Amino-acetanilide

More than 130 different organic chemicals are currently employed as herbicides in the U.S. All of the main families of organic compounds are represented aromatic, aliphatic, and heterocyclic. Herbicidal activity is found in a variety of classes of compounds haloaliphatic, phenoxy, and benzoic acids carbamates dinitroanilines acetanilides amino triazines quaternary pyridinium salts uracils and ureas. A few selected key examples are reviewed below. 

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 ... 

Other substituents which belong with this group have already been discussed. These include phenol, anisole and compounds related to it ( 5.3.4 the only kinetic data for anisole are for nitration at the encounter rate in sulphuric acid, and with acetyl nitrate in acetic anhydride see 2.5 and 5.3.3, respectively), and acetanilide ( 5.3.4). The cations PhSMe2+, PhSeMe2+, and PhaO+ have also been discussed ( 9.1.2). Amino groups are prevented from showing their character ( — 7 +717) in nitration because conditions enforce reaction through the protonated forms ( 9.1.2). 

Conversion of aniline to acetanilide [103-84-4] by reaction with acetic anhydride, is a convenient method for protecting the amino group. The acetyl group can later be removed by acid or base hydrolysis. 

Nitration. Direct nitration of aromatic amines with nitric acid is not a satisfactory method, because the amino group is susceptible to oxidation. The amino group can be protected by acetylation, and the acetylamino derivative is then used in the nitration step. Nitration of acetanilide in sulfuric acid yields the 4-nitro compound that is hydroly2ed to -rutroaruline [100-01-6]. 

The resulting acetyl compound is usually hydrolyzed with aqueous alkaU to give the free amine. Other A/-acyl derivatives may be used, particularly for the less soluble succinyl and phthaloyl products. The use of -nitrobenzenesulfonyl chloride, followed by reduction of the nitro to an amino function, is much more expensive and is rarely used. A/-Acetylsulfanilyl chloride [121 -60-8] is obtained by the chlorosulfonation of acetanilide [103-84-4] which is the basic material for most of the sulfonamides. 

In a 500-ml. round-bottomed flask equipped with a reflux condenser and a magnetic stirrer (Note 6) are placed 150 ml. of methanol, 150 ml. of 6N hydrochloric acid, and the total yield of 4,4 -bis(acetamido)azobenzene. The mixture is heated under reflux for 1.5 hours. The reaction mixture is cooled and the violet solid collected on a Buchner funnel (Note 7). The damp product is suspended in 500 ml. of water in a 1-1. beaker equipped with a stirrer, and the mixture is slowly neutralized by the addition of 2.5N sodium hydroxide. In the course of the neutralization, the salt dissolves and the free base separates. The 4,4 -diaminoazo-benzene is collected on a Buchner funnel, washed with water, and dried under reduced pressure. The yield of yellow product, m.p. 238-241° (dec.),is ll-12g. The over-all yield from/ -amino-acetanilide is 52-56%. 

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. 

A solution of 3 g of 2-amino-2 -(2-chlorobenzoyl)acetanilide in 50 ml of pyridine was refluxed for 24 hours after which time the pyridine was removed in vacuo. The residue was recrystallized from methanol and a mixture of dichloromethane and ether giving crystals of 5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2( 1 H)-one melting at 212° to 213°C. 

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. 

To get a complex set of substituents by direct derivatization of benzotriazole is not feasible. In such situations, it is better to have all the substituents in place first and later construct the heterocyclic ring. High reactivity of anilines and their well-developed chemistry makes them good stating materials. In an example shown in Scheme 215, acetanilide 1288 is nitrated to afford nitro derivative 1289 in 73% yield. Catalytic reduction of the nitro group provides methyl 4-acetylamino-3-amino-5-chloro-2-methoxybenzoate 1290 in 96% yield. Nitrosation of compound 1290 in diluted sulfuric acid leads to intermediate 1291, which without separation is heated to be converted to 7-chloro-4-methoxy-l//-benzotriazole-5-carboxylic acid 1292, isolated in 64% yield <2002CPB941>. 

Sodium perborate, coupling of -amino-acetanilide to 4,4 -bis(acetamido)-azobenzene using, 40, 19 Sodium polysulfide as agent to reduce 1,3 dinitro-4,6-diaminobenzene to 2,4,5-triaminonitrobenzene,... 

Aniline is very easily sulphonated, for example, by heating its sulphate ( baking process). This change recalls that of aniline acetate into acetanilide. Actually, it is very probable that an analogous product acylated at the amino-group, a sulphaminic acid, is first formed, since examples of this type of change are known, e.g. the conversion of phenylhydroxylamine to p-aminophenol and of phenylnitramine to... 

FIGURE 9 Moderately rapid gradient separation. Column XTerra MS C, IS, 4.6x 20mm 3.5p.m. Gradient 0 to 100% B over 4min,A 0.1% formic acid in water, B 0.1% formic acid in acetonitrile. Flow rate 3.0mL/min. Temperature 30°C. Detection UV at 254 nm. Instrument Alliance 2795 with 996 photodiode array detector. Compounds (I) acetanilide, (2) triamcinolone, (3) hydrocortisone, (4) 2-amino-7-chloro-5-oxo-5H-[l]benzopyrano[2,3-b]pyridine-3-carbonitrile, (5) 6a-methyl-17a-hydroxyprogesterone, (6) 3-aminofluoranthene, (7) 2-bromofluorene, (8) perylene, (9) naphtho(2,3-a)pyrene. 

Acetamido-4-amino-6-chloro-s-triazine, see Atrazine Acetanilide, see Aniline, Chlorobenzene, Vinclozolin Acetic acid, see Acenaphthene, Acetaldehyde, Acetic anhydride. Acetone, Acetonitrile, Acrolein, Acrylonitrile, Aldicarb. Amyl acetate, sec-Amyl acetate, Bis(2-ethylhexyl) phthalate. Butyl acetate, sec-Butyl acetate, ferf-Butyl acetate, 2-Chlorophenol, Diazinon. 2,4-Dimethylphenol, 2,4-Dinitrophenol, 2,4-Dinitrotoluene, 1,4-Dioxane, 1,2-Diphenylhydrazine, Esfenvalerate. Ethyl acetate, Flucvthrinate. Formic acid, sec-Hexyl acetate. Isopropyl acetate, Isoamyl acetate. Isobutyl acetate, Methanol. Methyl acetate. 2-Methvl-2-butene. Methyl ferf-butvl ether. Methyl cellosolve acetate. 2-Methvlphenol. Methomvl. 4-Nitrophenol, Pentachlorophenol, Phenol. Propyl acetate. 1,1,1-Trichloroethane, Vinyl acetate. Vinyl chloride Acetoacetic acid, see Mevinphos Acetone, see Acrolein. Acrylonitrile. Atrazine. Butane. 

Upon excitation to the singlet state [87], acetanilide (100) reacts to 2-amino-acetophenone (101), 4-aminoacetophenone (102), and aniline (Scheme 31). The quantum yield of product formation is considerably lower than that of phenyl... 

Fig. 2. Plots of reciprocal energy transfer efficiency (y) against the concentration of benzene (B) and against reciprocal concentration of acetanilide (A) by the photo-rearrangement of acetanilide in cyclohexane, (o) 2-Aminoacetophenone ( ) 4-amino-acetophenone.

Dinitw4 etbyl l metbyl benzener CH CcH CaHB(NOa)3 mw 210.20, N13.33% yel crysts, mp 48.5° Prepd from 5-ethyl 2 methyl-acetanilide by nitration at -1Q8-mp 177-8°, hydrolysis to the aniline-mp 186° followed by diazotization/removal of the amino group... 

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