Electrophilic substitution

Lab 1

Electrophilic substitution chemical reactions in which an electrophile

displaces a group in a compound, typically but not always hydrogen.

Electrophilic substitutionElectrophilic aromatic substitution Electrophilic aliphatic substitution

electrophilic aliphatic substitutionchemical reactions in which an electrophile

displaces a functional group in aliphatic compounds.

Mechanism of reaction: two electrophilic reaction mechanisms SE1 and SE2

electrophilic aliphatic substitutionSE1 course of action the substrate first ionizes into

a carbanion and a positively charged organic residue. The carbanion then quickly recombines with the electrophile.

SE2single transition state in which the old bond

and the newly formed bond are both present.

electrophilic aliphatic substitutionNitrosationKetone halogenationKeto-enol tautomerismaliphatic diazonium couplingcarbene insertion into C-H bonds

Electrophilic aromatic substitutionatom appended to the aromatic ring, usually

hydrogen, is replaced by an electrophile. TypeNitration halogenation sulfonation acylation and alkylating Friedel-Crafts reactions.

X2, FeX3

(x = Cl, Br)

X

HX

R

CR

O

SO3H

NO2

HONO2

H2SO4

SO3

H2SO4

RCl, AlCl3

(R can rearrange)

RC Cl, AlCl3

O

H2O

HCl

HCl

+

+

+

+

Halogination

Nitration

sulfonation

Friedel-Crafts alkylation

Friedel-Crafts acylation

Mechaniism of EAS: arenium ions

E AE

H

E

H

E

H

Step 1

Arenium ions

(nonaromatic cyclohexadienyl cation)

E

H

:A-

EH A+

Step 2

Mechaniism of EAS: arenium ions

The proton is removed by any of the bases, for example by the anion derived from the electrophile

Benzene does not react with Br2 or CL2 unless a Lewis acid is present in mixture

Lewis acid is an electron-pair acceptorLewis acids most commonly used to effect

bromination and chlorination reactions are FeCl3,FeBr3 and AlCl3

Halogenation of benzene

Br

+ Br2FeBr3

heat + HBr

Bromobenzene (75%)

Bromonation of benzene

Electrophilic Aromatic Bromination Br Br + FeBr3 Br Br FeBr3

Br Br FeBr3 slow

HBr

HBr

H Br

Step 1

Step 2

Bromine combines with FeBr3 to form acomplex that dissocates to form apostive bromine ion and

FeBr4-

Arenium ions

Postive bromine ion is attacked by benzen to form an arenium ion

Electrophilic Aromatic Bromination

HBr

Br FeBr3Br

+ H Br + FeBr3

Step 3

Proton is removed from the arenium ion to become bromobenzene

Nitration of Benzene

+ HNO3 + H2SO450-55 oC

NO2

+ H3O+ + HSO4-

(85%)

Nitration of Benzene

HO3SO H + H O NO

O(H2SO4)

H O

H

N

O

O

+ HSO4-

In this step nitric acid accepts a proton from the stronger acid, sulfuric acid.

H O

H

N

O

O

O

N+

O

H2O +

Nitronium ion

Now that it is protonated, nitric acid can dissociateto form a nitronium ion.

Step 1

Step 2

Nitration of BenzeneH

NO2

H

NO2

O

N

O

slow

H

NO2

H O H

H

NO2

+

O H

H +

H

NO2

Step 3

Step 4

Arenium ions

The nitronium ion is the actual electrophile in nitration ; it reacts with benzene to form a resonance-stabilized arenium ion

The arenium ion then loses a proton to a Lewis base and becomes nitrobenzene

Sulfonation of benzene

SO3H

+ H2SO4 + H2O

Benzenesulfonic acid

Sulfonation of benzeneBenzene react with fuming sulfuric acid at

room temperature to produce benzensulphonic acid

Fuming sulfuric acid is sulfuric acid that contain added sulfur trioxide (SO3)

Sulfonation can takes place in conc sulfuric acid, alone but more slowly

S

O

O

O H +

O

SOO

25oC

concd H2SO4

Sulfurtrioxide Benzenesulfonic acid

(56%)

In either reaction the electrophile appears to be sulfur trioxide. In concentrated sulfuricacid, sulfur trioxide is produced in an equilibrium in which H2SO4 acts as both as an acidand a base(see step 1 of the following mechanism).

Sulfonation of benzene

Sulfonation of benzene

2 H2SO4 SO3 + H3O+ + HSO4-

This equilibrium produces SO3 inconcentrated H2SO4

O

SO O

+slow S

H

O -O

O other resonance structures

Step 1

Step 2

SO3,is the actual electrophile that reacts with benzene to form an arenium ion

HSO4- +

S

H

O

O O

fastS O

O

O

+ H2SO4

A proton is removed from the arenium ion to form the benzenesulfonate ion.

S

O

O

O + H O H

H

S

O

O

O H + H2O

The benzenesulfonate ion accepts a proton to become benzenesulfonic acid.

Sulfonation of benzeneStep 3

Step 4

Friedel-Crafts Alkylation

Friedel-Crafts AlkylationMechanism for reaction start with formation

of carbocation (step 1 )The carbocation then act as an electrophile

and attack benzene ring to form an arenium ion (step 2)

The arenium ion then loses a proton to generate alkylbenzene (step 3)

Cl

Al

ClCl

Cl Al Cl

Cl

Cl

Cl Cl Al - Cl

Cl

Cl

++

This is a Lewis acid-basereaction.

The complex dissociate to form a carbocation and AlCl4-.

H

Cl

Al -Cl

Cl

Cl HCl + +

Cl

Al

ClCl

The carbocation, actingas an electrophile, reactswith benzene to producean arenium ion.

A proton is removed from the areniumion to form isopropylbenzene. This stepalso regenerates the AlCl3 and liberatesHCl.

Friedel-Crafts AlkylationStep 1

Step 2

+

Friedel-Crafts Acylation

acetyl groupbenzoyl group

Friedel-Crafts Acylation reaction is mean introducting an acyl group into aromatic ring

Two common acyl groups are acetyl group and benzoyl group

Friedel-Crafts AcylationThe reaction is carried out by treating the

aromatic compound with acyl halide( often an acyl chloride)

The reaction requires the addition of a Lewis acid (such as AlCl3 )

The product of reaction is an aryl ketone.

O

CClR + AlCl3

O

CClR AlCl3

O

CClR AlCl3 R C O R C O + AlCl4

Friedel-Crafts AcylationStep 1

Step 2

Acyl halide

Acylium ion

C

H

R

OC

O

Rother resonance structures(draw them for practice)

CH

R

OC

R

OCl Al Cl

Cl

Cl +

+ HCl +

Cl

AlCl Cl

Friedel-Crafts AcylationStep 3

Step 4

A proton is removed from the arenium ion, forming the aryl ketone

The acylium ion, acting as an electrophile, reacts with benzene to form the arenium ion

C

R

O Al

Cl

Cl

Cl + 3H2O

C

R

O +

OH

Al OHHO + 3HCL

Friedel-Crafts Acylation

Step 6

Treating the complex with water liberates the ketone and hydrolyzes the Lewis acid

C

R

OC

R

O Al Cl

Cl

Cl

Cl

AlCl Cl +

Step 5

The ketone acting as lewis base ,reacts with alaminum chloride (Lewis acid) to form a complex

Preparation of nitrobenzene

+ HNO3 + H2SO450-55 oC

NO2

+ H3O+ + HSO4-

(85%)

By nitration of benzene in pesent of sulphoric acid replace hydrogen atom by (NO2) groups

benzene nitrobenzene

Preparation of nitrobenzeneNitrations are usually carried out at

comparatively low temperatures At high temp may loss of material b/c of

oxidaising action of nitric acid

Preparation of nitrobenzeneSuphoric acid furnish astrong acid.

medium to convert nitric acid into highly reactive nitronium ion NO2

+

HNO3 + 2H2SO4 NO2+ + H3O+ + 2HSO4

-

Procedure:Add 9ml of nitric acid and add, in

portion,with shaking conc. Sulphuric acid(10ml) to round-bottemed flask

Place the mixture in cold water and keep the temp between 50◦-55◦ use thermometer

Add slowly (1-2ml) pure benzene 7ml shake after each addition

When addition is complete warm the flask in water bath 60° for 10-15 min with continued shaking.

Thank you