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EAS-Alkylation

Alkylation (Friedel-Crafts Alkylation)

Friedel-Crafts alkylation is a classic example of an Electrophilic Aromatic Substitution (EAS) reaction where an alkyl group is introduced into an aromatic ring, such as benzene. This reaction is facilitated by a Lewis acid catalyst, such as aluminum chloride (AlCl₃), which activates the alkyl halide, making it a more reactive electrophile. Friedel-Crafts alkylation is widely used in organic synthesis to modify aromatic compounds, providing pathways to a diverse range of complex molecules.

Friedel-Crafts Alkylation of Benzene: A Step-by-Step Mechanism

  1. Formation of the Electrophile: The first step involves the interaction of an alkyl halide (e.g., R−Cl) with a Lewis acid catalyst (e.g., AlCl3). The Lewis acid coordinates to the halide leaving group, increasing the electrophilic character of the carbon atom and facilitating its departure. This results in the formation of a carbocation (R+) or a complex that acts as the electrophile in the subsequent step.


    Here is a real example with isopropyl chloride which generates an isopropyl cation.

  2. Electrophilic Attack and Formation of the Sigma Complex: The carbocation (R+) electrophile attacks the π electrons of the aromatic ring, forming a high-energy carbocation intermediate known as the sigma complex or arenium ion. This intermediate is stabilized by resonance, allowing the positive charge to be delocalized across the ring.

  3. Deprotonation and Restoration of Aromaticity: A base, often the chloride ion (Cl−) from the AlCl4− complex, abstracts a proton (H+) from the carbon adjacent to the newly attached alkyl group. This step restores the aromaticity of the ring by re-establishing the conjugated π\pi electron system, resulting in the formation of the alkylated aromatic compound.

  4. Regeneration of the Catalyst: Finally, the Lewis acid catalyst is regenerated when the AlCl4− releases a Cl− ion and recovers AlCl3, ready to catalyze another reaction.

The Friedel-Crafts alkylation mechanism underscores the importance of the Lewis acid catalyst in enhancing the electrophilicity of the alkyl group, facilitating its attachment to the aromatic ring. This reaction is valuable for constructing carbon-carbon bonds, thereby enabling the synthesis of a wide variety of complex aromatic compounds. However, it's worth noting that Friedel-Crafts alkylation can lead to polysubstitution and rearrangement of the carbocation intermediate, which may complicate the reaction outcome.

 

Limitations

  1. Only alkyl halides undergo Friedel-Crafts alkylation, since only alkyl halides can form stable carbocations.  For a stable cation to form the halide atom must be bonded to an sp3 C atom.  

    For example, the following reaction will not proceed since chlorobenzene can not form the required carbocation.
  2. Be careful of carbocation rearrangements.

    For example if you were to attempt the following Friedel-Crafts a rearrangement would occur.

    The following carbocation rearrangment occurs, yielding a isopropyl radical since it is secondary carbocation (i.e. more stable).


  3. Addition of an alkyl group activates the ring for further alkylation.  Its difficult to achieve mono-alkylation since the mono-alkylated product is more reactive.

    Alkyl groups are considered EDG (Electron Donating Groups) and activate the ring.  In general methyl, ethyl, t-butyl and other alkyl groups will activate the ring.
  4. Some functional groups (eg. NO2, C=O) are not compatible with the AlCl3.