One of the most important reactions of arenes is electrophilic aromatic substitution, in which an electrophile reacts with the ring, forming a new bond to a ring carbon with the loss of one hydrogen. In general, these reactions require a Lewis acid catalyst, as shown below for the reaction of bromine with benzene, catalyzed by FeBr₃. The role of the FeBr₃ is to complex the bromine to form a bromonium cation-like species (which is often simply referred to as Br+) which is the actual electrophilic agent.

This electrophile first forms a loose complex with the p-cloud, which rearranges to a cationic sigma-complex, in which the electrophile is directly bonded to a ring carbon. Since the ring is a conjugated system, the cationic charge which forms on the adjacent carbon is delocalized over the ring, with partial positive charge developing on the carbons which are ortho- and para- to the position where the electrophile bonded. Loss of H⁺ from the sigma-complex regenerates the aromatic p-system (with its associated stability), and gives bromobenzene and HBr as the final products.

Chlorination proceeds by a similar mechanism; for iodination, I₂/CuCl₂ is typically utilized to generate the electrophilic I+ cation.

Aryl fluorides cannot be prepared by this direct method, but can be prepared using thallium trifluoroacetate to form an intermediate aryl-thallium compound, which then reacts with fluoride anion to give the desired product.

Arenes can also be nitrated by a similar mechanism using a mixture of nitric and sulfuric acids to generate the electrophile NO₂⁺, which adds to the ring to form a sigma complex, and looses a proton to give the nitro compound.

Fuming sulfuric acid (H₂SO₄ saturated with SO₃) contains an equilibrium concentration of SO₃H⁺, which is a strongly electrophilic agent. The final product of the addition of SO₃H⁺ to the ring is the aryl sulfonic acid.

Perhaps the most notable (and useful) example of electrophilic aromatic substitution is the introduction of alkyl groups using the Friedel-Crafts reaction. In this reaction, a Lewis acid complexes with an alkyl halide to give a species with electrophilic character on the carbon of the alkyl halide. This then reacts by the standard mechanism to give an intermediate sigma-complex, and the alkylated benzene as the final product.

There are several limitations of the Friedel-Crafts alkylation reaction, as shown below. Summarizing, only alkyl halides can be utilized (not aryl- or vinyl halides); the ring must be activated, since the electrophile is generally less reactive than those encountered previously; multiple substitutions are possible, and perhaps most important, since the carbon of the alkyl halide has carbocation character, rearrangements often occur. In general this means that an alkyl halide such as 1-bromopropane is not suitable in this reaction, since it would be prone to rearrange to the more stable isopropyl carbocation.

A derivative of the Friedel-Crafts alkylation is the Friedel-Crafts acylation reaction in which the arene is converted to an aryl ketone. The electrophile in this reaction is an acylium ion-like species which is formed by reaction of an acid halide, or an acid anhydride, with the Lewis acid. Unlike the alkylation reaction, rearrangements do not occur (the acylium cation is a very stable, resonance-stabilized carbocation), although an activated ring is still required.

Orientation Effects in Electrophilic Aromatic Substitution

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When electrophilic aromatic substitution occurs on a ring already bearing one or more substituent, the nature of that substituent will impact both the rate of the reaction and the regiochemistry of the reaction (where on the ring the substitution occurs). In the table shown below, activating substituents will react faster than benzene itself, and deactivating substituents will react more slowly. Further, substituents are grouped into two categories; ortho- or para- directing, and meta-directing.

A substituent is activating if it releases electron density into the ring either inductively, or through resonance (the electrophile is, after all, looking for electrons; the more electron density, the faster the reaction). The orientation effect is seen by considering the family of resonance forms which can be drawn for a substituent such as an alkoxy group; these clearly show enhanced electron density localized ortho- and para- to the point of attachment.

Meta-directing substituents such as the nitro group can be seen to function by removing electron density from the ring ortho- and para- to themselves, leaving only the meta-positions with sufficient electron density to support the electrophilic (electron-seeking) reaction. Thus, meta-directing substituents don't really activate the meta-positions towards substitution, they deactivate everywhere else.

Halogens are somewhat unique in that they deactivate inductively (and are therefore less reactive than benzene), but they direct ortho- and para- since they enhance the electron density at these positions by resonance, as shown below.

When there are multiple substituents on a ring, the effects are generally either cumulative, or the most strongly activating substituent ultimately directs the regiochemistry.