AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Topic 8: Reactions of Aryl Groups

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Electrophilic Aromatic Substitution of Aryl Amines, synthesis by

reduction of nitro group, control of electrophilic substitution by
conversion to amide, diazonium salts and their use, preparation of
diazonium salts from primary aromatic amines, azo compounds and
their preparation, diazoalkanes and preparation of diazoalkanes
from N-alkyl-N-nitroso compounds.

Topic Content

Electrophilic Aromatic Substitution of Aryl Amines

NH2 NH2 NH2

+ E
E +
+ + H

E
Para Ortho

• Arylamines are potentially very reactive towards electrophilic

aromatic substitution

• This is because -NH2, -NHR and -NR2 are very strong

activators and are ortho and para- directing.

• However the basicity of the amino group means it is

unsuitable for reactions with acids (e.g. H2SO4 or AlCl3) such
as nitration, sulfonation and Friedel-Craft alkylation or
acylation

• Polysubstitution can also be a problem.

• For example, bromination is very rapid, even in the absence

of a catalyst, leading to bromination in all available ortho-
and para- positions.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

NH2 NH2
Br2 Br Br

Br

• To avoid these problems, it is important to protect aryl

amines as their N-acyl derivatives (an amide) which can later
be removed by either acid or base hydrolysis.
O

NH2 O O O NH

Cl or O

H3O or NaOH
Amine Heat Amide

• The amide is a less powerful activating group than the simple

amino group, -NH2 since resonance within the N-acetyl group
of the amide competes with delocalisation of the N lone pair
into the ring.
.. ..
:O
: O:
: NH
NH

• Steric effects in the amide also often lead to a decrease in

the amount of the ortho-products.

• In principle, the sequence (i) protect, (ii) substitute then (iii)

deprotect is equivalent to being able to substitute the aniline
directly.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Electrophilic Aromatic Substitution of Aryl Halides

X X X
+ E
E +
+ + H

para ortho

• Aryl halides are reactive towards electrophilic aromatic

substitution but they are less reactive than benzene.

• This is because halides are weak deactivators.

• Halides direct subsequent reactions ortho/para.

• This makes them a little unusual (activators are usually

ortho, para-directing, deactivators meta-directing).

• The weak deactivation is due to the electronegativity of the

halogen making the intermediate cations less stable than
those produced when benzene undergoes substitution:

δ
X
δ H
E

• The directing effect is due to the resonance stabilisation of

the cationic intermediates derived by ortho or para attack but
not by meta attack. For example, the stabilisation during
ortho attack is shown below:

.. ..
:X: X:
H H
E E

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Preparation of Aryl diazonium (benzenediazonium) salts

A very useful reaction of primary aryl amines, Ar-NH2, is that
which gives aryl diazonium salts, Ar-N2+ which can then be used to
prepare substituted benzenes. Primary aryl amines yield diazonium
salts (hence the diazotisation reaction).

Preparation of aniline from benzene

Aniline can be prepared in the lab by nitration of aromatic
compounds followed by reduction of the nitro group.

NO2 NH3Cl NH2

HNO3 Fe NaOH

H2SO4 HCl

• A mixture of iron filings and conc. HCl is a common reducing

agent. This produces a protonated amine.

• Treatment by a base (NaOH) then generates the free amine.

• Other reducing agents which will also reduce NO2 group to

NH2 group are Sn/HCl, H2/Ni cat., N2H4/Ni cat., LiAlH4,
NaBH4.

• If aniline is treated with cold nitrous acid (HNO2) in HCl a

diazonium chloride is produced.

• HNO2 is produced in situ by reaction of sodium nitrite

(NaNO2) with HCl.

• The reaction must be kept cold (0oC) as diazonium salts are

very reactive and unstable.

NH2 N NCl

NaNO2
+ H2O
HCl

• Diazonium Salts are highly reactive as N2 gas is an excellent

leaving group.
• The diazonium group may be easily replaced by nucleophiles,
e.g. I-.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

• Some of the substitution reactions are thought to proceed by

a radical reaction.
• Others go by a reaction similar to SN1 by an intermediate
carbocation, (carbonium ion C+)

N N Nu

N2 Nu:

• Usually the diazonium salt is prepared but not isolated. The

nucleophile reagent is then added and the mixture allowed to
warm. Yields are usually about 70-95%

Reactions of Diazonium Salts: Aryl Halides and Nitriles

• The diazonium group is easily displaced by F-, Cl-, Br-, I-, CN-.
• Aryl fluorides, iodides and nitriles cannot be obtained by
direct electrophilic substitution of benzene compounds.
• Aryl chlorides and bromides can be synthesised by
electrophilic substitution but are often contaminated by
disubstituted products. The use of diazonium salts is therefore a
better method to use for preparation of Aryl chlorides and
bromides.
Cl

+ N2

CuCl

NH2 N NCl Br

NaNO2 CuBr
+ N2
HCl

+ H2O
CuCN
CN
KCN

+ N2

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

• A Copper (I) salt is used to prepare chlorides, bromides and

nitriles. The Cu+ acts as a catalyst and the reaction mixture
needs to be warmed to 50-100 oC (Sandmeyer reaction).
• Nitriles can be hydrolysed to acids.

CN CO2H

H3O

Benzoic acid

Aryl iodides and fluorides are prepared with potassium iodide KI

(no catalyst) or fluoroboric acid HBF4 respectively.

l
+ N2
Kl
NH2
N NCl
NaNO2
HCl
HBF4
N NBF4 F
+ H2O
Heat
+ N2

Isolated
and dried

Diazonium reactions are used to prepare compounds that

cannot be synthesised by other routes.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Preparation of phenol
• Phenol can be prepared by the reaction of a diazonium salt
with hot aqueous acid. This provides a lab route to phenol.

 Note that if there are other groups on the ring they are
uneffected.

NH2 OH
N NCl
NaNO2 H3O

HCl 100 oC NO2

NO2 NO2
+ H2O
m-nitroaniline m-nitrophenol (86%)

Preparation of arenes
• The N2+ group can be replaced with H by treating the
diazonium salt with hypo-phosphorous acid H3PO2. This
provides removal of an NH2 group from an aromatic ring.

N NCl
H3PO2

0 oC

• This reaction can be used when the directing effect of the

NH2 group is necessary. i.e. you wish to add ortho- or para-
derivatives, BUT the NH2 group is not actually required in the
final product.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Diazonium Coupling Reactions

• Diazonium compounds can also undergo coupling reactions to
form brightly coloured azo compounds (ArN=NAr’) which are
used as dyes.
• In these reactions the diazonium ion acts as an electrophile
• Resonance structures for the ion show that each nitrogen
atom carries a partial +ve charge.

..
N N: N N:

• The terminal nitrogen attacks the para- position of an

activated benzene ring. i.e. one with an electron donating
group such as NH2 or OH.
• The product contains an azo group (-N=N-) and is called an
azo compound.

..
N N: + G N N G

G = OH, NH2 or NR2

E.g.
CH3 CH3
N N: + N N N N
CH3 CH3

N,N-dimethylaniline p-(dimethylamino)-azobenzene

• Azo-coupled products are widely used as dyes because with

their extended conjugated π system they absorb in the visible
region.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Aryl carboxylic acids

• Aryl carboxylic acids can be made by oxidising an alkyl side
chain.
• Although alkyl groups are usually non-reactive, alkyl groups
bonded to an aromatic ring show a unique reactivity.
• The carbon adjacent to an aromatic ring is a benzylic carbon.

A benzylic cation, radical and anion are all resonance stabilised by

the benzene ring. Therefore the benzylic carbon is the site of attack
in many reactions.
Benzylic cabons

CH3 CH2CH3 CH2CH2CH3

• The alkyl group can be oxidised by hot KMnO4 but because of

the reactivity of the benzylic carbon they all yield the same
product i.e. benzoic acid. – C6H5COOH
• Note that the benzene ring is not oxidised under these
conditions.

E.g. methylbenzene (toluene) to benzoic acid or butylbenzene to

benzoic acid.

CH3 COOH
KMnO4

H 2O

CH2(CH2)2CH3
CO2H
KMnO4
H2O

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

• However oxidation cannot be used to make p-toluic acid (p-

methylbenzoic acid) from p-xylene (p-dimethylbenzene)
because both methyl groups would be oxidised to COOH
groups.
CH3 CO2H
KMnO4
H2O

CH3 CO2H

• Instead it must be prepared using a diazonium salt

NH2 N CN CO2 H
NCl
NaNO2 CuCN H3 O

HCl KCN

CH3 CH3 CH3 CH3

+ H2 O + N2 p-toluic acid

• Free-radical halogenation can also take place at the benzylic

position.

Br
CH2CH3 CHCH3
Br2
hν

hν = photon of light i.e. light energy is needed for the reaction to

proceed.
c.f. methane + chlorine gas in the presence of uv light, which is a
free radical substitution reaction.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Preparation of 1,3,5-tribromobenzene from aniline

(Bromination of aniline).

NH2 NH2
Br2 Br Br

FeBr3

Br
1,3,5-tribromobenzene

Aniline readily undergoes tribromination as the NH2 group makes

the ring very susceptible to electrophilic substitution.

NH2
N NCl
Br Br
NaNO2 Br Br
H3PO2 Br Br

HCl, 0 oC 0 oC
Br
Br Br
+ H2O

Although the amino group is a ring-activator and o- and p-

directing, its character changes in a reaction mixture containing a
Lewis acid such as H2SO4, HNO3 or AlCl3. The reason is that the
amino group reacts with the Lewis acid to yield a meta-directing,
deactivating ammonium ion group.

NH2 NH3 HSO4

H2SO4

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Selective Reduction of NO2 groups

• m-dinitrobenzene can be selectively reduced to m-nitroaniline

using sodium polysulphide Na2S2 or ammonium sulphide if molar
quantities are used.

NO2 NO2
Na 2S2

NO2 NH2

TNT (Trinitrotoluene)
• Trinitrotoluene is an explosive
• It can be prepared from toluene by nitration.
• The methyl group can then be oxidised to give 2,4,6-
trinitrobenzoic acid.
• The COOH group is deactivating and meta-directing so if toluene
is oxidised to benzoic acid first and then nitrated the compound
formed would be m-nitrobenzoic acid.

CH3 CO2H
CH3
NO2 NO2 NO2 NO2
HNO3 H2CrO4
H2SO4 heat
NO2 NO2

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Topic Activities
Tutorial

1. Using a diazotisation reaction at some stage, show by equations

how the following may be synthesised.
(i) Fluorobenzene from benzene
(ii) 1,3,5-Tribromobenzene from aniline
(iii) m-chloronitrobenzene from m-dinitrobenzene
(iv) 2,4,6-Tribromobenzoic acid from nitrobenzene.
(v) o-Chlorophenol from aniline.
(vi) benzoic acid from aniline
(vii) 3,5-dibromotoluene from p-aminotoluene

2. Show by equations how the following compounds may be

synthesised from the starting materials given:

NH2
Br Br

(i) from

Br

CO2H NO2

(ii) from

OH NO2

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Answers:
1.
NO2 NH2
HNO3 H2
(i)
H2SO4 Pd/C

NaNO2
HCl
F N NBF4 N NCl
Heat HBF4
+ H2O

+ N2 Isolated
and dried

(ii)

NH2 NH2 N N Cl
Br Br Br Br
Br2 NaNO2
+ H2O
FeBr3 HCl, 0oC

Br Br

H3PO2
0oC

Br Br

Br

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

NO2 NH2 N NCl

H2 NaNO2
(iii) Pd/C HCl, 0 oC
NH2 N NCl
NO2

H3PO2
0 oC
NO2 NO2

Cl2 HNO3

FeCl3 H2SO4
Cl

Alternatively you could use selective reduction of one of the NO2

groups using Na2S2

NO2 NO2 NO2

Na2 S2 NaNO 2/ HCl

0oC
NO2 NH2 N NCl

CuCl

NO2

Cl

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

NH2 NH2
NO2
Br Br
H2 Br2
(iv)
Pd/C FeCl3
Br

NaNO2
HCl, 0 oC

N NCl
Br Br Br
H3PO2 Br

0 oC
Br Br

CH3Cl
AlCl3
CO2H
CH3 Br
Br
Br Br KMnO4
H2O
Br
Br

NH2 N NCl OH
NaNO2 NaOH
(v)
HCl, 0 oC heat

Cl2
FeCl3

OH
Cl

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

NH2 N NCl
NaNO2 H3PO2
(vi)
HCl, 0 oC 0 oC
CH3Cl
AlCl3

CO2H CH3
KMnO4

H2O

CH3 CH3 CH3

Br2 NaNO2
(vii)
FeBr3 Br HCl, 0 oC Br Br
Br
NH2 NH2 N NCl

H3PO2
0 oC

CH3

Br Br

 Both the NH2 group and the CH3 group are o- and p-directing
but NH2 is the more powerful and so takes preference.

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

2.

NH2 NH2
N NCl
Br Br
Br Br
Br2 NaNO2
(i) + H2O
FeBr3 HCl, 0 oC
Br
Br

H3PO2
0 oC

Br Br

Br

NO2 NH2 N NCl

H2 NaNO2
(ii) Pd/C HCl, 0 oC
NH2 N NCl
NO2

H3PO2
0 oC
CO2H CH3

KMnO4 CH3Cl

H2O AlCl3

Cl2
FeCl3

CO2H CO2H

NaOH
heat
Cl OH
.

Further Reading
W H Brown & C. S. Foote, Organic Chemistry, (2nd Edit.) Saunders
College Publishing (1998) pp 855-867

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AS2232 Organic chemistry Topic 8: Reactions of Aryl Groups

Or
P Y Bruice, Essential Organic Chemistry, Ch 16. Pearson Prentice
Hall Publishing (2006)

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