Lab.

Chemistry II (Degree in Chemistry) Course 2011-2012 Practice 4 - Page 1

PRACTICE 4: Synthesis and purification of an organic compound:

ACETANILIDE.

OBJECTIVES
General objective:

In this experience we are going to carry out the synthesis, isolation, and purification of a compound.
organic, the acetanilide according to the reaction

H
NH2 O O N CH3
+ + CH3COOH
H3C O CH3 O

1. Learn to properly dose the reagents.

2. Set up a reflux system.
3. Isolate the reaction product by vacuum filtration.
4. Purify the product by crystallization.
5. Determine the purity of the product
a. determine its melting point.
b. analyze the presence of the reagent.

INTRODUCTION
Organic synthesis allows for the planned obtaining of complex molecules from
from other simpler ones through reactions of organic compounds. These are generally
slow and incomplete, when compared to ionic reactions, as they involve breaking of
covalent bonds which usually require a solvent (to facilitate mobility and
interaction of the reactants) and an activation, usually heating as occurs in cooking.
To avoid solvent loss during prolonged reaction times, recourse is made to
assembly called reflux. The fact that complex mixtures are often required of
reaction and that they are not quantitative (giving rise to variable amounts of products not
desired or secondary), implies that at the end of the reaction itself, it must be
proceed to a stage of separation of the components of said mixture and to a purification of the
desired product once isolated. For this process, generally more laborious than the
the synthesis itself, many of the techniques introduced in the Laboratory are of great utility
Chemistry I.
Acetanilide is used as a peroxide inhibitor, stabilizer, and especially as a compound
intermediate for the obtaining of numerous dyes and compounds of pharmacological interest.
Acetanilide by itself has analgesic and antipyretic properties but cannot be used.
directly since its prolonged use causes an increase in methemoglobin in the blood.
This hemoglobin with the central Fe(III) atom instead of Fe(II) does not allow transport.
reversible of oxygen. This side effect does not occur in the derivative with a phenol group.
instead of phenyl and such, Paracetamol (4'-hydroxyacetanilide) is widely used for its
effects similar to those of acetylsalicylic acid (aspirin).
Chemistry Lab II (Degree in Chemistry) Course 2011-2012 Practice 4 - Page 2

EXPERIMENTAL
Material Reagents Devices
Capillaries Metal tweezers Acetone Melting point apparatus
Matches Pipe wrenches Acetic anhydride Vacuum pump
Cork Plates for (dosage of 1.5 mL) Heating blanket
Dropper chromatography Aniline (dosed at 1 mL) Power regulator
Büchner funnel 10 mL Aniline dropper
Cone-shaped funnel Soda Activated carbon
Spatula Scissors HCl 1M
Kitasato Flask Tripod + grid Mix for CCF
Round flask 100 mL Test tubes hexano:ethyl acetate
50 mL Erlenmeyer flask Rod 1:1
Nuts 250 mL glass Methyl orange
Filter paper 50 mL glass
Indicator paper Vial
Watch glass

1. OBTAINING ACETANILIDE
1 mL of aniline is taken (the bottle is located in the display case and is already dosed to 1 mL). For
the plunger of the dispenser rises and is gently pushed over a 100 mL flask of
frosted mouth and round bottom. 10 mL of water is added to the flask and after a light
agitation, 1.5 mL of acetic anhydride (in the showcase, the bottle already has a dispenser). It is added
a glass bead or boiling germ. Note the changes that are observed.
The reflux system is installed paying attention to the safety elements, pressure of the
clamps and sealing of the joints and the refrigerant is connected. It is heated to reflux during
10 minutes counted from the start of boiling. After this time, the process is interrupted.
heating and the synthesized content is added to a 50 mL glass. 15 mL of water is added.
It is allowed to cool on the bench and then in a water bath, while the filter is prepared for
Büchner and the filter for conical funnel.
The filtrate drains into the Büchner funnel while a vacuum is applied. If there is acetanilide left in the
the glass can be cleaned with a bit of cold deionized water
Determine the pH of the mother waters from the filtration and dispose of them in the waste container.

2. PURIFICATION OF THE OBTAINED ACETANILIDE

A very small amount of filtered solid is separated into a vial (S1) and the rest is transferred to the
50 mL glass that has just been used. Add 20 mL of deionized water and the tip of
an activated carbon spatula. The flask is heated and a stable Erlenmeyer is mounted.
50mL with a conical funnel with a filter so that it also heats up slightly.
The mixture is boiled until the acetanilide is completely dissolved (the dissolution must be observed)
transparent between the carbon particles), gently shaking the glass (use the tongs to
take the glass).
Filter the very hot acetanilide solution. An additional 5 mL of boiling water will be used to
drag the acetanilide retained in the filter.
The flask is left to cool for about 10 minutes on the workbench until room temperature.
for 3-4 more minutes in a water bath until the complete recrystallization of acetanilide. Meanwhile,
The filter is prepared for the Büchner and the Kitasatos is set up on the vacuum pump.
Chemistry Lab II (Degree in Chemistry) Academic Year 2011-2012 Practice 4 - Page 3

It is filtered to empty and the crystals are allowed to drain and dry in the Büchner funnel. It can be
complete the drying of the crystals by placing them in the oven at 70ºC. Melting point of the
acetaminophen: 115 ºC. Compare the color of the product obtained now (S2) with that stored in the vial.
before the purification with activated carbon (S1).
Both dry products (S1 and S2) are weighed separately to obtain the yield of the
reaction and are saved for conducting the tests.

3. PURITY ESSAYS

-BY THIN LAYER CHROMATOGRAPHY (T.L.C.)

Dissolve separately, in three vials, a very small amount of: aniline, S1 and S2 in
acetone (1 mL). Draw with pencil a line (with three evenly spaced marks) to a
centimeter from the bottom edge of a thin layer chromatography plate Transfer by
Capillarity takes a aliquot of each of those solutions to the marks. Place the plate in
the elution vessel, where we have previously added (until reaching less than 8
millimeters of level) a 10% solution of acetone in dichloromethane. Wait until the
the eluent reaches approximately 1 cm below the top edge of the plate.
Remove the plate by marking with a pencil the level reached by the solvent and reveal it under UV light.
marking with pencil the spots that are observed. Note the number of spots in each
case and calculate the value of Rf that corresponds to each of them.

FOR DETERMINATION OF MELTING POINTS

A small sample of dry product S1 is crushed with the spatula on a balance.
and its melting point is determined. Noting the start and end temperature of melting. Do the
same with S2dry. Compare both melting points and the corresponding intervals.

4. Basicity Tests
2 mL of water and 2 drops of methyl orange are placed in 2 test tubes.
A tiny amount of the synthesized acetanilide is placed in the first tube (what remains
adhered when touched with the wet rod) and is slightly heated to the flame.
In the second, 2 drops of aniline are added and it is also lightly heated. HCl is added.
1M drop by drop into the 2 tubes until color change. Count the drops used in each.
tube.

Observations:
Waste collection: There is a container for the synthesized acetanilide.
Cleaning of material: The residues of acetanilide from the round-bottom flask are cleaned with
hot water.
Lab. Chemistry II (Degree in Chemistry) Course 2011-2012 Practice 4 - Page 4

QUESTIONS
Preliminary matters
1. Based on the data listed on the labels or safety data sheets, indicate the
possible risks that may be involved in the handling of each of the following reagents
and the precautions that should be taken in each case: aniline (C6H5NH2) and anhydride
acetic (C4H6O3).
Read the section of this practice where it says the operational mode and complete the scheme.
(flow diagram) of what is going to be done in it following that of the next page.
Before starting the session, the teacher will ask for the diagrams and check that everyone has them.
Students are clear about what is going to be done.
3. What is the mission of activated carbon?
4. Why is it recommended that crystallization be slow?
5. Calculate the amount of acetic anhydride (d=1.08 g/mL) that will react completely with
1 mL of aniline (d=1.03 g/mL) according to the stoichiometry of the reaction.
6. What is the limiting reagent of the reaction with the amounts used in this?
experience?
7. Calculate the amount of acetanilide that can be obtained assuming that the reaction
It is progressing with a 90% performance.

Issues following the experimental work

1. What behavior does aniline exhibit, acidic or basic? Justify the answer by writing
a reaction.
2. What is the pH of the mother waters from the first filtration? What product is present in the medium?
of reaction that gives that pH?
3. What conclusions can be drawn from the acid reaction tests conducted with
aniline and acetanilide?
4. Why do acetanilide crystals dry at 70ºC? What could happen if they are dried at a higher temperature?
higher temperature?
5. What differences do we find between the melting points and the c.c.f. of pure crystals and
impure? Given the result, would you propose these two techniques as the most suitable for
determine the purity of a reagent?

BIBLIOGRAPHY
1.R.Q. Brewster. C.A. Vander Werf. W.E. McEwen. Practical Course of Organic Chemistry.
Ed. Alhambra. Experiences 53 and 55-II
2. Pavia, Lampman, Kriz. Introduction to Organic Laboratory Techniques a contemporary
approach.Experiment 2. Saunders Golden Sunburst series.

Note: The practice is shown in the video Acetanilide Synthesis, accessible at:
http://mmedia.uv.es/buildhtml?lang=en_US&user=tcliment&name=acetanilida_2008.mp4&path=/LABORATORY/&id=7254
Lab. Chemistry II (Degree in Chemistry) Course 2011-2012 Practice 4 - Page 5

SCHEME FOR SEPARATION OF THE SYNTHESIS OF ACETANILIDE

(complete)

to heat

to cool
add H2O

filter

wash with H2O

To crystallize