Transcript Document
Electrophilic Aromatic Substitution
(Aromatic compounds) Ar-H = aromatic compound
1. Nitration
Ar-H + HNO 3 , H 2 SO 4
2. Sulfonation
Ar-H + H 2 SO 4 , SO 3 Ar-NO 2 + H Ar-SO 3 H + H 2 O 2 O
3. Halogenation
Ar-H + X 2 , Fe Ar-X + HX
4. Friedel-Crafts alkylation
Ar-H + R-X, AlCl 3 Ar-R + HX
Friedel-Crafts alkylation (variations) a) Ar-H + R-X, AlCl 3 Ar-R + HX b) Ar-H + R-OH, H + Ar-R + H 2 O c) Ar-H + Alkene, H + Ar-R
HNO 3 H 2 SO 4 SO 3 H 2 SO 4 Br 2 , Fe CH 3 CH 2 -Br AlCl 3 NO 2 SO 3 H Br CH 2 CH 3
toluene CH CH 3 CH 3 3 HNO H H 2 2 SO SO 3 3 SO 4 4 Br 2 , Fe CH 3 NO 2 + CH 3 NO 2 CH 3 SO 3 H + CH 3 CH 3 Br + SO 3 H CH 3 Br faster than the same reactions with benzene
nitrobenzene NO 2 HNO 3 H 2 SO 4 NO 2 NO 2 NO 2 SO 3 H 2 SO 4 NO 2 SO 3 H NO 2 NO 2 Cl 2 , Fe Cl 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
-CH 3 activates the benzene ring towards EAS directs substitution to the
ortho-
&
para-
positions -NO 2 deactivates the benzene ring towards EAS directs substitution to the
meta
- position
Common substituent groups and their effect on EAS:
-NH 2 , -NHR, -NR 2 -OH -OR -NHCOCH 3 -C 6 H 5 -R -H -X -CHO, -COR -SO 3 H -COOH, -COOR -CN -NR 3 + -NO 2
ortho/para meta
directors directors
OCH CHO HNO 3 , H 2 SO 4 Br 3 Br H 2 2 , Fe SO 4 , SO 3 OCH 3 Br + OCH 3 Br faster than benzene CHO NO 2 slower than benzene Br SO 3 H + Br SO 3 H 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.
CH 3 Br 2 , Fe OH NHCOCH 3 HNO 3 , H 2 SO 4 CH 3 CHO Cl 2 , Fe OCH 3 CH 3 OH Br NHCOCH 3 NO 2 CH 3 CHO OCH 3 + Cl Cl CHO OCH 3
Orientation and synthesis .
Order is important!
synthesis of
m
-bromonitrobenzene from benzene: NO 2 NO 2 HNO 3 H 2 SO 4 Br 2 , Fe Br synthesis of
p
-bromonitrobenzene from benzene: Br Br Br Br 2 , Fe HNO 3 H 2 SO 4 + NO 2 NO 2 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.
synthesis of 1,4-dibromo-2-nitrobenzene from benzene Br 2 , Fe Br Br Br Br Br 2 , Fe Br + HNO 3 H 2 SO 4 Br Br separate pure para isomer from ortho/para mixture NO 2 HNO 3 H 2 SO 4 NO 2 Br 2 , Fe NO 2 Br Br 2 , Fe NO 2 Br + Br Br NO 2 Br cannot assume that these can be separated!
synthesis of benzoic acids by oxidation of –CH 3 CH 3 COOH CH 3 Br AlCl 3 KMnO 4 heat CH 3 Br AlCl 3 CH 3 KMnO 4 heat COOH HNO 3 H 2 SO 4 COOH NO 2 CH 3 Br AlCl 3 CH 3 HNO 3 H 2 SO 4 CH 3 NO 2 + ortho KMnO 4 heat COOH NO 2
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-NO 2 + H 2 SO 4
+
H 2 O-NO 2 + HSO 4 -
+
H 2 O-NO 2
+
H 2 O + NO 2 H 2 SO 4 + H 2 O HSO 4 + H 3 O + HNO 3 + 2 H 2 SO 4 H 3 O + + 2 HSO 4 + NO 2 +
nitration: 1) HONO 2 + 2 H 2 SO 4 H 3 O + + 2 HSO 4 + NO 2 + electrophile 2) + NO 2 + RDS
resonance NO 2 H NO 2 H NO 2 H NO 2 H
Mechanism for nitration:
1) HONO 2 + 2 H 2 SO 4 H 3 O + + 2 HSO 4 + NO 2 + 2) + NO 2 + RDS NO 2 H 3) NO 2 H NO 2 + H +
Mechanism for sulfonation:
1) 2 H 2 SO 4 H 3 O + + HSO 4 + SO 3 2) + SO 3 RDS SO 3 H 3) SO 3 H SO 3 + H + 4) SO 3 + H 3 O + SO 3 H + H 2 O
Mechanism for halogenation
: 1) Cl 2 + FeCl 3 2) Cl-Cl-FeCl + Cl-Cl-FeCl 3 RDS 3 3) Cl H + FeCl 4 Cl H + FeCl 4 Cl + HCl + FeCl 3
Mechanism for Friedel-Crafts alkylation
: 1) R-X + AlX 3 R + AlX 4 2) + R RDS R H 3) R H + AlX 4 R + HX + AlX 3
Mechanism for Friedel-Crafts with an alcohol & acid
1) R-OH + H + ROH 2 + 2) ROH 2 + R + H 2 O RDS 3) + R R H 4) R H R + H +
Mechanism for Friedel-Crafts with alkene & acid:
1) C C + H + R 2) 3) R H + R RDS R H R + H + electrophile in Friedel-Crafts alkylation = carbocation
“Generic” Electrophilic Aromatic Substitution mechanism:
1) + Y + Z RDS Y H + Z 2) Y H + 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
R N R R R N R H N H R H N unshared pair of electrons on the nitrogen
resonance donating groups
(weaker inductive withdrawal) strong
inductive withdrawal
(no unshared pair of electrons on the nitrogen & no resonance possible
H O
resonance donation
(weaker inductive withdrawal) R O O H 3 C C N H
resonance donation
(weaker inductive withdrawal)
resonance donation
(weaker inductive withdrawal)
resonance donation
H 3 C X—
inductive donation
sp3 sp2 ring carbon
inductive withdrawal
O H C O C R O HO C O RO C
resoance withdrawal and inductive withdrawal
N C O O N
resonance and inductive withdrawal resonance and inductive withdrawal
Common substituent groups and their effect on reactivity in EAS: -NH 2 , -NHR, -NR 2 -OH -OR -NHCOCH 3 -C 6 H 5 -R -H -X -CHO, -COR -SO 3 H -COOH, -COOR -CN -NR 3 + -NO 2 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 CH 3
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
CF 3 electron withdrawing = deactivating &
meta
-director PO 3 H electron withdrawing = deactivating &
meta
-director PH 2 electron donating = activating &
ortho-/para-
director
Br 2 , Fe Br +
ortho-
O O NO 2 Br 2 , Fe Br Br 2 , Fe NO 2 + ortho O O Br + ortho
How to draw resonance structures for EAS Y Y H Y H Y H
G Y H G Y H G Y H
ortho-
attack G H Y G H Y G H Y G H Y G H Y
meta-
attack G
para-
attack H Y
G Y H G H Y If G is an electron donating group , these structures are especially stable .
G Y H G Y H G Y H
ortho-
attack G H Y G H Y G H Y G H Y G H Y
meta-
attack G
para-
attack H Y
Electron donating groups stabilize the intermediate carbocations for
ortho-
and
para meta-
. The Eact’s for
ortho-/para-
in EAS more than for are lower and the rates are faster.
Electron donating groups direct ortho-/para- in EAS
G Y H G H Y If G is an electron withdrawing group, these structures are especially unstable .
G Y H G Y H G Y H
ortho-
attack G H Y G H Y G H Y G H Y G H Y
meta-
attack G
para-
attack H Y
Electron withdrawing groups destabilize the intermediate carbocations for
ortho meta-
.
and
para-
The Eact’s for
ortho-/para-
in EAS more than for 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 Y H X Y H X Y H X Y H
ortho-
X H Y X X X H Y X X H Y X H Y H Y H Y H Y halogens are deactivating in EAS but direct ortho and para
meta-
para-
Common substituent groups and their effect on EAS:
-NH 2 , -NHR, -NR 2 -OH -OR -NHCOCH 3 -C 6 H 5 -R -H -X -CHO, -COR -SO 3 H -COOH, -COOR -CN -NR 3 + -NO 2
ortho/para meta
directors directors