CN
Friedel–Crafts Acylation
Reaction
The Friedel–Crafts acylation is the reaction of an arene with acyl chlorides or anhydrides using a strong Lewis acid catalyst. This reaction proceeds via electrophilic aromatic substitution to form monoacylated products.1,2
Figure 1.Friedel–Crafts acylation reaction shown as molecular structures
Friedel–Crafts Acylation Mechanism
The Friedel–Crafts Acylation reaction involves formation of a complex between the Lewis acid and the chlorine atom of the acid chloride. An acylium ion is formed by the cleavage of C-Cl bond of the complex. The acylium ion has a positive charge on the carbon and is resonance stabilized. This acylium ion acts as an electrophile and reacts with the arene to yield the monoacylated product (aryl ketone).1
Figure 2.Friedel-Crafts acylation mechanism with an AlCl3 catalyst shown as molecular structures
The Friedel–Crafts acylation reaction is named after Charles Friedel and James Mason Crafts who developed the reaction in 1877 to attach substituents to an aromatic ring.3
Precautions
Please consult the Safety Data Sheet for information regarding hazards and safe handling practices.
Applications
The Friedel–Crafts acylation reaction is useful for the synthesis of:
- Diarylacetic acid derivatives4
- Poly(oxy-1,3-phenylenecarbonyl-1,4-phenylene) or mPEK5
- 1,5-Bis(4-fluorobenzoyl)-2,6-dimethylnaphthalene6
- Aromatic ketones7
- Dissymmetric aromatic amines8
- Cyclic ketones such as 1-indanone and 1-tetralone9
- 2-Acetyl-6-methoxynaphthalene, an intermediate for the synthesis of naproxen10
Research and Trends
- Poly(4-vinylpyridine) supported trifluoromethanesulfonic acid has been employed as efficient and an easy-to-handle, solid, superacid catalyst system in Friedel–Crafts reactions. One pot solvent-free synthesis of various diarylacetic acid derivatives was achieved by Friedel–Crafts hydroxyalkylation reaction of glyoxylic acid with arenes under mild conditions.4
Scheme of the above synthesis:
Figure 3.One pot solvent-free synthesis of diarylacetic acid derivatives by Friedel–Crafts hydroxyalkylation reaction of glyoxylic acid
- An imidazolium-based ionic liquid catalyzed the Friedel–Crafts acylation of aromatic compounds with acetyl chloride.11
- Erbium trifluoromethanesulfonate is reported to be a good catalyst for the microwave-assisted Friedel–Crafts acylation of arenes containing electron-donating substituents.12
- The intramolecular Friedel–Crafts acylation is used in the direct and short construction of the ACDE ring system of daphenylline, a novel daphniphyllum alkaloid.13
- The acid-promoted domino Friedel–Crafts acylation reaction has been developed for building the core 6,5,6-ABC tricyclic skeleton of taiwaniaquinoids. It is also used in the syntheses of diterpenoids (±)-taiwaniaquinol B and (±)-dichroanone.14
- Novel poly(aryl ether ketone)s and poly(aryl ether ketone sulfone)s containing 1,4-naphthylene units have been synthesized by electrophilic Friedel–Crafts acylation polycondensation reactions.15
- The Friedel–Crafts acylation of toluene with acetic anhydride over triphenyltin grafted on SBA-15 mesoporous silica has been reported.16
- Indium triflate in the ionic liquid, 1-isobutyl-3-methylimidazolium dihydrogen phosphate ([i-BMIM]H2PO4), forms an efficient green catalyst system for the Friedel–Crafts acylation of aromatic compounds with acid anhydrides.17
- Friedel–Crafts acylation of 25,27-dialkoxycalix[4]arenes using acyl chlorides and AlCl3 in 1,2-dichloroethane have been reported.18
1.
Fox MA, Whitesell JK. 1994. Organic Chemistry. Boston: Jones and Bartlett.
2.
Li JJ. 2009. Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications. Springer.
3.
Sartori G, Maggi R. Advances in Friedel-Crafts Acylation Reactions. https://doi.org/10.1201/9781420067934
4.
Prakash GS, Paknia F, Kulkarni A, Narayanan A, Wang F, Rasul G, Mathew T, Olah GA. 2015. Taming of superacids: PVP-triflic acid as an effective solid triflic acid equivalent for Friedel?Crafts hydroxyalkylation and acylation. Journal of Fluorine Chemistry. 171102-112. https://doi.org/10.1016/j.jfluchem.2014.08.020
5.
Baek J, Lyons CB, Tan L. 2004. Grafting of Vapor-Grown Carbon Nanofibers via in-Situ Polycondensation of 3-Phenoxybenzoic Acid in Poly(phosphoric acid). Macromolecules. 37(22):8278-8285. https://doi.org/10.1021/ma048964o
6.
Ohno M, Takata T, Endo T. 1995. Synthesis of a novel naphthalene-based poly(arylene ether-ketone) by polycondensation of 1,5-bis(4-fluorobenzoyl)-2,6-dimethylnaphthalene with bisphenol a. J. Polym. Sci. A Polym. Chem.. 33(15):2647-2655. https://doi.org/10.1002/pola.1995.080331511
7.
de Noronha RG, Fernandes AC, Romão CC. 2009. MoO2Cl2 as a novel catalyst for Friedel?Crafts acylation and sulfonylation. Tetrahedron Letters. 50(13):1407-1410. https://doi.org/10.1016/j.tetlet.2009.01.039
8.
Nordlander JE, Payne MJ, Njoroge FG, Balk MA, Laikos GD, Vishwanath VM. 1984. Friedel-Crafts acylation with N-(trifluoroacetyl)-.alpha.-amino acid chlorides. Application to the preparation of .beta.-arylalkylamines and 3-substituted 1,2,3,4-tetrahydroisoquinolines. J. Org. Chem.. 49(22):4107-4111. https://doi.org/10.1021/jo00196a001
9.
Tran PH, Huynh VH, Hansen PE, Chau DN, Le TN. 2015. An Efficient and Green Synthesis of 1-Indanone and 1-Tetralone via Intramolecular Friedel-Crafts Acylation Reaction. Asian Journal of Organic Chemistry. 4(5):482-486. https://doi.org/10.1002/ajoc.201402274
10.
Kobayashi S, Komoto I. 2000. Remarkable Effect of Lithium Salts in Friedel?Crafts Acylation of 2-Methoxynaphthalene Catalyzed by Metal Triflates. Tetrahedron. 56(35):6463-6465. https://doi.org/10.1016/s0040-4020(00)00610-4
11.
Cai M, Wang X. 2014. Activity of Imidazolium-Based Ionic Liquids as Catalysts for Friedel-Crafts Acylation of Aromatic Compounds. Asian J. Chem.. 26(18):5981-5984. https://doi.org/10.14233/ajchem.2014.16354
12.
Tran PH, Hansen PE, Nguyen HT, Le TN. 2015. Erbium trifluoromethanesulfonate catalyzed Friedel?Crafts acylation using aromatic carboxylic acids as acylating agents under monomode-microwave irradiation. Tetrahedron Letters. 56(4):612-618. https://doi.org/10.1016/j.tetlet.2014.12.038
13.
Wang W, Li G, Wang S, Shi Z, Cao X. 2015. Direct and Short Construction of the ACDE Ring System of Daphenylline. Chem. Asian J.. 10(2):377-382. https://doi.org/10.1002/asia.201403152
14.
Tang S, Xu Y, He J, He Y, Zheng J, Pan X, She X. 2008. Application of a Domino Friedel?Crafts Acylation/Alkylation Reaction to the Formal Syntheses of (±)-Taiwaniaquinol B and (±)-Dichroanone. Org. Lett.. 10(9):1855-1858. https://doi.org/10.1021/ol800513v
15.
Wen H, Wang P, Cheng S, Yan T, Cai M. 2015. Synthesis and characterization of novel organosoluble poly(aryl ether ketone)s and poly(aryl ether ketone sulfone)s containing 1,4-naphthylene units. High Performance Polymers. 27(6):705-713. https://doi.org/10.1177/0954008314557707
16.
Deng Q, Qin Z, Yang Y, Song W. 2015. Synthesis, characterization of triphenyltin grafted on SBA-15 mesoporous silica and its catalytic performance for the synthesis of 4-methylacetophenone. Chinese Journal of Chemical Engineering. 23(2):384-388. https://doi.org/10.1016/j.cjche.2013.12.001
17.
Tran PH, Hansen PE, Hoang HM, Chau DN, Le TN. 2015. Indium triflate in 1-isobutyl-3-methylimidazolium dihydrogen phosphate: an efficient and green catalytic system for Friedel?Crafts acylation. Tetrahedron Letters. 56(17):2187-2192. https://doi.org/10.1016/j.tetlet.2015.03.051
18.
Skácel J, Budka J, Eigner V, Lhoták P. 2015. Regioselective Friedel?Crafts acylation of calix[4]arenes. Tetrahedron. 71(13):1959-1965. https://doi.org/10.1016/j.tet.2015.02.021
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