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

 

Mechanism of the reaction:

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

 

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.

Materials

     

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

Recent 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:






  • 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

References

  1. Fox, M.A. and Whitesell J.K. Organic Chemistry, 2004.
  2. Li, J.J. Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications, 2007.
  3. Sartori, G. and Maggi, R. Advances in Friedel-Crafts Acylation Reactions: Catalytic and Green Processes, 2010, 1.
  4. Prakash, G. S.; Paknia, F.; Kulkarni, A.; Narayanan, A.; Wang, F.; Rasul, G.; Mathew, T. and Olah, G. A.  J. Fluorine Chem. 2014, 171, 102.
  5. Baek, J. B.; Lyons, C. B.; Tan, L-S. Macromolecules 2004, 37, 8278.
  6. Ohno, M.; Takata, T.; Endo, T. J. Polym. Sci., Part A: Polym. Chem. 1995, 33, 2647.
  7. de Noronha, R. G.; Fernandesb, A. C.; Romão, C. C. Tetrahedron Lett. 2009, 50, 1407.
  8. Nordlander, J. E.; Payne, M. J.; Njoroge, F. G.; Balk, M. A.; Laikos, G. D.; Vishwanathet, V. M. J. Org. Chem. 1984, 49, 4107.
  9. Tran, P. H.; Huynh, V. H.; Hansen, P. E.; Chau, D. K. N. and Le, T. N. Asian J. Org. Chem. 2015.
  10. Kobayashi, S. and Komoto, I.Tetrahedron, 200056, 6463.
  11. Mingjian, C. and Wang, X. Asian J. Chem. 2014, 26, 5981.
  12. Tran, P. H.; Hansenb, P. E.; Nguyena, H. T.; Le, T. N. Tetrahedron Lett. 2014, 56, 212.
  13. Wang, W.; Li, G-P.; Wang, S-F.; Shi, Z-F.; Cao, X-P. Chem.- Asian J. 2015, 10, 377.
  14. Tang, S.; Xu, Y.; He, J.; He, Y.; Zheng, J.; Pan, X.; Sheet, X. Org. Lett. 2008, 10, 1855.
  15. Wen, H.; Wang, P.; Cheng, S.; Yan, T. Cai M. High Perform. Polym. 2014.
  16. Deng, Q.; Qin, Z.; Yang, Y.; Song, W. Chin. J. Chem. Eng. 2015, 23, 384.
  17. Tran, P. H.; Hansen, P. E.; Hoang, H. M.; Chau, D. K. N. and Le, T. N. Tetrahedron Lett.  2015, 56, 2187.
  18. Skácel, J.; Budka, J.; Eigner, V. and Lhoták, P. Tetrahedron 2015, 71, 1959.

 

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