C22J

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C22J
AROMATIC CHEMISTRY
Text Organic Chemistry by T. W. Solomons C.
B. Fryhle Eighth edition.
8 lectures 3 - 4 Tutorial classes Part of two
in-course tests Lab. exercise
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Overview This course
- builds on the organic chemistry you learned at
C10J and C10K.
- contains a significant amount of new
information
- aims to encourage you to take a creative and
imaginative approach to organic chemistry.
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1. Review of - the concepts of aromaticity,
Huckel rule, and the structure and stability of
benzene nomenclature of benzene
derivatives. 2. Non-benzenoid aromatic
systems aromatic ions annulenes
fullerenes heterocycles. 3. Reactions of
benzenoid aromatic compounds. Review
electrophilic substitution of benzene -
halogenation, nitration, sulfonation,
Friedel-Crafts alkylation and acylation.
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Substitution of monosubstituted
benzene. Substitution of disubstituted
benzene. Reaction of side chain of
alkylbenzenes. Application of these reactions in
synthesis of substituted benzenoid compounds.
Phenols and Aryl halides Anilines Polynuclear
aromatics naphthalene, anthracene,
phenanthrene. Some reactions of simple
heterocyclic compounds. (Aromatic Heterocyclic
Chemistry, monograph by David Davies and
Organic Chemistry by L. G. Wade,
Jr.)
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Objectives At the end of these 8 lectures you
should be able to- a) Predict and rationalize
the outcome of reactions of aromatic systems by
applying the principles governing organic
reactivity. b) Devise short syntheses of
simple aromatic compounds.
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TENACITY
NEVER LET DEFEAT HAVE THE LAST WORD!
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David vs Goliath?
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Why do this course at all?
Vast number of aromatic compounds exists, many of
them very useful to man.
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Review Solomons
Aromatic - a term used years ago to describe
substances which are fragrant, e.g. benzaldehyde
and toluene.
These compounds are highly unsaturated, and show
very different chemical behaviour from most other
organic compounds. Aromaticity now associated
with benzene and its derivatives, and no longer
with fragrance.
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Benzene isolated in 1825 by Michael Faraday
from the oily residue left by gas used in London
street lamps. This gas had been made by
pyrolysis of whale oil.
synthesised in 1834 by E. Mitscherlich (German
chemist) by decarboxylation of benzoic acid
using CaO.
molecular formula C6H6. Highly unsaturated.
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What are some of the reactions that you would
expect of unsaturated compounds?
Benzene undergoes none of these reactions.
Reaction with H2/cat. will occur under very
driving conditions, and addition goes very slowly.
Benzene will react with bromine, but only in
presence of a Lewis acid catalyst, e.g. FeBr3,
and the reaction is not addition, but
substitution.
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Why is benzene unreactive (stable) w.r.t. other
alkenes? Why does benzene undergo substitution
and not addition, when treated with bromine and
Lewis acid?
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Stability of Benzene.
Potential Energy
BENZENE
-360 kJ/mol
-208 kJ/mol
-232 kJ/mol
-120 kJ/mol
Cyclohexane
Benzene more stable than the hypothetical 1,3,5-
cyclohexatriene by (360 - 208) 152 kJ/mol.
This resonance energy of benzene.
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Recall the Kekulé structure of benzene.
A
B
Six C atoms in a ring joined by alternating
single and double bonds, and in rapid
equilibrium. This was a good postulate in its
time but it does not explain the unusual
stability of benzene.
All carbon-carbon bonds of benzene have been
found to be of equal length, and are shorter than
C-C but longer than CC.
Resonance Theory states that structures A and B
(which differ only in the position of their
electrons) should be used as resonance
contributors to the picture of the real molecule
of benzene. Benzene should be depicted as-
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Carbon-carbon bonds
are neither single nor double. bond
length 1.39Å, cf C-C single bond (1.47Å) and
CC (1.33Å).
The 152 kJ/mol of energy which benzene does not
contain wrt 1,3,5-cyclo- hexatriene is the
resonance energy of benzene and is responsible
for its AROMATIC properties.
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Benzene

• Benzene contains delocalized e-s but many
  unsaturated molecules have
• delocalized e-s and are still not as stable,
  i.e. still not aromatic.
• How do we explain the stability of benzene and
  other aromatic cpds?
• Answer We look more closely at the
  structure.
• Each C-atom is sp2-hybridized and all bond
  angles are equal (1200),
• Each p-orbital contains one electron and these
  orbitals overlap very effectively

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The molecular orbital theory

• As a result of the delocalized e-s, benzene
  behaves as a nucleophile in rxns

• NB All organic rxns involve a nucleophile and
  an electrophile

• NB The delocalized e-s only partially explain
  stability of benzene

To account fully for it we have to look to
Molecular Orbital Theory.
MOT tells us that the six overlapping p-orbitals
combine to form six new MOs
All new bonding MOs are filled with paired e-s
there are no e-s in the high energy
anti-bonding MOs. This is termed a closed shell.
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Aromatic Character.
What properties do all aromatic compounds have in
common?
From experimental viewpoint - - highly
unsaturated - undergo substn. reactions rather
than addition - are unusually stable, i.e. low
heats of hydrogenation low heats
of combustion.
From theoretical viewpoint, aromatic compounds
are- - cyclic - planar - conjugated -
must contain cyclic clouds of delocalised
p-electrons above and below the plane of the
molecule.
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Aromaticity is exhibited by benzene and its
derivatives, e.g.
These are termed benzenoid aromatic
compounds. There are, however, many other
compounds which are aromatic. Some of these bear
little resemblance to benzene.
Is this compound aromatic?
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The Huckel (4n2) p-electron rule
Remember the criteria for aromaticity -

• - cyclic
• - planar
• - conjugated
• must contain cyclic clouds of delocalised
  p-electrons
• above and below the plane of the molecule.

Another important condition. For monocyclic,
planar systems, the p-cloud must contain (4n2)
p-electrons. n 0, 1, 2, 3, etc.
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Aromaticity (review)
Non-benzenoid aromatics are of four types

• Aromatic ions
• Heterocyclic cpds

In pyridine the lone e--pair are located in a
sp2 orbital and are not part of aromatic sextet
In pyrrole, furan and thiophene, a p-orbital of
the heteroatom donates 2e-s to the ?-system.

• Annulenes other aromatic monocyclics apart from
  benzene
• - Nomenclature- no. of
  C-atomsannulene

Internal Hs interfere with each other and cause
the molecule to twist losing coplanarity. As ring
size increases, internal Hs interfere less and
the tendency to twist out of shape decreases.
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Aromaticity (review)

• Complex aromatics such as

Fullerenes - C60 molecule shaped like a soccer
ball
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Aromatic Ions
.
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Aromaticity
How would you illustrate the molecule before and
after the ion is formed, using atomic
orbitals,? Show MO diagrams for each molecule
Whats the hybridization state of the various C
atoms across?
NB Radicals can never be aromatic
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Heterocyclic compounds Have element other than C
present as a ring atom
Bonding in pyrrole?
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Reactions of Benzenoid Aromatics
Electrophilic Aromatic Substitution
Electrophilic Aromatic Substitution - typical
reaction of aromatic compounds.
Nitration, sulfonation, halogenation, and
Friedel-Craft alkylation and acylation, i.e.
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General Mechanism for EAS
Step 1.
Step 2.
Loss of proton from arenium ion. Aromaticity is
restored.
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Free energy diagram for EAS.
Electrophilic aromatic substitution General
Mechanism
1st TS
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Nitration
Sulfonation
Halogenation
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Electrophilic aromatic substitution
Mechanism-Nitration
Benzene reacts slowly with HNO3 to give
nitrobenzene. With highly protic acids such as
H2SO4, the rxn is much faster.
Step 1 Nitric acid is protonated by Sulfuric
acid in a reversible reaction. essentially HNO3
acts as a base in the presence of the stronger
H2SO4
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Electrophilic aromatic substitution
Mechanism-Nitration
Step 2 The protonated nitric acid dissociates in
the presence of more H2SO4 to form the effective
electrophile, the nitronium ion.
Step 3 The nitronium ion attacks the ring to
form the arenium ion.
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Electrophilic aromatic substitution
Mechanism-Nitration
Step 4 The bisulfate ion assists in
re-aromatization by helping to remove the proton
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Sulfonation
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Alkylation (Friedel-Craft)
Acylation (Friedel-Craft)
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The Friedel-Craft alkylation reaction
Note Aniline will not undergo F-C alkylation.
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3. Aryl and vinyl halides cannot be used as R-X.
X
4. Polyalkylations often occur. Why should this
be?
Would you expect a similar situation for the
acylation reaction?
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Friedel-Crafts acylation
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Applications of the Friedel-Craft Reaction in
Synthesis.
Alkylation usefulness sometimes limited.
major product?
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How then can we make propylbenzene?
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How can we make propylbenzene?
Clemmensen reduction note the conversion.
Reaction of benzene with a cyclic anhydride.
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Substitution of Mono-substituted Benzenes.
Toluene undergoes nitration 25 times as fast as
benzene, under same reaction conditions.
We say toluene is ACTIVATED towards EAS,
and that the methyl group is an ACTIVATING GROUP.
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes

• A substituent Y on the ring has two effects on
  the reactivity
• of benzene
• It dictates how fast the molecule will react.
• It dictates where on the molecule rxn will occur.

• All substituents fall into two categories
• Activators that increase the e-- density (ER) of
  the ring making it more reactive for
• EAS than benzene such that milder rxn conditions
  are required.

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Substituents with lone pairs of electrons are
activating, o-/p-directors.
Activating, o-/p-directors.
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes
Activators push e-s into the ring and the e--
density is increased mainly in the o and
p positions so that these two positions are more
favourable to attack by incoming electrophiles.
NB Same positions are affected by ER and EW
gps, only in opposite ways

• Deactivators EW substituents
• - They decrease e-- density esp
  in the
• o and p positions so that the m
• position is now the most favourable
• (less deactivated) for attack by
  electrophiles.
• Deactivators are thus m directors.

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Nitration of toluene.
Note nitration occurs most at the ortho- and para
positions.
Methyl group ortho-/para director.
Comparison of observed product ratio and
predicted product ratio
59437
404020
For actual reaction, strong predominance for
o-/p-substitution, only trace of meta.
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For EAS, toluene reacts much faster than benzene.
Reaction Mechanism
Nitration of benzene
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Nitration of toluene
Ortho attack of nitronium ion on toluene
Para- attack of nitronium ion.
Meta- attack of nitronium ion.
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Methyl group stabilizes arenium ion and the TS
leading to its formation.
ALL alkyl groups are activating and
o-/p-directing.
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Effect of alkyl groups - Inductive stabilization,
occurs through sigma bond joining alkyl gp. with
benzene ring.
Inductive Effect and Resonance Effect.
Inductive effect- i) depends on
electronegativity ii) weakens with increasing
distance from rxn. centre.
Resonance effect-
involves delocalization of ?- electrons
(location)
e.g.
not stabilised by resonance
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Effect of substituents with non-bonding electrons
(on EAS).
Consider anisole
undergoes nitration 10,000 times as fast as
benzene, and 400 times as fast as toluene,
under same reaction conditions.
O electronegative atom, but stabilizes the
developing arenium ion.
C stabilized by lone pair on oxygen.
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Methoxyl group is activating and
ortho-/para-directing.
Nitration of anisole - reaction mechanism.
Ortho attack.
B
C
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Nitration of anisole meta- attack
Nitration of anisole para- attack
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(No Transcript)
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Deactivating, meta-directing groups.
Nitration of nitrobenzene 10,000 times SLOWER
than benzene. Requires T gt 1000C. Gives
meta-product almost exclusively.
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes
Deactivators include
Carbonyls that are directly attached to the
aromatic ring
NB all m-directing gps have either a partial or
full ve charge on the atom that is
directly attached to the ring.
The two forces at work to determine reactivity
and orientation when a substituent is already
present on the aromatic ring resonance and
induction..
These forces are at work for all monosubstituted
benzenes but in some cases, one or the other may
be insignificant or both may reinforce or they
may oppose each other.
The case of Halobenzenes Weak deactivators but
o/p directors - Exemplifies
resonance and induction at odds
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes
TS is a developing carbocation. ER gps pump e-s
into the ring hence making it better able to
accommodate the developing charge. The stable
aromatic state is therefore more easily
interrupted.
TS is stabilized
TS is destabilized
Substituents with lone pairs have a resonance
effect, i.e., they may either increase or
decrease the resonance stabilization of the
intermediate.
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes
Explaining directivity of some activating and
deactivating groups by looking at the formation
of the possible arenium ions.
1. Substitution in trifloromethyl-benzene
Ortho
Highly unstable contributor
Meta
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes
Para
Highly unstable contributor
NB Highly unstable contributor is absent in m-
attack and this this must be the preferred rxn
pathway of the three.
Remember to show hybrid ion for all possible
arenium ions.
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes
Substitution of halobenzenes. - Halogen
atoms are very electronegative and are therefore
EW by induction. This determines their
electronic influence on the ring and make them
deactivators.
- The atoms are however surrounded by lone
e--pairs allowing them to have a strong
resonance effect. This property determines where
the electrophile is added.
E.g Chlorobenzene
Ortho
Relatively stable contributor
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Electrophilic aromatic substitution
Substitution of monosubstituted benzenes
Meta
Para
Relatively stable contributor
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EAS in disubstituted benzenes

Depends on relative position of the groups

• Groups positioned such that their directive
  effects reinforce each
• other e.g.

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Mononitration of m-xylene.
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B. Groups positioned such that their directive
effects oppose each other e.g.
i)
More powerful activating group determines outcome
of reaction.
No 2-nitro cpd. Why?
Activating groups win out over deactivating
groups.
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C. Directive effects of substituent groups are
similar, but not reinforcing each other.
Results here are not as clear-cut as in
previous 2 cases.
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Reactions of the Side Chain of Alkylbenzenes.
V. stable intermediates. Stabilised by resonance.
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Halogenation of Alkylbenzenes.
Note that-
O
N-bromosuccinimide NBS
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Bromination by NBS.
1 Initiation Homolytic cleavage of N-Br bond.
2. Chain Propagation.
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Halogenation without Lewis Acid
If xs chlorine used, multiple halogenation occurs.
Reaction mechanism.
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The Alkenylbenzenes.
Formation
Alkenylbenzene, only product.
1. Non-terminal alkene.
2. CC is conjugated with aromatic system
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Addition to CC of alkenylbenzenes.
via more stable C
via more stable C.
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Oxidation of side chain of alkylbenzenes.
Most alkyl grps, even those much longer than
CH3 are ultimately degraded to benzoic acid.
This is known oxidative side-chain degradation.
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Organic Synthesis.
a) How would you make o-bromonitrobenzene from
benzene?
Order in which rxns are done is important re the
products
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b) How would you make 3-ethyl chlorobenzene from
benzene?
Reagents i), ii), iii)?
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Effect of amino and hydroxyl groups.
V. powerful activating groups. Activates ring
to EAS and to oxidation.
New substituent is a strong meta-director
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c) How would you make p- nitroaniline from
aniline?
This example demonstrates the use of a
protecting group
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d) How would you make o- nitroaniline from
aniline?
This example demonstrates the use of a
blocking group
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Phenols
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Russians protest about phenol levels
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Acidity of Phenols
Alcohols dissociate in the following manner
Phenols dissociate in like manner, but are much
stronger acids.

• Generally, acidity depends on
• The strength of the O-H bond.
• Stability of the conjugate base.

For phenol, the 2nd condition is very pronounced
as the conjugate base is resonance stabilized.
Substituents on the ring, however, may influence
1st condition and their influence depends on
whether they are ER or EW and where they are
located on the ring relative to the OH of the
phenol.
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Acidity of Phenols
What does the resonance hybrid look like?
EW gps increase the acidity of phenols as they
reduce the e--density of the ring and through an
inductive effect cause the e-s of the O-H bond
to draw nearer to the O-atom, thus increasing
the polarity of the bond, weakening it.
The converse is true for ER substituents.
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Phenol is a much stronger acid than cyclohexanol.

Lone pair on oxygen delocalised over ring. Oxygen
atom more ve. Weakens O-H bond.
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Acidity of Phenols

• Substituted phenols

o-nitrophenol is the strongest of the three
acids. Why?
ltlt
NB The same holds true for different benzoic
acids. EW groups on the ring make them stronger
acids, especially when they are located at the
o-position.
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Preparation of phenols
Laboratory Synthesis - by the Sandmeyer reaction.
Very mild reaction conditions. Other functional
groups within molecule unaffected.
Industrial Synthesis - see Solomons, 7th ed. Ch.
21, Sec. 4B.
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1. Williamson Synthesis of Ethers.
Note use of Na or NaH to form the alkoxide anion.
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• Bromination, nitration, sulfonation etc. will
• occur more readily than in benzene

For bromination, no Lewis acid is required.
Tribrominated product obtained.
When monobromination is required, note use of
conditions that lower the electrophilicity of
bromine.
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Nitration produces o- and p- nitrophenols on
treatment with dilute HNO3.
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Reactions of arylhalides
Reactions.
Alkyl halides react by SN1 and SN2 mechanisms
Simple aryl halides (and vinyl halides) are
unreactive towards nucleophilic substitution e.g.

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SN2 reaction? The benzene ring prevents backside
attack of the C bearing the Cl group.
SN2 reaction will not occur.
SN1 reaction?
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C Halogen bonds of aryl (and vinyl) halides are
shorter and stronger than those of alkyl,
allylic and benzylic halides
Note the double-bond character of the C X bond
of aryl and vinyl halides.
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So NORMALLY, aryl halides will not undergo
nucleophilic aromatic substitution.
Some factors/conditions which allow aryl halides
to undergo nucleophilic substitution
A. When strong electron-withdrawing groups,
(e.g. NO2) are ortho- or para- to the
halogen atom.

• B. When the aryl halides are allowed to react
  under forcing
• conditions e.g. aqueous NaOH, high P and T
  3500C.

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Nucleophilic aromatic substitution
NB as EW gps are increased, milder rxn conditions
suffice. EW gps therefore activate the ring
towards NAS
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Nucleophilic aromatic substitution
There are two possible mechanism for NAS

• Bimolecular Displacement mechanism (BDM) or the
  addition-elimination or
• SNAr mechanism or the occurs when powerful EW
  substituents are on the ring.

BDM results in ipso substitution, i.e.,
substitution at an atom that already had a
substituent.
B) Elimination-addition mechanism
A) For the BDM
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Nucleophilic aromatic substitution
The Meissenheimer complex is stablized by EW gps
o or p to the halogen.
In the last step the C-Cl bond is cleaved because
it is more polar, making Cl a better leaving gp.
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Nucleophilic aromatic substitution
B) For the Elimination-addition. Looking at two
examples.
Conversion of Chlorobenzene to phenol.
Conversion of Bromobenzene to aniline
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Nucleophilic aromatic substitution
The rxns occurs through elimination-addition and
involves the formation of an interesting
intermediate called a benzyne.
The rxn begins with the amide abstracting an
o-proton that triggers elimination of Br.
-Highly unstable thus highly reactive

• The o-proton is abstracted for two reasons
• It is the most acidic
• The ve charge that develops on the o-carbon is
  better stabilized in this position.

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Benzyne Mechanism
Benzyne - unstable. 3rd bond is due to sp2 sp2
overlap of orbitals which are perpendicular to
the p- orbitals of the aromatic ring.