Download Lecture 16 Aromatic Diazonium Salts

NPTEL – Chemistry – Principles of Organic Synthesis
Lecture 16 Aromatic Diazonium Salts
7.1.1 The Formation of Diazonium Salts
Addition of aqueous solution of NaNO2 to a solution of amine hydrochloride in presence
of excess of HCl which is cooled by an ice-bath such that the temperature of the reaction
remains below 5 ◦C diazotization of primary aromatic amine occurs.
NH2
N2 Cl
NaNO2
o
HCl,< 5 C
Mechanism
H
HO NO
-OH2
NO
HN N OH
HN NO
H2N NO
NH2
-H
H2O NO
NO+
-H
N N OH
N N
H
H
N N
OH2
-H2O
If electron withdrawing groups are attached to aromatic nucleus then the aromatic amines
are difficult to diazotize because the nucleophilicity of the amino-nitrogen is reduced by
the partial withdrawal of the unshared electron pair into the nucleus.
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NH2
O
N
NH2
N
O
O
O
7.1.2 The Reaction of Diazonium Salts
7.1.2.1 Reactions of nucleophiles at nitrogen
Nucleophiles react with diazonium ions to give covalent diazo-compounds. For example,
phenol via phenoxide ion couples with diazonium salt at pH 9-10 to afford paraazophenols in good yield.
N N Ar
H
O
O
tautomerizes
HO
N N
Ar
N
N Ar
7.1.2.2 SN1 Reaction
Diazonium salts decompose on warming into nitrogen and aryl cation which is highly
reactive and could be attacked by any nucleophile in its vicinity.
N2
-N2
H2O
OH2
-H
OH
warm
7.1.2.3 One Electron Reductions
Diazonium ions could be reduced by single electron transfer to give an aryl radical and
nitrogen. Copper(I) is frequently used for this purpose and the aryl radical is highly
reactive capable of abstracting a ligand from the transition metal ion or a hydrogen atom
from a covalent bond.
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N2 Cl
CuCl
.
+ Cl Cu Cl
Cl
-CuCl
-N2
7.2 Reactions in which Nitrogen Eliminated
7.2.1 Replacement by Hydroxyl
Diazonium salt on warming in water gives phenol via SN1 mechanism. The reaction is
generally performed in acidic solution to preserve phenol in its unionized form.
N2 Cl
OH
H2O/H
warm
7.2.2 Replacement by Halogen
7.2.2.1 Schiemann Reaction
Treatment of an aqueous solution of diazonium salt with fluoroboric acid under cold
conditions gives diazonium fluoroborate as precipitate, which could be dried and gently
heated to afford the flurobenzene by decomposition.
The reaction involves SN1
mechanism.
N
N
Cl
Aq. MBF4, cold
N
N
BF4
dry ppt
M = Na, H, NH4
salt precipitates
- MCl
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heat
F
F B F
F
BF4
-BF3
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F
NPTEL – Chemistry – Principles of Organic Synthesis
Examples:
NH2
S
F
NaNO2, HCl
CO2Me
HPF6
CO2Me
S
47%
A. Kiryanov, A. Seed, P. Sampson, Tetrahedron Lett. 2001, 42, 8797.
OH
OH
NaNO2
OH
N
F
F B
OH
F. Dolle, L. Dolei, H. Valette, F. Hinnen, F. Vaufrey, H. Guenther, C. Fuseasu, C. Coulon, M. Buttalender,
C. Crouzel, J. Med. Chem. 1999, 42, 2251.
N
NH2
Me
Me
NH2
NaNO2, H
Me
HBF4
Br
F
Me
Br
H. Hart, J. F. Janssen, J. Org. Chem. 1970, 35, 3637.
7.2.2.2 Sandmeyer Reaction
This method provides an effective route for the preparation of aromatic bromides and
chlorides. Addition of cold aqueous solution of diazonium chloride to a solution of CuCl
in HCl medium gives a sparingly soluble complex which is separated and heated to give
aryl chloride or bromide by decomposition.
NH2
HONO
HX
X = Br, Cl, CN
N2 X
CuX
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.
+ X-Cu-X + N2
-N2
-CuX
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X
NPTEL – Chemistry – Principles of Organic Synthesis
Examples:
N
NH2
S
Me
N
NaNO2, HCl
CuSO4
Cl
S
53%
Me
N. Zou, J.-F. Liu, B. Jiang, J. Combin. Chem. 2003, 5, 754.
NH2
HONO
Me
CuCN
CN
Me
H. T. Clarke, R. R. Reed, Org. Synth. 1941, 1, 514.
F
NH2
F
Br
HNO2, CuBr
N
N
HBr
O
O
65%
B. Mallesham, B. M. Rajesh, P. R. Reddy, D. Srinivas, S. Trehan, Org. Lett. 2003, 5, 7963.
7.2.3 Replacement by Aromatic Carbon
A number of methods lead to arylation of aromatic carbon by diazonium salts.
7.2.3.1 Pschorr Reaction
This reaction describes the synthesis of phenanthrene and its derivatives via diazotation
followed by intramoecular cyclization using copper powder.
G
NH2
G
HNO2, H
Cu(0)
G = CH=CH, CH2-CH2, CO, NH, CH2, others
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Mechanism
The reactive intermediate depends on the reaction conditions. Under acidic conditions,
the diazonium salt is believed to decompose into aryl cation and nitrogen. The aryl cation
is highly reactive and attacked by the aryl ring that leads to cyclization. On the other
hand, under neutral and basic conditions, the diazonium salt is reduced by single electron
transfer to give aryl radical which proceeds reaction intramolecularly with benzene ring
to give the cyclized product.
In acid solution:
G
N2
G
G
-N2
H
H
-HH
G
Cu(0) + H
In neutral or basic solution:
G
N2
G
Cu(0)
-N2
.
+
Cu(I)
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G .
Cu(I) + H
.
H
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NPTEL – Chemistry – Principles of Organic Synthesis
Examples:
O
O
NaNO2, H2SO4
Me2N
Cu-Sn, Na2SO4
NMe2
NH2
Me2N
65%
NMe2
S. G. R. Guinot, J. D. Hepworth, M. Wainwright, J. Chem. Res. Synop. 1997, 183,.
O
O
Bn
HNO2
N
N
Bn
N
N
H2N
P. Tapolcsanyi, B. U. W. Maes, K. Monsieurs, G. L. F. Lemiere, Z. Riedl, G. Hajos, B. Van den Driessche, R. A.
Dommisse, P. Maytyus, Tetrahedron 2003, 59, 5919.
7.2.3.2 Reduction by Copper(I) Ammonium Ion
Diazotized anthranilic acid with copper(I) ammonium hydroxide gives diphenic acid in
90% yield.
CO2H
N2
2
CO2H CO2H
Cu(NH3)2OH
The process probably takes place via one-electron reduction of the diazonium ion
followed by dimerization of the resulting aryl radicals.
7.3 Reactions in which Nitrogen is Retained
The reaction of the terminal nitrogen of a diazonium salt with nucleophile affords a
covalent azo-compound.
7.3.1 Reduction to Arylhyrazones
The reduction of aromatic diazonium salts can be accomplished with sodium sulfite or
SnCl2 or electrolysis to provide arylhydrazines. In case of sodium sulfite based reduction,
the diazonium ion with a sulfite anion may give a covalent azo-sulfite that, having a
double bond conjugated to an electron-accepting group, may add to a second nucleophilic
sulfite ion which on hydrolysis provides the hydrazine.
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N N
O
O
S
O
N
O
H
O
S
N
O
O
S
O
O
N S O
N
SO O
3
O
N S O
N
SO O
3
O
2H
H O
N S O
N
SO O
-2SO3
3
N
H
NH2
7.3.2 Coupling Reactions
Diazonium ions are weak electrophiles, however, they undergo coupling with activated
aromatic nuclei such as aryl amines, phenols and aromatic heterocyclic compounds. For
example, N,N-dimethylaniline reacts with diazonium ion almost at the para-position.
However, the careful control of the pH of the reaction medium is necessary for the
success of the process.
..
Me2N
N N-Ar
-H
H
N N
Me2N
Me2N
Ar
N
N Ar
In case of primary and secondary aromatic amines, the reaction preferentially takes place
at the nitrogen atoms of the diazonium ions. For example, aniline adds to the aromatic
diazonium salt to give diazoaminobenzene.
..
NH2
N N-Ph
NH
N N
-H
Diazoaminobenzene
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7.4 The Synthetic Value of Diazo-Coupling
7.4.1 Dye-stuffs
Aromatic azo-compounds are coloured. Several of those compounds synthesized by the
diazo-coupling are employed as dye-stuffs. These compounds can be classified into three
groups.

First group of azo-compounds are neutral which are used as azoic combination (or
ingrain) dyes. An example is para red which is prepared by coupling of 2-napthol
with p-nitrobenzenediazonium salt.
NO2
N
N
O+
OH
N N
NO2
Para red

The second group of azo-compounds posses either a sulfonic acid group or an
amino group which are generally adsorbed directly on the fiber from aqueous
solution. Examples are orange II (an acidic dye) and Bismarck brown R (a basic
dye).
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SO3H
N
N
O+ N N
OH
SO3
-
orange II (acidic dye)
Me
H2N
N
Me
N
Me
NH2
+
NH2
2
N2
-2H
N
+
N
H2N
NH2

N2
Me
NH2
Me
Bismarck brown R
Azo-compounds that contain chelating groups to bind with a metal ions such as
Al(III) are used a mordant dyes. An example is alizarin yellow R, which contains
phenolic and carboxyl chelating groups.
O
OH
Al
CO2H
O
O
N2
OH
Al(III)
CO2H
+
N N
N N
NO2
NO2
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NO2
alizarin yellow R
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7.4.2 Indicators
Azo-compounds that contain both an acidic and a basic group can be utilized as
indicators since the colours of the conjugate acid and the conjugate base are different.
Examples are methyl orange and methyl red which are prepared by coupling of
dimethylaniline with diazotized sulfanilic acid and diazotized anthranilic acid,
respectively.
HO3S
CO2H
N
N
N
NMe2
Methyl red
N
Methyl orange
NMe2
7.4.3 Synthesis of Amines
Azo-compounds are susceptible to hydrogenolysis to give amines. For example, the
coupling of 1-naphthol with benzenediazonium chloride gives azo-compound which
could be reduced to 4-amino-1-naphthol in the presence of dithionite.
OH
O-
OH
Na2S2O4
PhN2
N
+ PhNH2
NH2
N
Ph
7.4.4 Synthesis of Quinones
The ortho and para diamines and aminophenols readily oxidize to give quinones. Both
classes of compounds can be readily prepared by diazo-coupling followed by reduction.
Ph
N
N
O-
PhN2
+
O
NH2
OH
Na2S2O4
OH
O
FeCl3/O2
Quinone
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Problems:
A. How would you obtain the following compounds?
CO2H
HO3S
N
N
N
N
NMe2
NMe2
O
OH
N
N
O
B. Complete the following reactions.
O
Me
CuI
1.
N2
CHO
+
2.
O
3.
Cl
CO2Et
CO2H
Ac2O
NaOAc
PhN2
Text Books:
R.O.C. Norman and C. M. Coxon, Principles of Organic Synthesis, CRC Press, New
York, 2009.
B. P. Mundy, M. G. Ellerd, F. G. Favaloro Jr, Name Reactions and Reagents in Organic
Synthesis, Wiley Interscience, New Jersey, 2005.
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