd.valenciacollege.edu/file/vprasadpermaul/Example%20of%20Lab%20Notebook%20%20Barnett%202012.pdf
Amide synthesis
http://www.organic-chemistry.org/synthesis/C1N/amides.shtm
Preparation of Acetanilide
http://sites.psu.edu/lburns/wp-content/uploads/sites/3465/2013/04/ch.6-formalreport.pdf
Preparation of Organic Compounds - Unit 10
http://ncert.nic.in/ncerts/l/lelm110.pdf
Preparation of Acetanilide
http://www.studymode.com/essays/Preparation-Of-Acetanilide-1265917.html
Benzanilide
www.orgsyn.org/demo.aspx?prep=CV1P0082
Paracetamol
en.wikipedia.org/wiki/Paracetamol
Paracetamol
http://www.rsc.org/learnchemistry/content/filerepository/CMP/00/000/047/Paracetamol_web.pdf

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