Amines selective acetylations, acetic anhydride

Selective trifluoroacetylation of primary amines in the presence of secondary amines can be accomplished by reaction with a stoichiometric amount of ethyl trifluoroacetate (bp 60-62 °C) in THF, acetonitrile or dioxane at 0 °C. The product is simply isolated by evaporation of the solvent and liberated ethanol,45-47 Perhaps the most common method entails acylation of the amine with trifluoro-acetic anhydride in the presence of a suitable base such as trie thy lamine or pyridine in dichloromethane [Scheme 8.26],40 New reagents for the N-trifluoro-acetylation of amines include Af-ftrifluoroacetyOsuccinimide,48 a solid and storable reagent, W-(trifluoroacetoxy)succinimide,49 which must be stored in a frozen benzene matrix, and l-(trifluoroacetyl)-l,2,3-benzotriazole.50 The latter reagent is a stable, crystalline reagent (mp 89-91 °C) prepared in quantitative... 

Das B, Thirupathi P (2007) A Highly Selective and Efficient Acetylation of Alcohols and Amines with Acetic Anhydride Using NaHS04.Si02 as a Heterogeneous Catalyst. J Mol Catal A Chem 269 12... 

A unique method for selective acylation of secondary amines in the presence of primary amines involves the use of 18-Crown-6 with acetic anhydride and triethylamine. It is believed that the 18-crown-6 complexes primary alkylammonium salts more tightly than the secondary salts, allowing selective acetylation. 

The acetylation of amines with isopropenyl acetate appears to be a transition between the highly exothermic reactions of acyl halides and anhydrides with amines on the one hand and the reaction of amines with more conventional esters on the other. While this reagent is of particular value in the preparation of enol acetate, it has been used for the preparation of amides. One interesting aspect of its use is that acetone forms as a coproduct which may distill off as the reaction proceeds. Isopropenyl acetate and other isopropenyl esters may also be used to Y-acylate amides and imides. By the judicious selection of starting amides and isopropenyl esters, tertiary amides with three different acyl groups may be synthesized. This may very well be one of very few reaction systems which permits the synthesis of this rare group of tertiary amides. 

Unsymmetric anhydrides that react selectively on one side are useful. Although formic anhydride is unstable above 10°C, acetic formic anhydride can be prepared by stirring sodium formate with acetyl chloride in ether (64% yield, bp 27-28°C) [22]. It is useful for the formylation of alcohols and amines. A stable solid formylating agent is the mixed anhydride prepared in 89% yield from p-methoxybenzoyl chloride and sodium formate catalyzed by a polymeric pyridine oxide [23]. Ethyl chlorofor-mate gives mixed anhydrides with various carboxylic acids which are then susceptible to nucleophilic substitution at the carboxylic carbonyl carbon. 

Acyl donors for hydrolase-catalyzed acylations. Reactive acyl donors like (a) vinyl acetate and (b) succinic anhydride react effectively irreversibly with alcohols. The tautomerization of the vinyl alcohol to the keto form makes the acylation favorable. These acyl donors are not suitable for amines because they react spontaneously. Simple esters like (c) triacetin are less expensive acyl donors. All three acetyl groups from triacetin can react. For alcohols, these simple ester acyl donors are reversible so are not suitable when kinetically controlled selectivity is important. Simple esters are good, effectively irreversible, acyl donors for amines. 

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