Preparation of P-Nitroaniline from P-Nitroacetanilide

Step 1: Acetylation of Aniline

In the first step we need to put the removable acetyl protecting group on the

nitrogen of aniline. The acetyl group is electron withdrawing and it therefore makes the

lone pair on the nitrogen less reactive either in an oxidation reaction or a protonation

reaction. The nitric acid used in the nitration step is a fairly strongly oxidizing agent and

we could form an N-oxide. The nitration conditions (nitric acid and sulfuric acid) are

strongly acidic. Protonation of the nitrogen of aniline makes it a very strong deactivating

group, making the aromatic ring less susceptible to reaction with the nitrating agent and

the NH3

+ group would be a meta director. Another value of the acetyl protecting group is

that it is bulky group and preferentially directs the nitration to the para position rather

than the ortho position.

The full mechanism for the reaction is given in Figure 14.2. Acetic anhydride is

partially protonated by the acetic acid. This makes the anhydride an even better

electrophile for the nucleophilic nitrogen of aniline. This attacks to form the tetrahedral

intermediate, which, after proton transfer, loses acetic acid.

Figure 14.2 Mechanism of Acetylation Reaction

H2N

aniline

+

CH3

C

O

C

CH3

O O

NH C

O

CH3 +

O

C

CH3

O

acetanilide

acetic anhydride acetic acid

+

H

CH3

C

O

C

CH3

O O

H

CH3

C

O

C

CH3

O O

H

CH3

C C

O O

H

CH3

H N H

O

+ O

C

CH3

O

O

C

CH3

O

CH3

C

O

O

H

CH3

C C

O O

H

CH3

H N

O

H

O

C

CH3

O

HO

C

CH3

O

Physical Constants

Compound Mol. Wt

(g/mol)

Density

(g/mL)

b.p. (oC) m.p. (oC)

Aniline 93.13 1.022 184 -6

Acetic anhydride 102.09 1.082 138-142 -73

Acetic acid 60.05 1.049 116-117 15-16

Nitric acid (conc. 15.8

M)

63.01 1.420 - -

Sulfuric acid (conc. 36

M)

98.09 1.840 330 -

Acetanilide 135.17 solid - 113-115

p-nitroacetanilide 180.16 solid - 215-217

p-nitroaniline 138.13 solid - 147-148

Procedure:

The set-up for your apparatus is shown in Figure 14.3. Note that there is NO

STOPPER at the top of the condensing column. This is left open to the atmosphere so as

to avoid a pressure build -up inside the flask when heating. Remember: NEVER HEAT

A CLOSED SYSTEM.

Dissolve 4.0 mL of aniline in 10 mL of acetic acid in a 100 mL round bottom

flask. To this solution, add 5 mL of acetic anhydride and mix well by swirling.

CAUTION: the reaction is exothermic and the flask becomes warm. Add two boiling

chips, attach a condensing column and attach the hoses for water cooling (water-in at the

bottom and water-out at the top). Heat at a gentle reflux for fifteen minutes.

Work up

After fifteen minutes, lower the iron ring under your heating mantle and allow the

flask to cool slightly. CAUTIOUSLY add 5 mL of cold water through the top of the

condenser into