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Part 1
H E
E (an electrophile)
Generic reaction:
1
Introduction
Fact: Alkenes undergo electrophilic addition
•Addition reaction: Increases the number of groups attached to the substrate at the
expense of a pi bond
Br
Br Br
- + Br- Br+
Br Br
Br
X
Br2
No reaction occurs (NR)
Br
H H H
Br Br
Resonance-stabilized carbocation
3
So What It Up With Benzene?
How else is benzene different from an alkene?
Br Br Br
H H H
Br Br
Br Br FeBr3 Br Br FeBr3
More electrophilic
Electrophile = e deficient
-
than Br2 alone
Therefore take e- away from Br 4
Reaction and Mechanism
Br2
product
FeBr3
Mechanism?
Br Br FeBr3 Br Br FeBr3
Useful reminder
H H H
Br Br Br
Br Br FeBr3
Arenium ion
H
Br
Arenium ion resonance hybrid:
5
Arenium Ion Fate?
Arenium ion = a carbocation, so carbocation fates apply
H H
Br Br
Capture a nucleophile: + FeBr3
Br FeBr3 Br
H Br FeBr3
Br
Be deprotonated; form pi bond: Br
+ HBr + FeBr3
•Weak base adequate
Aromaticity restored
6
Reaction Name and Kinetics
Overall reaction
Br
Br2
FeBr3
+ HBr + FeBr3 Electrophilic aromatic substitution (EAS)
Br
•Carbocation formed
Br Br FeBr3 •Aromaticity lost
Rate-determining step
H Br FeBr3
Br
Br
+ HBr + FeBr3
•Carbocation quenched
•Aromaticity restored
Reaction rate depends on: Nucleophilicity of benzene ring
Arenium ion stability
Strength of electrophile 7
What If Benzene Ring Has Substituent(s)?
Br
Br2
FeBr3
Only one product possible
Benzene
H H Br
Br2
FeBr3
+ +
H H Br
H Br
8
Which Product is Major?
Number of positions (probability) Steric hindrance to electrophilic attack
9
Which Product is Major?
Arenium ion stability
CH3 CH3 CH3 CH3
H H H
Br Br FeBr3
Ortho attack: Br Br Br
More
stable
2o 2o 3o
CH3 CH3 CH3 CH3
Br Br FeBr3
Less
Meta attack: Br Br Br stable
H H H
2o 2o 2o
CH3 CH3 CH3 CH3
More
Para attack:
stable
H Br H Br H Br
Br Br FeBr3
2o 3o 2o
Br
Br
Conclusion: arenium ion stability >>> number of positions > steric effects
Ortho/para directors
Alkyl groups (-CH3, -CH2CH3, etc.)
Pi bonds: alkene, alkyne, aromatic rings
}
Lone pairs (-X:) -OH, -OR Electron donation (resonance)
-NH2, -NHR, -NR2 outweighs
-F, -Cl, -Br, -I electron withdrawing (induction)
Others...
In general... If it stabilizes a carbocation it is an ortho/para director.
12
Substituent Effects: Kinetics
CH3
H H
14
Activating Effects: An Exception
Are all ortho/para directors also activators?
Yes, except F, Cl, Br, and I
Why? Balance of electron-donation versus electron-withdrawal
Does transition state look more like benzene ring or arenium ion?
Net effect: F, Cl, Br, I are ortho/para directors, but deactivators
Example: OCH3
OCH3 OCH3
Br2
•OCH3 is ortho/para director
Br
FeBr3
+
•OCH3 is activator
Reaction faster than benzene + Br2/FeBr3
Br
F
F F
Br2
•F is ortho/para director
Br
+ •F is deactivator
FeBr3
Reaction is slower than benzene + Br2/FeBr3
Br
15
Substituent Effects: the Nitro Group (NO2)
Predict major product:
Nitro group
NO2
NO2 NO2 NO2
Br2 Br
+ +
FeBr3
Br
Br
O O
O O
16
Electrophilic Aromatic Substitution
Part 2
O O
S
Na O
OH
N
N
OCH3
CH3
O S
O Na
O
17
Part 1 Summary
Electrophilic aromatic substitution (EAS): electrophilic attack on aromatic ring leads to hydrogen
atom replacement
CH3
CH3 CH3 CH3
Br2
Example: FeBr3
+ +
Br Br
Br
CH3 CH3
H Br FeBr3
Br
Br
Br2 Br
+ +
FeBr3
Br
Br
O O
O O
19
Substituent Effects: the Nitro Group (NO2)
Arenium ion stability O O
NO2 NO2 NO2 NO
N 2 Bad !
H H H
Br Br FeBr3
Br Br Br
Ortho attack:
2o 2o 2o
Para attack:
H Br H o Br H Br
Br Br FeBr3 2o 2 2o
Meta directors
-NO2
O
-+NH3, -+NH2R, -+NHR2, -+NR3
-C=O (ketone, aldehyde, ester, carboxylic acid, etc.)
-CN O
-CF3 S
O
21
Substituent Effects: Kinetics
NO2
Conclusion: Br2/FeBr3 reacts more slowly with nitrobenzene than with benzene
22
Other Electrophiles: Bromination
Ar-H Ar-Br
--or--
Br Br FeBr3 Br + FeBr4
Br2 Br
Example: +
FeBr3
Br
--or--
Cl Cl AlCl3 Cl + AlCl4
o/p director
EDG CH3 CH3 CH3 more hindered
Cl2 Cl Cl
Example: ** ** AlCl3
+
CH3 CH3
**
CH3
major minor
Br Br + electrophile
Bromination: comes from
CH3 CH3
Cl + Cl
Chlorination: comes from
CH3 CH3
Elec Elec +
General EAS: comes from
25
Other Electrophiles: Nitration
Ar-H Ar-NO2
Electrophile: +NO2 O N O
O O O
O O O
--or--
O O
N OH N OH
O H OH2 HO
o/p director: Br
Br Br
NO2
NO2
meta director
NO2 NO2
Br2
Br
director
G
Elec
Generic EAS reaction:
27
Other Electrophiles: Sulfonation
Ar-H Ar-SO3H (sulfonic acid)
O
Electrophile: +SO3H S OH
O O
O O
--or--
O
S O
meta director
EWG O
O
SO3
Example: H2SO4 O
S
O
OH
Electrophile: R+ (a carbocation)
Cl How?
C(CH3)3
Example: AlCl3
C(CH3)3 Electrophile = +C(CH3)3
29
Other Electrophiles: Friedel-Crafts Acylation
O
Ar H Ar (a ketone)
R
O O
O O O
Origin of electrophile: C C C
R Cl AlCl3 R Cl AlCl3
R
O
OCH3
OCH3 CH3
How? Cl
Example: CH3
CH3 Electrophile =
AlCl3
O
30
Other Electrophiles: Diazo Coupling
Ar N
Ar H
N Ar
Na O N O
Origin of electrophile: Ar NH2
aq. HCl
Ar N N
Example:
NaNO2 N
NH2 N N
aq. HCl N OH
31
EAS Application Example:
Synthesis of Allura Red C
O O
N
Ar-N=N-Ar suggests N
synthesis via diazo
OCH3
coupling
CH3
O S
O Na
O
HO3S
OH
N
Na2CO3 N
Allura Red AC
OCH3
CH3
SO3H
33