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
NO2
SO3H
Br
CH2CH3
HNO3
H2SO4
SO3
H2SO4
Br2, Fe
CH3CH2-Br
AlCl3
toluene
CH3
CH3
CH3CH3
CH3
CH3CH3
CH3
CH3
Br
Br
NO2
NO2
SO3H
SO3H
HNO3
H2SO4
SO3
H2SO4
Br2, Fe
+
+
+
faster than the same
reactions with
benzene
nitrobenzene
NO2
NO2
NO2
NO2
NO2
NO2
NO2
SO3H
Cl
HNO3
H2SO4
H2SO4
SO3
Cl2, Fe
slower than the same
reactions with
benzene
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
incr
easi
ng r
eact
ivit
y ortho/para directors
meta directors
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
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
OH
NHCOCH3
CH3
CHO
OCH3
Br2, Fe
HNO3, H2SO4
Cl2, Fe
CH3
OH
Br
NHCOCH3
CH3
NO2
CHO
OCH3
Cl
CHO
OCH3
Cl
+
Orientation and synthesis. Order is important!
synthesis of m-bromonitrobenzene from benzene:
NO2
Br
NO2HNO3
H2SO4
Br2, Fe
synthesis of p-bromonitrobenzene from benzene:
Br Br Br
NO2
NO2
+
Br2, Fe HNO3
H2SO4
You may assume that you can separate a pure para-
isomer 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.
Br Br
Br
Br
Br
NO2 NO2
Br
NO2
Br
Br
NO2
Br
Br
Br
Br
NO2
+
+
Br2, Fe Br2, Fe
Br2, Fe Br2, FeHNO3
H2SO4
HNO3
H2SO4
synthesis of 1,4-dibromo-2-nitrobenzene from benzene
separate pure para isomer from ortho/para mixture
cannot assume that these can be separated!
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 of –CH3
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
+ HO-NO2 + H2SO4 H2O-NO2 + HSO4
- + + H2O-NO2 H2O + NO2 H2SO4 + H2O HSO4
- + H3O+
HNO3 + 2 H2SO4 H3O
+ + 2 HSO4- + NO2
+
nitration
nitration:
1) HONO2 + 2 H2SO4 H3O+ + 2 HSO4- + NO2
+
2) + NO2+ RDS
electrophile
H
NO2
H
NO2
H
NO2
H
NO2
resonance
Mechanism for nitration:
1) HONO2 + 2 H2SO4 H3O+ + 2 HSO4- + NO2
+
2) + NO2+
H
NO23)
RDS
NO2 + H+
H
NO2
Mechanism for sulfonation:
1) 2 H2SO4 H3O+ + HSO4- + SO3
2) + SO3
RDS
H
SO3-
3)H
SO3-
SO3- + H+
4) SO3- SO3H+ H3O+ + H2O
Mechanism for halogenation:
1) Cl2 + AlCl3 Cl-Cl-AlCl3
2) + Cl-Cl-AlCl3
RDS
H
Cl+ AlCl4
-
3)H
Cl+ AlCl4
-Cl + HCl + AlCl3
Mechanism for Friedel-Crafts alkylation:
1) R-X + FeX3 R + FeX4-
2)+ R
RDS
3)
H
R
H
R+ FeX4
-R + HX + FeX3
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
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
“Generic” Electrophilic Aromatic Substitution mechanism:
1) + Y+Z-RDS
H
Y
+ Z-
2)H
Y+ Z- Y + 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
N
H
H
unshared pair of electrons on the nitrogenresonance donating groups(weaker inductive withdrawal)
N
R
R
N
R
H
NR
R
Rstrong inductive withdrawal(no unshared pair of electrons on thenitrogen & no resonance possible
H3C C
O
N
H
resonance donation(weaker inductive withdrawal)
H
Oresonance donation(weaker inductive withdrawal)
R
Oresonance donation(weaker inductive withdrawal)
resonance donation
H3Cinductive donationsp3 sp2 ring carbon
inductive withdrawal X—
H
C
O
HO
C
O
RO
C
O
R
C
O
resoance withdrawal andinductive withdrawal
N
O
O
resonance andinductive withdrawal
resonance andinductive withdrawal
CN
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
incr
easi
ng r
eact
ivit
y
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
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.
CF3
PH2
PO3H
electron withdrawing = deactivating & meta-director
electron withdrawing = deactivating & meta-director
electron donating = activating & ortho-/para-director
Br2, Fe
Br + ortho-
NO2
Br2, Fe
NO2Br + ortho-
O
OBr2, Fe
O
O
Br+ ortho-
How to draw resonance structures for EAS
Y
H
Y
H
Y
H
Y
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
G
H
YG
H Y
If G is an electron donating group, these structures are
especially stable.
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
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
H
Y
G
H Y
If G is an electron withdrawing group, these structures
are especially unstable.
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
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.
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
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
incr
easi
ng r
eact
ivit
y ortho/para directors
meta directors
