Electrophilic aromatic substitution

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Electrophilic aromatic substitution
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Substitution?
The characteristic reactions of benzene involve
substitution in which the resonance stabilized
ring system is maintained
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Reactivity
- an electron source, benzene reacts with
electron deficient reagents - electrophilic
reagents.
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Electrophilic aromatic substitution
1. Nitration
ArNO2 H2O
ArH HNO3/H2SO4
2. Sulfonation
ArSO3H H2O
ArH H2SO4/SO3
3. Halogenation
ArX HX
ArH X2/FeX3
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Friedel - Crafts reactions
4. Friedel - Crafts alkylation
ArR HCl
ArH RCl/AlCl3
5. Friedel - Crafts acylation
ArH RCOCl/AlCl3
ArCOR HCl
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Substituent effects
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Toluene is more reactive than benzene.....
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Reactivity
How is reactivity determined in the lab?

• Compare the time required for reactions to
  occur under identical conditions.
• Compare the severity of reaction conditions.
• Make a quantitative comparison under identical
  reaction conditions.

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Substituent effects
In some way, the methyl group makes the ring more
reactive than that of the unsubstituted benzene
molecule.
It also directs the attacking reagent to the
ortho and para positions on the ring.
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Substituent effects
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Nitrobenzene undergoes substitution at a slower
rate than does benzene. It yields mainly the
meta isomer.
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Substituent effects
A group which makes the ring more reactive than
that of benzene is called an activating group.
A group which makes the ring less reactive than
benzene is called a deactivating group.
A group which leads to the predominant formation
of ortho and para isomers is called an ortho -
para directing group.
A group which leads to the predominant formation
of the meta isomer is called a meta directing
group.
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Activating, o,p directors
All activating groups are o,p directors.
strongly activating
-OH -NH2 -NHR -NR2 moderately activating -OR -NHCO
R weakly activating -aryl -alkyl
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Deactivating, m directors
All m directors are deactivating.
-NO2 -SO3H -CO2H -CO2R -CONH2 -CHO -COR -C
N


-NH3 -NR3
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Deactivating, o, p directors
-F, -Cl, -Br, -I
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Orientation in disubstituted benzenes
Here the two directing effects are additive.
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Orientation in disubstituted benzenes
When two substituants exert opposing directional
effects, it is not always easy to predict the
products which will form. However, certain
generalizations can be made....
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Orientation in disubstituted benzenes

• Strongly activating groups exercise a far
  greater influence than weakly activating and all
  deactivating groups.

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Orientation in disubstituted benzenes

• If there is not a great difference between the
  directive power of the two groups, a mixture
  results

58 42
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Orientation in disubstituted benzenes

• Usually no substitution occurs between two meta
  substituents due to steric hindrance

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......nitration
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Synthesis of m-bromonitrobenzene
In order to plan a synthesis, we must consider
the order in which the substituents are
introduced.......
If, however, we brominate and then nitrate, the o
and p isomers will be formed.
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Orientation and synthesis
If a synthesis involves the conversion of a
substituants into another, we must decide exactly
when to do the conversion.
Lets look at converting a methyl group into a
carboxylic acid
Now lets see how we can make the three
nitrobenzoic acids
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The nitrobenzoic acids
m-nitrobenzoic acid
bp 225oC bp 238oC
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The nitrobenzoic acids
o-nitrobenzoic acid
p-nitrobenzoic acid
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Nitration
H3O 2HSO4- NO2
HONO2 2H2SO4
nitronium ion - a Lewis acid
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The structure of the intermediate carbocation
The positive charge is not localized on any one
carbon atom. It is delocalized over the ring but
is particularly strong on the carbons ortho and
para to the nitro bearing carbon.
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Sulfonation
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Halogenation
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Friedel - Crafts alkylation
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An electrophilic carbocation?
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An electrophilic carbocation?
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An electrophilic carbocation?
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An electrophilic carbocation?
When RX is primary, a simple carbocation does not
form. The electrophile is a complex
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Limitations

• Aromatic rings less reactive than the
  halobenzenes do not undergo Friedel - Crafts
  reactions.

• A polysubstitution is possible - the reaction
  introduces an activating group!
• Aromatic compounds bearing -NH2, -NHR or -NR2
  do not undergo Friedel - Crafts substitution.
  Why?

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Friedel - Crafts acylation - the reaction
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Friedel - Crafts acylation
acylium ion
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Limitations
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The mechanism
slow, rate determining step
fast
Evidence - there is no significant deuterium
isotope effect.
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Isotope effects
A difference in rate due to a difference in the
isotope present in the reaction system is called
an isotope effect.
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Isotope effects
If an atom is less strongly bonded in the
transition state than in the starting material,
the reaction involving the heavier isotope will
proceed more slowly.
The isotopes of hydrogen have the greatest mass
differences. Deuterium has twice and tritium
three times the mass of protium. Therefore
deuterium and tritium isotope effects are the
largest and easiest to determine.
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Primary isotope effects
These effects are due to breaking the bond to the
isotope.
Thus the reaction with protium is 5 to 8 times
faster than the reaction with deuterium.
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Evidence for the E2 mechanism - a large isotope
effect
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The mechanism
slow, rate determining step
fast
Evidence - there is no significant deuterium
isotope effect.
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The reactivity of aromatic rings
The transition state for the rate determining
step
Factors which stabilize carbocations by dispersal
of the positive charge will stabilize the
transition state which resembles a carbocation
it is a nascent carbocation.
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Carbocation stability
electron donation stabilizes the carbocation
electron withdrawal destabilizes the carbocation
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Orientation
An activating group activates all positions on
the ring but directs the attacking reagent to the
ortho and para positions because it makes these
positions more reactive than the meta position.
A deactivating group deactivates all positions on
the ring but deactivates the ortho and para
positions more than the meta position. Why?
Examine the transition state for the rate
determining step for ortho, meta and para attack.
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CH3 - an o/p director
ortho attack
3
meta attack
para attack
3
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NO2 - a m director
ortho
meta
para
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NO2 - a m director
para
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NH2 - an o/p director??
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Halogen - a deactivating group
Deactivation results from electron withdrawal
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Halogen - an o/p directing group
o/p directors are electron donating. How can a
halogen substituent donate electrons?
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Halogen - an o/p directing group
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