Chapter 22 - Reactions of Benzene and Its Derivatives

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• %%Aromatic rings, such as benzene, react with highly strong, generally positively charged electrophiles, resulting in ring hydrogen substitution.%%

  • The general mechanism includes weakly nucleophilic aromatic p electrons attacking the electrophile to generate a resonance-stabilized cation intermediate on the ring that loses a proton to give a substituted arene.
  • An arenium ion is a resonance-stabilized cation intermediate.

• Aromatic rings react with Cl2 in the presence of the Lewis acid catalyst FeCl3 to produce chloroarenes in a halogenation process.

  • Bromoarenes are formed when they react with Br2 in the presence of the Lewis acid catalyst FeBr3.
  • Aromatic rings react with SO3 in the presence of sulfuric acid to produce arylsulfonic acids in a sulfonation process.

• There is no electrophilic aromatic substitution process in which the amino group is introduced directly into the aromatic ring.

  • Aromatic rings react with haloalkanes in the presence of a Lewis acid, such as AlCl3, to form alkylbenzenes in a Friedel-Crafts alkylation. Overalkylation and rearrangements might be an issue.
  • Aromatic rings react with acid chlorides in the presence of a Lewis acid, such as AlCl3, to generate acylbenzenes in a Friedel-Crafts acylation.
  • The acylbenzene products of Friedel-Crafts acylation reactions can be reduced to the corresponding alkylbenzene via Clemmensen or Wolff-Kishner reductions, providing a convenient method of producing alkylbenzenes that cannot be produced in high yield via Friedel-Crafts alkylation due to rearrangement or over-alkylation issues.

• Other electrophilic aromatic substitution processes include extremely strong electrophiles interacting with weakly nucleophilic aromatic p electrons to generate an intermediate resonance-stabilized cation on the ring, which loses a proton to yield the substituted arene.

  • Using an alkene in the presence of a strong acid to form a carbocation that yields an alkylbenzene is one example of a reaction.

  

• A halonium ion is produced as an ion pair by the interaction of chlorine or bromine with a Lewis acid. An initial reaction between Cl2 and FeCl3 produces a molecular complex that can rearrange to form a Cl1, FeCl4 2 ion pair.

  • As a very strong electrophile, the Cl1 combines with the weakly nucleophilic aromatic p cloud to generate a resonance-stabilized cation intermediate that loses a proton to yield the chloroarene product.

• The nitronium ion, NO2 1, produced by the reaction of nitric acid with sulfuric acid, is the electrophile.

  • The method includes protonation of nitric acid by sulfuric acid, followed by water loss to produce the nitronium ion NO2 1.
  • As a very strong electrophile, the nitronium ion combines with the weakly nucleophilic aromatic p cloud to generate a resonance-stabilized cation intermediate that loses a proton to yield the end product.
    • Electrophile: refers to a carbocation that forms as an ion pair when a haloalkane interacts with a Lewis acid. It is usual to see rearrangements from a less stable carbocation to a more stable carbonation.
    • An initial reaction between the haloalkane and the Lewis acid AlCl3 produces an intermediate that may be thought of as a carbocation/AlCl4 2 ion pair.
    • %%The ion pair's carbocation combines as a very strong electrophile with the weakly nucleophilic aromatic p cloud to generate a resonance-stabilized cation intermediate, which loses a proton to yield the final product.%%

• Rearrangements can be an issue since carbocations are involved in the action, especially with primary or secondary haloalkanes or any other haloalkane that would form a carbocation prone to rearrangement.

  • An acyl cation (an acylium ion) is generated as an ion pair by the interaction of an acyl halide with a Lewis acid.

• An initial reaction between the acid chloride and the Lewis acid AlCl3 produces an intermediate that may be thought of as a resonance-stabilized acylium ion/AlCl4 2 ion pair.

• The acylium ion in the ion pair combines as a very strong electrophile with the weakly nucleophilic aromatic p cloud to generate a resonance-stabilized cation intermediate, which loses a proton to yield the final product.

• There are no rearrangements because acylium ions do not rearrange like carbocations. When one or more highly electron-withdrawing groups are present on the ring, the reaction fails. It is simple to halt the response after it has begun.

  • Other than hydrogen substituted groups on an aromatic ring impact the reaction rate and substitution pattern in electrophilic aromatic substitution processes.
  • @@Substituents, in particular, can drive new groups meta or ortho-para, speeding up (activating) or slowing down (deactivating) the reaction.@@

• Substituents are classified into three types:

  • Alkyl groups and all groups in which the atom linked to the ring contains an unshared pair of electrons are ortho-para directing, and the majority are electron releasing; hence, they are activating toward electrophilic aromatic substitution as compared to benzene.
  • Halogens are an anomaly in that they are ortho-para directing but electron withdrawing, hence they are mildly deactivating toward electrophilic aromatic substitution when compared to benzene.
  • All groups on the atom have a partial positive charge.

• Orientation and activating/deactivating effects are important in practice since the sequence of addition of the substituents must be considered while manufacturing polysubstituted aromatics.

• When making m-bromonitrobenzene from benzene, for example, the nitro group (meta directing) must be added before the bromine atom (ortho-para directing).

• When o-bromonitrobenzene and p-bromonitrobenzene are synthesized from benzene, the bromine (ortho-para directing) must come first, followed by the nitro group (meta directing).

  • Substituent directing and activation/deactivation effects are caused by two types of interactions on the cation intermediate:
  • An inductive effect in which the substituent withdraws more electron density from (deactivates) or releases more electron density into (activates) the positively charged intermediate (relative to H atoms).

• Although electrophilic aromatic substitution is by far the most prevalent mechanism for aromatic ring reactions, aromatic rings can also react with nucleophiles in rare cases.

  • At high temperatures (300°C to 500°C), haloarenes react with extremely strong bases (NaNH2) or moderate bases (NaOH) to produce products in which the halogen is replaced.
  • As a result of the benzyne intermediates, the base/nucleophile group ends up on the ring carbon atom that was originally linked to the halogen, as well as locations neighboring (ortho) to it.

• Haloarenes that have ortho and/or para highly electron withdrawing groups react with strong nucleophiles such as hydrazine to generate regioselective substitution.

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