Friedel-Crafts Alkylation

• General Characteristics

-Lewis acid-catalyzed electrophilic alkylation of aromatic rings (S_EAr reaction) is called the Friedel-Crafts alkylation.

-The shortcoming of this reaction is the byproduct formation due to overalkylation and alkyl rearrangement. Primary alkyl halides are particularly prone to undergoing the Wagnar-Meerwein rearrangement because of their inability to form stable cations. For these reasons, the F-C alkylation is better suited for intramolecular reactions than for intermolecular reactions. The F-C acylation is synthetically more useful for intermolecular applications.

• General References

・Friedel, C.; Crafts, J. M. J. Chem. Soc. 1877, 32, 725.
・Friedel, C.; Crafts, J. M. Bull. Soc. Chim. France 1877, 27, 530.
・Calloway, N. O. Chem. Rev. 1935, 17, 327. DOI: 10.1021/cr60058a002
・Price, C. C. Org. React. 1946, 1.
・Olah, G. A. Comprehensive Organic Synthesis 1991, 3, 293.

• Reaction Mechanism

The alkylation proceeds by electrophilic aromatic substitution (S_EAr) pathway, in which more electron-rich aromatic rings react faster. The alkylated products are generally more reactive than the starting materials since the alkyl groups increase their electron density. Overalkylation therefore becomes the main side reaction. For primary alkyl halides that cannot form a stable carbocationic intermediate, the Wagnar-Meerwein rearrangement and β-elimination may compete, giving rise to more byproducts.

• Examples

• Experimental Procedure

• Experimental Tips

• References

[1] Patil, M. L.; Borate, H. B.; De Clercq, E.; Pannecouque, C.; Witvrouw, M.; Stup, T. L.; Turpin, J. A.; Buckheit, R. W., Jr.; Cushman, M. Tetrahedron Lett. 1999, 40, 4437. doi:10.1016/S0040-4039(99)00766-2

• Related Books

 

aromatic alkylation, electrophilic aromatic substitution, lewis acid