Download Aromatic Compounds

4/18/2011
9.8 Substituent Effects in Electrophilic
Substitutions
Substituent effects in the electrophilic substitution of an
aromatic ring
• Substituents affect the reactivity of the aromatic ring
•
•
•
Some substituents activate the ring, making it more reactive
than benzene
Some substituents deactivate the ring, making it less reactive
than benzene
Relative rates of aromatic nitration
Substituent Effects in Electrophilic
Substitutions
• Substituents affect the orientation of the reaction
•
•
The three possible
disubstituted
products – ortho,
meta, and para –
are usually not
formed in equal
amounts
The nature of the
substituent on the
ring determines the
position of the
second substitution
Substituent Effects in Electrophilic
Substitutions
Substituents can be classified into three groups
•
•
•
ortho- and para-directing activators
ortho- and para-directing deactivators
meta-directing deactivators
•
There are no meta-directing activators
All activating groups are ortho- and para- directing
All deactivating groups other than halogens are meta-directing
The halogens are unique in that they are deactivating but ortho- and
para-directing
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Substituent Effects in Electrophilic
Substitutions
Substituent Effects in Electrophilic
Substitutions
Activating and Deactivating Effects
• The common characteristic of all activating groups is that
they donate electrons to the ring
•
•
•
Makes the ring more electron-rich
Stabilize the carbocation intermediate
Lower activation energy
• The common characteristic of all deactivating groups is that
they withdraw electrons from the ring
•
•
•
Makes the ring more electron-poor
Destabilizes the carbocation intermediate
Raising the activation energy for its formation
Substituent Effects in Electrophilic
Substitutions
Electrostatic potential maps of benzene, phenol (activated),
chlorobenzene (weakly deactivated), and benzaldehyde
(more strongly deactivated)
• The –OH substituent makes the ring more negative (red)
• The –Cl makes the ring less negative (orange)
• The –CHO makes the ring still less negative (yellow)
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Substituent Effects in Electrophilic
Substitutions
The electron donation or electron withdrawal may occur by
either an inductive effect or a resonance effect
•
Inductive effect
•
Due to an electronegativity difference between the ring and the
attached substituent
Substituent Effects in Electrophilic
Substitutions
•
Resonance effect
• Due to overlap between a p orbital on the ring and an orbital on
the substituent
Substituent Effects in Electrophilic
Substitutions
Inductive effects and resonance effects don’t
necessarily act in the same direction
• Halogen, hydroxyl, alkoxyl, and amino substituents have
electron-withdrawing inductive effects due to the
electronegativity of the –X, –O , or –N atom and electrondonating resonance effects because of the lone-pair
electrons on those –X, –O , or –N atoms
• When the two effects act in opposite directions the
stronger effect dominates
•
•
Hydroxyl, alkoxyl, and amino substituents are activators
because of their stronger electron-donating resonance
effect
Halogens are deactivators because of their stronger
electron-withdrawing inductive effect
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Substituent Effects in Electrophilic
Substitutions
Orienting Effects: Ortho and Para Directors
•
•
Alkyl groups have an electron-donating inductive effect
Nitration of toluene occurs ortho and para to the alkyl group
because a resonance form places the positive charge directly on
the alkyl-substituted carbon where it can be stabilized by the
electron-donating inductive effect of the alkyl group
Substituent Effects in Electrophilic
Substitutions
Orienting Effects: Ortho and Para Directors
•
•
Halogen, hydroxyl, alkoxyl, and amino groups are ortho
and para directors because the atom attached to the
ring – halogen, O, or N – has a lone pair of electrons
Ortho and para substitutions allow the intermediate to
be stabilized by more resonance forms than the meta
substitution intermediate
Substituent Effects in Electrophilic
Substitutions
Nitration of phenol
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Substituent Effects in Electrophilic
Substitutions
Orienting Effects: Meta Directors
Any substituent that has a positively polarized atom (d+) 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
Orienting Effects: Meta Directors
•
Nitration of benzaldehyde
Substituent Effects in Electrophilic
Substitutions
A Summary of Substituent Effects in Electrophilic
Substitutions
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Worked Example 9.3
Predicting the Product of an Electrophilic
Aromatic Substitution Reaction
Predict the major product of the sulfonation of
toluene.
9.9 Nucleophilic Aromatic Substitution
Aryl halides that have electron-withdrawing substituents can
undergo a nucleophilic substitution reaction
Nucleophilic Aromatic Substitution
• Reaction of proteins with 2,4-dinitrofluorobenzene (Sanger’s
reagent) attaches a “label” to the terminal NH 2 group of an
amino acid by a nucleophilic aromatic substitution reaction
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Nucleophilic Aromatic Substitution
Mechanism of nucleophilic aromatic substitution reactions
Nucleophilic Aromatic Substitution
Nucleophilic aromatic substitution occurs only if the
aromatic ring has an electron-withdrawing substituent in
a position ortho or para to the leaving group to stabilize
the anion intermediate through resonance
Nucleophilic Aromatic Substitution
Comparison of electrophilic and nucleophilic aromatic
substitution reactions
• Electrophilic substitutions are favored by electrondonating substituents which stabilize the carbocation
intermediate
• Nucleophilic substitutions are favored by electronwithdrawing substituents which stabilize a carbanion
intermediate
• Electron-withdrawing groups that deactivate rings for
electrophilic substitution (nitro, carbonyl, cyano, and so
on) activate rings for nucleophilic substitution
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9.10 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 KMnO 4 or Na2Cr2O7 and are
converted into carboxyl groups – CO2H
•
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 b -monooxygenase
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Oxidation and Reduction of Aromatic
Compounds
Hydrogenation of Aromatic Rings
•
Alkene double bonds can be reduced selectively in the presence
of an aromatic ring
Oxidation and Reduction of Aromatic
Compounds
•
To hydrogenate an aromatic ring it is necessary to use a platinum
catalyst with hydrogen gas at several hundred atmospheres
pressure or a more effective catalyst such as rhodium on carbon
Oxidation and Reduction of Aromatic
Compounds
Reduction of Aryl Akyl Ketones
Aromatic ring 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
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