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Chapter 16
Reactions
of
Substituted
Benzenes
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Chemical Modification of Substituents of Benzene
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The resulting halide product can undergo a nucleophilic
substitution reaction:
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Remember that halo-substituted alkyl groups can also
undergo E2 and E1 reactions (Section 9.8)
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Substitutions with double and triple bonds can undergo
catalytic hydrogenation (Sections 4.11 and 6.9)
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Oxidation of an alkyl group bonded to a benzene ring…
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The same reagent that oxidizes alkyl substituents will
oxidize benzylic alcohols:
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However, aldehydes or ketones can be generated if a
milder oxidizing agent is used:
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Reducing a Nitro Substituent
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It is possible to selectively reduce just one of the two
nitro groups:
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Examples of Substituted Benzenes
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Nomenclature of Substituted Benzenes
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The two substituents are listed in alphabetical order:
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• Common names are preferred in naming certain
substituted benzenes, e.g., toluene, aniline, phenol.
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Some disubstituted benzenes have common names that
incorporate both substituents:
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Naming Polysubstituted Benzenes
The substituents are numbered in the direction that
results in the lowest possible number:
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The substituent incorporated into the common name is
the 1-position:
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Substituted benzenes undergo the five electrophilic
aromatic substitution reactions discussed in Chapter 15:
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The slow step of an electrophilic aromatic substitution
reaction is the formation of the carbocation intermediate:
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Inductive Electron Withdrawal
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Resonance Electron Donation and Withdrawal
Substituents such as NH2, OH, OR, and Cl donate
electrons by resonance, but they also withdraw electrons
inductively:
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Substituents such as C=O, CΞN, SO3H, and NO2
withdraw electrons by resonance:
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Electron-donating substituents
increase the reactivity of
the benzene ring toward
electrophilic aromatic substitution
Electron-withdrawing substituents
decrease the reactivity of the
benzene ring toward electrophilic
aromatic substitution
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Electron-Donating Substituents
Electron donation into the benzene ring by resonance is
more significant than inductive electron withdrawal from
the ring:
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Resonance donation into the benzene ring competes
with resonance donation into the carbonyl
Inductive withdrawal into the benzene ring also occurs
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These substituents are less effective in donating
electrons into the ring because…
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Alkyl, aryl, and CH=CHR groups are weakly activating
substituents because they are slightly more electron
donating than they are electron withdrawing:
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These substituents donate into the ring by resonance
and withdraw electrons from the ring inductively:
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These substituents are powerful electron-withdrawing
groups:
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The substituent already attached to the benzene ring
determines the location of the new substituent:
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All activating substituents are ortho–para directors:
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The weakly deactivating halogens are ortho–para
directors:
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All substituents that are more deactivating than halogens
are meta directors:
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An ortho,para-directing substituent:
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An ortho,para-directing substituent:
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An meta-directing substituent:
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The Effect of Substituents on pKa
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The more electronic deficient a substituent on phenol,
the stronger the acid:
Unstable
Why?
Because the benzene ring is
cross conjugated with the
carboxylate anion
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The ortho–para product ratio decreases with an increase
in the size of the substituents:
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Methoxy and hydroxy substituents are so strongly
activating that halogenation is carried out without a
Lewis acid:
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A benzene ring with a meta director cannot undergo a
Friedel–Crafts reaction:
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Aniline and N-substituted anilines do not undergo
Friedel–Crafts reaction:
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The Friedel–Crafts acylation must be carried out first,
because the nitro group is strongly deactivating:
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In the synthesis of para-chlorobenzoic acid from toluene,
the methyl group is oxidized after chlorination:
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To synthesize p-propylbenzenesulfonic acid:
• Introduce the propyl group by Friedel–Crafts
acylation followed by reduction.
• Sulfonation of the propylbenzene product affords
the para derivative.
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Steric hindrance makes the position between the
substituents less accessible
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A strongly activating substituent will win out over a
weakly activating substituent or a deactivating
substituent
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If the two substituents have similar activating properties,
neither will dominate:
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Synthesis of Substituted Benzenes
Using Arenediazonium Salts
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Preparation of the Diazonium Salt
Mechanism:
Nitrosonium ion formation
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Diazonium ion formation:
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The reaction stops because a secondary amine lacks a
second proton:
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The bulky dialkyl amino group blocks the approach of the
nitrosonium ion to the ortho position:
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Consider the synthesis of para-chloroethylbenzene:
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Fluorination and Iodination of Benzene
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Hydroxylation of Benzene
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Summary of Diazonium Reactions
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Synthesis Example
Propose a
Synthetic target: synthesis from a
monosubstituted
benzene
Answer:
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The Arenediazonium Ion as an
Electrophile
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Mechanism:
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Diazo Dyes
Diazonium coupling affords synthetic dyes:
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Diazo Dyes and Sulfa Drugs
Gerhard Domagk studied the antibiotic properties of diazo
dyes. He was awarded the Nobel Prize for medicine in 1939
for his work.
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Nucleophilic Aromatic Substitution
Reactions
Nucleophilic aromatic substitution reactions require at least one
strongly electron-withdrawing substituent to occur:
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Electron-withdrawing substituents increase the reactivity
of the benzene ring toward nucleophilic substitution and
decrease the reactivity of the benzene ring toward
electrophilic substitution
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The electron-withdrawing substituents must be ortho or
para to the site of nucleophile attack,
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