R
9
Nitration of acetanilide
The third step in the synthesis of p-nitroaniline
is nitration of acetanilide using a mixture
of concentrated sulfuric and nitric acids to
obtain nitroacetanilide (Scheme 3). In this
electrophilic aromatic substitution reaction,
the acetamido group (−NHCOCH
3
) directs
the nitronium ion (
+
NO
2
) to the ortho and para
positions of the aromatic ring.
6
Thus, nitration
of acetanilide principally produces ortho- and
para-nitroacetanilides, with the para compound
being the major product. Separation of the
ortho- and para-nitroacetanilides is achieved by
recrystallistion from ethanol. The colourless major
product, p-nitroacetanilide, is almost insoluble in
ethanol and can be ltered out, while the yellow
ortho isomer remains in the ltrate.
Safety
Fuming nitric acid, sulfuric acid and glacial
acetic acid are highly corrosive, use with caution
and perform the experiment in a fume hood
with the protective glass door pulled down.
p-Nitroacetanilide is an irritant, avoid contact
with skin, eyes and clothing. Deuterated dimethyl
sulfoxide (DMSO-d
6
) is dangerous because it
increases the permeability of the skin to other
substances. Avoid all contact with skin and
clothing.
Procedure
Place glacial acetic acid (1.5 mL) in a boiling tube
and add 1.5 g of acetanilide. Stir the mixture and
add concentrated sulfuric acid (3 mL). Cool the
hot reaction mixture in an ice/salt bath until the
temperature drops to about 0.5 °C. With stirring,
slowly add fuming nitric acid (0.6 mL), making sure
that the temperature does not rise above 20 °C.
Once addition is complete, bring the reaction
mixture to room temperature and allow to stand
for 20 min. Pour the mixture onto ice (15 g) and
allow to stand for a further 20 min. Collect the
crude yellow solid by ltration, wash thoroughly
with water and dry in the air. Recrystallise from
the minimum amount of hot ethanol to obtain
p-nitroacetanilide as a cream-coloured crystalline
solid (Figure 9). Dry in the air and record your yield.
Scheme 3. Synthesis of p-nitroacetanilide.