33.

Arene Diazonium Ion Reactions

A. Introduction

In the previous laboratory experiment, you explored the functionalization of benzene via
electrophilic aromatic substitution reactions. In these reactions, a hydrogen on the aromatic ring
is substituted with some electrophile. In this experiment, you will expand upon the
functionalization of benzene by substitution of a diazonium ion (-N2⊕) with a variety of different
species.

First, the diazonium ion must be generated. A diazonium ion is generated by reacting an amine
with nitrous acid generated by mixing sodium nitrite (NaNO2) and a strong acid such as H2SO4
or HCl. When the amine is on an aromatic ring, an aryldiazonium ion is formed. Generation of
the aryl amine is relatively simple. First, benzene or a benzene derivative is subjected to
electrophilic nitration conditions to provide nitrobenzene. The nitro group is then reduced to the
amino group. One commonly employed reduction is Sn/HCl. Alternatively, H2, Pd/C can be used
to reduce a nitro group to an amine. (Figure 1)

NO 2 NH 2 N 2 HSO 4
HNO 3 Sn NaNO 2
H 2SO 4 HCl H 2SO 4

Electrophilic Nitro Group Diazonium Ion

Aromatic Reduction Formation
Substitution

Figure 1. Generation of the Arene Diazonium Ion

Diazonium ion formation begins by mixing sodium nitrite (NaNO2) with a strong acid such as
sulfuric acid (H2SO4). This results in the in situ generation of nitrous acid, HNO2 (Step 1, Figure
2). Next, as shown in figure 2, step 2, the nitrous acid is protonated followed by the loss of water
to form the nitrosonium ion, which is a very powerful electrophile. The nitrosonium then adds to
the amine as shown in figure 2, step 3. After several steps, water is lost and the aryldiazonium
ion is formed.

The aryldiazonium ion is relatively stable and can exist for an extended period of time when
maintained at a low temperature. Due to their enhanced stability the aryldiazonium ions are
much more useful than their alkyl diazonium ion
counterparts. Alkyl diazonium ions rapidly lose N2 fast
nitrogen gas to form a carbocation that N 2(g) +
HSO 4
decomposes via a variety of reaction pathways.

Experiment 33 – Arene Diazonium Ion Reactions Page 1 of 5

 NaNO 2
Ph NH 2 Ph N N + HSO 4
H 2SO 4

1. Generation of Nitrous Acid

NaNO 2 + H 2SO 4 HNO 2 + NaHSO 4
2. Generation of the Nitrosonium Ion Electrophile
O O -H2O O
H
N N N
OH OH 2

3. Reaction of a Primary Amine with the Nitrosonium Ion (Diazonium Ion Formation)

O H O Proton O H
Transfer
Ph NH 2 + N Ph N N Ph N N
H H

H Proton O H
-H2O O H Transfer
Ph N N
Ph N N Ph N N H

Figure 2. Mechanism for Diazonium Ion Formation

Reaction of the aryldiazonium ion N

with a variety of nucleophilic N HSO 4 Nu
Nu
reagents allows for the preparation
+ N2 + HSO 4
of an array of different aromatic
molecules. Many of these
reactions are shown in figure 3.
The preparation of aryl chlorides
and bromides via reaction of the OH Br
aryldiazonium ion with CuCl and
CuBr, respectively, is known as
the Sandmeyer reaction. Similarly, H
2O HSO 4 Br
reaction with CuCN produces an Cu
N
aryl nitrile and reaction with CN
N
Cl
CuNO2 replaces the diazonium ion
with a nitro group. When copper CuCN CuCl
conditions are employed, the
reaction is thought to proceed via 2
NO KI
a radical pathway. Other Cu
conditions include reacting the aryl NO 2 HBF 4 I
diazonium ion with water to
provide phenol, potassium iodide F
to provide an aryl iodide, and
tetrafluoroboric acid to provide an
aryl fluoride.

Figure 3. Typical Diazonium Ion Displacement Reactions

Experiment 33 – Arene Diazonium Ion Reactions Page 2 of 5
 In the laboratory experiment, you will start with anthranilic acid (ortho-aminobenzoic acid). The
amino group will be first be converted into a diazonium ion. This diazonium ion will be divided
into two equal portions. One portion will be hydrolyzed with water to provide salicylic acid. The
second portion will be reacted with potassium iodide to provide o-iodobenzoic acid. (Figure 4)
O OH

HO

HSO 4
H 2O salicylic acid
N
O NH 2
NaNO 2 O N
HO
H 2SO 4 HO
KI

anthranilic acid O I

HO

o-iodobenzoic acid

Figure 4. Conversion of Anthranilic Acid to the Diazonium Ion and Subsequent Displacement
Reactions

B. Experimental Procedure
1. Preparation of the Aryldiazonium Ion
Add 300 mg of anthranilic acid to a small Erlenmeyer flask. Dissolve the solid in 3.5 mL of water
and add 1.2 mL of 1.0 M H2SO4. Carefully warm the solution until all anthranilic acid has
dissolved at which time you should cease heating and cool the solution in an ice bath for 5 min.
You may see the formation of precipitate during the cooling stage.

In a small test tube supported in an ice bath prepared using a small beaker, Dissolve 188 mg of
sodium nitrite in 2.3 mL of water. Allow this solution to cool in the ice bath for 5 min.

At this point, both solutions should be thoroughly cooled. Using a pipet, slowly add the sodium
nitrite solution to the anthranilic acid solution. You should swirl the flask during addition to aid in
mixing. Following addition, a clear solution should result.

The reaction can be monitored by testing for a slight excess of sodium nitrite. The presence of
sodium nitrite can be determined using starch iodide paper. Dip a glass rod into the solution and
then touch the rod onto the starch iodide paper. A dark blue color indicates the presence of
excess sodium nitrite. If a positive test is not obtained, add additional sodium nitrite to the
solution until excess is present.

At this stage, you should have approximately 7 mL of solution containing the diazonium ion of
anthranilic acid. Divide this solution equally into two 6-inch test tubes cooled in an ice bath. You
will carry out one reaction with the first portion and your lab partner will carry out the second
reaction with the second portion of solution.

Approximately how many mmol of aryldiazonium is present in each portion? _________

Experiment 33 – Arene Diazonium Ion Reactions Page 3 of 5

 2. Synthesis of Salicylic Acid
Take the first portion of aryldiazonium ion, and heat this solution in a boiling water bath for 10
min then cool the solution in an ice bath. Record any observations as to how the solution
changes during these two steps. Collect the solid by Hirsch filtration. Wash the solid thoroughly
with ice-cold water.

To purify the product, dissolve the solid in ~1 mL of methanol in a small test tube. Filter this
solution through a pipet filtration assembly prepared from a small cotton plug, 1 cm of sand, 1
cm of activated charcoal, and a second 1 cm of sand. Collect the solution in a pre-weighed vial.
Flush the filter with 0.5 mL of methanol and collect this filtrate along with the first portion. Add
1.5 mL of water and scratch the wall of the vial to initiate crystallization. Cool the solution in an
ice bath for 10-15 min and collect the resulting solid via Hirsch filtration. Record the yield,
melting point, and IR spectrum of the product.

Chemical Test to Detect the Presence of a Phenol

The product of the reaction, salicylic acid, contains a phenol group. The FeCl3 chemical test can
be used to test for the presence of phenols. Dissolve a few milligrams of your product in
methanol and add a few drops of FeCl3 solution. Record the results of this chemical test in your
notebook.

3. Synthesis of ortho-Iodobenzoic Acid

Remove the second portion of diazonium ion solution from the ice bath. Add 193 mg (1.16
mmol) of potassium iodide dissolved in 1 mL of water. Heat this solution in a boiling water bath
for 10 min. Allow the solution to cool to room temperature and add several drops of and
aqueous solution NaHSO3 to reduce excess iodine. Cool the solution in an ice bath then collect
the crystals via Hirsch filtration. Wash the solid product with ice-cold water.

To purify the product, dissolve the solid in ~1 mL of methanol in a small test tube. Filter this
solution through a pipet filtration assembly prepared from a small cotton plug, 1 cm of sand, 1
cm of activated charcoal, and a second 1 cm of sand. Collect the solution in a pre-weighed vial.
Flush the filter with 0.5 mL of methanol and collect this filtrate along with the first portion. To this
solution, add water (~1.5 mL) dropwise via pipet until the solution becomes cloudy. Heat this
solution to dissolve the precipitate then allow it to cool slowly at room temperature at which time
crystals should form. Cool the mixture containing the crystals in an ice bath for 10 min. Collec
the crystals via Hirsch filtration washing with ice-cold water. Record the yield, melting point, and
IR spectrum of the product.

Just as in part 2, dissolve a few milligrams of product in methanol and add FeCl3 solution to test
for the presence of phenol. Record the results in your notebook and compare these with the
results in part 2.

Experiment 33 – Arene Diazonium Ion Reactions Page 4 of 5

 C. Pre-Lab Questions
1. Explain why aryldiazonium ions are more stable than alkyldiazonium ions?

2. You will prepare ortho-iodobenzoic acid and salicylic acid in the laboratory experiment.
Which of these products do you expect to give a positive FeCl3 text? Explain.

3. Secondary amines cannot be converted to diazonium ions. Using the mechanism shown in
figure 2 as a guide, show the reaction of dimethylamine with the nitrosonium ion. Where in
the mechanism does the reaction stop? Show this product and the mechanistic steps
leading up to it.

D. Post-Lab Questions
1. Describe the results of the FeCl3 test in parts 2 and 3 of the experiment. Which product gave
a positive chemical test?

2. Starting with benzene, show how the molecules shown below can be prepared using
reactions discussed in the past two experiments.
Br
Br Br
(a)

Br

CN Cl CN
(a)

3. What absorptions in the IR spectrum of each of your products can be used to help you
confirm their structures?

Experiment 33 – Arene Diazonium Ion Reactions Page 5 of 5