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Aromatic Compounds: © 2006 Thomson Higher Education
Aromatic Compounds: © 2006 Thomson Higher Education
Monosubstituted Benzenes
• Systematically named in same manner as other
hydrocarbons
• – Benzene used as parent name
• C6H5Br is bromobenzene
• C6H5NO2 is nitrobenzene
• C6H5CH2CH2CH3 is propylbenzene
Naming Aromatic Compounds
Arenes
• Alkyl-substituted benzenes
• Named depending on the size of the alkyl group
• Alkyl substituent smaller than the ring (6 or fewer
carbons), named as an alkyl substituted benzene
• Alkyl substituent larger than the ring (7 or more
carbons), named as a phenyl-substituted alkane
Phenyl
• Derived from the Greek pheno (“I bear light”)
• Michael Faraday discovered benzene in 1825 from the
oily residue left by illuminating gas used in London
street lamps
• Used for the –C6H5 unit when the benzene ring is
considered as a substituent
Naming Aromatic Compounds
Benzyl
• Used for the C6H5CH2– group
Naming Aromatic Compounds
Disubstituted benzenes
• Named using one of the prefixes
1. ortho- (o-)
• Ortho-disubstituted benzene
has two substituents in a 1,2
relationship
2. meta- (m-)
• Meta-disubstituted benzene
has its substituents in a 1,3
relationship
3. para- (p-)
• Para-disubstituted benzene
has its substituents in a 1,4
relationship
Naming Aromatic Compounds
Benzenes with more than two substituents
• Named by numbering the position of each so that the
lowest possible numbers are used
• The substituents are listed alphabetically when writing the
name
a. b. c.
Cl
CH2 CH3
d.
e. f.
Br
Br Br Br
Br
Ph
NH2
g.
(Ph)3CH
Structure and Stability of
Benzene
Benzene
• Benzene is unsaturated
• Benzene is much less reactive than typical alkene
and fails to undergo the usual alkene reactions
• Cyclohexene reacts rapidly with Br2 and gives the
addition product 1,2-dibromocyclohexane
• Benzene reacts only slowly with Br2 and gives the
substitution product C6H5Br
Structure and Stability of
Benzene
A quantitative idea of benzene’s stability is obtained
from heats of hydrogenation
• Benzene is 150 kJ/mol (36 kcal/mol) more stable
than might be expected for “cyclohexatriene”
Structure and Stability of
Benzene
Carbon-carbon bond lengths and angles in benzene
• All carbon-carbon bonds are 139 pm in length
• Intermediate between typical C-C single bond (154 pm) and
typical double bond (134 pm)
• Benzene is planar
• All C-C-C bond angles are 120°
• All six carbon atoms are sp2-hybridized with p orbital
perpendicular to the plane of the ring
Structure and Stability of
Benzene
All six carbon atoms and all six p orbitals in benzene
are equivalent
• Each p orbital overlaps equally well with both
neighboring p orbitals, leading to a picture of benzene
in which the six electrons are completely delocalized
around the ring
• Benzene is a hybrid of two equivalent forms
• Neither form is correct by itself
• The true structure of benzene is somewhere in between
the two resonance forms
Aromaticity and the Hückel
4n + 2 Rule
Benzene and other benzene-like aromatic molecules
share similar characteristics:
• Benzene is cyclic and conjugated
• Benzene is unusually stable, it is 150 kJ/mol (36
kcal/mol) more stable than might be expected
• Benzene undergoes substitution reactions that retain
the cyclic conjugation rather than electrophilic addition
reactions that would destroy the conjugation
• Benzene is a resonance hybrid whose structure is
intermediate between two line-bond structures
Aromaticity and the Hückel
4n + 2 Rule
The Hückel 4n + 2 rule
• Theory devised in 1931 by the German physicist
Erich Hückel
• A molecule is aromatic only if it has a planar,
monocyclic system of conjugation and contains a
total of 4n + 2 electrons, where n is an integer
(n = 0, 1, 2, 3,…)
• Only molecules with 2, 6, 10, 14, 18,…
electrons can be aromatic
• Molecules with 4n electrons (4, 8, 12, 16,…)
can not be aromatic, said to be antiaromatic
because delocalization of their electrons would
lead to their destablization
Aromaticity and the Hückel
4n + 2 Rule
Examples of the Hückel 4n + 2 rule
• Cyclobutadiene
• Contains four electrons
• The electrons are
Strategy
• Recall the requirements for aromaticity
• A planar, cyclic, conjugated molecule with
4n + 2 electrons
• See how requirements for aromaticity apply to
thiophene
Worked Example 8.1
Accounting for the Aromaticity of a Heterocycle
Solution
• Thiophene is the sulfur analog of pyrrole
• The sulfur atom is sp2-hybridized and has a lone pair of
electrons in a p orbital perpendicular to the plane of the
ring
• Sulfur also has a second lone pair of electrons in the
ring plane
8.5 Polycyclic Aromatic Compounds
Aromaticity of Naphthalene
• Naphthalene has a cyclic, conjugated electron system,
with p orbital overlap both around the ten-carbon
periphery of the molecule and across the central bond
• 10 is a Hückel number (4n + 2 when n = 2) so there is
electron delocalization and consequent aromaticity in
naphthalene
Polycyclic Aromatic Compounds
dihydroxyphenyl acetate
• The reaction is catalyzed by p-hydroxyphenylacetate-3-
RO-OH + H+ ROH
8.7 Alkylation and Acylation of
Aromatic Rings
Alkylation
• The introduction of an alkyl group onto the benzene ring
• Called the Friedel-Crafts reaction after its discoverers
• Among the most useful electrophilic aromatic
substitution reactions in the laboratory
• The reaction is carried out by treating the aromatic
compound with an alkyl chloride, RCl, in the presence
of AlCl3 to generate a carbocation electrophile, R+
• Aluminum chloride catalyzes the reaction by helping the
alkyl halide to dissociate
• Loss of H+ completes the reaction
Alkylation and Acylation of
Aromatic Rings
Mechanism of the Friedel-Crafts alkylation reaction
• The electrophile
is a carbocation,
generated by
AlCl3-assisted
dissociation of
an alkyl halide
Alkylation and Acylation of
Aromatic Rings
Friedel-Crafts alkylation has several limitations
1. Only alkyl halides can be used
• Aromatic (aryl) halides and vinylic halides do not
react because aryl and vinylic carbocations are too
high in energy to form under Friedel-Crafts conditions
• Vinylic means that a substituent is attached directly
to a double bond, C=C-Cl
Alkylation and Acylation of
Aromatic Rings
2. Friedel-Crafts reactions do not succeed on aromatic
rings that are substituted either by a strongly
electron-withdrawing group such as carbonyl (C=O)
or by an amino group (-NH2, NHR, -NR2)
• The presence of a substituent group already on a ring
can have a dramatic effect on that ring’s subsequent
reactivity toward further electrophilic substitution
Alkylation and Acylation of
Aromatic Rings
• A skeletal rearrangement of the alkyl carbocation electrophile
sometimes occurs during a Friedel-Crafts reaction, particularly
when a primary alkyl halide is used
• Carbocation rearrangements
occur either by hydride shift or
alkyl shift
• Alkylation of benzene with
1-chloro-2,2-
dimethylpropane yields
(1,1-
dimethylpropyl)benzene
Alkylation and Acylation of
Aromatic Rings
An aromatic ring is acylated by reaction with a carboxylic
acid chloride, RCOCl, in the presence of AlCl3
• An acyl group is substituted onto an aromatic ring
• The reactive electrophile is a resonance-stabilized acyl
cation
• An acyl cation is stabilized by interaction of the vacant
• Resonance effect
• Due to overlap between a p orbital on the ring and an orbital
on the substituent
Substituent Effects in
Electrophilic Substitutions
Orienting Effects: Ortho and Para Directors
• The ortho and para intermediates are more stable than the
meta intermediate because they have more resonance
forms
Substituent Effects in
Electrophilic Substitutions
Any substituent that has a lone pair of electrons on the atom
directly bonded to the aromatic ring allows an electron-
donating resonance interaction to occur
• Additional electron-donating resonance interaction lowers the
energy of the hybrid
• Electron-donating substituent increases electrophilicity of ortho
and para positions and acts as an ortho and para director
Substituent Effects in
Electrophilic Substitutions
Orienting Effects:
Meta Directors
Substituent Effects in
Electrophilic Substitutions
Any substituent that has a positively polarized atom (+) directly
attached to the ring increases the activation energy leading to
the intermediate hybrid for ortho and para substitutions
• Substitution at ortho or para position gives a higher energy
intermediate
• Meta substitution avoids higher energy intermediate and has a
lower activation energy
• Approaching electrophile is directed to the meta positions
Substituent Effects in
Electrophilic Substitutions
A Summary of Substituent Effects in Electrophilic
Substitutions
Worked Example 8.3
Predicting the Product of an Electrophilic
Aromatic Substitution Reaction
Predict the major product of the sulfonation of
toluene.
Worked Example 8.3
Predicting the Product of an Electrophilic
Aromatic Substitution Reaction
Strategy
• Identify the substituent present on the ring
• Decide whether the substituent is ortho- and
para-directing or meta-directing
• According to Figure 8.15 an alkyl substituent is
ortho- and para-directing
• Sulfonation of toluene will give primarily a mixture
of o-toluenesulfonic acid and p-toluenesulfonic
acid
Worked Example 8.3
Predicting the Product of an Electrophilic
Aromatic Substitution Reaction
Solution
8.9 Oxidation and Reduction of
Aromatic Compounds
Alkyl substituents on aromatic rings containing a benzylic
hydrogen react readily with common laboratory
oxidizing agents such as aqueous KMnO4 or Na2Cr2O7
and are converted into carboxyl groups
• Net conversion of an alkylbenzene into a benzoic acid
Ar-R Ar-CO2H
• Oxidation of butylbenzene into benzoic acid
Oxidation and Reduction of
Aromatic Compounds
• The mechanism of side-chain oxidation involves
reaction of a C-H bond at the position next to the
aromatic ring (the benzylic position) to form an
intermediate benzylic radical
• Benzylic radicals are stabilized by resonance and
thus form more readily than typical alkyl radicals
Oxidation and Reduction of
Aromatic Compounds
Side chain oxidations occur in various biosynthetic
pathways
• The neurotransmitter norepinephrine is biosynthesized
from dopamine by a benzylic hydroxylation reaction
• Radical reaction
• Reaction catalyzed by the copper-containing enzyme
dopamine -monooxygenase
Oxidation and Reduction of
Aromatic Compounds
Aromatic ring
• Activates a neighboring (benzylic) C-H position toward
oxidation
• Activates a neighboring carbonyl group toward reduction
• An aryl alkyl ketone prepared by Friedel-Crafts acylation
of an aromatic ring can be converted into an
alkylbenzene by catalytic hydrogenation over a palladium
catalyst
• Propiophenone is
reduced to
propylbenzene
by catalytic
hydrogenation
8.10 An Introduction to Organic Synthesis:
Polysubstituted Benzenes
There are many reasons for carrying out
laboratory synthesis of an organic molecule
• In the pharmaceutical industry, new molecules
are designed and synthesized in the hope that
some might be useful drugs
• In the chemistry industry, syntheses are done
to devise more economical routes to known
compounds
• In biochemistry laboratories molecules
synthesized to probe enzyme mechanisms
An Introduction to Organic Synthesis:
Polysubstituted Benzenes
Planning a successful multistep synthesis of a
complex molecule requires knowledge of the
uses and limitations of numerous organic
reactions
The trick to planning an organic synthesis is to work
backward, often referred to as the retrosynthetic
direction
• Keep starting material in mind and work backward to it
• Look at the final product and determine possible
immediate precursors of that product
• Work backward one step at a time
An Introduction to Organic Synthesis:
Polysubstituted Benzenes
Examples of synthetic planning using
polysubstituted aromatic compounds as the
targets
• Electrophilic substitution on a disubstituted benzene
ring is governed by the same resonance and
inductive effects that affect monosubstituted rings
• Must consider the additive effects of two groups
An Introduction to Organic Synthesis:
Polysubstituted Benzenes
1. If the directing effects of the two groups reinforces
each other, the situation is straightforward
• In p-nitrotoluene both the methyl and the nitro group
direct further substitution to the same position (ortho
to the methyl = meta to the nitro). A single product is
thus formed on electrophilic substitution
An Introduction to Organic Synthesis:
Polysubstituted Benzenes
2. If the directing effects of the two main groups
oppose each other, the more powerful activating
group has the dominant influence
• Nitration of p-methylphenol yields primarily 4-methyl-
2-nitrophenol because –OH is a more powerful
activator than –CH3
An Introduction to Organic Synthesis:
Polysubstituted Benzenes
3. Further substitution rarely occurs between the two
groups in a meta-disubstituted compound because
this site is too hindered
• Aromatic rings with three adjacent substituents must
therefore be prepared by some other route
• The substitution of an ortho-disubstituted compound
Worked Example 8.4
Synthesizing a Polysubstituted Benzene
Strategy
1. Draw the target molecule
2. Identify the substituents
• The three substituents on the ring are a bromine, a
methyl group, and a nitro group
3. Recall how each group can be introduced separately
• A bromine can be introduced by bromination with
Br2/FeBr3, a methyl group can be introduced by Friedel-
Crafts alkylation with CH3Cl/ AlCl3, and a nitro group can
be introduced by nitration with HNO3/H2SO4
4. Then plan retrosynthetically
Worked Example 8.4
Synthesizing a Polysubstituted Benzene
Solution
• The final step will involve introduction of one of the
three groups – bromine, methyl, or nitro
• Three possibilities:
Worked Example 8.4
Synthesizing a Polysubstituted Benzene
• Immediate precursors of p-bromotoluene
• Toluene
• Because the methyl group would direct bromination
to the ortho and para positions
• Bromobenzene
• Because Friedel-Crafts methylation would yield a
mixture of ortho and para products
Worked Example 8.4
Synthesizing a Polysubstituted Benzene
• The immediate precursor of toluene
• Benzene, which could be methylated in a Friedel-Crafts
reaction
• The immediate precursor of bromobenzene
• Benzene, which could be brominated
• Two valid routes possible from benzene to 4-bromo-2-
nitrotoluene
Worked Example 8.5
Synthesizing a Polysubstituted Benzene
Solution
• The final step will involve introduction of one of the
three groups – chlorine, propyl, or sulfonic acid
• Three possibilities:
Worked Example 8.5
Synthesizing a Polysubstituted Benzene
• The immediate precursors to m-chloropropylbenzene
• Because the two substituents have a meta relationship, the first
substituent placed on the ring must be a meta director so that the
second substitution will take place at the proper position
• Because primary alkyl groups such as propyl cannot be
introduced directly by Friedel-Crafts alkylation, the precursor of
m-chloropropylbenzene is probably m-chloropropiophenone,
which could be catalytically reduced
Worked Example 8.5
Synthesizing a Polysubstituted Benzene
• The immediate precursor
of m-chloropropiophenone
• Propiophenone, which
could be chlorinated in
the meta position