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Reactions of Aromatic Compounds (overall)

Friedel-Crafts Alkylation

Friedel-Crafts alkylation, named after Charles Friedel and James M. Crafts, is a method of introducing an alkyl substituent into an aromatic compound through electrophilic aromatic substitution. As an alkyl-containing reagent, an alkyl halide, which already possesses a positively polarized, electrophilic carbon atom, is applied. However, the alkyl halide's electrophilicity is not strong enough to obtain a reasonable reaction rate. Therefore, the presence of a Lewis acid catalyst is required. By interacting with the Lewis acid, the polarization of the alkyl halide's halogen-carbon bond is intensified. In contrast to Friedel-Crafts acylation, in Friedel-Crafts alkylation only catalytic amounts of a Lewis acid must be applied, since the Lewis acid is recovered during the reaction by its release from the reactants. The following, in order of decreasing activity, are examples of Lewis acids that are appropiate for application as a catalyst in Friedel-Crafts alkylation: AlBr3, AlCl3, FeCl3, BF3, TiCl4, ZnCl2 and SnCl2.

Formation of the polarized alkyl halide-Lewis acid complex.
Electrostatic potential surfaces in the formation of the polarized complex from ethyl bromide and aluminium tribromide.

Results of a semiempirical-quantum-mechanical calculation (red means a more negative potential, blue means a more positive potential).

Usually, the electrophile that is attacked by the aromatic π electron system is the alkyl halide-Lewis acid complex.

Attack of the aromatic π electrons on the electrophilic polarized complex.

The transition state's energy and, thus, the Friedel-Crafts alkylation's activation energy decrease accordingly with an increase in the interaction between the aromatic compound's HOMO and the alkyl halide's LUMO. This type of interaction is all the more stronger the smaller the energy difference between the two frontier molecular orbitals is. The energy of the alkyl halide's LUMO is noticeably decreased by complexation with a Lewis acid. As a result, the LUMO then approaches the aromatic compound's HOMO. Consequently, the transition state's energy and, thus, the activation energy also decrease. In the final analysis, the application of a Lewis acid catalyst considerably speeds up the reaction.

HOMO - LUMO energy diagram.

The degree of the alkyl halide's polarization in the alkyl halide-Lewis acid complex depends not only on the Lewis acid but also on the alkyl halide's structure. In an extreme case, a carbenium ion may even be generated if it is particularly stabilized, such as is the case with tertiary carbenium ions (e.g. from tert-butyl bromide).

Attack of the aromatic π electrons on a carbenium ion.

Alternatively, alcohols or alkenes may be applied as sources of alkyl groups in Friedel-Crafts alkylation in place of alkyl halides. They are converted into the corresponding carbenium ions through treatment with a Brönstedt acid.

Conversion of alcohols and alkenes in carbenium ions by protonation.

Friedel-Crafts alkylation does not occur when the aromatic compound is deactivated by a substituent with a -I and/or a -M effect. Amino and alkylamino groups, which are normally activating substituents, are transformed into electron-withdrawing, deactivating substituents through complexation with the Lewis acid. They are therefore inadequate starting products for Friedel-Crafts alkylation.

The practical, preparative use of Friedel-Crafts alkylation is noticeably restricted by several side reactions. Multiple alkylation, for instance, may occur, as the aromatic compound is additionally activated by each alkyl group, due to its +I effect.

Multiple alkylation in Friedel-Crafts alkylation.

Multiple alkylation is not observed if the attack on an additional alkylating electrophile is prevented by strong steric interactions. The portion of multiple-alkylated products may also be minimized by the application of a large excess of the aromatic compound.

A further side reaction may be the alkyl group's isomerization. This is partially obtained when the positive charge of the polarized complex, or carbenium ion, respectively, is more effectively stabilized as a result of rearrangement. Therefore, Friedel-Crafts alkylation usually cannot be utilized for the synthesis of aromatic compounds that contain linear alkyl side chains, as the reaction with linear alkyl halides mainly yields aromatic compounds that have branched (isomeric) alkyl side chains.

Isomerization in Friedel-Crafts alkylation.

Under the Lewis-acidic conditions, isomerizations can also occur when the alkylated aromatic compound has already been formed. Thus, isomerization may not only lead to alkyl chain branchings but also to an alteration of the relative position of the aromatic compound's substituents. For instance, p-xylene is largely converted into the more stable m-xylene when it is heated in the presence of AlCl3 / HCl.

Furthermore, Friedel-Crafts alkylation is reversible. A Lewis acid-catalyzed dealkylation can therefore occur, too. Consequently, a tert-butyl substituent can be removed from an aromatic compound. That is, it is exchanged for hydrogen (a proton) in an aromatic electrophilic ipso attack.

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