Lewis acids acyl chlorides/anhydrides, electrophilic

The general picture emerging is that acid chlorides are sufficiently electrophilic to N-acylate carbazole directly but that acid anhydrides require a Lewis acid or protonic acid catalyst. Direct and efficient N-trifluoroacetyla-tion with trifluoroacetic anhydride nicely illustrates the balance, this more reactive anhydride requiring no catalyst. ... 

This electrophilic aromatic substitution allows the synthesis of monoacylated products from the reaction between arenes and acyl chlorides or anhydrides. The products are deactivated, and do not undergo a second substitution. Normally, a stoichiometric amount of the Lewis acid catalyst is required, because both the substrate and the product form complexes. 

Complementary to the acylation of enolate anions is the acid-catalyzed acylation of the corresponding enols, where the regiochemistry of acylation can vary from that observed in base-catalyzed reactions. Although the reaction has been studied extensively in simple systems, it has not been widely used in the synthesis of complex molecules. The catalysts most frequently employed are boron trifluoride, aluminum chloride and some proton acids, and acid anhydrides are the most frequently used acylating agents. Reaction is thought to involve electrophilic attack on the enol of the ketone by a Lewis acid complex of the anhydride (Scheme 58). In the presence of a proton acid, the enol ester is probably the reactive nucleophile. In either case, the first formed 1,3-dicarbonyl compound is converted into its borofluoride complex, which may be decomposed to give the 3-d>ketone, sometimes isolated as its copper complex. 

An acylium ion is the electrophile required for a Friedel-Crafts acylation reaction. This ion is formed by the reaction of an acyl chloride or an acid anhydride with AICI3, a Lewis acid. 

The Friedel-Crafts acylation reaction can be performed without any catalyst, but very harsh conditions are necessary [5], Conventionally, and more efficiently, this electrophilic acylation using acyl chlorides or anhydrides is catalyzed by Lewis acids (such as ZnClj, AlClj, FeCl, SnCl, and TiCl ) when carboxylic acids are directly utilized as acylating reagents, strong protic acid catalysts (such as HjSO and HF) are needed. The simplified mechanism of the reaction involving an acyl chloride and AlClj is depicted in Scheme 3.1. 

The Friedel-Crafts reaction includes both alkylation and acylation although here only acylation is exemplified. For the Friedel-Crafts acylation, the electrophile could be either an acid chloride or an anhydride. The catalyst could be either a Lewis or protic acid. 

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