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.