chapter 14faperta.ugm.ac.id/download/bahan_kuliah/tutik_dw/kimia_organik/ch... · organic chemistry...

Organic Chemistry OnLine ©2000

Chapter 14

Electrophilic Aromatic Substitution-II

© 2000, Paul R. YoungUniversity of Illinois at Chicago

All Rights Reserved


Electrophilic Aromatic Substitution

Acylation

Alkylation

Sulfonation

Nitration

Halogenation

C

O

R

R

SO3H

NO2

X X+

NO2+ HSO3

+ R+

RC O+


Br2/FeBr3

Br

Fe

Br

Br

Br

Br Brδ δ

FeBr3 functions as a Lewis Acid, binding Br2 andcreating a source of the bromonium cation, Br+


Br

Br

H

Br

H

H

Br

Br loss of H+

...the driving force for loss of H+ is therestoration of the aromatic system.


Br

H

Br

H

H

Br

An electrostatic potential map showing chargedistribution in the cyclohexadienyl cation intermediate.

Electron donatingsubstituents at these

positions will stabilizethe cationic

intermediate.


Cl2/FeCl3

ClCl

H

II

HI2

CuCl2

I

...CuCl2/I2 serves to generate I+


NO2

NO2+

NO2

H

H2SO4 + HNO3 H2O + NO2+

Nitration


SO3H

H

H2SO4 + SO3 SO3H+

+ HSO4-

SO3H+

SO3H

Sulfonation


Friedel-Crafts Alkylation

CH3

CH3

HCH3

Cl

AlCl3

δ

δ

δδ

CH3 Cl AlCl3CH3Cl + AlCl3


Limitations of the Friedel-Crafts Alkylation

1. Reaction limited to alkyl halides; aryl or vinyl halides donot react.

2. Reaction does not occur on rings containing strongelectron withdrawing substituents.

3. Multiple substitutions often occur.

4. Carbocation rearrangements can occur, particularly with1˚ alkyl halides.

NO2 CN SO3H CHO COR

COOH COOR NR3+


O

CH3H

O

CH3

CH3

O

Friedel-Crafts Acylation

Cl AlCl3

CH3

O δ δ

ClH3C

O

+ AlCl3


Friedel-Crafts Acylation

1. Multiple substitutions do not occur.

2. Carbocation rearrangements do not occur.

3. Reaction does not occur on rings containing strongelectron withdrawing substituents.

4. Acid anhydrides can also be used.

O

CH3

...ring is deactived after mono-substitution;multiple substitutions do not occur.

H3C O CH3

O O


1. Predict the products of the following reactions.

AlCl3

AlCl3

Cl

Cl

O

HNO3/H2SO4



AlCl3

AlCl3

Cl

Cl

O

HNO3/H2SO4

O

CH3



AlCl3

AlCl3

Cl

Cl

O

HNO3/H2SO4

O

CH3

NO2


1.(con't) Predict the products of the following reactions.

AlCl3

O

O O

FeCl3

Cl2

SO3/H2SO4



AlCl3

O

O O

FeCl3

Cl2

SO3/H2SO4

Cl



AlCl3

O

O O

FeCl3

Cl2

SO3/H2SO4

Cl

SO3H



AlCl3

O

O O

FeCl3

Cl2

SO3/H2SO4

Cl

SO3H

O

CH2CH3


H2/Pd25˚ C, 1 atm

Catalytic Reduction of AromaticCompounds


H2/Pd25˚ C, 1 atm


H2/Pd25˚ C, 1 atm

H2, Pt/C 25˚ C2000 psi


H2/Pd25˚ C, 1 atm

H2, Rh/C25˚ C; 1 atm

H2, Pt/C 25˚ C2000 psi


The Reduction of Aryl Nitro Groups and ArylKetones

O

H2/Pd25˚ C, 1 atm

NO2

H2/Pd25˚ C, 1 atm

NH2

...or...SnCl2/H3O

+


+

O

Zn(Hg)H3O

+

Aryl ketones can also be reduced to thehydrocarbon using the Clemmensen Reduction.


Suggest a synthesis of propylbenzene, beginning with benzene.


AlCl3CH3CH2CH2Cl


Cl AlCl3 AlCl3CH3CH2CH2Cl


1,2-hydride shift

Cl AlCl3

Cl AlCl3 AlCl3CH3CH2CH2Cl

H

H


Suggest a synthesis of propylbenzene, beginning with benzene.


O

CH3CH2 C

O

Cl

AlCl3


AlCl3

H2/Pd25˚ C, 1 atm

CH3CH2 C

O

Cl

O


Reactions of Arylamines

H2/Pd25˚ C, 1 atm

NO2NH2

...or...SnCl2/H3O

+


Reactions of Arylamines

H2/Pd25˚ C, 1 atm

NO2NH2

...or...SnCl2/H3O

+

NH2 N

N

HNO2H2SO4

A diazonium salt.


H3PO2, H 2O

HCl, CuCl

HBr, CuBr

KI

N2+


H3PO2, H 2O

HCl, CuCl

HBr, CuBr

KI

N2+

Cl

Sandmeyer Reaction


H3PO2, H 2O

HCl, CuCl

HBr, CuBr

KI

N2+

Cl

Br


H3PO2, H 2O

HCl, CuCl

HBr, CuBr

KI

N2+

Cl

Br

I


KCN, CuCN

H+/H2O

OH

N

CH3

CH3

N2+


KCN, CuCN

H+/H2O

OH

N

CH3

CH3

N2+

CN


KCN, CuCN

H+/H2O

OH

N

CH3

CH3

N2+

CN

OH


KCN, CuCN

H+/H2O

OH

N

CH3

CH3

N2+

CN

OH

NN

OH


OH

The oxygen atom in phenol is electron-releasing by resonance,activating the ring to electrophilic aromatic substitutionortho- and para- to the oxygen.


OH


OH


OH


OH

OH


OH OH

OHOH



OHδ

δ δ

Because of the increased electron density, an electrophile willattack the phenol ring preferentially at these positions.


OHδ

δ δ


NN

A diazonium salt acting asan electrophile.


NN

OH

OHδ

δ δ

NN

H+

OH

NN

HH



NN

OH

OHδ

δ δ

NN

H+

OH

NN

HH


A diazonium“coupling” product.


KCN, CuCN

H+/H2O

OH

N

CH3

CH3

N2+

CN

OH

NN

OH


KCN, CuCN

H+/H2O

OH

N

CH3

CH3

N2+

CN

OH

NN

OH

NN

N

CH3

CH3


NH2 NH2

Br

Br

Br

Br2

OH

OH

Br

Br

Br

Br2

Arylamines and Phenols are so highly activated towardselectrophilic aromatic substitution that they react withbromine in the absence of a catalyst to give tribromo adducts.


Reactivity of Substituted Benzenes

1. Substituents effect the reactivity of aromatic rings.

2. Substituents also effect the orientation orregiochemistry of the reaction.


NO2CN

SO3H

CHO

CORCOOHCOOR

NR3+

NH2

OCH3

OH

N

H

C

O

CH3CH3

F

BrCl

I

H

stronglyactivating

stronglydeactivating


Electrostatic potential maps clearly show the effect ofsubstituents on electron density in a substituted benzene ring.

Aniline, stronglyactivating

Benzene Benzonitrile,strongly deactivating


δ

OCH3

δ

δ

δ

E

OCH3

OCH3 OCH3 OCH3


Br

H

Br

H

H

Br



intermediate.

Recall that positive charge in the cyclohexadienyl cationintermediate is delocalized to the ortho- and para- positions.


δ

OCH3

δ

δ

δ

E

Because of this, attack to form the cationic intermediate willoccur predominately ortho- and para- to an electron donatingsubstituent.



intermediate.


ortho &para

directing

NO2CN

SO3H

CHO

CORCOOHCOOR

NR3+

NH2

OCH3

OH

N

H

C

O

CH3CH3

F

BrCl

I

H

stronglyactivating



Cl

Cl Cl Cl

δ

Cl

δ

δ

δ

E ...halogens are deactivating inductively,but activate the ring through resonance.


CH3

HNO3/H2SO4

CH3

NO2

CH3

NO2

CH3

NO2

63% 3%

34%

...the alkyl group is activating and increases electron densityin the ortho and para positions; thus, nitration generates

predominately ortho and para products.


CH3

H

E

CH3

E

H

CH3

E

H

CH3

+

E

a tertiarycarbocation

...alkyl groups activate ortho and para because the sigma-complex intermediates yield more stable tertiary carbocations.


CN

HNO3/H2SO4

CN

NO2

CN

NO2

CN

NO2

17% 81%

2%

...the cyano group is deactivating; nitration generatespredominately meta product.


δ

δ

δ

δNO2

NOO

NOO

NOO

E

NOO


Recall that electron donatingsubstituents ortho- and para-

to the sigma intermediate willstabilize the cationic

intermediate.

Deactivating meta-directing groups...

δ

δ

δ

δNO2


When electron withdrawing substituentsare present ortho- or para- to the sigma

intermediate substitution is forced meta-because there is reduced electron density in

the other positions.

Deactivating meta-directing groups...

δ

δ

δ

δNO2


NOO

E

NOO

NOO

NOO

NO2

δ

δ

δ

δ

...electrophilic attack occurs at the metapositions because the ortho and para

positions are electron deficient.


ortho- &para-

directing

NO2CN

SO3H

CHO

CORCOOHCOOR

NR3+

NH2

OCH3

OH

N

H

C

O

CH3CH3

F

BrCl

I

H

stronglyactivating


meta-directing


CH3

NO2

HNO3/H2SO4

Orientation Effects in Disubstituted Benzenes


CH3

NO2

HNO3/H2SO4

CH3

NO2

NO2

CH3

NO2

NO2O2N

methyl directs ortho

nitro directs meta

Trinitrotoluene


CH3

NO2

HNO3/H2SO4

CH3

NO2

NO2

CH3

NO2

NO2O2N

methyl directs ortho

nitro directs meta

TriNitroToluene


CH3

OCH3

Br2/FeBr3



CH3

OCH3

Br2/FeBr3

CH3

OCH3

Br

...when substituents direct to different positions, themost powerful group will dominate.


CH3

Cl

Cl2/FeCl3



CH3

Cl

Cl2/FeCl3

CH3

Cl

Cl

CH3

Cl

Cl

CH3

Cl

Cl

+

...product not observed;too hindered


Nucleophilic Aromatic Substitution

F

NO2

NO2

HO-

OH

NO2

NO2


F

NO2

O2N

HO-

...SN2 attack is not possible;SN1 would generate the unstable aryl cation.

F

NO2

NO2

NO2

NO2


F

NO2

NO2

HO-

NO2

NO2

OHF

NO2

NO2

OH

NO2

NO2

OHF

...addition

...elimination

The Addition-Elimination Mechanism


N

NO2

OHF O

ON

NO2

OHF O

O

...the carbanion at the ortho- position is stabilizedbyresonance with the oxygens of the nitro group


N

NO2

OHF O

ON

NO2

OHF O

O

+ F

NO2

OH

N

O

O

elimination


CH3

SO3H

NO2

Br2/FeBr3

I2/CuCl2

Cl2/FeCl3


CH3

SO3H

NO2

Br2/FeBr3

I2/CuCl2

Cl2/FeCl3CH3

Cl + ortho isomer


CH3

SO3H

NO2

Br2/FeBr3

I2/CuCl2

Cl2/FeCl3CH3

Cl

SO3HBr

+ ortho isomer


CH3

SO3H

NO2

Br2/FeBr3

I2/CuCl2

Cl2/FeCl3CH3

Cl

SO3HBr

NO2I

+ ortho isomer


CH3

CH(CH3)2

ClSO3/H2SO4

excess HNO3/H2SO4

Cl

O

C

AlCl3


CH3

CH(CH3)2

ClSO3/H2SO4

excess HNO3/H2SO4

Cl

O

C

AlCl3

Cl

HO3S+ ortho isomer


CH3

CH(CH3)2

ClSO3/H2SO4

excess HNO3/H2SO4

Cl

O

C

AlCl3

CH3

NO2

O2N NO2

Cl

HO3S+ ortho isomer


CH3

CH(CH3)2

ClSO3/H2SO4

excess HNO3/H2SO4

Cl

O

C

AlCl3

CH3

NO2

O2N NO2

CH(CH3)2

O

Cl

HO3S+ ortho isomer

chapter 14faperta.ugm.ac.id/download/bahan_kuliah/tutik_dw/kimia_organik/ch... · organic chemistry...

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