Acetylation of aniline

Thus, acetylation of aniline affords acetanilide (20), an analgesic widely used in proprietary headache remedies. A similar transformation on p-aminophenol gives the analgesic, acetaminophen (21). It is of interest that the latter is also formed in vivo on administration of 21. An interesting preparation of this drug involves Schmidt rearrangement of the hydrazone (24) from p-liydroxyacetophenone. ... 

Mononltroanllines or Nitroanilines, OjN.Q" H4.NHj, exist in three isomeric forms ortho-, meta-, and para. They are commercially available and extensively used in industry. None of these isomers can be obtained in good yield by direct nitration of aniline and it is necessary to employ indirect methods such as che Holleman method of acetylation of aniline to acetanilide followed by nitration(Ref 2) or by ammonolysis... 

As an example, let us look at a method for acetylating aromatic amines in aqueous solution. This reaction has a special name—the Lumiere-Barbier method. We shall consider the acetylation of aniline PhNH2 (a basic aromatic amine) using acetic anhydride. The procedure for this reaction is as follows. 

Acetylation of Aniline Hydrochloride with Acetic Anhydride... 

The acetylation of aniline in aqueous solution to give acetanilide serves to protect the amine group from reaction with chlorosulfonic acid. The acetylation takes place readily in aqueous solution. Aniline reacts with acid to give the water-soluble anilinium ion ... 

Figure 16 Acetylation of aniline by acetyl CoA A/-acetyltransferase activity.

Acetone Cl mass spectra of aniline and other monosubstituted aromatic compounds were also studied98. For aniline, protonation was found to be the main reaction channel, but acetylation is also observed. Typically, the acetylation of aniline occurs mostly at the nitrogen atom. 

Derivation Acetylation of aniline with glacial acetic acid. 

The importance of the acetylation of aniline cannot be overemphasized. Acetanilide is always a preferred route not only because aniline is easily oxidized, but also because a reaction with aniline would lead to extensive meta substitution due to the presence of — lOloCl... 

How does acetic acid help in the acetylation of aniline ... 

Does the acetylation of aniline protect the free amino group ... 

Acetylation of aniline produces acetanilide (2) and protects the amino group from the reagent to be used next. Treatment of 2 with chlorosulfonic acid brings about an electrophilic aromatic substitution reaction and yields/>-acetamidobenzene-sulfonyl chloride (3). Addition of ammonia or a primary amine gives the diamide, 4 (an amide of both a carboxylic acid and a sulfonic acid). Finally, refluxing 4 with dilute hydrochloric acid selectively hydrolyzes the carboxamide linkage and produces a sulfanilamide. (Hydrolysis of carboxamides is much more rapid than that of sulfonamides.)... 

It is always important to consider possible side reactions that may occur. One example in this procedure is diacetylation (Eq. 21.4). Although the acetylation of aniline in pure acetic anhydride does give substantial quantities of the diacetyl compound 16, this side reaction is minimized in aqueous solution. 

Imides are diacyl derivatives of ammonia or primary amines. The reaction is similar in its scope and mechanism to the acetylation of aniline or 1,4-phenylene-diamine presented in Experiments [23A] and [23B], As illustrated in the present experiment, cyclic anhydrides produce cyclic imides. Cyclic anhydrides are prepared in Experiments [25A] and [25B], Derivatives of imides have been suggested for use in the treatment of arthritis, tuberculosis, and epilepsy. Several also have been found to be growth stimulants. Imide-based polymers are used in many applications, including fire-resistant woven fabrics. The N-phenyl-maleimide prepared in this experiment is also a good dienophile in the Diels-Alder reaction (see Experiments [14] and [15]), and in fact has been used as a reagent to characterize 1,3 dienes. 

Acetylation of aniline with polystyrene anhydride gives benzanilide in 90% yield. Similarly, ethyl benzoate is obtained in 90% yield by acylation of ethanol. 

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). 

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