Reactions of Benzene and its Derivatives

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Reactions of Benzene and itsDerivatives
Chapter 22

• Chapter 22

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Reactions of Benzene

• The most characteristic reaction of aromatic
  compounds is substitution at a ring carbon.
• This is Electrophilic Aromatic Substitution (EAS).

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Reactions of Benzene
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22.1 Electrophilic Aromatic Substitution

• Electrophilic aromatic substitution (EAS) a
  reaction in which a hydrogen atom of an aromatic
  ring is replaced by an electrophile.
• To study
• several common types of electrophiles.
• how each is generated.
• the mechanism by which each replaces hydrogen.

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A. Chlorination of Benzene

• Step 1 formation of a chloronium ion.
• Step 2 attack of the chloronium ion on the ring.

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Chlorination

• Step 3 proton transfer regenerates the aromatic
  character of the ring.

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EAS General Mechanism

• A general mechanism
• General question what is the electrophile and
  how is it generated ?

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Bromination of Benzene

• Figure 22.1 Energy diagram for the bromination
  of benzene.

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B. Formation of the Nitronium Ion

• Generation of the nitronium ion, NO2
• Step 1 proton transfer to nitric acid.
• Step 2 loss of H2O gives the nitronium ion, a
  very strong electrophile.

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Nitration of Benzene

• Step 1 attack of the nitronium ion (an
  electrophile) on the aromatic ring (a
  nucleophile).
• Step 2 proton transfer regenerates the aromatic
  ring.

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Reduction of the Nitro Group

• A particular value of nitration is that the nitro
  group can be reduced to a 1 amino group.
• Reduction occurs with other reagents such as an
  active metal (Fe, Sn or Zn) in HCl.

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Sulfonation of Benzene

• Carried out using concentrated sulfuric acid
  containing dissolved sulfur trioxide.
• Concentrated sulfuric acid containing dissolved
  sulfur trioxide is fuming sulfuric acid.
• The sulfonation reaction is reversible whereas
  the halogenation and nitration reactions are not.

Benzene
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C. Friedel-Crafts Alkylation of Benzene

• Friedel-Crafts alkylation forms a new C-C bond
  between an aromatic ring and an alkyl group.

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Friedel-Crafts Alkylation

• Step 1 formation of an alkyl cation as an ion
  pair.
• Step 2 attack of the alkyl cation on the ring.
• Step 3 proton transfer regenerates aromaticity.

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Limitations on Friedel-Crafts Alkylation

• There are three major limitations on
  Friedel-Crafts alkylations.
• 1. carbocation rearrangements are common.

-

H
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Limitations on Friedel-Crafts Alkylation

• 2. F-C alkylation fails on benzene rings bearing
  one or more of these strongly electron-withdrawing
  groups.

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Limitations on Friedel-Crafts Alkylation

• 3. Polyalkylation An alkyl group added to the
  ring activates the ring and further alkylation
  occurs.
• Limitations 1 3 do not apply to Friedel-Crafts
  Acylation reactions.

x


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Friedel-Crafts Acylation of Benzene

• Friedel-Crafts acylation forms a new C-C bond
  between a benzene ring and an acyl group.

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Friedel-Crafts Acylation

• The electrophile is an acylium ion.

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Friedel-Crafts Acylation

• an acylium ion is a resonance hybrid of two major
  contributing structures.
• F-C acylations are free of two major limitation
  of F-C alkylations acylium ions do not
  rearrange nor do they polyacylate.

O

O

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Friedel-Crafts Acylation

• A special value of F-C acylations is preparation
  of unrearranged alkylbenzenes.

Wolff-Kishner reduction, pg 623
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D. Other Aromatic Alkylations

• Carbocations are also generated from alkenes and
  alcohols
• by treatment of an alkene with a protic acid,
  most commonly H2SO4, H3PO4, or HF/BF3,

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Other Aromatic Alkylations

• by treating an alkene with a Lewis acid,
• and by treating an alcohol with H2SO4 or H3PO4.

Benzene
Cyclohexene
Phenylcyclohexane
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Di- and Polysubstitution of Benzene

• Orientation
• certain substituents direct preferentially to
  ortho para positions others to meta positions.
• substituents are classified as either ortho-para
  directing or meta directing toward further
  substitution.
• Rate
• certain substituents cause the rate of a second
  substitution to be greater than that for benzene
  itself others cause the rate to be lower.
• substituents are classified as activating or
  deactivating toward further substitution.

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Di- and Polysubstitution

• -OCH3 is ortho-para directing.
• -CO2H is meta directing.

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Di- and Polysubstitution, Table 22.2
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Di- and Polysubstitution

• From the information in Table 21.1, we can make
  these generalizations
• alkyl, phenyl, and all other substituents in
  which the atom bonded to the ring has an unshared
  pair of electrons are ortho-para directing all
  other substituents are meta directing.
• all ortho-para directing groups except the
  halogens are activating toward further
  substitution the halogens are weakly
  deactivating.

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22.2 A. Di- and Polysubstitution, Table 22.1

• Orientation on nitration of monosubstituted
  benzenes.

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Di- and Polysubstitution

• the sequence of reactions is important.

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B. Theory of Directing Effects

• The rate of EAS is limited by the slowest step in
  the reaction.
• For almost every EAS, the rate-determining step
  is attack of E on the aromatic ring to give a
  resonance-stabilized cation intermediate.
• The more stable this cation intermediate, the
  faster the rate-determining step and the faster
  the overall reaction.

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Theory of Directing Effects

• For ortho-para directors, ortho-para attack forms
  a more stable cation than meta attack.
• ortho-para products are formed faster than meta
  products.
• For meta directors, meta attack forms a more
  stable cation than ortho-para attack
• meta products are formed faster than ortho-para
  products.

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Theory of Directing Effects

• -OCH3 events during an unfavored meta attack.

Only three resonance structures and the cation
never appears on oxygen.
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Theory of Directing Effects

• -OCH3 events during a favored ortho-para
  attack.

Four resonance structures here and the cation
does appear on oxygen.
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Theory of Directing Effects

• -CO2H events during a favored meta attack.

The cation never appears adjacent to the ()
carbon of CO.
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Theory of Directing Effects

• -CO2H events during an unfavored ortho-para
  attack.

The cation appears adjacent to a () carbon of
CO.
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C. Activating-Deactivating Effects

• Any resonance effect, such as that of -NH2, -OH,
  and -OR, that delocalizes the positive charge on
  the cation intermediate lowers the activation
  energy for its formation, and has an activating
  effect toward further EAS.
• Any resonance or inductive effect, such as that
  of -NO2, -CN, -CO, and -SO3H, that decreases
  electron density on the ring deactivates the ring
  toward further EAS.

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Activating-Deactivating

• Any inductive effect, such as that of -CH3 or
  other alkyl group, that releases electron density
  toward the ring activates the ring toward further
  EAS.
• Any inductive effect, such as that of halogen,
  -NR3, -CCl3, or -CF3, that decreases electron
  density on the ring deactivates the ring toward
  further EAS.

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Activating-Deactivating

• for the halogens, the inductive and resonance
  effects run counter to each other, but the former
  is somewhat stronger with respect to
  deactivation.
• the net effect is that halogens are deactivating
  but ortho-para directing.

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Relative rates of EAS

• Relative rates of reaction for substituted
  benzenes compared to unsubstituted benzene.
• rel. rate
• Aniline 106 strongly activating NH2
• Toluene 25 weakly activating CH3
• Benzene 1 neutral
• Chlorobenzene 0.03 weakly deactivating Cl
• Nitrobenzene 10-6 strongly deactivating NO2

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22.3 Nucleophilic Aromatic Substitution

• Aryl halides do not undergo nucleophilic aromatic
  substitution (NAS) by either SN1 or SN2.
• They do undergo nucleophilic substitutions, but
  by mechanisms quite different from those of
  nucleophilic aliphatic substitution.
• There are two common mechanisms
• The benzyne mechanism.
• The addition-elimination mechanism.
• Nucleophilic aromatic substitutions are far less
  common than electrophilic aromatic substitutions.

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A. Benzyne Intermediates

• When heated under pressure with aqueous NaOH,
  chlorobenzene is converted to sodium phenoxide.
• neutralization with HCl gives phenol.

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Benzyne Intermediates

• the same reaction with 2-chlorotoluene gives a
  mixture of ortho- and meta-cresol.
• the same type of reaction can be brought about
  using of sodium amide in liquid ammonia.

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Benzyne Intermediates

• ?-elimination of HX gives a benzyne intermediate,
  that then adds the nucleophile to give products.

Benzyne is unstable due to poor orbital
overlap, brackets mean that this is a transient
intermediate.
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B. Addition-Elimination

• when an aryl halide contains electron-withdrawing
  NO2 groups ortho and/or para to X, nucleophilic
  aromatic substitution takes place more readily.
• neutralization with HCl gives the phenol.

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Meisenheimer Complex

• reaction involves a Meisenheimer complex
  intermediate.

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Reaction of Benzene and its Derivatives
End Chapter 22