Electrophilic Aromatic Substitution (Aromatic compounds) Ar-H = aromatic compound 1.

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

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

HNO3 H2SO4

NO2

SO3 H2SO4 SO3H

Br2, Fe

Br

CH3CH2-Br AlCl3 CH2CH3

toluene
CH3 HNO3 H2SO4 NO2 CH3 NO2 + CH3

CH3 SO3 H2SO4

CH3 SO3H +

CH3

faster than the same reactions with benzene

SO3H

CH3 Br2, Fe

CH3 Br +

CH3

Br

nitrobenzene

NO2 HNO3 H2SO4

NO2

NO2

NO2 SO3 H2SO4

NO2

slower than the same reactions with benzene

SO3H

NO2 Cl2, Fe

NO2

Cl

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

or meta- direction

-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

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

increasing reactivity

ortho/para directors

meta directors

OCH3 Br2, Fe

OCH3 Br +

OCH3 faster than benzene Br

CHO HNO3, H2SO4

CHO slower than benzene NO2

Br H2SO4, SO3

Br SO3H +

Br slower than benzene SO3H

If there is more than one group on the benzene ring: 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.

CH3 Br2, Fe

CH3

Br

OH NHCOCH3 HNO3, H2SO4

OH

NHCOCH3 NO2

CH3 CHO Cl2, Fe

CH3

CHO Cl + OCH3 Cl

CHO

OCH3

OCH3

Orientation and synthesis. Order is important!

synthesis of m-bromonitrobenzene from benzene:
HNO3 H2SO4 NO2 Br2, Fe NO2

Br

synthesis of p-bromonitrobenzene from benzene:

Br Br2, Fe HNO3 + H2SO4 NO2 Br Br NO2

You may assume that you can separate a pure paraisomer from an ortho-/para- mixture.

note: the assumption that you can separate a pure para isomer from an ortho/para mixture does not apply to any other mixtures.
synthesis of 1,4-dibromo-2-nitrobenzene from benzene Br Br2, Fe Br2, Fe Br Br + Br Br HNO3 H2SO4 Br Br NO2

separate pure para isomer from ortho/para mixture

NO2 HNO3 H2SO4 Br2, Fe

NO2 Br2, Fe Br

NO2 Br + Br Br

NO2

Br

cannot assume that these can be separated!

synthesis of benzoic acids by oxidation of CH3

CH3 CH3Br AlCl3 KMnO4 heat COOH

CH3 CH3Br AlCl3 KMnO4 heat

COOH HNO3 H2SO4

COOH

NO2

CH3 CH3Br AlCl3 HNO3 H2SO4

CH3 KMnO4 heat NO2 + ortho-

COOH

NO2

Links to problem sets on the web involving EAS:

http://chemistry2.csudh.edu/organic/aromatics/reactions.html Reactivity and sites on monosubstituted benzene Reaction Sties on disubstituted benzenes Synthesis of disubstituted benzenes Synthesis of trisubstituited benzenes

nitration
HO-NO2 + H2SO4 + H2O-NO2 + H2O-NO2 + HSO4-

+ H2O + NO2

H2SO4 + H2O HSO4- + H3O+

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

nitration:

1) HONO2 + 2 H2SO4

H3O+

2 HSO4- + NO2+

electrophile
2) + NO2+ RDS

resonance

NO2 H

NO2 H

NO2 H

NO2 H

Mechanism for nitration:

1) HONO2 + 2 H2SO4

H3O+

2 HSO4- + NO2+

2)

NO2+

RDS

NO2 H

NO2 3) H

NO2

+ H+

Mechanism for sulfonation:

1) 2 H2SO4 H3O+ + HSO4+ SO3

RDS 2) + SO3

SO3H

3)

SO3H

SO3-

H+

4)

SO3- + H3O+

SO3H

+ H2O

Mechanism for halogenation:

1)

Cl2 + AlCl3

Cl-Cl-AlCl3

RDS 2) + Cl-Cl-AlCl3

Cl H

+ AlCl4-

Cl 3) H

AlCl4-

Cl

+ HCl + AlCl3

Mechanism for Friedel-Crafts alkylation:

1)

R-X

FeX3

R RDS

FeX4R H

2)

+ R

R 3) H

+ FeX4-

HX

+ FeX3

Mechanism for Friedel-Crafts with an alcohol & acid

H+ ROH2+

1)

R-OH

2)

ROH2+

+ H2O RDS R H

3)

+ R

R 4) H

+ H+

Mechanism for Friedel-Crafts with alkene & acid:

1) C C + H+ R

RDS 2) + R

R H

R 3) H R +

H+

electrophile in Friedel-Crafts alkylation = carbocation

Generic Electrophilic Aromatic Substitution mechanism:

RDS 1) + Y+Z-

Y H + Z-

2)

Y H + ZY + HZ

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

O H

resonance donation (weaker inductive withdrawal)

O R

resonance donation (weaker inductive withdrawal)

O H3C C N H

resonance donation (weaker inductive withdrawal)

resonance donation

H3 C

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:

-NH2, -NHR, -NR2 -OH -OR -NHCOCH3 -C6H5 -R -H -X -CHO, -COR -SO3H -COOH, -COOR -CN -NR3+ -NO2

electron donating

increasing reactivity

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.

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.

NO2

CF3 electron withdrawing = deactivating & meta-director

PO3H electron withdrawing = deactivating & meta-director

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

Br2, Fe Br + ortho-

Br2, Fe NO2 Br NO2 + ortho-

O O

Br2, Fe

O + orthoO Br

How to draw resonance structures for EAS Y H

Y H

Y H

Y H

Y H

Y H ortho-attack

G Y H

G Y H

G Y H meta-attack

G para-attack H Y

H Y

H Y

G
Y H

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

Y H

Y H

Y H ortho-attack

G Y H

G Y H

G Y H 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 Eacts for ortho-/para- are lower and the rates are faster.

Electron donating groups direct ortho-/para- in EAS

G Y H H Y

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

Y H

Y H

Y H ortho-attack

G Y H

G Y H

G Y H 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 Eacts 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.

Y H

Y H

Y H

Y H ortho-

X Y H

X Y H

X Y H meta-

X para-

H Y

H Y

H Y

H Y

halogens are deactivating in EAS but direct ortho and para

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

increasing reactivity

ortho/para directors

meta directors