18.11 : Limitations of Friedel–Crafts Reactions

Several restrictions limit the use of Friedel–Crafts reactions. First, the halogen in the alkyl halide must be attached to an sp³-hybridized carbon for the Friedel–Crafts reactions to occur. Vinyl or aryl halides do not react since the carbocations formed are unstable under the reaction conditions. Second, Friedel–Crafts alkylation is susceptible to carbocation rearrangement, and the major products obtained have a rearranged carbon skeleton. In contrast, the acylium ion is stabilized by resonance, so no carbocation rearrangement occurs in Friedel–Crafts acylation. Third, polyalkylation frequently occurs with the Friedel–Crafts alkylation reactions. An alkyl group is an activator, and when added to the benzene ring, it activates the ring towards further alkylation. Contrastingly, polyacylation does not occur in Friedel–Crafts acylation. The acyl group is a deactivator toward electrophilic substitution and does not promote further acylation of the benzene ring. Forth, both Friedel–Crafts alkylation and acylation reactions fail on benzene rings bearing either powerful electron-withdrawing groups or a basic amino group that can be protonated. Such substituents make the ring less reactive by making it electron-deficient, which deactivates it towards further electrophilic substitution.