electro philic substitution

7/27/2019 Electro Philic substitution

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Electrophilic Aromatic Substitution (Aromatic compounds)

Ar-H = aromatic compound1. Nitration

Ar-H + HNO3, H2SO4 Ar-NO2 + H2O

2. Sulfonation

Ar-H + H2SO4, SO3 Ar-SO3H + H2O

3. Halogenation

Ar-H + X2, Fe Ar-X + HX

4. Friedel-Crafts alkylation

Ar-H + R-X, AlCl3 Ar-R + HX


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Friedel-Crafts alkylation (variations)

a) Ar-H + R-X, AlCl3 Ar-R + HX

b) Ar-H + R-OH, H+ Ar-R + H2O

c) Ar-H + Alkene, H+ Ar-R


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NO2

SO3H

Br

CH2CH3

HNO3

H2SO4

SO3

H2SO4

Br2, Fe

CH3CH2-Br

AlCl3


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toluene

CH3

CH3

CH3CH3

CH3

CH3CH3

CH3

CH3

Br

Br

NO2

NO2

SO3H

SO3H

HNO3

H2SO4

SO3

H2SO4

Br2, Fe

+

+

+

fasterthan the same

reactions withbenzene


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nitrobenzene

NO2

NO2

NO2

NO2

NO2

NO2

NO2

SO3H

Cl

HNO3

H2SO4

H2SO4

SO3

Cl2, Fe

slowerthan the samereactions with

benzene


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Substituent groups on a benzene ring affect electrophilic

aromatic substitution reactions in two ways:

1) reactivity

activate (faster than benzene)or deactivate (slower than benzene)

2) orientation

ortho- +para- direction

ormeta- direction


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-CH3

activates the benzene ring towards EAS

directs substitution to the ortho- &para- positions

-NO2

deactivates the benzene ring towards EAS

directs substitution to the meta- position


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Common substituent groups and their effect on EAS:

-NH2, -NHR, -NR2

-OH-OR

-NHCOCH3

-C6H5

-R-H

-X

-CHO, -COR

-SO3H

-COOH, -COOR

-CN

-NR3+

-NO2

in

creasingr

eac

tivity ortho/para directors

meta directors


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OCH3

CHO

Br

Br2, Fe

HNO3, H2SO4

H2SO4, SO3

OCH3

Br

OCH3

Br

+ faster than benzene

CHO

NO2

slower than benzene

+

Br Br

SO3H

SO3H

slower than benzene


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If there is more than one group on the benzenering:

1. The group that is more activating (higher

on the list) will direct the next

substitution.

2. You will get little or no substitution

between groups that are meta- to each

other.


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CH3

OH

NHCOCH3

CH3

CHO

OCH3

Br2, Fe

HNO3, H2SO4

Cl2, Fe

CH3

OH

Br

NHCOCH3

CH3

NO2

CHO

OCH3

Cl

CHO

OCH3

Cl

+


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Orientation and synthesis. Order is important!

synthesis ofm-bromonitrobenzene from benzene:

NO2

Br

NO2HNO3

H2SO4

Br2, Fe

synthesis ofp-bromonitrobenzene from benzene:

Br Br Br

NO2

NO2+

Br2, Fe HNO3

H2SO4

You may assume that you can separate a purepara-

isomer from an ortho-/para- mixture.


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note: the assumption that you can separate a pure para

isomer from an ortho/para mixture does not apply to anyother mixtures.

Br Br

Br

Br

Br

NO2 NO2

Br

NO2

Br

Br

NO2

Br

Br

Br

Br

NO2

+

+

Br2, Fe Br2, Fe

Br2, Fe Br2, FeHNO3H2SO4

HNO3H2SO4

synthesis of 1,4-dibromo-2-nitrobenzene from benzene

separate pure para isomer from ortho/para mixture

cannot assume that these can be separated!


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CH3

CH3

CH3

COOH

COOH COOH

CH3 COOH

NO2

NO2 NO2

+ ortho-

CH3Br

AlCl3

CH3Br

CH3Br

AlCl3

AlCl3

KMnO4

KMnO4

KMnO4

heat

heat

heat

HNO3

H2SO4

HNO3

H2SO4

synthesis of benzoic acids by oxidation ofCH3


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Links to problem sets on the web involving EAS:

http://chemistry2.csudh.edu/organic/aromatics/reactions.html

Reactivity and sites on monosubstituted benzeneReaction Sties on disubstituted benzenes

Synthesis of disubstituted benzenes

Synthesis of trisubstituited benzenes
http://chemistry2.csudh.edu/organic/aromatics/reactions.htmlhttp://chemistry2.csudh.edu/organic/aromatics/startEASreactivity.htmlhttp://chemistry2.csudh.edu/organic/aromatics/startsitesdi.htmlhttp://chemistry2.csudh.edu/organic/aromatics/startsynthesis.htmlhttp://chemistry2.csudh.edu/organic/aromatics/starttrisynthesis.htmlhttp://chemistry2.csudh.edu/organic/aromatics/starttrisynthesis.htmlhttp://chemistry2.csudh.edu/organic/aromatics/startsynthesis.htmlhttp://chemistry2.csudh.edu/organic/aromatics/startsitesdi.htmlhttp://chemistry2.csudh.edu/organic/aromatics/startEASreactivity.htmlhttp://chemistry2.csudh.edu/organic/aromatics/reactions.html


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+

HO-NO2 + H2SO4 H2O-NO2 + HSO4-

+ +H2O-NO2 H2O + NO2

H2SO4 + H2O HSO4- + H3O

+

HNO3 + 2 H2SO4 H3O+ + 2 HSO4

- + NO2+

nitration


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nitration:

1) HONO2 + 2 H2SO4 H3O+ + 2 HSO4

- + NO2+

2)+ NO

2

+ RDS

electrophile


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H

NO2

H

NO2

H

NO2

H

NO2

resonance


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Mechanism for nitration:

1) HONO2 + 2 H2SO4 H3O+ + 2 HSO4

- + NO2+

2) + NO2+

H

NO23)

RDS

NO2 + H+

H

NO2


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Mechanism for sulfonation:

1) 2 H2SO

4H

3O+ + HSO

4

- + SO3

2) + SO3

RDS

H

SO3-

3)H

SO3-

SO3- + H+

4) SO3- SO3H+ H3O

+ + H2O


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Mechanism for halogenation:

1) Cl2 + AlCl3 Cl-Cl-AlCl3

2) + Cl-Cl-AlCl3

RDS

H

Cl + AlCl4-

3)H

Cl+ AlCl4

-Cl + HCl + AlCl3


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Mechanism for Friedel-Crafts alkylation:

1) R-X + FeX3 R + FeX4-

2) + R

RDS

3)

H

R

H

R+ FeX4

-R + HX + FeX3


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1) R-OH + H+ ROH2+

3)+ R

RDS

4)

H

R

H

RR

2) ROH2

+ R + H2O

+ H+

Mechanism for Friedel-Crafts with an alcohol & acid


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2)+ R

RDS

3)

H

R

H

RR

1) C C + H+ R

+ H+

Mechanism for Friedel-Crafts with alkene &

acid:

electrophile in Friedel-Crafts alkylation = carbocation


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Generic Electrophilic Aromatic Substitution mechanism:

1) + Y+Z-RDS

H

Y+ Z-

2)H

Y+ Z- Y + HZ


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Why do substituent groups on a benzene ring affect the

reactivity and orientation in the way they do?

electronic effects, pushing or pulling electrons by

the substituent.

Electrons can be donated (pushed) or withdrawn

(pulled) by atoms or groups of atoms via:

Inductiondue to differences in electronegativities

Resonancedelocalization via resonance


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N

H

H

unshared pair of electrons on the nitrogenresonance donating groups

(weaker inductive withdrawal)

N

R

R

N

R

H

NR

R

Rstrong inductivewithdrawal(no unshared pair of electrons on thenitrogen & no resonance possible


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H3C CO

N

H

resonance donation


H

Oresonance donation


R

Oresonance donation



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resonance donation

H3Cinductive donation

sp3 sp2 ring carbon

inductive withdrawalX


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H

C

O

HO

C

O

RO

C

O

R

C

O

resoance withdrawal andinductive withdrawal


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N

O

O

resonance and

inductive withdrawal

resonance and

inductive withdrawal

CN


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Common substituent groups and their effect on reactivity in EAS:

-NH2, -NHR, -NR2

-OH-OR

-NHCOCH3 electron donating

-C6H5

-R

-H

-X

-CHO, -COR

-SO3H

-COOH, -COOR electron withdrawing-CN

-NR3+

-NO2

in

creasingr

eac

tivity


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Electron donating groups activate the benzene ring to

electrophilic aromatic substitution.

1. electron donating groups increase the electron density

in the ring and make it more reactive with electrophiles.

2. electron donation stabilizes the intermediatecarbocation, lowers the Eact and increases the rate.

H Y

CH3


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H Y

NO2

Electron withdrawing groups deactivate the benzene ring to

electrophilic aromatic substitution.

1. electron withdrawing groups decrease the electron density

in the ring and make it less reactive with electrophiles.

2. electron withdrawal destabilizes the intermediate

carbocation, raising the Eact and slowing the rate.


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CF3

PH2

PO3H

electron withdrawing = deactivating & meta-director

electron withdrawing = deactivating & meta-director

electron donating = activating & ortho-/para-director


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Br2, Fe

Br + ortho-

NO2

Br2, Fe

NO2Br + ortho-

O

OBr2, Fe

O

O

Br+ ortho-


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How to draw resonance structures for EAS

Y

H

Y

HY

HY


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G G G

G G G

G G

H H H

Y Y Y

H

Y

H

Y

H

Y

H Y H Y

G

H Y

ortho-attack

meta-attack

para-attack


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G

H

YG

If G is an electron donating group, these structures are

especially stable.


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G G G

G G G

G G

H H H

Y Y Y

H

Y

H

Y

H

Y

H Y H Y

G

H Y

ortho-attack

meta-attack

para-attack


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Electron donating groups stabilize the intermediatecarbocations forortho- andpara- in EAS more than for

meta-. The Eacts forortho-/para- are lower and the

rates are faster.

Electron donating groups direct ortho-/para-in EAS


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G

H

YG

H Y

If G is an electron withdrawing group, these structures

are especially unstable.


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G G G

G G G

G G

H H H

Y Y Y

H

Y

H

Y

H

Y

H Y H Y

G

H Y

ortho-attack

meta-attack

para-attack


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Electron withdrawing groups destabilize the intermediatecarbocations forortho- andpara- in EAS more than for

meta-. The Eacts forortho-/para- are higher and the

rates are slower.

Electron withdrawing groups direct meta- in EAS


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Halogens are electron withdrawing but are ortho/para

directing in EAS.

The halogen atom is unusual in that it is highly

electronegative but also has unshared pairs of electronsthat can be resonance donated to the carbocation.


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X X X

X X X

X X

H H H

Y Y Y

H

Y

H

Y

H

Y

H Y H Y

X

H Y

X

H Y

X

H

Y

ortho-

meta-

para-

halogens are deactivating in EAS but direct ortho and para


47/47

Common substituent groups and their effect on EAS:

-NH2, -NHR, -NR2

-OH-OR

-NHCOCH3

-C6H5

-R

-H

-X

-CHO, -COR

-SO3H

-COOH, -COOR-CN

-NR3+

-NO2

in

creasingr

eac

tivity ortho/para directors

meta directors

electro philic substitution

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