Related Alkylation and Acylation Reactions

There are a number of variations of the Friedel-Crafts reactions that are useful in synthesis. The introduction of chloromethyl substituents is brought about by reaction with formaldehyde in concentrated hydrochloric acid and halide salts, especially zinc chloride.62 The reaction proceeds with benzene and activated derivatives. The reactive electrophile is probably the chloromethylium ion. 

Chloromethylation can also be carried out using various chloromethyl ethers and SnCl4.63 

Carbon monoxide, hydrogen cyanide, and nitriles also react with aromatic compounds in the presence of strong acids or Friedel-Crafts catalysts to introduce formyl or acyl substituents. The active electrophiles are believed to be dications resulting from diprotonation of CO, HCN, or the nitrile.64 The general outlines of the mechanisms of these reactions are given below. 

ArH + HC=NH2 — ArCH=i IH2H-22 ArCH=0 Acylation with nitriles  

Many specific examples of these reactions can be found in reviews in the Organic Reactions series.65 Dichloromethyl ethers are also precursors of the formyl group via alkylation catalyzed by SnCl4 or TiCl4.66 The dichloromethyl group is hydrolyzed to a formyl group. 

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