Acyl trifluoroacetates, acylating agents

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 imidazole by-product is relatively inert and does not cause decomposition of the derivatives [69]. As with the use of ethyl trifluoroacetate as an acylating agent, the unfavourable properties of trifluoroacetic acid produced are eliminated [70]. With the addition of hexamethylenediamine the reaction proceeds rapidly at 60—70°C and the yield is about 70%. If dry ammonia is added to the reaction mixture, the reaction proceeds quantitatively. Ammonia probably neutralizes the residues of trifluoroacetic acid produced by the hydrolysis of the ester and in this way eliminates a competitive acylation reaction. 

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 rate of acetylation of 0-(hydrox3Tnethyl)cellulose (and other hydroxy compounds) by mixtures of carboxylic acids and their anhydrides has been found to increase greatly in the presence of trifluoroacetic acid. The acceleration is very much less with mono- and tri-chloroacetic acids, presumably because they form unsymmetrical anhydrides which are less effective acylating agents than acyl trifluoroacetates. The exceptional acylating power of the latter anhydrides is shown by their use in the synthesis of alkyl aryl ketones from polyalkylbenzenes, phenyl ethers, furan, and thiophene under mild conditions. The principle has been extended to include acids... 

The use of other acylating agents is illustrated by the following. 4-Amino-l-methyl-5-oxamoylaminomethyltriazole (24) (as tosylate salt), when refluxed in an excess of trifluoroacetic acid, produced l-methyl-5-oxamoylamino-methyl-4-trifluoroacetamidotriazole (1 day, 83%) [81J(P1)887]. 4-Amino-... 

Acylations. Activation of carboxylic acids including pivalic acid and trifluoroacetic acid for acylation is achieved by treatment with PhjP and NBS. Acyloxytriphenyl-phosphonium bromides are the acylating agents. 

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. 

Trifluoroacetic anhydride obtained by action of P203 on the acid is widely used in organic chemistry as an acylating agent in presence of acid. 

The rate of reaction of carboxylic esters with amines can often be increased by using as acylating agents esters that exchange their alcohol residues with particular ease. With this in mind Schwyzer781 recommends the use of cyano-methyl esters, RCOOCH2CN. The cyanomethyl esters of N-protected amino acids react readily even at room temperature with amino esters and are thus particularly suitable for peptide synthesis. Also, phenyl trifluoroacetate has been recommended for trifluoroacetylation of amino acids and peptides.782 The possibilities offered by such activated esters for peptide synthesis are reviewed in the monograph by Schroder and Liibke.783... 

Carboxylic acids react with trifluoroacetic anhydride to give reactive acylating agents that are especially useful for the acylation of hindered alcohols and phenols ... 

The eonversion of 34 to 35 aeeording to Cohen and eo-workers was speculated to go through a mechanism that involved a triacylated species as the requisite intermediate. The facility of the reaction with trifluoroacetic anhydride was due to its high reactivity as an acylating agent and/or the high electrophilic reactivity of the trifluoroacetyl carbonyl group. 

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