Electrophilic Aromatic Substitution Part 1

1
Electrophilic Aromatic SubstitutionPart 1
Optional reading OCATSA email for access
harding_at_chem.ucla.edu
2
Introduction

• Fact Alkenes undergo electrophilic addition
• Addition reaction Increases the number of groups
  attached to the substrate at the expense of a pi
  bond

How is the Br-Br dipole induced?
DEN 0 No bond dipole
Weak CC/Br-Br repulsion Weak Br-Br polarization
Strong Br-Br polarization
3
Addition to Benzene Pi Bonds?
Question Benzene has pi bonds...also adds Br2?
X
No reaction occurs (NR)

• Why NR? What is special about benzene?
• Is benzene a nucleophile? Benzene has pi
  electrons ? Benzene is a nucleophile
• Is Eact too large? Benzene Br2 gives a stable
  intermediate ? Eact probably ok

Resonance-stabilized carbocation
4
So What It Up With Benzene?
How else is benzene different from an alkene?
Aromatic

• Aromaticity - worth 36 kcal mol-1 of
  stabilization
• Loss of aromaticity large increase in Eact
  mechanism step too expensive
• How to solve this problem?
• Make Br2 more electrophilic

FeBr3
More electrophilic than Br2 alone
5
Reaction and Mechanism
Mechanism?
Arenium ion resonance hybrid
6
Arenium Ion Fate?
Arenium ion a carbocation, so carbocation fates
apply
Capture a nucleophile
Aromaticity not restored

• Be deprotonated form pi bond
• Weak base adequate

Aromaticity restored
7
Reaction Name and Kinetics
Overall reaction
Mechanism
Kinetics Which is rds?

• Carbocation formed
• Aromaticity lost
• Rate-determining step

• Carbocation quenched
• Aromaticity restored

Reaction rate depends on Nucleophilicity of
benzene ring Arenium ion stability Strength of
electrophile
8
What If Benzene Ring Has Substituent(s)?
Only one product possible
2-Bromotoluene Ortho-bromotoluene
3-Bromotoluene Meta-bromotoluene
4-Bromotoluene Para-bromotoluene
Toluene
9
Which Product is Major?
Number of positions (probability)
Steric hindrance to electrophilic attack
Ortho attack (between CH3 and H) More hindered
Two ortho positions Two meta positions One para
position
Meta attack (between H and H) Less hindered
Product ratio conclusion 40 ortho, 40 meta,
20 para
Para attack (between H and H) Less hindered
Product ratio conclusion meta, para gt ortho
10
Which Product is Major?
Arenium ion stability
More stable
Ortho attack
3o
2o
2o
Less stable
Meta attack
2o
2o
2o
More stable
Para attack
2o
2o
3o
Product ratio conclusion ortho, para gt meta
11
Which Product is Major?

• Summary
• Number of positions ortho, meta gt para
• Steric effects meta, para gt ortho
• Arenium ion stability ortho, para gt meta

Which factor dominates? Ask Mother Nature...
60
lt1
40
Conclusion arenium ion stability gtgtgt number of
positions gt steric effects
12
Directing Effects

• CH3 is an ortho/para director
• Why? Arenium ion stability
• CH3 stabilizes adjacent carbocation by
  electron-donating inductive effect

Extension Any carbocation stabilizing group
ortho/para director Ortho/para directors Alkyl
groups (-CH3, -CH2CH3, etc.) Pi bonds alkene,
alkyne, aromatic rings Lone pairs (-X) -OH,
-OR -NH2, -NHR, -NR2 -F, -Cl, -Br, -I Others...
In general... If it stabilizes a carbocation it
is an ortho/para director.
13
Substituent Effects Kinetics
or
?
Which reacts faster with Br2/FeBr3

• Rate-determining step electrophile nucleophile
  ? arenium ion
• Electrophile same in both cases

• Nucleophile CH3 is electron-donating group (EDG)
• H is neither EDG or EWG

gt

• Arenium ion CH3 is electron-donating group
• H is neither EDG or EWG

gt
Conclusion Br2/FeBr3 reacts faster with toluene
than with benzene
14
Activating Effects
CH3 is an EAS activator

• Why? Relative to H...
• CH3 enhances benzene ring nucleophilicity
• CH3 increases arenium ion stability
• CH3 is electron-donating group stabilizes
  adjacent carbocation
• Extension Any carbocation-stabilizing group is
  an activator
• EAS Activating Groups
• Alkyl groups (-CH3, -CH2CH3, etc.)
• Pi bonds alkene, alkyne, aromatic rings

• Lone pairs (-X) -OH, -OR
• -NH2, -NHR, -NR2

Better electron donors more powerful activators
15
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 is ortho/para director
• OCH3 is activator
• Reaction faster than benzene Br2/FeBr3

• F is ortho/para director
• F is deactivator
• Reaction is slower than benzene Br2/FeBr3

16
Substituent Effects the Nitro Group (NO2)
Predict major product
Nitro group structure?
17
Electrophilic Aromatic SubstitutionPart 2
18
Part 1 Summary
Electrophilic aromatic substitution (EAS)
electrophilic attack on aromatic ring leads to
hydrogen atom replacement
ortho
meta
para
Mechanism
rds
Substituent effects CH3 is an ortho/para
director and activator
19
Substituent Effects the Nitro Group (NO2)
Predict major product
Nitro group structure?
20
Substituent Effects the Nitro Group (NO2)
Arenium ion stability
Ortho attack
2o
2o
2o
Meta attack
2o
2o
2o
Para attack
2o
2o
2o
Product ratio conclusion meta gt ortho gt para
21
Directing Effects

• NO2 is an meta director
• Why? Arenium ion stability
• NO2 destabilizes adjacent carbocation by
  electron-withdrawing inductive effect
• Extension Any carbocation destabilizing group
  meta director
• Meta directors
• -NO2
• -NH3, -NH2R, -NHR2, -NR3
• -CO (ketone, aldehyde, ester, carboxylic acid,
  etc.)
• -C?N
• -CF3
• -SO3H sulfonic acid
• Others...

In general If it destabilizes a carbocation it
is a meta director.
22
Substituent Effects Kinetics
or
?
Which reacts faster with Br2/FeBr3

• Rate-determining step electrophile nucleophile
  ? arenium ion
• Electrophile same in both cases

• Nucleophile NO2 is electron-withdrawing group
  (EWG)
• H is neither EDG or EWG

lt

• Arenium ion NO2 is electron-withdrawing group
• H is neither EDG or EWG

lt
Conclusion Br2/FeBr3 reacts more slowly with
nitrobenzene than with benzene
23
Other Electrophiles BrominationAr-H ? Ar-Br
Origin of electrophile
--or--

Example
Write out the complete mechanism for yourself
24
Other Electrophiles ChlorinationAr-H ? Ar-Cl
Origin of electrophile
--or--
EDG
Example
major minor
Write out the complete mechanism for yourself
25
What is the Electrophile?
A useful pattern for remembering EAS reactions...
comes from
Bromination
comes from
Chlorination
General EAS
comes from
26
Other Electrophiles NitrationAr-H ? Ar-NO2
Electrophile NO2
Origin of electrophile
--or--

Example
Write out the complete mechanism for yourself
27
Just Who Is In Charge Here?
Nitration of bromobenzene
Bromination of nitrobenzene
Generic EAS reaction
28
Other Electrophiles SulfonationAr-H ? Ar-SO3H
(sulfonic acid)
Electrophile SO3H
Origin of electrophile
--or--
EWG
Example
Write out the complete mechanism for yourself
29
Other Electrophiles Friedel-Crafts
AlkylationAr-H ? Ar-R (R alkyl group)
Electrophile R (a carbocation)
Origin of electrophile
Less stable carbocations
More stable carbocations

• Carbocation rearrangements possible

Example
Electrophile C(CH3)3
Write out the complete mechanism for yourself
30
Other Electrophiles Friedel-Crafts Acylation
Electrophile
Acylium ion
Origin of electrophile
Example
Write out the complete mechanism for yourself
31
Other Electrophiles Diazo Coupling
Electrophile
Diazonium cation
Origin of electrophile

• Mechanism? An OWLS problem

Example
Write out the complete mechanism for yourself
32
EAS Application ExampleSynthesis of Allura Red C

• Allura Red AC (an azo dye)
• Color due to extensive conjugation
• Many dyes are diazo compounds

33
Synthesis of Allura Red C
o/p director
Allura Red AC