Trifluoroacetic anhydrides, mixed, acylating agents

When carboxylic acids are treated with trifluoroacetic anhydride, mixed anhydrides (acyl trifluoroacetates) are formed. These compounds are useful acylating agents. What is the product of the reaction of an alcohol with acyl trifluoroacetate ... 

The active acylating agent may be the protonated mixed anhydride, or, alternatively, the anhydride m dissociate to the acylium and trifluoroacetate ions ... 

Mixed anhydrides with trifluoroacetic acid are particularly reactive acylating agents.48 For example, Entry 5 in Scheme 11.4 shows the use of a mixed anhydride in the course of synthesis of the anticancer agent tamoxifen. 

Electron-rich aromatic compounds such as durene, p-dimethoxybenzene, mesitylene, anisole, thiophene, and fluorene can be benzoylated or acetylated by the corresponding Af-acylimidazole in trifluoroacetic acid to give the corresponding benzophenone or acetophenone derivative in good yield (Method A). As the actual acylating agent, a mixed anhydride of trifluoroacetic acid and benzoic acid has been proposed 1973... 

The fact that, in the reaction formulated above, anisole yields the acetyl and not the trifluoroacetyl derivative means that the mixed anhydride is a more reactive acylating agent than trifluoroacetic anhydride. However, the pure anhydride alone is capable of effecting acylation. It reacts with azulene (blue) in carbon tetrachloride without catalyst at room temperature to give 1-trifluoroacetylazulene (red) in high yield. "... 

Acylations with carboxylic acids and anhydrides have been carried out with sulfuric acid as both solvent and catalyst, the reactive acylating agents from acyl halides probably being haloacyloxonium ions. Trifluoroacetic anhydride offers a rather milder reagent for reactions of carboxylic acids, with mixed anhydrides being likely intermediates. However, polyphosphoric acid remains the most widely used dehydrating agent for acylations by carboxylic acids. 

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