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Friedel-Crafts Alkylation

Friedel-Crafts alkylation is defined as a chemical reaction in which an alkyl halide (e.g. alkyl chloride, alkyl bromide) is added to an aromatic ring (e.g. benzene, toluene) in the presence of a Lewis acid catalyst (e.g. aluminum chloride, ferrous chloride). The history of Friedel-Crafts alkylation goes back to 1877 when it was first synthesized by French scientists Charles Friedel and his American co-worker James Crafts using electrophilic aromatic substitution[1].

Example of Friedel-Crafts alkylation

An example of Friedel-Crafts alkylation is the addition of methyl group to a benzene ring to form toluene.

Friedel-Crafts Alkylation

Mechanism of Friedel-Crafts alkylation

There are few common reagents used in Friedel-Crafts alkylation. Benzene is (C6H6) typically used as the starting aromatic compound because of the presence of unsaturated C=C bond and alkyl chloride is the preferred alkyl halide. Aluminum chloride (AlCl3) is the Lewis acid catalyst.

A typical Friedel-Crafts alkylation reaction involves a 4-step mechanism under anhydrous conditions [3].

Friedel-Crafts Alkylation Mechanism with Example

The above mechanism is an example of intermolecular Friedel-Crafts alkylation. In case of intramolecularFriedel-Crafts alkylation, both the nucleophile (aromatic ring) and the electrophile (alkyl halide) are in the same compound and are attached to one another through a tether [4].

Biphenyl can also be used as the starting reagent for Friedel-crafts alkylation. In this case, the alkyl halide used is tert-butylchloride, which reacts with biphenyl to give 4,4’ di-tert-butylphenyl [2].

Limitations and drawbacks of Friedel-Crafts alkylation

The basic limitations of Friedel-Crafts alkylation are as follows [5]:

  1. Carbocation rearrangement – The rearrangement of the carbocation takes place if the alkyl species added to the ring has more than two carbons.
  2. Compound limitations – The reaction will not proceed for certain deactivated aromatic compounds like nitrobenzene. Besides, aniline (C6H5NH2) as well as NHR, and NR2substituted aromatic compounds do not undergo Friedel-Crafts alkylation as they tend to react with the Lewis acid directly.
  3. Polyalkylation – The addition of more than one alkyl group to the benzene ring is called polyalkylation. The presence of the electron-donating alkyl group makes it easier for the benzene ring to undergo further alkylation.

Friedel-Crafts alkylation vs acylation

The Friedel-Crafts acylation was developed in order to overcome the limitations of Friedel-Crafts alkylation. In this type of reaction, an acyl group is added to the benzene ring to form an aldehyde or ketone. There are certain differences between the Friedel-Crafts alkylation and acylation. Unlike alkylation reaction, the Lewis catalyst in acylation reaction gets consumed and must be added in a stoichiometric amount to compensate for the loss. Moreover, Friedel-Crafts acylation has few advantages over alkylation and provides much better control over the formation of stable products [6].

Applications of Friedel-Crafts alkylation

Friedel-Crafts alkylation reaction forms an important part of the six main electrophilic aromatic substitution reactions; others being chlorination, bromination, nitration, sulfonylation, and acylation. One of the major applications of Friedel-Crafts alkylation is in the total synthesis of natural products and complex molecules, which in turn find their use in various biological activities [7].

References

  1. History of Friedel-Crafts alkylation – libretexts.org
  2. Friedel-Crafts alkylation of biphenyl – berkeley.edu
  3. Mechanism Friedel-Crafts alkylation – com, Chem.ucalgary.ca, Cliffsnotes.com
  4. Intramolecular Friedel-Crafts alkylation – com
  5. Limitations of Friedel-Crafts alkylation – libretexts.org
  6. Friedel-Crafts alkylation vs acylation – com, Masterorganicchemistry.com
  7. Applications of Friedel-Crafts alkylation – Pubs.rsc.org

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