Acetic anhydride with amines

Amides with an acyl group derived from acetic acid are called acetamides. Acetamides are generally produced from the reactions of acetic anhydride with amines. 

OS 8[ [R 25] [P 6] The acylation of acetic anhydride with various amines was investigated all yields ranged from 75 to 100% with the exception of one value of 46% [83]. The lowest yield was obtained for 1-naphfhylamine and the highest for 1-hexylamine. Throughputs were from 3.8 to 68.3 g... 

Imines are formed by condensation of aldehydes or ketones with primary amines, but they form with more difficulty than enamines.84,85 A special case of enamine preparation was described with 20-oxo-steroids.86 Treatment of these ketones with a primary amine gives a 20-ketimine, which is acetylated with acetic anhydride, with migration of the double bond and formation of 20-(A-acetylalkylamino)-J17(20)-pregnene (14) reduction of 14 with lithium aluminum hydride affords the enamine. 

N 20.89%, OB to CO3 minus 59.7% crysts (from ether), mp 103—104°(Ref 2), It was prepd by Blomquist St Fiedorek by dehydration of N,N-di(y3-nitroxyptopyl)-amine nitrate on heating at 40—45° with acetic anhydride with small amt-of HCl, followed by addition of chloride catalyst such as Zn chloride (Refs 2 Sc 3)... 

The results obtained for porcine elastase have revealed that the -amino groups of both lysines 224 and 87 have normal pX s (about 10.3) and nucleophilicities anticipated for primary amines of this pXg. That is, the second order rate constants for the reaction of the unprotonated -amino groups of these lysine residues with acetic anhydride fit approximately on the Bronsted plot for the reaction of acetic anhydride with a variety of amines. The results for valine-16, which is known to be in a salt linkage in the interior of the enzyme, indicate that this a-amino group has an apparent pX of 9.7 but a nucleo-philicity of only 4% of that anticipated from the Bronsted plot for an amine of this p/. The unusually low reactivity of this valine isconsistent with the significant steric hindrance that would be expected from a resi-... 

In the 1950 s, Emmons described the synthesis of various nitrobenzenes and nitroalkanes using peracetic acid under appropriate conditions. A typical procedure involved generating anhydrous solutions of peracetic acid by the acid-catalyzed reaction of acetic anhydride with 90% hydrogen peroxide carried out in an ice bath to moderate the highly exothermic reaction. The yields obtained with a number of aromatic amine substrates are shown below. 

XU 218 is produced by the reaction of an aromatic cycloaliphatic diamine, 5[6]-amino-1(4-aminophenyl) -1,3,3-trimethylindane (DAPI) with BTDA as shown below[11]. The intermediate polyamic acid is chemically imidized by acetic anhydride/tertiary amine. ... 

Diphenylpiperazine can be titrated in acetic anhydride with perchloric acid. The titration curve resulting from plotting millivolts vs. volume of titrant gives two equal and well-defined inflection points. Diphenylpiper-azine is a by-product in the synthesis of diphenylethylene-diamine and may be determined in the presence of the same by acetylation and titration in acetic acid with perchloric acid. It may be identified by separation and titration, obtaining the very characteristic curve in acetic anhydride. Interferences from other tertiary amines and aniline are dealt with in these determinations of diphenylpiperazine. 

A number of azides have been converted to the corresponding acetyl amines by heating them in an excess of acetic anhydride, with or without the addition of a catalytic amount of sulfiu-ic acid. > > >... 

CgHs-N C CHs+CHaC OH In the above equations, it should be noted that acetyl chloride does not convert aniline completely into the acetyl derivative since the by-product, aniline hydrochloride, is formed and this does not act readily with the reagent. On the other hand, with acetic anhydride the amine is converted quantitatively into the acyl derivative and therefore this latter reagent is of more importance in connection with the preparation of derivatives. It is also of value in quantitative estimations of the amine group, the excess of acetic acid which remains after the reaction being determined volumetrically. Benzoyl chloride, benzenesulfonyl chloride, and other acyl halides that may be used in aqueous solution may also convert the amine completely into an acyl derivative for the reason that they are usually used in the presence of alkali which will combine with the hydrochloric acid generated in the reaction. When benzoyl chloride is used, a small amount of benzoic acid may be formed, due to the following side-reaction ... 

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. 

Scheme 24.15 The Reaction of Acetic Anhydride with N-(silylmethyl)amines.

One disadvantage of using acetic anhydride is that with primary amines, traces of the diacctyl compound, RN(COCH3)2, niay be formed the chances of this secondary acetylation are, however, usually remote, and recrystallisation from an aqueous solvent will generally hydrolyse the diacetyl derivative rapidly back to the mono-acetyl compound. 

Although the acetylation of alcohols and amines by acetic anhydride is almost invariably carried out under anhydrous conditions owing to the ready hydrolysis of the anhydride, it has been shown by Chattaway (1931) that phenols, when dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, undergo rapid and almost quantitative acetylation if ice is present to keep the temperature low throughout the reaction. The success of this method is due primarily to the acidic nature of the phenols, which enables them to form soluble sodium derivatives, capable of reacting with the acetic... 

Acetylation. Place 1 ml. of the substance (or, if solid, i g. of the powdered amine) in a small flask fitted with a reflux condenser (or in a test-tube fitted with a cold-finger, as in Fig. 35, p. 62), add 5 ml. of an acetic anhydride-acetic acid mixture (equal volumes) and reflux... 

Acetyl derivatives of aromatic amines may be prepared either witli acetic anhydride or acetic acid or with a mixture of both reagents. Primary amines react readily upon warming with acetic anhydride to yield, in the first instance, the mono-acetyl derivative, for example ... 

In general, however, the diacetyl derivatives are unstable in the presence of water, undergoing hydrolysis to the mono-acetyl compound, so that when they (or a mixture of mono- and di-acetyl derivatives) are crystallised from an aqueous solvent, e.g., dilute alcohol, only the mono-acetyl derivative is obtained. A further disadvantage of the use of acetic anhydride in the absence of a solvent is that all the impm-ities in the amine are generally present in the reaction product. Heavily substituted amines, t.g., 2 4 6-tribromoaniline, react extremely slowly with acetic anhydride, but in the presence of a few drops of concentrated sulphuric acid as catalyst acetylation occurs rapidly, for example ... 

The disadvantages attending the use of acetic anhydride alone are absent when the acetylation is conducted in aqueous solution according to the following procedure. The amine is dissolved in water containing one equivalent of hydrochloric acid, slightly more than one equivalent of acetic anhydride is added to the solution, followed by enough sodium acetate to neutralise the hydrochloric acid, and the mixture is shaken. The free amine which is liberated is at once acetylated. It must be pointed out that the hydrolysis of acetic anhydride at room temperature is extremely slow and that the free amine reacts much more readily with the anhydride than does the water this forms the experimental basis for the above excellent method of acetylation. 

Acetyl derivatives. Primary and secondary amines are best acetylated with acetic anhydride ... 

Acetates. The acetates of monohydric phenols are usually liquids, but those of di and tri-hydric phenols and also of many substituted phenols are frequently crystaUine sohds. They may be prepared with acetic anhydride as detailed under Amines, Section IV,100,7. 

The quinaldine is separated from any unreacted aniline and from the alkyl-anilines by treatment with acetic anhydride, basified with sodium carbonate and steam distilled. Only the primary and secondary amines are acetylated the acetylated amines are now much less volatile so that separation from the steam-volatile quinaldine (a tertiary amine) is facile. 

Phenols, unlike amines, cannot be acetylated satisfactorily in aqueous solution acetylation proceeds readily with acetic anhydride in the presence of a little concentrated sulphuric acid as catalyst. Salicylic acid (o-hydroxy-benzoic acid) upon acetylation yields acetylsalicylic acid or aspirin ... 

Acetylation of the amine may also be effected by boiling with 20 ml. of glacial acetic acid and 14 ml. of acetic anhydride for 15-20 minutes, followed by decomposition of the excess of anhydride with water and, after boiling for 5 minutes, poirring with stirring into about 75 ml. of water the product is appreciably coloured. 

Anhydrides may often be hydrolysed in the cold with dilute alkali they also react with primary amines (compare Section 111,94). All anliydrides boil above 130° thus acetic anhydride has b.p. 140°. 

Reaction with ammonia and amines (Section 20 14) Acid an hydrides react with ammonia and amines to form amides Two molar equivalents of amine are required In the example shown only one acyl group of acetic anhydride becomes incor porated into the amide the other becomes the acyl group of the amine salt of acetic acid... 

Acylation. Aliphatic amine oxides react with acylating agents such as acetic anhydride and acetyl chloride to form either A[,A/-diaLkylamides and aldehyde (34), the Polonovski reaction, or an ester, depending upon the polarity of the solvent used (35,36). Along with a polar mechanism (37), a metal-complex-induced mechanism involving a free-radical intermediate has been proposed. 

The N-oxide function has proved useful for the activation of the pyridine ring, directed toward both nucleophilic and electrophilic attack (see Amine oxides). However, pyridine N-oxides have not been used widely ia iadustrial practice, because reactions involving them almost iavariably produce at least some isomeric by-products, a dding to the cost of purification of the desired isomer. Frequently, attack takes place first at the O-substituent, with subsequent rearrangement iato the ring. For example, 3-picoline N-oxide [1003-73-2] (40) reacts with acetic anhydride to give a mixture of pyridone products ia equal amounts, 5-methyl-2-pyridone [1003-68-5] and 3-methyl-2-pyridone [1003-56-1] (11). 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

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