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Benzenes & Aromatic Compounds

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Structure of Benzene

CC

CCC

CH

H

H

H

HHC6H6

Benzene is a colourless odourless liquid, boilingat 80oC and melting at 5oC. It is a suspected carcinogen. Benzene and its derivatives are said to be aromatic compounds

A cyclic conjugate molecule

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Resonance Structure

• Rearrange the bonding electrons• Delocalisation, Resonance-stabilise molecules, so

make them less reactive• Delocalised or Conjugated System – p-bonding

electrons can move within the molecule

1.5 bonds on average

=

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1. Aromatic compounds are cyclic, planar and conjugated.2. Aromatic compounds react with electrophiles to give substitution

products, in which cyclic conjugation is restrained.3. Must contain 4n+2π electrons (where n = 0, 1, 2, ...) –Hückel Rule

n = 1 , 6π electrons

Naphthalene Anthracene Phenanthrene10 π 14 π

Aromatic compounds have the following characteristics:

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An Interesting Aromatic Compound

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Selected drugs that contain a benzene rings

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Br

OH OOHN

+ OON

HH

CH3

Monosubstituted Benzenes

bromobenzene vinylbenzene methylbenzene(toluene)

nitrobenzene aminobenzene(aniline)

hydroxybenzene(phenol)

Benzene-carboxylic acid(benzoic acid)

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Disubstituted Benzenes

Prefixesortho- (o)metha- (m)para-(p)

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Polysubstituted Benzenes

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Reaction of Aromatic Compounds

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Electrophilic Aromatic Substitution• The characteristic reaction of aromatic compounds is substitution by a wide

variety of electrophilic reagents- electrophilic aromatic substitution.

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Examples of Electrophilic Aromatic Substitution Reactions

X2, FeX3

X = Cl, Br

XHalogenation

HONO2H2SO4

NO2Nitration

SO3H2SO4

SO3HSulfonation

RClAlCl3

R Friedel-CraftsAlkylation

RCClO=

AlCl3R

O=

C Friedel-CraftsAcylation

These reactions are commonly used synthetic procedures for modifying arenes. They proceed by a general mechanism initiated by addition of an electrophile E+ to the aromatic π-system, forming a nonaromatic carbocation intermediate called an arenium ion.

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Mechanism: Electrophilic Aromatic Substitution

Step 1 : Electrophilic attack: Slow, Rate Determining Step

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Step 2 : Fast Step is the loss of a proton

Mechanism: Electrophilic Aromatic Substitution

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Cl

BrBr2, FeBr3

Cl2, AlCl3

Halogenation

• Halogenation requires a Lewis acid catalyst to form the electrophile.

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Br Br FeBr3FeBr3Br-Br +

Mechanism: Halogenation

BrFeBr4Br Br FeBr3 H +

BrBrH

FeBr4+ HBr + FeBr3

Bromine-FeBr3 complex

Regenerate the catalyst – so only a small amount is required

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Aromatic Compounds are resonance stabilized. This gives them added stability. They undergo Electrophilic Substitution Reactions.Upon substitution, the fast step is the loss of a proton to regenerate aromaticity

H Br H Br H Br+

+

+

double-headed arrows

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HNO3, H2SO4NO2

---rapid re-aromatizationNitration of Benzene

Aromatic rings can be nitrated by reaction with a mixture of concentrate nitric and sulfuric acids. The electrophile in this reaction is the nitronium ion, NO2

+, which is generated from HNO3 by protonation and loss of water.

SO

OOO HH S

O

OOO

OH NO2 OH

HNO2

__+

H++ NO2

+ + H2O

2 H+

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ONO

NOO

O2NH

NOO

NO2

NOO

+

electrophile

+

_

electrophilic attack

+

slow

+

- H+

fast =

= +

_

+

+

Mechanism: Nitration

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Sulfonation of BenzeneBenzene reacts with fuming sulfuric acid (concentrated sulfuric acid plus added SO3, the actual electrophile) to give benzenesulfonic acid.

Fuming H2SO4

25 oC

SO3H

Benzenesulfonic acid

In concentrated sulfuric acid alone, an equilibrium-limited supply of SO3 effects slow sulfonation.

(1) Generation of the Electrophile

H-O-S-O-H:O:=

=

:O:

::

:: + H-O-S-O-H

:O:==

:O:

::

:: H-O-S-O:

:O:==

:O:

::

::

- + H-O-S-O-H:O:=

=

:O:

: ::

H

+

H-O-S-O-H:O:=

=:O:

: ::

H

+H3O+ + S=O

::=

=

::

Sulfur trioxideO

O....

S=O

::=

=

::

Sulfur trioxideO

O....

+

Sulfonation of Benzene

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(2) Electrophilic Attack

+slow

S=O

:::

:O

O....

HS

=

O:

:: -

:O:

=

+etc.

Arenium ion

O::

(3) Deprotonation and Re-aromatization

HS

=

O:

:: -

:O:

=

++ :O-S-O-H

:O:==

:O:

::

::

-

Hydrogen sulfate

fastO::S

:O:== O:

::

-+ H2SO4

O....

Benzenesulfonate ion

(4) Acid-Base Equilibrium

S:O:=

= O:

::

-+ H3O+ S

:O:== O-H

:: + H2O

Benzenesulfonic acid

fast

O.... O..

..

pKa = 0.699

Synthetic Applications

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Friedel-Crafts AlkylationDiscovered in 1877 by French chemist Charles Friedel and his American collaborator James Crafts, this alkylation reaction (one introducing an alkyl group) and the related acylation reaction (one introducing an acyl group) are among the most useful synthetic reactions.

Alkylation of an Arene

+ R-XAlCl3

R+ HX

Alkyl halide Alkylbenzene

This reaction requires a Lewis acid catalyst, typically aluminum chloride, AlCl3. Many variations of the Friedel-Crafts alkylation reaction have been developed. All proceed by similar mechanisms.

Friedel-Crafts Alkylation

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A Mechanism for the Alkylation ReactionThe Lewis acid catalysts generally required in Friedel-Crafts reactions promote formation of strong electrophiles.

(1) Generation of the Electrophile

R-Cl:

:: + AlCl3

Lewis acid

R-Cl-AlCl3

::

-+

ComplexLewis base

With 1o halides, the complex itself, acting as an R+ transfer agent, reacts with the arene.

R-Cl-AlCl3

::

-+R+ AlCl4-+

With 2o and 3o alkyl halides, dissociation to carbocation intermediates seems to occur, and the resulting R+ species react with the arene.

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(2) Electrophilic Attack

R-Cl-AlCl3

::

-++

or

+ R+ AlCl4-

HR

+etc. + AlCl4

-

Arenium ion

(3) Deprotonation and Re-aromatizationHR

++ Al:Cl

::

:Cl

::

:Cl

:

:

Cl:

::

-

Lewis base

R+ HCl + AlCl3

AlkylbenzeneRegenerated catalyst

Note : Tertiary carbocations are usually effective in Friedel-Crafts alkylation

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Friedel-Crafts Acylation

Acylation is the introduction of an acyl group, R-C- , into a structure. Two important acyl groups are:

O=

CH3C-O= C

O=

Acetyl Benzoyl

The Friedel-Crafts acylation reaction attaches an acyl group to an arene. A Lewis acid catalyst is required to generate the electrophile from an acyl halide reactant.

+ RCClO= AlCl3

C-RO=

+ HClAcid (or acyl) chloride A phenyl ketone

Friedel-Crafts Acylation

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A Mechanism for Friedel-Crafts Acylation(1) Generation of the Electrophile

R-C-Cl::O:= :

: + AlCl3Lewis acidAcid chloride

(Lewis base)

R-C-Cl:O:= :

: AlCl3-+

Acylium ions are generally thought to be the electrophilic intermediates in Friedel-Crafts acylation reactions. As shown, these ions have two contributing resonance structures.

R-C=O

::

+ R-C O:+

Acylium ion

+ AlCl4-

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(2) Electrophilic Attack

R-C=O

::

++

slow stepHC=

:O:R

+etc.

Arenium ion

(3) Deprotonation and Re-aromatizationHC=

:O:R

+ + :Cl-AlCl3

::

- C-RO=

+ HCl + AlCl3

Aryl ketone

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Limitations of the Friedel-Crafts Reactions(1) Rearrangements during Alkylations

Whenever carbocation intermediates are formed, they are subject to rearrangements that produce more stable species.Example: During the Friedel-Crafts reaction of benzene with butyl bromide a 1,2-hydride shift, possibly concurrent with dissociation, produces some of the more stable sec-butyl carbocation. A mixture of products results.

AlCl3-+

ComplexBr

Br AlCl3- BrAlCl3-

H

Butylbenzene (32-36%) sec-Butylbenzene (64-68%)

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Substituent Effects on Benzene Ring

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Inductive effect

Inductive effects stem from the electronegativity of the atoms in the substituent and the polarizability of the substituent group.

♦ Atoms more electronegative than carbon —including N, O, and X—pull electron density away from carbon and thus exhibit an electron-withdrawing inductive effect.♦ Polarizable alkyl groups donate electron density, and thus exhibit an electron-donating inductive effect.

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N N N NO O O O O O O O

NH2 NH2 NH2 NH2

Resonance effectResonance effects are only observed with substituents containing lone pairs or π bonds.

Withdraw electron density

Donate electron density

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Electrophilic Aromatic Substitution of Substituted Benzenes

A substituent affects two aspects of electrophilic aromatic substitution:

♦ The rate of reaction: A substituted benzene reacts faster or slower than benzene itself.♦ The orientation: The new group is located either ortho, meta, or para to the existing substituent. The identity of the first substituentdetermines the position of the second substituent.

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Toluene

Toluene reacts faster than benzene in all substitution reactions. Thus, its electron-donating CH3 group activates the benzene ring to electrophilic attack. Although three products are possible compounds with the new group ortho or para to the CH3 group predominate. The CH3 group is therefore called an ortho, para director.

CH3 called activating group which causes the rate of electrophilic aromatic substitition to be higher than benzene.

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Nitrobenzene

Nitrobenzene reacts more slowly than benzene in all substitution reactions. Thus, its electron withdrawing NO2 group deactivates the benzene ring to electrophilic attack. Although three products are possible, the compound with the new group meta to the NO2 group predominates. The NO2 group is called a meta director.

NO2 call deactivating group causes the rate of electrophilicaromatic substitition to be lower than benzene

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1. Ortho, para directors and activatorsSubstituents that activate a benzene ring and direct substitution ortho and para.

2. Ortho, para deactivatorsSubstituents that deactivate a benzene ring and direct substitution ortho and para.

Three Types of Substituents

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Three Types of Substituents

3. Meta directors- Substituents that direct substitution meta. - All meta directors deactivate the ring.

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The CH3 Group—An ortho, para Director

The CH3 group directs electrophilic attack ortho and para to itself because an electron-donating inductive effect stabilizes the carbocation intermediate.

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The NH2 Group—An ortho, para Director

The NH2 group directs electrophilic attack ortho and para to itself because the carbocation intermediate has additional resonance stabilization.

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The NO2 Group—A meta Director

With the NO2 group (and all meta directors), meta attack occurs because attack at the ortho or para position gives a destabilized carbocationintermediate..

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Quiz

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Halogenation of Activated Benzenes

Benzene rings activated by strong electron donating groups—OH and NH2undergo polyhalogenation when treated with X2 and FeX3. For example, aniline (C6H5NH2) and phenol (C6H5OH) both give a tribromo derivative when treated with Br2 and FeBr3. Substitution occurs at all hydrogen atoms ortho and para to the NH2 and OH groups.

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What happens in electrophilic aromatic substitution when a disubstituted benzene ring is used as starting material?

Rule 1: When the directing effects of two groups reinforce, the new substituent is located on the position directed by both groups.

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Rule 2 : If the directing effects of two groups oppose each other, the more powerful activator "wins out."

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Rule 3: No substitution occurs between two meta substituentsbecause of crowding.

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Quiz

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Oxidation of Substituted Benzenes

Arenes containing at least one benzylic C-H bond are oxidized with KMnO4 to benzoic acid, a carboxylic acid with the carboxy group (COOH) bonded directly to the benzene ring. With some alkyl benzenes, this also results in the cleavage of carbon-carbon bonds, so the product has fewer carbon atoms than the starting material.

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Substrates with more than one alkyl group are oxidized to dicarboxylicacids. Compounds without a benzylic C - H bond are inert to oxidation.

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Reduction of Substituted Benzenes

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Example: The nitration and side-chain oxidation of toluene

CH3

Toluene

(1) KMnO4, HO-, heat

(2) H3O+

COOH

HNO3

H2SO4

CH3 CH3

+NO2

NO2

HNO3

H2SO4

COOH

NO2m-Nitrobenzoic acid

(1) KMnO4, HO-

heat(2) H3O+

(1) KMnO4, HO-

heat(2) H3O+

COOH COOH

+NO2

NO2ortho para

All three possible positionalisomers of nitrobenzoic acidmay be synthesized by carefulsynthetic design.

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Reduction of Nitro GroupsA nitro group (NO2) is easily introduced on a benzene ring by nitration with strong acid. This process is useful because the nitro group is readily reduced to an amino group (NH2) under a variety of conditions. The most common methods use H2 and a catalyst, or a metal (such as Fe or Sn) and a strong acid like HCl.

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Quiz

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Quiz 15.01

Draw the three contributing resonance structures of the arenium ion intermediate produced in the addition of an electrophile, E+, to benzene.

+ E+

H E+

H E H E

+

+

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:Br-Br-Fe-Br::Br:

:Br:

:

::

::

::

:

+ -

Quiz 15.02

Draw the complex formed between bromine (Br2) and FeBr3 that is believed to be involved in the electrophilic bromination of benzene and other aromatics. Show the polarization of charge in the complex.

:Br-Br:

::

:: + FeBr3

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Solution

NO2+ is a 16 valence electron system. The proper Lewis structure must

conform to the Octet Rule and have formal charge(s) indicated, so the

answer is:O=N=O

::

::

+

Quiz 15.03a

Draw the Lewis structure of the nitronium ion, NO2+, a

strong electrophile.

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Quiz 15.03b

Draw the resonance structures of the arenium ion intermediate formed from electrophilic attack of the nitronium ion on benzene.

+ O=N=O

::

::

+

Note: Disregard resonance structures of the nitro group.

N=O

::

:O:

: -

H+ N=O

::

:O:

: -

H+

N=O

::

:O:: -

H+

+ + +

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Quiz 15.05

Draw the contributing resonance structures of the acylium ion produced in the reaction below.

R-C-ClO=

+ AlCl3: :

R-C=O

::

+R-C O

:+

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Quiz 15.07

Predict the major products (ortho/para or meta) from the nitration of the following substituted benzenes.

CH3

Cl

CCH3

O=

HNO3

H2SO4

HNO3

H2SO4

HNO3

H2SO4

I

II

IIIWhat is the order of reactivity of the three substituted benzenes in the nitration reaction? > >

ortho/para

ortho/para

meta

I IIIII

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CH3

H Br+

CH3

H Br

+CH3

H Br+

CH3

BrH

+CH3

BrH

+CH3

BrH+

Quiz 15.08

Draw the contributing resonance structures for the arenium ion intermediates formed from para and meta addition of Br+ to toluene.

CH3

CH3

H Br

BrH

δ+

δ+

δ+

δ+

δ+δ+

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Quiz 15.11

Draw the structure of the major monosubstitution product from each of these reactions.

CH3

Br

HNO3H2SO4

COOH

CH3

Br2

Fe

CH3

Br

NO2

COOH

CH3

Br

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Quiz

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Quiz

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Quiz

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Phenol

Phenols are stronger acids than alcohols

OH OH

pKa = 17 pKa = 10

OH O O O

Resonance Stabilised Phenoxide anion

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Synthesis of Phenols

• The only widely used laboratory synthesis of phenols is that from the corresponding anilines through a process called diazotization. This route from benzenoid compounds to phenols starts with the nitration reaction, followed by reduction of the nitro group (—NO2) to an amino group (—NH2), diazotization of the amine to a diazonium ion (—N2

+), and finally displacement of the diazonium group by the hydroxyl group (—OH) upon heating in water:

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Electrophilic Aromatic Substitution of Phenols

very strong activator

AlCl3

/ FeBr3

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O-Alkylation of Phenols(Williamson Ether Synthesis)

• Because phenols are acidic and can be converted easily into their phenoxide anions, it is very easy to form phenyl alkyl ethers via the Williamson ether synthesis of ethers usually brought about using methyl iodide for convenience. The methyl group can be readily removed by a typical ether cleavage.