18.11:
Limitations of Friedel–Crafts Reactions
Friedel–Crafts reactions suffer from several limitations.
Firstly, Friedel–Crafts alkylations work only with alkyl halides where the halide is attached to an sp3 hybridized carbon. Vinylic and aryl halides cannot be used because they form unstable carbocations under the reaction conditions.
Secondly, Friedel–Crafts alkylations are prone to carbocation rearrangement to form a more stable carbocation. Therefore, the major products have a rearranged carbon skeleton.
No carbocation rearrangements occur for Friedel–Crafts acylations because the acylium ion is resonance-stabilized.
Thirdly, Friedel–Crafts alkylations often undergo polyalkylations, where the electron-donating alkyl group activates the ring towards further alkylation.
Conversely, Friedel–Crafts acylations favor monoacylation. The acyl group, an electron-withdrawing group, deactivates the ring for further substitutions.
Lastly, both the reactions fail on aromatic rings bearing either a strongly electron-withdrawing group or a basic amino group that can be protonated.
Such substituents make the ring electron-deficient, thereby decreasing the ring's reactivity towards further electrophilic substitution.
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.