UNIVERSIDAD DISTRITAL FRANCISCO JOS DE CALDAS

FACULTAD DE CIENCIAS Y EDUCACIN

PROYECTO CURRICULAR DE LICENCIATURA EN QUMICA
LABORATORIO DE QUMICA ORGNICA II
SNTESIS DE ACETANILIDA

1. GOAL
The purpose of this experiment is to prepare acetanilide from nitrobenzene

2. MATERIALS
A 250 mL round bottom flask, stirring heater, claisen adaptor, reflux system, separatory
funnel, spin bar beaker, test tube, graduated cylinder, distillate equipment, erlenmeyer,
melting point equipment, pipette, Buchner funnel, side-arm flask.

3. REAGENTS
Nitrobenzene, mossy tin, concentrated HCl, 50% NaOH, sodium acetate trihydrate, acetic
anhydride,

4. THEORETICAL BACKGROUND
Acetanilide was the first aniline derivative serendipitously found to possess analgesic as well
as antipyretic properties, and was quickly introduced into medical practice under the name
of Antifebrin. But its (apparent) unacceptable toxic effects, the most alarming
being cyanosis due to methemoglobinemia, prompted the search for supposedly less toxic
aniline derivatives such as phenacetin. After several conflicting results over the ensuing fifty
years, it was established in 1948 that acetanilide was
mostly metabolized to paracetamol (USAN: acetaminophen) in the human body, and that it
was the paracetamol that was responsible for the analgesic and antipyretic properties. The
observed methemoglobinemia after acetanilide administration was ascribed to the small
proportion of acetanilide that is hydrolyzed to aniline in the body. Acetanilide is no longer
used as a drug in its own right, although the success of its metabolite paracetamol
(acetaminophen) is well known.

5. EXPERIMENTAL PART
Reduction of nitrobenzene.
Place 30 mmoles of nitrobenzene and 65 mmoles of mossy tin in a 250 mL round bottom
flask, securely clamped above a stir motor. Place a Claisen adaptor on top of the flask; put a
water-cooled condenser on one outlet of the Claisen and a separatory funnel on the other.
Add a spin bar to the flask and turn on the stir motor. Place 15 mL of concentrated HCl in the
separatory funnel. Add the HCl to the nitrobenzene/tin mixture a few mLs at a time. After
each addition, monitor the flask so that it does not get too hot; if necessary, immerse the
reaction flask briefly in a cold water bath. After the initial reaction has subsided, add another
portion of the acid. Again, control the temperature of the reaction in a cold water bath.
Continue until all of the HCl has been added. After all of the acid has been added let the
mixture stir at room temperature for about 10 min. Remove the separatory funnel (and rinse
it) and place a ground glass stopper on the open Claisen outlet (the other outlet still has the
water-cooled condenser). Place a heating mantle under the reaction mixture and heat and
stir for 20 min. Test to see if the reaction has gone to completion by testing for unreacted
nitrobenzene (below). If nitrobenzene remains, heat and stir for an additional 10 min and
test again. Test for unreacted nitrobenzene: Put a few drops of the reaction mixture in a
small amount of water in a test tube; a clear solution (no oily drops) indicates that there is
no nitrobenzene present. When the reaction is complete, cool the reaction flask to room
temperature. While stirring, carefully add 18 mL of 50% NaOH through the Claisen adaptor.
This reaction is exothermic, so have a cool water bath (not an ice bath) ready in case the
flask gets too warm. The mixture must be strongly alkaline to ensure complete liberation of
the aniline.
Dilute the reaction mixture with 40 mL of water and then steam distill the mixture using a
heating mantle as the heat source. Collect the distillate in a 100 mL graduated cylinder: the
first 18 mL or so of distillate should be quite cloudy because you are distilling over a mixture
of aniline and water. Once the distillate ceases to be turbid, collect an additional 4 mL.
Transfer the entire volume of distillate to an Erlenmeyer (do not stopper the flask until the
solution is cool!) and save for use in the acetylation step. Place the pot residue in the
Aqueous Waste carboy in the main hood.

Preparation of acetanilide.
Dilute the distillate from the previous step with water to a final volume of 65 mL. Add a spin
bar and place it over a stir motor. Add 2,5 mL of concentrated hydrochloric acid and stir to
obtain a homogeneous solution. Dissolve 4,5 g of sodium acetate trihydrate in 10 mL of
water in a beaker. Measure 3,5 mL of acetic anhydride into a graduated cylinder. Warm the
solution of aniline/hydrochloric acid to 50C on a steam bath, add the acetic anhydride, stir,
then add the sodium acetate solution all at once with stirring. Remove the heat source; a
white solid should begin to precipitate. Continue to stir the mixture for 20 min then cool it in
an ice bath to complete crystallization. Isolate the product by suction filtration, wash it with
cold water, and allow it to dry. Determine the melting point and the yield of dry acetanilide.

6. REFERENCES
Document was taken and adapted from:
Online edition for students of organic chemistry lab courses at the University of Colorado,
Boulder, Dept of Chem and Biochem. (2004)