Electro Phil i c Aromatic Substitution

nitration

HO-NO2 + H2SO4 + H2O-NO2



+ H2O-NO2  + HSO4-

+  H2O + NO2

H2SO4 + H2O



HNO3 + 2 H2SO4

HSO4- + H3O+



H3O+ + 2 HSO4- + NO2+

nitration:

H3O+

1) HONO2 + 2 H2SO4

+

2 HSO4- + NO2+

electrophile 2)

+

NO2+

RDS

nitration:

H3O+

1) HONO2 + 2 H2SO4

+

2 HSO4- + NO2+

electrophile 2)

+

NO2+

RDS

resonance

NO2

NO2

NO2

H

H

H

NO2 H

Mechanism for nitration:

H3O+

1) HONO2 + 2 H2SO4

+

2)

NO2+

RDS

2 HSO4- + NO2+

+

NO2 H

3)

NO2 H

NO2

+ H+

Mechanism for sulfonation: 1)

H3 O +   +

2 H2SO4

RDS 2)

+ SO3

HSO 4-

+

SO3

SO3H

3)

SO3H

4)

SO 3- + H3O+

SO3-

+

H+

SO3H

+ H2 O

Mechanism for halogenation:

1)

Cl-Cl-AlCl3

Cl2  + AlCl3

RDS +

2)

Cl

Cl-Cl-AlCl3

+ AlCl4-

H

Cl 3)

H

+

AlCl4-

Cl

+ HCl + AlCl3

Mechanism for Friedel-Crafts alkylation:

1)

R-X

+

FeX3

+ R

2)

3)

R RDS

+

FeX4R H

R H

+ FeX4-

R

+

HX

+

FeX 3

Mechanism for Friedel-Crafts with an alcohol & acid

1)

R-OH

2)

ROH2+

+

ROH2+

R

+ R

3)

4)

H+

+ H2O RDS

R H

R H

R

+ H+

Mechanism for Friedel-Crafts with alkene & acid: 1)

+

C C

+ R

2)

3)

H+

R

RDS

R H

R R

+

H+

H

electrophile in Friedel-Crafts alkylation = carbocation

“Generic” Electrophilic Aromatic Substitution mechanism:

2)

Y+Z-

+

1)

Y H

+

Z-

RDS

Y +

H

Y

+

Z-

HZ

Common substituent groups and their effect on EAS:

  y    t    i   v    i    t   c   a   e   r   g   n    i   s   a   e   r   c   n    i

-NH2, -NHR, -NR 2 -OH -OR -NHCOCH3 -CH3 -R -H -X -CHO, -COR -SO3H -COOH, -COOR -CN -NR 3+ -NO2

ortho/para directors

meta directors

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Electrons can be donated (―pushed‖) or withdrawn (―pulled‖) by atoms or groups of atoms via: Induction –  due to differences in electronegativities Resonance –  delocalization via resonance

H N H

R N H

unshared pair of electrons on the nitrogen resonance donating groups (weaker inductive withdrawal)

R N R R R N R

strong inductive withdrawal (no unshared pair of electrons on the nitrogen & no resonance possible

resonance donation

O H

(weaker inductive withdrawal)

resonance donation

O R

(weaker inductive withdrawal)

O H3C C N H

resonance donation

(weaker inductive withdrawal)

resonance donation

H3C

X — 

inductive donation sp3 sp2 ring carbon

inductive withdrawal

O C H

O C R resoance withdrawal and inductive withdrawal

O C HO

O C RO

N C

resonance and inductive withdrawal

O N O

resonance and inductive withdrawal

Common substituent groups and their effect on reactivity in EAS:

  y    t    i   v    i    t   c   a   e   r   g   n    i   s   a   e   r   c   n    i

-NH2, -NHR, -NR 2 -OH -OR -NHCOCH3 -C6H5 -R -H -X -CHO, -COR -SO3H -COOH, -COOR -CN -NR 3+ -NO2

electron donating

electron withdrawing

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 intermediate carbocation, lowers the Eact and increases the rate.

H

Y

CH3

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.

H

Y

NO 2

CF3 electron withdrawing = deactivating & meta-director 

PO3H electron withdrawing = deactivating & meta-director 

PH2 electron donating = activating & ortho-/para-director 

Br 2, Fe Br 

+ ortho-

Br 2, Fe NO2

O O

Br 

Br 2, Fe

NO2

+ ortho-

O + orthoO

Br 

How to draw resonance structures for EAS

Y

Y H

Y

Y H

H

G

G

Y H

H

H

Y H

Y H

Y H

G

Y ortho-attack

G

G

G

G

G

Y

meta-attack

G  para-attack

H Y

H Y

H Y

G

G Y H

If G is an electron donating group, these structures are especially stable.

G

G

Y H

Y H

H

Y H

Y H

Y H

G

Y ortho-attack

G

G

G

G

G

meta-attack

G  para-attack

H Y

H Y

H Y

Electron donating groups stabilize the intermediate carbocations for ortho- and para- in EAS more than for meta-. The Eact’s for ortho-/para- are lower and the rates are faster.

Electron donating groups direct ortho-/para-  in EAS

G

G Y H H Y

If G is an electron withdrawing group, these structures are especially unstable.

G

G

Y H

H

H

Y H

Y H

Y H

G

Y ortho-attack

G

G

G

G

G

Y

meta-attack

G  para-attack

H Y

H Y

H Y

Electron withdrawing groups destabilize the intermediate carbocations for ortho- and para- in EAS more than for meta-. The Eact’s for ortho-/para- are higher and the rates are slower.

Electron withdrawing groups direct meta-  in EAS

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 electrons that can be resonance donated to the carbocation.