Aromáticos

Michael Faraday (1791-1867)

•Mais conhecido por suas descobertas sobre

fenômenos elétricos. Contudo, iniciou sua carreira

com estudos na área da química.

• Isolou o benzeno do resíduo oleoso encontrado na

postes de iluminação à gás das ruas de Londres e

determinou que a razão C:H era de 1:1.

•O nome do grupamento fenila, usado quando o uma unidade de benzeno

encontra-se como um substituinte, deriva de sua origem, pois a palavra

grega pheno significa “Eu tenho a luz”.

•O benzeno foi sintetizado em 1834 por Eilhard Mitscherlich, o qual

determinou sua fórmula molecular como C6H6.

•Outros compostos com uma baixa razão C:H apresentavam um aroma

agradável, desta maneira foram classificados como aromáticos.

Aromatic Compounds

• Aromatic was used to described some fragrant compounds in early 19th century

– Not correct: later they are grouped by chemical behaviour

– Current: distinguished from aliphatic compounds by electronic configuration

CHO

OMe

CH CH CHO

OH

OH

CH2

OMe

CH CH2

CHO

anisaldehyde

(anise)

cinnamaldehyde

(cinnamon)

thymol

(thyme)eugenol

(cloves)cuminaldehyde

(cumin)

Sources of Aromatic Hydrocarbons

• From high temperature distillation of coal tar

• Heating petroleum at high temperature and pressure

over a catalyst

Naming Aromatic Compounds

• Many common names (toluene = methylbenzene; aniline = aminobenzene)

• Monosubstituted benzenes systematic names as hydrocarbons with –benzene

– C6H5Br = bromobenzene

– C6H5NO2 = nitrobenzene, and C6H5CH2CH2CH3 is propylbenzene

SOME SPECIAL NAMES

CH3

NH2

toluene aniline anisole

O CH3

CH3

CH3

o-xylene m-xylene

p-xylene

phenol

CH3

CH3

CH3

CH3

OH

COOH

benzoic

acid

The Phenyl Group

• When a benzene ring is a substituent, the term phenyl is

used (for C6H5 )

– You may also see “Ph” or “f” in place of “C6H5”

• “Benzyl” refers to “C6H5CH2”

Ripso

ortho

meta

para

ortho, meta and para Positions

CH3

NO2

m-nitrotoluene

3-nitrotoluene

1-methyl-3-nitrobenzeneo-

m-

p-

1

2

3

4

5

6

Cl

Cl

p-dichlorobenzene

1,4-dichlorobenzene

Disubstituted Benzenes

Naming Benzenes With More Than Two

Substituents

• Choose numbers to get lowest possible values

• List substituents alphabetically with hyphenated numbers

• Common names, such as “toluene” can serve as root name (as in TNT)

AROMATICITY

THE HUCKEL RULE

HUCKEL 4n+2 RULE..

Prediction: Compounds that have 4n+2 pi electrons in

a cyclic array will be aromatic.

AROMATICITY

POLYCYCLIC AROMATIC COMPOUNDS

benzene naphthalene anthracene

6 10 14

1814

4n+2 series = 2, 6, 10, 14, 18, 22, 26, 30 …….. etc.

The rule was derived by observation of

BENZENE

6p electrons

E

N

E

R

G

Y

closed*

shell

AROMATIC

Aromatic

compounds

will have all

of the occupied

p M.O. levels

completely

filled with no

unpaired

electrons.

(*completed

level)

BENZENEIsodensity surfaces - electron potential mapped in color.(van der Waal’s)

Color adjusted

to enhance the

pi system.

Highest

electron density

is red.

Note the symmetry.

MO Derivation of

Hückel’s Rule • Lowest energy MO has 2 electrons.

• Each filled shell has 4 electrons.

=>

The “Double Bonds” in a Benzene Ring Do Not React Like Others

Alkene Benzene

RClH

R

H

Cl

ClH+ +no

reaction

RCl

2

R

Cl

Cl

Cl2+ +

no

reaction

RBr

2

R

Br

Br

Br2+ +

no

reaction

R R ORCO

3H RCO

3H+ +

no

reaction

Tipos de Reações Orgânicas

• Reações de :

– Adição – duas moléculas se combinam

– Eliminação – uma molécula quebra em duas

– Substituição – partes de duas moléculas

trocam

– Rearranjo – a molécula sofre mudanças no

modo como seus átomos são conectados.

Electrophilic

Aromatic SubstitutionElectrophile substitutes for a hydrogen on

the benzene ring.

=>

Mechanism

=>

ENERGY PROFILE FOR AROMATIC SUBSTITUTION

H

E

E

H

E+

+

Ea

H+

benzenium

intermediate(+)

(+)

Transition

state 1

Transition

state 2

STEP 1 STEP 2

slow fast

activation

energy

intermediate

Bromination of Benzene• Requires a stronger electrophile than Br2.

• Use a strong Lewis acid catalyst, FeBr3.

Br Br FeBr3 Br Br FeBr3

Br Br FeBr3

H

H

H

H

H

H

H

H

H

H

HH

Br+ + FeBr4

_

Br

HBr+

Energy Diagram

for Bromination

=>

Chlorination

and Iodination• Chlorination is similar to bromination. Use

AlCl3 as the Lewis acid catalyst.

• Iodination requires an acidic oxidizing

agent, like nitric acid, which oxidizes the

iodine to an iodonium ion.

H+

HNO3 I21/2 I

+NO2 H2O+ ++ +

=>

Formation of the Chloronium Ion Complex

Cl Cl Al Cl

Cl

Cl

Cl Cl Al Cl

Cl

Cl

Al Cl

Cl

Cl

ClCl

:: :

:

:

:

:

: :

:

:

:

:

:: :

:

: :

:

.. ..

.. ..

..

..

..

.. d+

.. ..

..

..

..

..

..

..

..

..

..

..

..

+ -

d-

Al

Cl

Cl

Cl

chloronium

ion complex

sp2

..

..

..

Electrophilic aromatic halogenations occur in

the biosynthesis of numerous naturally

occurring molecules, particularly those

produced by marine organisms

– Thyroxine, synthesized in the

thyroid gland in humans, is a

thyroid hormone involved in

regulating growth and

metabolism

Reactions of Aromatic Compounds:

Electrophilic SubstitutionAromatic Nitration

• Aromatic rings can be nitrated

with a mixture of concentrated

nitric and sulfuric acids

– The electrophile is the

nitronium ion, NO2+ which is

generated from HNO3 by

protonation and loss of water

– The nitronium ion reacts with benzene to yield a carbocation intermediate, and loss of H+

– The product is a neutral substitution product, nitrobenzene

Aromatic nitration

• Does not occur naturally

• Important in the laboratory

– The nitro-substituted product can be reduced by

reagents such as iron or tin metal or to yield an

arylamine, ArNH2

– Attachment of an amino group to an aromatic ring

by the two-step nitration-reduction sequence is a

key part of the industrial synthesis of many dyes

and pharmaceutical agents

• Sulfur trioxide, SO3, in fuming sulfuric acid is the

electrophile.

The mechanism of electrophilic

sulfonation of an aromatic ring

Desulfonation

• All steps are reversible, so sulfonic acid

group can be removed by heating in

dilute sulfuric acid.

• This process is used to place deuterium

in place of hydrogen on benzene ring.

Benzene-d6

=>

D

D

D

D

D

D

D2SO4/D2O

large excess

H

H

H

H

H

H

O CH3

Nitration of Anisole

NO2

O CH3

NO2

O CH3

Reacts faster

than benzene

+

ortho para

= “ACTIVATED”

The -OCH3 group when it preexists on the ring gives only

ortho and para products, and no meta.

Substituents that cause this result are called o,p directors

HNO3

H2SO4

and they usually activate the ring.

anisole

CO

OMe

Nitration of Methyl Benzoate

C

O

NO2

OMe

Reacts slower

than benzene

meta

HNO3

H2SO4

= “DEACTIVATED”

methyl benzoate

The -COOMe group when it preexists on the ring gives only

meta, and no ortho or para products.

Substituents that cause this result are called m directors

and they usually deactivate the ring.

DEACTIVATED RING

Most ring substituents fall into one of these two categories:

o,p - directors m- directors

activate the ring deactivate the ring

SUBSTITUENT CATEGORIES

We will look at one of each kind in order to

understand the difference…..

G

NITRATION OF ANISOLE

H

HNO

2

O CH3

+

H

H

NO2

O CH3

+

H NO2

H

O CH3

+

O CH3

+ N

O

O

+

Nitration of Anisole

NO2

O CH3

NO2

O CH3

BENZENIUM ION INTERMEDIATES

actual

products

activated

ring

ortho meta para

ortho para+

H NO2

H

O CH3

+

H NO2

H

O CH3

+

H NO2

H

O CH3

+

H NO2

H

O CH3

+

H

H

NO2

O CH3

+

H

H

NO2

O CH3

+

H

H

NO2

O CH3

+H

H

NO2

O CH3

+

H

HNO

2

O CH3

+

H

HNO

2

O CH3

+

H

HNO

2

O CH3

+

ortho

meta

para :

:

EXTRA!

EXTRA!

Energy Profiles

meta

ortho

para

NITRATION OF ANISOLEbenzenium

intermediateRECALL:

HAMMOND

POSTULATE

Ea

benzenium

intermediates

have more

resonance

ortho-paradirector

The Hammond Postulate

• If carbocation intermediate is more stable than another, why is the reaction through the more stable one faster?

– The relative stability of the intermediate is related to an equilibrium constant (DGº)

– The relative stability of the transition state (which describes the size of the rate constant) is the activation energy (DG‡)

– The transition state is transient and cannot be examined

Transition State Structures

• A transition state is the highest energy species in a reaction step

• By definition, its structure is not stable enough to exist for one vibration

• But the structure controls the rate of reaction

• So we need to be able to guess about its properties in an informed way

• We classify them in general ways and look for trends in reactivity – the conclusions are in the Hammond Postulate

Statement of the Hammond

Postulate

• A transition state should be similar to an

intermediate that is close in energy

• Sequential states on a reaction path that are close

in energy are likely to be close in structure - G. S.

Hammond

carbocation

G

Reaction

In a reaction

involving a

carbocation, the

transition states look

like the intermediate

Energy Profiles

meta

ortho

para

NITRATION OF ANISOLEbenzenium

intermediateRECALL:

HAMMOND

POSTULATE

Ea

benzenium

intermediates

have more

resonance

ortho-paradirector

H

HNO

2

O CH3

+

:B elimination_

H

NO2

O CH3

H

HNO

2

O CH3

+:B

addition

_

H

HNO

2

B

O CH3

doesn’t happen

resonance would be lost

restores aromatic ring

resonance

ADDITION REACTION

ELIMINATION REACTION

BENZENIUM IONS GIVE ELIMINATION INSTEAD OF ADDITION

( 36 Kcal / mole )

X

The Amino Group

Aniline reacts with bromine water (without a

catalyst) to yield the tribromide. Sodium

bicarbonate is added to neutralize the

HBr that’s also formed.

NH2

Br23

H2O, NaHCO3

NH2

Br

Br

Br

=>

Summary of

Activators

=>

Deactivating Meta-

Directing Substituents• Electrophilic substitution reactions for

nitrobenzene are 100,000 times slower than for benzene.

• The product mix contains mostly the meta isomer, only small amounts of the ortho and para isomers.

• Meta-directors deactivate all positions on the ring, but the meta position is lessdeactivated.

=>

Ortho Substitution

on Nitrobenzene

=>

Para Substitution

on Nitrobenzene

=>

Meta Substitution

on Nitrobenzene

=>

Energy Diagram

=>

Structure of Meta-

Directing Deactivators

• The atom attached to the aromatic ring

will have a partial positive charge.

• Electron density is withdrawn inductively

along the sigma bond, so the ring is less

electron-rich than benzene.

=>

Summary of Deactivators

=>

More Deactivators

=>

Halobenzenes

• Halogens are deactivating toward

electrophilic substitution, but are ortho,

para-directing!

• Since halogens are very electronegative,

they withdraw electron density from the

ring inductively along the sigma bond.

• But halogens have lone pairs of electrons

that can stabilize the sigma complex by

resonance. =>

Sigma Complex

for Bromobenzene

Br

E+

Br

H

E

(+)

(+)(+)

Ortho attack

+ Br

E+

Br

H E

+

(+)

(+)(+)

Para attack

Ortho and para attacks produce a bromonium ion

and other resonance structures.

=>

Meta attack

Br

E+

Br

H

H

E

+

(+)

(+)No bromonium ion

possible with meta attack.

Energy Diagram

=>

Summary of

Directing Effects

=>

Substituent Effects in

Electrophilic SubstitutionsElectrostatic potential maps of benzene, phenol (activated),

chlorobenzene (weakly deactivated), and benzaldehyde (more strongly deactivated)

• The –OH substituent makes the ring more negative (red)

• The –Cl makes the ring less negative (orange)

• The –CHO makes the ring still less negative (yellow)

DIRECTIVITY OF SINGLE GROUPS

ortho, para - Directing Groups

X

Groups that donate

electron density

to the ring.XX :

+I Substituent +R Substituent

CH3-

R-

CH3-O-

CH3-N-

-NH2

-O-H

These groups also

“activate” the ring, or

make it more reactive.

E+

The +R groups activate

the ring more strongly

than +I groups.

..

..

..

..

..

..

increased

reactivity

PROFILE:

X YY

meta - Directing Groups

X

Groups that withdraw

electron density from

the ring.

These groups also

“deactivate” the ring,

or make it less reactive.

E+

-I Substituent -R Substituent

d+ d-

C

O

R

C

O

OR

C

O

OH

C N

N

O

O

N

R

R

R

CCl3

-SO3H

+

decreased

reactivity

+

-

PROFILE:

Halides - o,p Directors / Deactivating

X

E+

: :..

Halides represent a special case:

They are o,p directors (+R effect )

They are deactivating ( -I effect )

Most other other substituents fall

into one of these four categories:

1) +R / o,p / activating

2) +I / o,p / activating

3) -R / m / deactivating

4) -I / m / deactivating

+R / -I / o,p / deactivating

They are o,p directing groups

that are deactivating

-F

-Cl

-Br

-I

THE EXCEPTION

CH3

O CH3

NO2

C

O

O CH3

PREDICT !

o,p m

o,p m

DIRECTIVITY OF MULTIPLE GROUPS

GROUPS ACTING IN CONCERT

O CH3

NO2

m-director

o,p director

HNO3

H2SO4 O CH3

NO2

NO2

major

product

very

little

formed

O CH3

NO2

O2N

steric

crowding

When groups direct to the

same positions it is easy to

predict the product.

GROUPS COMPETING

o,p-directing groups win

over m-directing groups

HNO3

H2SO4

O CH3

NO2

NO2

O CH3

NO2

O2N

O CH3

NO2

too

crowded

X+

HNO3

H2SO4

RESONANCE VERSUS INDUCTIVE EFFECT

O CH3

CH3

NO2

O CH3

CH3

+R

+I

resonance effects are more

important than inductive effects

major

product

SOME GENERAL RULES

1) Activating (o,p) groups (+R, +I) win over

deactivating (m) groups (-R,-I).

2) Resonance groups (+R) win over inductive (+I)

groups.

3) 1,2,3-Trisubstituted products rarely form due to

excessive steric crowding.

4) With bulky directing groups, there will usually be

more p-substitution than o-substitution.

5) The incoming group replaces a hydrogen, it will not

usually displace a substituent already in place.

HOW CAN YOU MAKE ...

C

O

O CH3

NO2

CH3

NO2

NO2

NO2

O2N

CH2CH

2CH

2CH

3

only,

no para

BROMINE - WATER REAGENT

PHENOLS AND ANILINES

H O

H

Br Br H O

H

Br Br

OMe

Br O

H

H

H

Br

OMe

..

.... .. ..

.. ..

..

..

..

..

..

..

:: : : :

:

+

+

-

BROMINE IN WATER

+

This reagent works only with highly-activated rings

such as phenols, anisoles and anilines.

bromonium

ion

etc

OH

Br2

H2O

OH

Br

BrBr

All available

positions are

bromiated.NH

2

CH3

NH2

CH3

Br

BrBr2

H2O

PHENOLS AND ANILINES REACT

Friedel-Crafts Alkylation

• Synthesis of alkyl benzenes from alkyl

halides and a Lewis acid, usually AlCl3.

• Reactions of alkyl halide with Lewis acid

produces a carbocation which is the

electrophile.

• Other sources of carbocations:

alkenes + HF or alcohols + BF3.

=>

Examples of

Carbocation Formation

CH3 CH CH3

Cl

+ AlCl3

CH3

C

H3C H

Cl AlCl3+ _

H2C CH CH3

HFH3C CH CH3

F+

_

H3C CH CH3

OHBF3

H3C CH CH3

OH BF3+

H3C CH CH3

++ HOBF3

_

=>

Formation of

Alkyl Benzene

C

CH3

CH3

H+

H

H

CH(CH3)2+

H

H

CH(CH3)2

B

F

F

F

OH

CH

CH3

CH3

+

HF

BF

OHF

=>

+

-

Limitations of

Friedel-Crafts

• Reaction fails if benzene has a substituent

that is more deactivating than halogen.

• Carbocations rearrange. Reaction of

benzene with n-propyl chloride and AlCl3produces isopropylbenzene.

• The alkylbenzene product is more reactive

than benzene, so polyalkylation occurs.

=>

Friedel-Crafts

Acylation

• Acyl chloride is used in place of alkyl

chloride.

• The acylium ion intermediate is

resonance stabilized and does not

rearrange like a carbocation.

• The product is a phenyl ketone that is

less reactive than benzene.

=>

Mechanism of Acylation

R C

O

Cl AlCl3 R C

O

AlCl3Cl+ _

R C

O

AlCl3Cl+ _

AlCl4 +

_ +R C O R C O

+

C

O

R

+

H

C

H

O

R

+

Cl AlCl3

_C

O

R +

HCl

AlCl3

=>

Clemmensen ReductionAcylbenzenes can be converted to

alkylbenzenes by treatment with aqueous

HCl and amalgamated zinc.

+ CH3CH2C

O

Cl1) AlCl3

2) H2O

C

O

CH2CH3Zn(Hg)

aq. HCl

CH2CH2CH3

=>

Gatterman-Koch

Formylation

• Formyl chloride is unstable. Use a high

pressure mixture of CO, HCl, and catalyst.

• Product is benzaldehyde.

CO + HCl H C

O

ClAlCl3/CuCl

H C O+

AlCl4

_

C

O

H

+ C

O

H+ HCl+

=>

Chlorination of Benzene

• Addition to the benzene ring may occur

with high heat and pressure (or light).

• The first Cl2 addition is difficult, but the

next 2 moles add rapidly.

• The product, benzene hexachloride, is

an insecticide.

=>

Catalytic Hydrogenation

• Elevated heat and pressure is required.

• Possible catalysts: Pt, Pd, Ni, Ru, Rh.

• Reduction cannot be stopped at an

intermediate stage.

=>

CH3

CH3

Ru, 100°C

1000 psi3H2,

CH3

CH3

Birch Reduction:

Regiospecific

• A carbon with an e--withdrawing group

is reduced.

• A carbon with an e--releasing group

is not reduced.

C

O

OH Na, NH3

CH3CH2OH

C

O

O

H

_

OCH3 Li, NH3

(CH3)3COH, THF

OCH3

=>

Birch Mechanism

=>

Side-Chain OxidationAlkylbenzenes are oxidized to benzoic acid

by hot KMnO4 or Na2Cr2O7/H2SO4.

CH(CH3)2

CH CH2

KMnO4, OH-

H2O, heat

COO

COO

_

_

=>

Side-Chain Halogenation

• Benzylic position is the most reactive.

• Chlorination is not as selective as

bromination, results in mixtures.

• Br2 reacts only at the benzylic position.

=>

CHCH2CH3

Br

hBr2,

CH2CH2CH3