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‫‪Chem 212 Exam‬‬

‫ﺳﻴﻌﻘﺪ اﻣﺘﺤﺎن اﻷول ﻟﻤﺴﺎق اﻟﻜﻴﻤﻴﺎء اﻟﻌﻀﻮﻳﺔ‬
‫ﻳﻮم اﻟﺨﻤﻴﺲ اﻟﻤﻮاﻓﻖ ‪2010/11/4‬‬
‫‪5:15-4:15‬‬
‫اﻟﻘﺎﻋﺔ‬ ‫اﻟﺸﻌﺒﺔ‬
‫‪PH2 102‬‬ ‫‪1‬‬
‫‪P1 103‬‬ ‫‪2‬‬
‫‪P1 102‬‬ ‫‪3‬‬

‫‪© 2011 Pearson Education, Inc.‬‬
Organic Chemistry
6th Edition
Paula Yurkanis Bruice

Chapter 16

Reactions
of
Substituted
Benzenes

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Chemical Modification of Substituents of Benzene

Reactions of alkyl substituents:

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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…

Provided that a hydrogen is bonded to the benzylic
carbon,

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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

In disubstituted benzenes, the relative positions of the
two substituents are indicated by numbers or by prefixes:

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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.

• Do not deconstruct the common name; e.g., do not change
“toluene” to “methylbenzene.”

• The substituent that is part of the common name is
position 1, but do not label as such in the chemical name.

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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:

Always give substituents the lowest possible numbers!

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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:

• Electron-donating substituents increase the rate of
substitution reactions by stabilizing the carbocation
intermediate.

• Electron-withdrawing substituents decrease the rate of
substitution reactions by destabilizing the carbocation
intermediate.

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Inductive Electron Withdrawal

Electron Donation by Hyperconjugation

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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

Overall, these substituents weakly release electrons

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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:

They withdraw electrons inductively more strongly than
they donate electrons by resonance
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These substituents withdraw electrons both inductively
and by resonance:

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These substituents are powerful electron-withdrawing
groups:

Except for the ammonium ions, these substituents
withdraw electrons both inductively and by resonance

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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

Electron-withdrawing groups stabilize a base and
therefore increase the strength of its conjugate acid

Electron-donating groups destabilize a base and thus
decrease the strength of its conjugate acid

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The more electronic deficient a substituent on phenol,
the stronger the acid:

To understand the relative pKa values, consider the delocalization
of the phenolate anion (stars show anion distribution):

Unstable

More stable anion =
Stable: “through resonance”
lower pKa
of anion into nitro 41
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The more electronic deficient a substituent on benzoic
acid, the stronger the acid:

Substituent effect on pKa is minimal in benzoic acids
because only inductive electronic effects are present:

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:

The presence of Lewis acid and excess bromine
generates the tribromo derivative:

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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:

Phenol and anisole undergo Friedel–Crafts reactions at
the ortho and para positions
Aniline cannot be nitrated, because it is oxidized by nitric
acid
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In designing a disubstituted benzene, consider
the order of substitution:

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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:

In the synthesis of meta-chlorobenzoic acid, the methyl
group is oxidized before 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.

How is the meta derivative prepared?
• Friedel–Crafts acylation
• Sulfonation
• Carbonyl reduction
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What is the best method for carrying out the
following reaction?

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Provide the major organic product(s) of the reactions
below.

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Synthesis of Trisubstituted Benzenes

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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:

Caution: Diazonium salts are explosive!

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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:

[unnumbered fig, pg 690]

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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

Only highly activated benzene rings can undergo this
reaction
Substitution takes place preferentially at the para
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However, if the para position is blocked …

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Mechanism:

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Diazo Dyes
Diazonium coupling affords synthetic dyes:

Large dipole results in deep color (high extinction
coefficient):
Electronic “push-pull”
produces a dipole

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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.

The dye prontosil is
reduced to the sulfa
Domagk cured his drug sulfanilamide
daughter of strep
with sulfanilamide

Sulfanilamide looks like PABA, a bacterial nutrient:

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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,

so that electrons of the attacking nucleophile can be
delocalized into these substituents
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The incoming group has to be a stronger base than the
group that is being replaced:

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