Friedel-Crafts Acylation-百灵威

Adding a keto group to an aromatic or aliphatic substrate using an acyl halide or anhydride in the presence of a Lewis acid catalyst is called the Friedel-Crafts acylation. The reactive electrophile in this aromatic substitution is either an acylium ion or an acyl chloride-Lewis acid complex. ^[1] Benzene and slightly deactivated derivatives tend to go through the acylium ion. ^[2] The aryl ketone can be converted to an alkyl chain via catalytic hydrogenation or the Clemmensen or Wolff-Kishner reduction.

Lab Tips:

Electron donating groups on the ring are often required to obtain the desired ketone in good yields. Aromatic rings with strong electron-withdrawing groups do not undergo acylation. ^[3]
Quinolines and pyridines also do not undergo acylation, but the Minisci reaction can be used to introduce acyl groups directly onto heteroaromatic rings. ^[3]
Order of reactivity: acyl iodides > acyl bromides > acyl chlorides > acyl fluorides. ^[3]
Very reactive acylating agents such as acyloxy triflates or very electron-rich substrates require little or no catalyst. ^[4]
More than one equivalent of the Lewis acid is needed since the acylating agent itself coordinates with one equivalent of the Lewis acid. ^[3]
Acylations never occur more than once as the acylated product deactivates the ring to further attack. ^[3]
Lewis basic functional groups such as amines should be protected as acylations will preferentially take place on these functional groups instead of the aromatic ring. ^[3]

_{1. Jensen, F. R., Goldman, G. (1964). Friedel-Crafts and related reactions, Vol. III, Chapter XXXVI (Olah, G. ed.). New York: Interscience Publishers Inc.
2. Sato, Y., Yato, M., Ohwada, T., Saito, S., Shudo, K. Involvement of dicationic species as the reactive intermediates in Gattermann, Houben-Hoesch, and Friedel-Crafts reactions of nonactivated benzenes. J. Am Chem. Soc. 1995, 117, 3037-3043.
3. Kürti, L., Czakó, B. (2005). Strategic Applications of Named Reactions in Organic Synthesis; Background and Detailed Mechanisms. Burlington, MA: Elsevier Academic Press.
4. Pearson, D. E., Buehler, C. A. Friedel-Crafts acylations with little or no catalyst. Synthesis 1972, 533-542.}

Reagents: Lewis Acid (AlX₃, FeC_l3, Lanthanide Triflates, etc.) or Protic Acid (H₂SO₄, H₃PO₄)
Reactant: Aromatic, Acyl Halide or Anhydride
Product: Aryl Ketone
Type of Reaction: Electrophilic Substitution