Acetanilide preparation

Acetanilide. Prepare 6 g of acetanilide according to directions given in Experiment 52(A). 

On acetylation it gives acetanilide. Nitrated with some decomposition to a mixture of 2-and 4-nitroanilines. It is basic and gives water-soluble salts with mineral acids. Heating aniline sulphate at 190 C gives sulphanilic add. When heated with alkyl chlorides or aliphatic alcohols mono- and di-alkyl derivatives are obtained, e.g. dimethylaniline. Treatment with trichloroethylene gives phenylglycine. With glycerol and sulphuric acid (Skraup s reaction) quinoline is obtained, while quinaldine can be prepared by the reaction between aniline, paraldehyde and hydrochloric acid. 

Dissolve I g. of finely powdered acetanilide in 5 ml. of cold glacial acetic acid contained in a 25 ml. conical flask. Then in another small flask prepare a solution of 0 42 ml. (1 34 g.) of bromine (care ) in 6 ml. of glacial acetic acid, and add this solution slowly to the acetanilide solution, shaking the latter throughout the addition to ensure thorough mixing. Allow the final mixture to stand at room temperature for 15 minutes. Then... 

Sulphanilamide, the simplest member of a large series of bacteriostatic drugs, can readily be prepared by the following reactions. Acetanilide, when treated v ith an excess of chlorosulphonic acid, gives p-acetaniidobenzencsulphonyl chloride (Reaction A), w hich readily reacts with ammonia to give p-acetamido-benzenesulphonamide (Reaction H). The acetamido-group in the latter... 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

The reaction may be more easily controlled and the chlorosulphonic acid added all at once if the acetanilide is employed in the form of a hard cake. The latter is prepared by melting the acetanilide in the flask over a free flame and causing the compound to solidify over the lower part of the flask by swirling the liquid. If the reaction becomes too vigorous under these conditions, cool the flask momentarily by immersion in an ice bath. 

Acetanilide (IV,45, Method 2, J scale boil reaction mixture for 15 minutes). Use product for preparations 24 and 25. 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

In a useful extension to the Meth-Cohn quinoline synthesis, pyridoquinolin-2-ones 27 are readily prepared in a one-pot procedure by sequential treatment of an acetanilide 3, firstly with the Vilsmeier reagent from DMF and POCI3 to afford the intermediate 16, which is then further reacted in situ with another secondary amide. ... 

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. ... 

Preparation of Intermediate Compound 4-Chloro-5-Sulfamyl-N-Acetylanthranilic Acid To a hot solution (80°C) of 366 g (1.482 mols) of magnesium sulfate (Epsom salts) in 2.8 liters of water was added 130 g (0.495 mol) of powdered 5-chloro-2-methyl-4-sulfamyl-acetanilide. With stirring and maintaining the temperature at 83°C, 234 g (1.482 mols) of potassium permanganate was added portionwise over a period of 2 hours. The mixture was then kept at 85°C with stirring for an additional 3 hours. By this time the pink color of the permanganate had been discharged. 

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

It has also proved possible to close larger rings in this manner 8 and even 12-membered. Triarylamines have been prepared in a similar manner from Arl and Ar NLi, even with unactivated Arl. In the Goldberg reaction, an aryl bromide reacts with an acetanilide in the presence of K2CO3 and Cul to give an N-acetyl-diarylamine, which can be hydrolyzed to a diarylamine ArBr-I- Ar NHAc—> ArAr NAc. ... 

Compounds containing two primary amino groups attached to a benzene ring can be prepared by the reduction of dinitro compounds and of nitroanilines, usually with tin or stannous chloride and hydrochloric acid or with iron and very dilute hydrochloric acid. Pam-diamines may also be obtained by the reduction of aromatic amino-azo compounds (e.g., p-aminodimethylaniline from methyl orange, see Section IV,78). p-Phenylenediamine may also be prepared from p-nitroacetanilide reduction with iron and acid yields p-amino-acetanilide, which may be hydrolysed to the diamine. 

The specific ortho functionalization of arylamines is obviously important in quinoline synthesis (cf. the rc-allyl procedure devised for the preparation of o-allylanilines used as indole and quinoline precursors).76 Recently acetanilides have been subjected to orthopalladation and the ensuing complexes converted into useful precursors of 2-substituted quinoline derivatives (Scheme 143).215... 

Primary and secondary amines are acylated by acid chlorides and anhydrides, in particular also by the chloride of benzene sulphonic add (p. 192). The preparation of acetanilide has already been described (pp. 125, 128). The acetyl- and benzoyl-derivatives of all the simpler primary amines of the benzene and naphthalene series are known, so that these derivatives can always serve for purposes of identification. 

M. Kiese, G. Renner, The Hydrolysis of Acetanilide and Some of Its Derivatives by Enzymes in the Microsomal and Soluble Fraction Prepared from Livers of Various Species , N.-S. Arch. Exp. Path. Pharmakol. 1966, 252, 480-500. 

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