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Reduction of the Nitro Group
NO2
Zn, Sn, or Fe
aq. HCl
NH2
Treatment with zinc, tin, or iron in dilute acid will reduce the nitro to an
amino group.
This is the best method for adding an amino group to the ring.
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Nitration of Toluene
Toluene reacts 25 times faster than benzene.
The methyl group is an activator.
The product mix contains mostly ortho and para substituted molecules.
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Ortho and Para Substitution
Ortho and para attacks are preferred because their resonance structures
include one tertiary carbocation.
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Meta Substitution
When substitution occurs at the meta position, the positive charge is not
delocalized onto the tertiary carbon, and the methyl groups has a smaller
effect on the stability of the sigma complex.
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Alkyl Group Stabilization
CH2CH3
Br2
FeBr3
CH2CH3
Br
CH2CH3
Br
CH2CH3
Br
+ +
o-bromo
(38%)
m-bromo
(< 1%)
p-bromo
(62%)
Alkyl groups are activating substituents and ortho, para-directors.
This effect is called the inductive effect because alkyl groups can donate
electron density to the ring through the sigma bond, making them more
active.
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Effect of Multiple Substituents
The directing effect of the two (or more) groups may
reinforce each other.
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Effect of Multiple Substituents (Continued)
The position in between two groups in Positions 1 and 3 is
hindered for substitution, and it is less reactive.
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Effect of Multiple Substituents (Continued)
OCH3
O2N
Br2
FeBr3
OCH3
O2N
Br
OCH3
O2N
Br
If directing effects oppose each other, the most powerful
activating group has the dominant influence.
major products obtained
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11. Lec. 4
Devise a synthesis of p-nitro-t-butylbenzene from benzene.
To make p-nitro-t-butylbenzene, we would first use a Friedel–Crafts reaction to
make t-butylbenzene. Nitration gives the correct product. If we were to make
nitrobenzene first, the Friedel–Crafts reaction to add the t-butyl group would
fail.
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Nucleophilic Aromatic Substitution
A nucleophile replaces a leaving group on the aromatic ring.
This is an addition–elimination reaction.
Electron-withdrawing substituents activate the ring for nucleophilic
substitution.
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Mechanism of Nucleophilic Aromatic Substitution
Step 1: Attack by hydroxide gives a resonance-stabilized complex.
Step 2: Loss of chloride gives the product. Step 3: Excess base deprotonates the product.
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Activated Positions
Nitro groups ortho and para to the halogen stabilize the
intermediate (and the transition state leading to it).
Electron-withdrawing groups are essential for the reaction
to occur.
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Benzyne Reaction: Elimination-Addition
Reactant is halobenzene with no electron-withdrawing
groups on the ring.
Use a very strong base like NaNH2.
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Benzyne Mechanism
Sodium amide abstract a proton.
The benzyne intermediate forms when the bromide is expelled
and the electrons on the sp2 orbital adjacent to it overlap with the
empty sp2 orbital of the carbon that lost the bromide.
Benzynes are very reactive species due to the high strain of the
triple bond.
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Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic acid by heating in
basic KMnO4 or heating in Na2Cr2O7/H2SO4.
The benzylic carbon will be oxidized to the carboxylic
acid.
CH2CH3
(or Na2Cr2O7, H2SO4 , heat)
CO2H
KMnO4, NaOH
H2O, 100oC
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Side-Chain Halogenation
CH2CH3
Br2 or NBS
h
CHCH3
Br
The benzylic position is the most reactive.
Br2 reacts only at the benzylic position.
Cl2 is not as selective as bromination, so results in
mixtures.
