Bromo-acetanilide

Method 2 (Alkaline hydrolysis). Use a solution of 15 g. of p-bromo-acetanilide in 30 ml. of boiling ethyl alcohol, and add a solution of 7 6 g. of potassium hydroxide in 10 ml. of water. Reflux for 40 minutes, dilute with 120 ml. of water, and distil imtil 75 ml. of distillate (alcohol and water) are collected pour the residue into 150 ml. of cold water. 

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

To a solution of 42 g of 2.amino.2 -chlorobenzophenone in 500 ml of benzene, 19 ml of bromoacetyl bromide was added dropwise. After refluxing for 2 hours, the solution was cooled, washed with 2N sodium hydroxide and evaporated. The residue was recrystallized from methanol giving crystals of 2-bromo.2. (2-chlorobenzoyl) acetanilide melting at 119° to 121°C. 

To a solution of 14.5 g of 2-bromo-2 -(2-chlorobenzoyl)acetanilide in 100 ml of tetrahy-drofuran, an excess of liquid ammonia (ca 150 ml) was added. The ammonia was kept refluxing with a dry-ice condenser for 3 hours after which time the ammonia was allowed to evaporate and the solution was poured into water. Crystals of 2-amino-2 -(2-chloro-benzoyOacetanilide were collected, which after recrystallization from ethanol melted at 162° to 164 C. 

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. 

The reaction of acetanilides with tetraalkylanunonium polyhalides, such as TBA Br3, BTMA Bf3, or BTMA Br2Cl in dichloromethane-methanol at room temperature gave bromo-substituted acetanilides in good yields, respectively. These bromination of acetanilides have usually given predominantly the corresponding p-bromo derivatives (Fig. 12) (ref. 17). Furthermore, the reaction of acetanilides with BTMA Br3 in acetic acid in the presence of ZnCl2 gave polybromo-substituted acetanilides which was not obtained from the reactions in dichloromethane-methanol (ref. 18). 

Acetal formation from pentaerythritol and benzaldehyde, 38, 65 Acetamide, 31, 17 Acetamide, N-bromo, 31,17 a-PHENYL-, 32, 92 Acetanilide, cz-benzoyl-, 37, 2 a -ben zoyl-2-mcth oxy-4-ni tro, 37, 4 Acetic acid, benzoyl-, ethyl ester, 37, 3, 32... 

Another side reaction which occurs is reduction in the reaction the —N2C1 or —N(NO)COCH3 group is replaced by hydrogen. wi-Bromo-toluene was isolated in 6% yield from the reaction between the sodium diazotate from 2-bromo-4-methylaniline and benzene, and in 10% yield in a similar reaction from 2-methyl-4-bromoaniline.4 Some nitrobenzene is obtained in the preparation of 3-nitrobiphenyl from nitroso-w-nitro-acetanilide (p. 250). The source of the hydrogen effecting the reduction has not been determined. f... 

The reactivity of the aniline may be modified by acetylation. Bromination of acetanilide with bromine in acetic acid gives 4-bro-moacetanilide (4.6). Under some conditions, bromination can take place first on the amide to give the A-bromo compound. This then undergoes a rearrangement known as the Orton rearrangement to give the para substituted product. 

Chloro-N-ethylacetanilide (CP 6936, 10) 2-Chloro-6-/-butyl-o-acetotoluidide (CP 31 675, 11) 2-Bromo-6 -/-butyl-o-acetotoluidide (CP 39 179, 12) 2-Bromo-6 -t-butyl-N-methoxymethyl-o-acetotoluidide (CP 45 592, 13) 2-Chloro-2, 6 -dimethyl-N-(isopropoxymethyl)acetanilide (CP 52 665, 14) 2-Chloro-2, 6 -dimethyl-N-(methoxyethyl)acetanilide (CGA 17 020, 15) 2-Chloro-N-(ethoxyethyI)-N-(2-methyl-6-propy 1-1 -cyclohexen-1 -y l)acetamide (CP 56 250, 16)... 

Aryloxybutyramides (effectively amido derivatives at the benzylic position in phenyl isopropyl ether) readily formed from 2-bromo-iso-butyramide and a variety of phenoxides in dioxane undergo the Smiles rearrangement in dimethylformamide containing 1,3-dimethyltetrahydropyrimidin-2(1H)-one (DMPU) solution and sodium hydride to form substiuted acetanilides with yields in the range 60-90%. Thence by hydrolysis aromatic amines are formed in good yields (ref. 168). 

Acetanilide (i.e., the acetyl derivative of aniline) on being subjected to bromination (with Bvg) in a medium of glacial acetic acid gives rise to the /jura-bromoacetanilide with the liberation of a mole of HBr. The acetamide (—NHCOCHg) is an ortho, para director function hence, the incoming bromo moiety shall yield both ortho- and para-isomers. The latter is produced predominantly (upto 90%) as a white solid. 

The angle between the C —N—CCO and the N—CCO—O plane is ea. 80° for acetanilide and its p-bromo-derivative in B, and within the range 65-85° for these substances and forp-chloro- and p-methyl-acetanilides in dioxan... 

---