Lecture 16 Aromatic Diazonium Salts - Nptel

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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

NaNO₂ HCl,< 5 ^oC

N₂Cl

Mechanism

NH₂

NO⁺

H₂N NO

H

HN NO HN N OH

N N OH N N

OH₂ -H₂O

N N -H

-H H

HO NO H₂O NO -OH₂ H NO

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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O N O N

NH₂

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 para- azophenols in good yield.

O

N N Ar O

H N N

Ar

tautomerizes

HO N

N Ar

7.1.2.2 S

N

1 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

warm

-N₂ H₂O OH₂ -H OH

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

CuCl ^. -CuCl

Cl Cu Cl +

N₂Cl Cl

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.

N₂Cl H₂O/H warm

OH

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 S_N1 mechanism.

N N Cl

Aq. MBF₄, cold M = Na, H, NH4

N N BF4

- MCl salt precipitates

dry ppt heat

BF4 F B

FF F

-BF₃ F

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Examples:

S NH₂

CO₂Me

NaNO₂, HCl

HPF₆ S

F

CO₂Me 47%

A. Kiryanov, A. Seed, P. Sampson, Tetrahedron Lett. 2001, 42, 8797.

N NH₂

OH NaNO₂ F B

OH OH

N F

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.

Me NH₂ Me Br

NaNO₂, H HBF₄

Me 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 N₂

HX

X CuX .

+ X-Cu-X + N₂

-N₂ -CuX

X

X = Br, Cl, CN

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Examples:

S N

NH₂ Me

NaNO₂, HCl

CuSO₄ S

N Cl Me

53%

N. Zou, J.-F. Liu, B. Jiang, J. Combin. Chem. 2003, 5, 754.

Me NH₂

CuCN HONO

Me CN

H. T. Clarke, R. R. Reed, Org. Synth. 1941, 1, 514.

F NH₂

N O

HNO₂, CuBr HBr

F Br

N

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

HNO₂, H Cu(0)

G

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.

G N₂

-N₂ H

G G

H -HH G In acid solution:

In neutral or basic solution:

G

N₂ -N₂

G G

H Cu(0)

. + Cu(I)

. Cu(I) + H Cu(0) + H

.

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Examples:

O

NMe₂ Me₂N NH₂

NaNO₂, H₂SO₄ Cu-Sn, Na2SO4

O

NMe2

Me2N

S. G. R. Guinot, J. D. Hepworth, M. Wainwright, J. Chem. Res. Synop. 1997, 183,.

65%

N N

O Bn

H₂N

HNO2 N

N O Bn

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 Cu(NH3)2OH

CO₂H CO₂H

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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O O S O

N N S O O O O O S O

N N S O O O SO₃

N N S O O O SO₃

H

N HN S

O O O SO₃

2H

-2SO₃ 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

Me₂N H

N N Ar

-H

N N Ar Me₂N

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.

N N-Ph NH₂

..

-H

NH N N

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.

O^-

N N

OH N

N

NO₂

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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N N

OH N

N

SO₃^-

SO₃H

orange II (acidic dye) +

+

Me NH₂

NH₂

2 +

Me N₂

N₂

-2H

Me N

N

N

N

H₂N NH₂ Me H₂N

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.

OH

CO₂H +

N₂

NO₂

OH

CO₂H

N N

NO₂

Al(III)

O

N N

NO₂ Al O

O

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.

N N

NMe₂ HO₃S

Methyl orange N N

NMe₂ Methyl red

CO₂H

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.

O^- OH

N N Ph

OH Na₂S₂O₄

NH₂

+ PhNH₂ PhN₂

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.

O^- PhN₂⁺

N N

OHNa₂S₂O₄ OH

NH₂ O

FeCl₃/O₂ O Ph

Quinone

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Problems:

N N

NMe₂ HO₃S

N N

NMe₂ CO₂H

O

O

N N OH

A. How would you obtain the following compounds?

B. Complete the following reactions.

O

N₂ Cl Me

1. CuI

2.

CHO

+ CO₂H Ac₂O

3. CO₂Et

O 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.