Acetylation of amines

Acetic anhydride is a useful solvent in certain nitrations, acetylation of amines and organosulfur compounds for mbber processing, and in pesticides. Though acetic acid is unexceptional as a fungicide, small percentages of anhydride in acetic acid, or in cold water solutions are powerful fungicides and bactericides. There are no reports of this appHcation in commerce. It is possible that anhydride may replace formaldehyde for certain mycocidal apphcations. 

At physiological pH values, acetylation of amine groups proceeds rapidly, requiring less than an hour to go to completion (Figure 1.119). 

The S-CoA derivative then acylates the amino group of the particular amino acid in an analogous way to the acetylation of amine groups described above, yielding a peptide conjugate. This is catalyzed by an amino acid N-acyltransferase, which is located in the mitochondria. Two such enzymes have been purified, each using a different group of CoA derivatives. 

Pantothenic acid participates as part of coenzvme A in carbohydrate metabolism (2-carbon transfer-acetate, or pyruvate), lipid metabolism (biosynthesis and catabolism of fatty acids, sterols, +phospholipids), protein metabolism (acetylations of amines and amino acids), porphyrin metabolism, acetylcholine production, isoprene production. 

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... 

D) Acetylation of Amines. Place 1 ml of aniline, dimethylaniline, and n-hutylamine in separate test tubes. Add to each of the tubes 2 ml of acetic acid (glacial) and 3 ml of acetic anhydride. Heat the tubes in boiling water for 3 minutes. Add slowly 10 ml of water. If no acetyl derivative forms, neutralize carefully with dilute ammonium hydroxide. Filter with suction, and wash the crystals with a small amount of water. Dry, place in small vials, label, and hand to the instructor. 

It will be noted that the hydroxy compounds yield esters and the amines yield substituted amides. Acid anhydrides may be used as the acylating agent (see page 175). For acetylation of amines, heating with glacial acetic acid may be used advantageously. 

Acetylation. Selective acetylation of amines (primary amines > secondary amines, arylamines) is readily accomplished. 

Acetylation of amines, phenols, and thiols. This reagent readily transfers two acetyl groups to amines, phenols, and thiols under mild conditions (25°) with conversion to 1,4-diacetylglycouril. Ahphatic primary amines react most readily in fact, primary amino groups can be selectively acetylated in the presence of a secondary amino group. Acetylation of aromatic amines is slower, but can be catalyzed by an acid (e. g., acetic acid). Phenols are also acetylated, but aminophenols can be selectively N-acetylated. Thiophenols and alkyl thiols are acetylated readily, but alcohols react only slowly, even at elevated temperatures. ... 

Dihydropyrimidin-2(lH)-ones are produced by the Biginelli reaction. The process involves reacting an aldehyde, a, P-ketoester, and urea or thiourea in the presence of an acid catalyst to produce dihydropyrimidinone. The reaction has been demonstrated in large scale using water as the medium under biphasic conditions at 50°C without any organic solvent. The product precipitates out of the reaction mixture. This water-based biphasic reaction strategy is adopted for the acetylation of amines as well. 

Traditionally, acetylation of amines is conducted by the treatment of the solution of an amino compound with an acid anhydride or acid chloride in the presence of pyridine and a solvent such as ether or dichloromethane. In contrast, the new process has an aqueous mixture of a water-immiscible amine, stirred vigorously with acetic anhydride to produce in minutes the insoluble amide, which precipitates at high purity, produced in more than 90% yield. 

Esters of carboxylic acids are prominent among the chemical structures of biological systems. The biosyntheses of only a few of the naturally occurring esters have been studied enzymatically. Among the known reactions are the syntheses of acetylchohne and of phosphatidic acids. Acetylcholine is formed by choline acetylase, which has been purified from nervous tissue. Nachmansohn and associates have prepared choline acetylase from rat brain, the electric organ of the electric eel, squid ganglia, and other tissues. It has been detected in muscle also, but not in liver or kidney. The reaction is very similar to the acetylation of amines. 

Although it has not yet been possible to study the synthesis of proteins in purified enzyme systems, a considerable number of model reactions which involve the formation of peptide or amide linkages have been investigated. These include the synthesis of glutamine, hippuric acid, acetylated amines, glutathione, and urea. It is of significance that every one of these model reactions, studied in isolated enzyme systems, has been shown to require ATP. In addition, two of these reactions, the formation of hippuric acid and the acetylation of amines, have been shown to require coenzyme A. 

Amines. The acetylation of amines has been known since 1853 when Gerhardt reported the acetylation of aniline. Acetamides are typically prepared by the reaction of the amine with acetic anhydride (eq 6). 

Ammonia, primary amines, and secondary amines all react easily with acid anhydrides to form am-ides. The by-product is the carboxylic acid used to originally form the anhydride. Acetic anhydride in acetic acid is an inexpensive reagent for the acetylation of amines. 

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. 

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