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Friedel-Crafts acylation

The Friedel-Crafts acylation is a type of electrophilic aromatic substitution reaction that involves the reaction of an arene with acyl chlorides or anhydrides using a Lewis acid catalyst, such as AlCl3. The reaction proceeds via the formation of a complex between the Lewis acid and the chlorine atom of the acid chloride, leading to the formation of an acylium ion. This acylium ion, which has a positive charge on the carbon and is resonance stabilized, acts as an electrophile and reacts with the arene to yield the monoacylated product[1].

Mechanism

The mechanism of the Friedel-Crafts acylation involves several steps[1][10]:

  1. The acyl halide reacts with the Lewis acid to form a complex.
  2. Loss of the halide to the Lewis acid forms an acylium ion.
  3. The acylium ion acts as an electrophile, reacting with the arene to form a carbocation.
  4. Deprotonation of the carbocation regenerates the aromatic system and the Lewis acid.

Reaction Conditions

The reaction conditions for the Friedel-Crafts acylation are similar to those for Friedel-Crafts alkylation. The reaction typically involves the use of a Lewis acid catalyst such as AlCl3, and the reaction is often carried out at elevated temperatures. In some cases, when the benzene ring is activated, Friedel-Crafts acylation can also be carried out with catalytic amounts of a milder Lewis acid (e.g., Zn(II) salts) or a Brønsted acid catalyst using the anhydride or even the carboxylic acid itself as the acylating agent[2][3][12].

Applications

The Friedel-Crafts acylation reaction is a powerful synthetic tool and has been extensively used in the synthesis of various organic compounds. It is particularly useful in the total synthesis of natural products and complex molecules exhibiting diverse biological properties. The reaction is also used in the industrial production of various chemical feedstocks and synthetic intermediates[3][5][9].

Citations:

[1] https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/organic-reaction-toolbox/friedel-crafts-acylation

[2] https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Arenes/Reactivity_of_Arenes/Friedel-Crafts_Acylation/Friedel-Crafts_Reactions

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091380/

[4] https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Arenes/Reactivity_of_Arenes/Friedel-Crafts_Acylation

[5] https://pubs.rsc.org/en/content/articlelanding/2018/ra/c8ra07325b

[6] https://www.masterorganicchemistry.com/2018/05/17/friedel-crafts-alkylation-acylation/

[7] https://pubs.acs.org/doi/10.1021/cr50002a001

[8] https://byjus.com/chemistry/friedel-crafts-acylation-alkylation/

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402163/

[10] https://www.chem.ucalgary.ca/courses/353/Carey5th/Ch12/ch12-7.html

[11] https://www.mt.com/us/en/home/applications/L1_AutoChem_Applications/L2_ReactionAnalysis/alkylation-reactions/friedel-crafts-alkylation.html

[12] https://en.wikipedia.org/wiki/Friedel%E2%80%93Crafts_reaction

[13] https://pubs.acs.org/doi/10.1021/ol800513v

[14] https://www.youtube.com/watch?v=yKccrM-Ayr8

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