Acetanilides, oxidation

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 ... 

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 relatively low pX values seen for the benzoyl acetanilides, especiaHy as two-equivalent couplers, minimize concerns over slow ionization rates and contribute to the couplers overaH reactivity. But this same property often results in slow reprotonation in the acidic bleach, where developer carried over from the previous step can be oxidized and react with the stiH ionized coupler to produce unwanted dye in a nonimage related fashion. This problem can be eliminated by an acidic stop bath between the developer and the bleach steps or minimized by careful choice of coupling-off group, coupler solvent, or dispersion additives. 

Pyridine has been phenylated with the following free-radical sources benzenediazonium chloride with aluminum trichloride the Gomberg reaction " phenylhydrazine and metal oxides A -nitroso-acetanilide dibenzoyl peroxide phenylazotriphenylmethane di-phenyliodonium hydroxide and electrolysis of benzoic acid. ° Although 2-phenylpyridine usually accounts for over 50% of the total phenylated product, each of the three phenyl derivatives can be obtained from the reaction by fractional recrystallization of the... 

Acetanilide and maleic acid are condensed to give /3-(p-acetaminoben2oyl)acrvlic acid which is hydrogenated to give methyl- y-(p-aminophenyl)butyrate. That is reacted with ethylene oxide and then with phosphorus oxychloride to give the methyl ester which is finally hy-droly2ed to give chlorambucil. 

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. 

Palladium-catalyzed room-temperature >rtfe>-alkenylations of anilides have been recently reported, employing benzoquinone as a stoichiometric oxidant. A kinetic isotope effect kn/koof 3 points to a slow C-H functionalization step. Electron-rich acetanilides react faster whereas anilines are unreactive (Equation (138)).120... 

Hartwig has reported an intramolecular/intermolecular process affording the 3-aryloxindoles 105 (Scheme 32).115 The intermolecular arylation of acetanilide derivative 104 is slower than the intramolecular arylation to form the oxindole. Thus, the overall transformation starts with cyclization followed by intermolecular arylation of indole. In order to slow down the intermolecular process and speed up the intramolecular reaction, chloroarene and bromine-substituted acetanilide precursors are used according to their respective reactivity with palladium(O) in the oxidative addition process. 

Catalysed oxidation of primary and secondary amines generally has little synthetic value. Primary amines yield either a mixture of nitriles and amides (ca. 30%) or, in the case of arylamines, the azo derivatives (42-99%) [39], Symmetrical and non-symmetrical azoarenes are also produced in good yields ( 60%) from the reaction of acetanilides with nitroarenes under basic solidtliquid conditions, although higher yields are obtained using TDA-1 [40],... 

Soil A reversible equilibrium is quickly established when aniline covalently bonds with humates in soils forming imine linkages. These quinoidal structures may oxidize to give nitrogen-substituted quinoid rings. The average second-order rate constant for this reaction in a pH 7 buffer at 30 °C is 9.47 x 10 L/g-h (Parris, 1980). In sterile soil, aniline partially degraded to azobenzene, phenazine, formanilide, and acetanilide and the tentatively identified compounds nitrobenzene and jD-benzoquinone (Pillai et ah, 1982). 

Palladium(II) effects orthometalation of acetanilides to form the corresponding palladacycles [185]. De Vries, van Leeuwen, and coworkers exploited this reactivity to achieve regioselective oxidative coupling of acetaniUdes and n-butyl acrylate that proceeds efficiently with BQ as the stoichiometric oxidant (Eq. 46) [ 186], The use of TsOH as an additive and acetic acid as a cosolvent significantly improves the results. Inferior results are observed with hydrogen peroxide or copper(II) acetate as the stoichiometric oxidant, but efforts to use molecular oxygen were not described. 

A freshly prepared solution of nitroguanidine in sulphuric acid contains no free nitric acid, but in the presence of substances which are readily nitrated it behaves as if this were so, e.g. the solution nitrates phenol, acetanilide and cinnamic acid and in the presence of mercury reacts in a nitrometer with the evolution of nitric oxide in the same way as nitric acid. Hence in certain cases a solution of nitroguanidine in sulphuric acid may be utilized as a nitrating mixture. 

Data have been presented on the kinetics of nitration of acetanilide in mixtures of nitric and sulfuric acids.29 A review discusses the several mechanisms operative in the nitration of phenol including /> / -sclective nitrosation-oxidation and mechanisms involving phenoxy radical-nitrogen dioxide reaction yielding a 55 45 ortho para nitration ratio.30 The kinetics of mononitration of biphenyl-2-carboxylic acid have been investigated in several solvents. The maximum ortho para product ratio of 8.4 is observed in tetrachloromethane.31 Nitration products were not formed in the presence of dioxane.31,32 Quantum-chemical AMI calculations were performed and the predominant formation of the ortho-nitro product is accounted for by stabilization of the cr-complex by the carboxyl group.33... 

Oxidations Cytochrome P450-dependen1 Aromatic hydroxylations R ft oxidations C T— C J i / °" j Acetanilide, phenobarbit phenylbutaz warfarin, 17 c naphthalene... 

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