Friedel-Crafts Acylation

• General Characteristics

-The acylation of aromatic rings using acyl halides or acid anhydrides mediated by Lewis acids is called the Friedel-Crafts acylation. Arenes substituted with electron donating groups are more reactive than those substituted with electron withdrawing groups.

-While the Friedel-Crafts alkylation tends to suffer from problems such as overalkylation and rearrangement except for certain intramolecular cases, the F-C acylation is easier to be used intermolecularly since the electron-withdrawing property of the first acyl group slows down the second and further acylations.

• General References

・Friedel, C.; Crafts, J. M. Compt. Rend. 1877, 84, 1450.
・Crafts, J. M.; Ador, E. Ber. 1877, 10, 2173.
・Crafts, J. M.; Ador, E. Bull. Soc. Chim. France 1880, 531.
・Price, C.C. Org. React. 1946, 3, 1.
・Gore, P. Chem. Rev. 1955, 55, 229. DOI: 10.1021/cr50002a001
・Groves, J. K. Chem. Soc. Rev. 1972, 1, 73. DOI: 10.1039/CS9720100073
・Eyley, S. C. Comprehensive Organic Synthesis 1991, 2, 707.
・Heaney, H. Comprehensive Organic Synthesis 1991, 2, 733.

• Reaction Mechanism

The reaction is an example of electrophilic aromatic substitution (S_EAr). The highly electrophilic acylium ion formed from an acid halide and AlCl₃ is considered to be the reactive species.

• Examples

The Friedel-Crafts alkylation is inherently associated with the problem of overalkylation. To circumvent it, the F-C acylation is occasionally used in combination with subsequent deoxygenation (e.g. Clemmensen reduction).^[1]

The synthesis of phenolphthalein.

• Experimental Procedure

• Experimental Tips

To quench the reaction, add the reaction mixture slowly into ice/water. The reverse (the addition of water to the reaction) would be dangerously exothermic.

• References

[1] Lee, C. C.; Zohdi, H. F.; Sallam, M. M. M. J. Org. Chem. 1985, 50, 705. DOI: 10.1021/jo00205a034

[2] Patil, M. L. et al. Tetrahedron 2002, 58, 6615.

• Related Books

[amazonjs asin=”3527310746″ locale=”US” title=”Handbook of C-H Transformations”]

 

aromatic acylation, electrophilic aromatic substitution, lewis acid, synthesis of ketones