Substituio Aromtica

Pricles B. Alves

BENZENO E AROMATICIDADE
1. Isolamento e Estrutura do benzeno
2. Compostos aromticos naturais e sintticos
3. Critrios de aromaticidade para um composto
4. Reatividade
4.1. Mecanismo geral da reao de substituio eletroflica
em aromticos:
5. Reaes dos substituintes no benzeno
6. O efeito dos substituintes na reatividade
7. O efeito dos substituintes na orientao da substituio
8. Reaes de oxidaes; Reaes de redues

Isolamento e estrutura do benzeno

Isolado pela primeira vez por Michael
Faraday em 1825
Aromatico em referencia ao aroma ou
cheiro em oposio ao aliftico.
Michael Faraday

Foi um dos compostos orgnicos mais

estudados.
Primeiro ex. de composto contendo
ligaes deslocalizadas.
Pricles B. Alves

HO
MeO
Anetol
"Extrato erva doce"

CH 3 O

CHO
Vanilina

CH 3 O

CHO

HO
Eugenol

OH

Cinamaldedo

Neste caso um grande equivoco

do critrio odor

(-)-Mentol

Reconhecimento de compostos aromticos apenas

pelo odor

Muito importante na industria qumica

Aromaticidade
HIDROCARBONETOS

Alifticos

alcanos

alcenos

Aromticos

alcinos

Pricles B. Alves

II
(Dewar)

CH2 CH C

C CH
V

III
(Ladenburg)

CH2

CH3

IV

CH3

VI

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O benzeno reagia somente sob condies vigorosas

ou com Br2/FeBr3:
Produto: C6H5Br (produto monobromado)
- todos os H eram equivalentes!!!

II
(Dewar)

CH2 CH C

C CH
V

CH2

III
(Ladenburg)

CH3

IV

C
VI

CH3
Pricles B. Alves

 Hohidrogenao
Reagente

Produto

(kJ/mol)

(kcal/mol)

ciclohexeno

ciclohexano

-206

-28,2

1,3-ciclohexadieno

ciclohexano

-230

-55,0

benzeno

ciclohexano

-118

-49,2

KMnO4

COOH
COOH

H3O+
OH
ciclohexeno

HCl
Cl

Porque era to estvel e inerte as reaes qumicas?

KMnO4

H3O+

no reage

no reage

benzeno
HCl

no reage

Molecular Orbital Description of Benzene

The 6 p-orbitals combine to give
3 bonding orbitals with 6 e-s,
3 antibonding with no electrons
Orbitals with same energy are degenerate

Ring Currents

Aromatic ring oriented perpendicular to a strong magnetic
field, delocalized electrons producing a small local
magnetic field

Opposes applied field in middle of ring but reinforces
applied field outside of ring

Propiedades Espectroscopicas do Benzeno

1H

1H

NMR Espectroscopia do grupo Aromatico

NMR: Aromatic Hs strongly deshielded

by ring and absorb between 6.5 and 8.0

Infravermelho (IR): Espectroscopia de aromticos

IR: Aromatic ring CH stretching at 3030 cm1 & peaks 1450 -1600 cm

The IR spectra of benzene and its derivatives

have characteristic bands at:
3030 cm-1

phenyl-H stretching

1500-2000 cm-1 aromatic C-C stretching

650-1000 cm-1

C-H out of plane bending

Espectrometria
aromticos

de

massas

de

compostos

 In benzene, the actual bond length (1.39 ) is intermediate

between the carboncarbon single bond (1.53 ) and the
carboncarbon double bond (1.34 ).

The Criteria for AromaticityHckels Rule

Four structural criteria must be satisfied for a compound to be
aromatic.
[1] A molecule must be cyclic
cyclic..

Erich Hckel

To be aromatic, each p orbital must overlap with p orbitals on adjacent atoms.

[2] A molecule must be planar

planar..
Todos os orbitais p adjacentes devem estar alinhados para
que a densidade de eltrons posa ser deslocalizada.

Since cyclooctatetraene is non-planar, it is not aromatic, and it undergoes addition

reactions just like those of other alkenes.

Pricles B. Alves

Non-aromatic
Cyclooctatetraene has four double bonds, reacting with Br2,
KMnO4, and HCl as if it were four alkenes
Distorts out of plane so C=Cs behave like ordinary alkenes

The molecular structure of cyclooctatetraene is non-planar and tub shaped.

The double bonds are nearly orthogonal and are not conjugated.

[3] A molecule must be completely conjugated

conjugated.
Aromatic compounds must have a p orbital on every
atom.

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[4] A molecule must satisfy Hckels rule, and

contain a particular number of electrons
electrons..
Hckel's rule:

Benzene is aromatic and especially stable because it contains

6 electrons. Cyclobutadiene is antiaromatic and especially
unstable because it contains 4 electrons.

Note that Hckels rule refers to the number of

electrons, not the number of atoms in a
particular ring.

 Two or more six-membered rings with alternating double and single

bonds can be fused together to form polycyclic aromatic
hydrocarbons (PAHs).
There are two different ways to join three rings together, forming
anthracene and phenanthrene.

As the number of fused rings increases, the number of resonance

structures increases. Naphthalene is a hybrid of three resonance
structures whereas benzene is a hybrid of two.


1,3-Cyclopentadiene
contains conjugated C=Cs
joined by a CH2 that blocks
delocalization

Removal of H+ at the CH2
produces a cyclic 6 esystem, which is stable
H-

Removal of
or H
generate nonaromatic 4
and 5 electron systems

Antiaromatic
(unstable)

Relatively acidic (pKa = 16)

because the anion is stable

Antiaromatic
(unstable)

Aromatic
(very stable)

Cycloheptatrienyl Cation
 3 conjugated C=Cs

joined by a CH2
 Removal of H-
leaves the cation
 The cation has 6e-s
and is aromatic

Aromatic
(stable)

Antiaromatic
(unstable)

Antiaromatic
(very unstable)

Substituio Electrofilica Aromatica (SEA)

Pricles B. Alves

Reao de Substituio
Aromtica (SEA):

Eletrofilica

Reactions typical of addition to alkenes do not

work on aromatic double bonds.

Need more electrophilic (more positive) halogen in order

to break an aromatic double bond.

 The energy changes in electrophilic aromatic substitution are

shown below:

SEA: Bromao
SEA ocorre em dois passos: Adio seguido de Eliminao
FeBr3 acts as a catalyst to polarize the bromine reagent and
so make it more positive (more electrophilic)
The electrons of the aromatic ring act as a nucleophile
toward the now more electrophilic Br2 (in the FeBr3 complex)

The cationic addition intermediate is called a sigma complex

SEA ocorre em dois passos: Adio seguido de Eliminao

The cationic addition intermediate
transfers a proton to FeBr4- (from Brand FeBr3)
This restores aromaticity (in contrast
with addition in alkenes)

 Chlorine and iodine (but not fluorine, which is too reactive) can
produce aromatic substitution products
Chlorination
requires FeCl3

Iodine must be
oxidized (with
Cu+ or peroxide)
to form a more
powerful I+
species

Halogenao
In halogenation, benzene reacts with Cl2 or Br2 in the presence of a Lewis acid
catalyst, such as FeCl3 or FeBr3, to give the aryl halides chlorobenzene or
bromobenzene respectively.
Analogous reactions with I2 and F2 are not synthetically useful because I2 is too
unreactive and F2 reacts too violently.

 Chlorination proceeds by a similar mechanism.

Sulfonao

Benzene ring reacts with fuming sulfuric acid (a

mixture of H2SO4 and SO3) to yield benzenesulfonic
acid
The reactive electrophile is either HSO3+ or neutral
SO3 depending on reaction conditions

 The reactive electrophile is either sulfur trioxide SO3

or its conjugate acid HSO3+

Nitrao
The combination of nitric acid and sulfuric acid produces NO2+
(nitronium ion)
The reaction with benzene produces nitrobenzene

The Nitro group can be reduced to an Amino group if needed

 Outro mtodo: dissolver HNO3 em anidrido

actico: gera nitrato de acetila

Um procedimento conveniente

A nitrio pode ser catalisada por sais de

latandeos
Pricles B. Alves

Desvantagens da alquilao:
Produtos de
rearranjos
Produtos
polialquilados
Produtos rearranjados:
CMe2CH2Me

Me3CCH2Cl/ AlCl3 +

Me3C

CH3

Me2C

CH2Me

A mesma reao com FeCl3

Me3CCH2Ph (produto no rearranjado).

Alquilao de FriedelFriedel-Crafts
intramolecular para gerar anis fundidos;
sendo anis de 6 mais fceis de formar que
anis de 5

Charles Friedel

James Mason Crafts

Mechanism for Alkylation

Mechanism for Acylation

Water is required here

 FriedelFriedel-Crafts alkylation is an electrophilic

aromatic substitution in which the electrophile is
a carbocation, R+.
AlCl3 catalyst promotes the formation of the alkyl
carbocation, R+, from the alkyl halide, RX
The Wheland (carbocation) intermediate forms
Alkylation is the attachment of an alkyl group to
benzene; R+ substitutes for H+

Pricles B. Alves

Friedel--Crafts Alkylation and FriedelFriedel

Friedel-Crafts Acylation

Friedel--Crafts Alkylation and FriedelFriedel

Friedel-Crafts Acylation
In Friedel-Crafts alkylation, treatment of benzene with an alkyl halide and a Lewis
acid (AlCl3) forms an alkyl benzene.

Pricles B. Alves

[2] Rearrangements can occur

occur..

These results can be explained by carbocation rearrangements.

Friedel--Crafts Alkylation Reaction: Mechanism

Friedel

 Aromatic ring activates neighboring carbonyl

group toward reduction
Ketone is converted into an alkylbenzene by
catalytic hydrogenation over Pd catalyst

 In Friedel-Crafts acylation, a benzene ring is treated with an

acid chloride (RCOCl) and AlCl3 to form a ketone.
Because the new group bonded to the benzene ring is called
an acyl group, the transfer of an acyl group from one atom to
another is an acylation.

 In Friedel-Crafts acylation, the Lewis acid AlCl3 ionizes the

carbon-halogen bond of the acid chloride, thus forming a
positively charged carbon electrophile called an acylium ion,
which is resonance stabilized.
The positively charged carbon atom of the acylium ion then
goes on to react with benzene in the two step mechanism of
electrophilic aromatic substitution.

 Benzene ring reacts with a carboxylic acid chloride,

RCOCl, in the presence of AlCl3 catalyst to yield an
acylbenzene
Acylation is the attachment of an acyl group,-COR,
to benzene; RCO+ substitutes for H+

 FriedelFriedel-Crafts acylation is an electrophilic aromatic

substitution in which the reactive electrophile is a
resonance-stabilized acyl cation, RCO+.
AlCl3 catalyst promotes the formation of the acyl
cation, RCO+, from the acyl chloride, RCOCl
The acyl cation, RCO+, does not rearrange; it is
resonance-stabilized
The Wheland (carbocation) intermediate forms

Pricles B. Alves

 The mechanism of FriedelFriedel-Crafts acylation is

similar to FriedelFriedel-Crafts alkylation

 Similar to alkylation
Reactive electrophile: resonance-stabilized acyl cation
An acyl cation does not rearrange

Can reduce carbonyl to get alkyl product

Methodologies Used for the Reduction Step

Pricles B. Alves

The energy diagrams below illustrate the effect of electron-withdrawing

and electron-donating groups on the transition state energy of the ratedetermining step.

Efeito do Substituente
+

E+

Substituintes que doam eletrons tornando mais nucleofilico.

Grupo Doador de Electrons (gde) ativam o anel nas reaes de SEA

Substituinte que retiram eletrons tornando o anel pouco

nucleofilico.

Grupo Retirador de Electrons (gre) desativam o anel nas reaes
de SEA

Efeito do Substituinte

Os substituintes afetam a reatividade do anel

aromtico.
Substituents may

activate the ring, make it (much) more reactive than

benzene or

deactivate the ring, make it (much) less reactive

than benzene

Classification of Substituent Effect

Substituents can be classified as:

ortho- and para-directing activators,

ortho- and para-directing deactivators, and
meta-directing deactivators

Reactivity and orientation in electrophilic aromatic

substitutions are controlled by an interplay of inductive
effects and resonance effects
effects:
Inductive effect - withdrawal or donation of electrons
through a bond
Resonance effect - withdrawal or donation of
electrons through a bond

Pricles B. Alves

Inductive effects - withdrawal or donation of electrons

through a bond due to electronegativity and polarity
of bonds in functional groups

Halogens, C=O, CN, and NO2 groups inductively

withdraw electrons through bond connected to
ring

Alkyl groups inductively donate electrons

Pricles B. Alves

Resonance effect - withdrawal or donation of electrons

through a bond due to the overlap of a p orbital on
the substituent with a p orbital on the aromatic ring

C=O, CN, and NO2 groups withdraw electrons from

the aromatic ring by resonance

Halogen, OH, alkoxyl (OR), and amino substituents

donate electrons to the aromatic ring by resonance

Pricles B. Alves

Ortho-- and ParaOrtho

Para-Directing Deactivators: Halogens

Halogens are deactivating

They have a strong electronelectron-withdrawing inductive
and a weak electron-donating resonance effect

Halogens are ortho and para directors

The ortho and para intermediates are the most
stabilized (lower in energy)
Halogens stabilize the positive charge by resonance
donation of a lone pair of electrons

Contrasting Effects:
Effects: Inductive vs Resonance

When the two effects act in opposite direction, the

strongest effects dominate.

Halogens have electron-withdrawing inductive effects

due to electronegativity

Halogens have electron-donating resonance effects due

to lone-pair electrons

Resonance interactions are generally weaker, affecting

orientation. Thus, halogens deactivate the ring

Pricles B. Alves

C=O, CN, and NO2 groups withdraw electrons from

the aromatic ring by resonance

electrons flow from the ring to the substituents,

placing a positive charge in the ring

Z is more electronegative than Y

Halogen, OH, alkoxyl (OR), and amino substituents

donate electrons to the aromatic ring by resonance

electrons flow from the substituents to the rings

placing a negative charge in the ring

Y has a lone pair of electrons

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

An electron-donating resonance effect is observed whenever an atom Z having a

lone pair of electrons is directly bonded to a benzene ring.

Halogens, C=O, CN, and NO2 inductively withdraw

electrons through bond connected to ring

An Explanation of Substituent
Effects
Activating groups donate electrons to the ring
ring,,
stabilizing the Wheland intermediate (carbocation
carbocation))

OH, OR, NH2 and R

Deactivating groups withdraw electrons from the

ring, destabilizing the Wheland intermediate

CN, C=O, NO2 and X

Pricles B. Alves

Ortho-- and ParaOrtho

Para-Directing Activators: Alkyl

Alkyl groups are activating

They have an electron
electron--donating inductive effect

Alkyl groups are ortho and para directors

The ortho and para intermediates are the most
stabilized (lower in energy)
The positive charge is directly on the alkyl3o carbon
carbon) and is stabilized by
substituted carbon (3
the inductive electron
electron--donating effect of the alkyl
group

The positive charge is directly on the alkyl-substituted

carbon (3
3o carbon
carbon) and is stabilized by the inductive
electron--donating effect of the alkyl group
electron

Ortho-- and ParaOrtho

Para-Directing Activators: OH and NH2

OH, OR and NH2 groups are activating

They have a strong electronelectron-donating resonance
and a weak electron-withdrawing inductive effect

OH, OR and NH2 groups are ortho and para directors

The ortho and para intermediates are the most
stabilized (lower in energy)
The positive charge is stabilized by resonance
donation of an electron pair from O or N

Pricles B. Alves

The ortho and para intermediates are more stable because

of resonance donation of an electron pair from O or N

The ortho and para intermediates are more stable because

of resonance donation of an electron pair from X

Meta--Directing Deactivators
Meta

All metameta-directing groups are strongly deactivating

They have electron-withdrawing inductive and
resonance effects that reinforce each other
The ortho and para intermediates are destabilized
The positive charge of the carbocation intermediate
in ortho and para attack is directly on the carbon
that bears the deactivating group and resonance
cannot produce stabilization
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The meta intermediate is more stable because resonance

does not place the positive charge directly on the carbon
that bears the deactivating group

 An electron-withdrawing resonance effect is observed in substituted benzenes

having the general structure
C6H5-Y=Z, where Z is more electronegative than
Y.
Seven resonance structures can be drawn for benzaldehyde (C6H5CHO).
Because three of them place a positive charge on a carbon atom of the benzene
ring, the CHO group withdraws electrons from the benzene ring by a resonance
effect.

 The inductive and resonance effects in compounds having the general

structure C6H5-Y=Z (with Z more electronegative than Y) are both
electron withdrawing.

 These compounds represent examples of the general structural features in

electron-donating and electron withdrawing substituents.

Pricles B. Alves

 Consider tolueneToluene reacts faster than benzene in all substitution

reactions.
The electron-donating CH3 group activates the benzene ring to electrophilic
attack.
Ortho and para products predominate.
The CH3 group is called an ortho, para director.

 Consider nitrobenzeneIt reacts more slowly than benzene in all substitution

reactions.
The electron-withdrawing NO2 group deactivates the benzene ring to electrophilic
attack.
The meta product predominates.
The NO2 group is called a meta director.

All substituents can be divided into three general types:

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Pricles B. Alves

 Keep in mind that halogens are in a class by themselves.

Also note that:

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 To understand how substituents activate or deactivate the ring, we

must consider the first step in electrophilic aromatic substitution.
The first step involves addition of the electrophile (E+) to form a
resonance stabilized carbocation.
The Hammond postulate makes it possible to predict the relative rate
of the reaction by looking at the stability of the carbocation
intermediate.

 The principles of inductive effects and resonance effects can now be

used to predict carbocation stability.

Orientation Effects in Substituted Benzenes

There are two general types of ortho, para directors and one general type of meta
director.
All ortho, para directors are R groups or have a nonbonded electron pair on the
atom bonded to the benzene ring.
All meta directors have a full or partial positive charge on the atom bonded to the
benzene ring.

 A CH3 group directs electrophilic attack ortho and para to itself

because an electron-donating inductive effect stabilizes the
carbocation intermediate.

 An NH2 group directs electrophilic attack ortho and para to itself

because the carbocation intermediate has additional resonance
stabilization.

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

Limitations in Electrophilic Aromatic Substitutions

Benzene rings activated by strong electron-donating groupsOH,
NH2, and their derivatives (OR, NHR, and NR2)undergo
polyhalogenation when treated with X2 and FeX3.

NO2

Fe, H3 O+

NH2

OH

NO2

SnCl2 , H3O+

NH2

OH

NO2

H2 , Pd/C

NH2

EtOH

Pricles B. Alves

Summary of Substituent Effects in Aromatic Substitution

Disubstituted Benzenes
1.

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

2.

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

Pricles B. Alves

3.

No substitution occurs between two meta substituents because of crowding.

Pricles B. Alves

Synthesis of Benzene Derivatives

In a disubstituted benzene, the directing effects indicate which substituent must be
added to the ring first.

Let us consider the consequences of bromination first followed by nitration, and

nitration first, followed by bromination.

Pricles B. Alves

Pathway I, in which bromination precedes nitration, yields the desired

product. Pathway II yields the undesired meta isomer.

1.

If the directing effects of the two groups are the

same, the result is additive

It gives a single product

2.

If the directing effects of two groups oppose each

other, the more powerful activating group determines
the principal outcome

It usually gives mixtures of products

3.

The position between the two groups in metametadisubstituted compounds is unreactive

The reaction site is too hindered

To make aromatic rings with three adjacent

substituents, it is best to start with an orthodisubstituted compound

Pricles B. Alves