The introduction of a keto group into an aromatic or aliphatic substrate by using an acyl halide or anhydride in the presence of a Lewis acid catalyst is called the Friedel crafts acylation. Friedel Crafts Acylation processes are widely used for the production of aromatic ketones, which are valuable intermediates in fine chemicals and pharmaceutical industry. Friedel crafts acylation is a useful step for the synthesis of important pharmaceutical compounds.
Friedel crafts acylations are more regioselective than the alkylations and a teo step process involving the acylation followed by reduction of the carbonyl groups may provide a clean route to the alkyl phenols.
Friedel Crafts AcylationBack to Top
Friedel crafts acylation is one of the most important methods for the synthesis of ketones. To achieve satisfactory reaction rates, "catalysts" such as aluminium chloride are usually needed in more than stoichiometric amounts because of complexation to starting materials or products.
Friedel-Crafts acylation of benzene leads to a strong decrease of electron density on the arene, which prevents further acylation.
For example, the friedel crafts acylation of anisole with acetic anhydride over different heterogeneous catalysts is shown below.
Friedel Crafts Acylation MechanismBack to Top
The mechanism of Friedel-Crafts acylation is the same as the Friedel-Crafts alkylation involving an acylium ion instead of a carbocation. As with the Friedel-Crafts alkylation a Lewis acid is required to generate the acylium ion does not rearrange since there is resonance stabilization from the oxygen.
The formation of acylium ion is as follows.
Limitations of Friedel-Crafts AlkylationBack to Top
The folloiwing points has describe the limitation:-
- The entering alkyl group can rearrange.
- The alkylbenzene is more reactive than benzene itself and can further alkylate giving mixtures of monoalkylated and polyalkylated products. (Polyalkylation can be avoided by using an excess of the arene compared with the catalyst).
- Rearrangement of kinetically controlled to thermodynamically controlled product can occur especially with 3oR's.
- Since the initial product of alkylation is more reactive than the parent arene, dialkylation or polyalkylation cannot usually be avoided.
- More than one alkyl group may be introduced onto the aromatic ring a process termed polyalkylation.
Friedel–Crafts AlkylationBack to Top
In Friedel-Crafts alkylations however no such deactivation occurs, and polyalkylated products will be obtained unless a large excess of arene is used. The reaction of aromatic compounds with alkyl halide in presence of anhydrous aluminium chloride gives the formation of alkyl substituted products. This reaction is known as Friedel crafts alkylation and is used for the synthesis of alkyl substituted aromatic compounds.
Friedel crafts alkylation can also involve carbenium ions generated from alcohols and alkenes with catalysis by Bronstead acids. For example, H2SO4 or H3PO4.