Aromatic hydroxylamines

Hydroxylamines ordinarily do not accumulate in the reduction of aromatic nitro compounds for, with some exceptions, most systems in competition will reduce the hydroxylamine function preferentially. Nonetheless, systems have been found that afford the intermediate aromatic hydroxylamine in excellent yield. With hydrogen gas as a reductant and platinum-on-carbon or -on-alumina and about I wt % of DMSO based on nitro compound as a modifier, aromatic hydroxylamines can be formed in 90% yield under mild conditions. The reduction slows markedly after absorption of the second mole of hydrogen and should be stopped at this stage (80). 

Two hydrogen-transfer systems have been developed that also give good yields of hydroxylamines. One uses 5% palladium-on-carbon in aqueous tetrahydrofuran with phosphinic acid or its sodium salt as hydrogen donor the other uses 5% rhodium-on-carbon in aqueous tetrahydrofuran and hydrazine as donor. These systems are complementary and which is the better may depend on the substrate (36). The reductions cannot be followed by pressure drop, and both require analysis of the product to determine when the reduction should be terminated. 

Sometimes hydroxylamines are formed in systems where the amino compound would have been expected. This occurs usually in compounds containing either sulfur or basic nitrogen impurities may have had an 

Phenylhydroxylamine rearranges in sulfuric acid to give mainly p-aminophenol. Industrial routes to this compound have been developed in which phenylhydroxylamine, formed by hydrogenation of nitrobenzene in sulfuric acid over platinum-on-carbon, is rearranged as it is formed. Conditions are adjusted so that the rate of rearran ment is high relative to the rate of hydrogenation of hydroxylamine to aniline (15,17,86). An easy way to obtain a favorable rate ratio is to carry out the reduction with about 1% DMSO present in the sulfuric acid (79,81). 

If the hydrogenation is carried out in hydrochloric instead of sulfuric acid, chloroaniline is formed (20), while in hydrofluoric acid, fluoroaniline is produced (37). 

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During hydrogenation, intermediate aromatic hydroxylamines may undergo various cyclization reactions in molecules containing a suitably disposed carbonyl group, or carbonyl derivative, such as an oxime (13). The cyclized product may or may not maintain the N—OH bond, depending on the solvent, the catalyst, and the electrophilicity of the carbonyl (27,28,29,32,67,68). 

Hydrazones of the form ArCH=NNH2 react with HgO in solvents such as diglyme or ethanol to give nitriles (ArCN). Aromatic hydroxylamines (Ar—NH-—OH) are easily oxidized to nitroso compounds (Ar—N=0), most commonly by acid dichromate. ... 

Some metabolites, most commonly aromatic hydroxylamines and quinone-type metabolites, can undergo redox cycling and generate reactive oxygen species, especially... 

One of the reactions which has been used to prepare azoxy compounds is the condensation of C-nitroso compounds with hydroxylamines. In the aliphatic series this reaction is quite general and permits the preparation of unsym-metrical azoxy compounds. In the case of aromatic compounds, however, only symmetrical azoxy compounds can be synthesized reliably. In the reaction of dissimilar aromatic nitroso compounds and aromatic hydroxylamines, a complex mixture of azoxy products is obtained. 

The oxidation of aromatic hydroxylamines with peracids in the presence of cupric ions produces nitroso compounds. In the rigorous absence of metallic ions, azoxy compounds are formed [32]. On the other hand, the air oxidation is strongly accelerated by metals, the approximate order of activity based on a kinetic study being cupric s ferric > manganous > nickel chromic > cobaltous ions. Silver and stannous ions appear to have no effect [33]. 

Aromatic hydroxylamines, oxidized in the presence of metallic ions, are converted into nitroso compounds. In the absence of such ions, azoxy compounds form. 

Fluorinated aromatic hydroxylamines can be selectively oxidized to the corresponding nitroso-benzenes 8 using iron(III) choridc as the oxidizing agent.248 The hydroxylamine is prepared in situ from the nitro compound.248... 

The oxidation of aromatic hydroxylamines has been widely used in the preparation of nitrosobenzenes. Among the methods described in the literature for this transformation, the most common procedure involves heterogeneous oxidation using iron(III) chloride [140]. This oxidation is normally slow, which can lead to the formation of the corresponding azoxy derivatives through coupling of the formed nitroso compound with the unreacted hydroxylamine. In addition, low yields are sometimes obtained due to the partial instability of the starting hydroxylamine and/ or nitroso product. Illustrative examples of this transformation are shown in Table 3.2 [141]. 

Aromatic hydroxylamines are frequently produced during the hydrogenation of aryl nitro groups. Generally, these are undesired intermediates because when they are present in excessive amounts, a potentially explosive situation caused by the exothermic disproportionation of the hydroxylamine can result. 2 This is usually not a problem, but care should be exercised to prevent the accumulation of large amounts of the hydroxylamine, particularly when the... 

Aromatic hydroxylamines bearing electron-donor substituents (OR, NR2, SR) exhibit a limited stability. Thus, reduction products are generally the corresponding anilines. The global mechanism is illustrated [56] below for the case of nitrophenol. 

Acylthiazoles can be quaternized with alkylating agents to give 2-acylthiazoIium salts which proved to be efficient catalysts in the 0-acylation of aromatic hydroxylamines <91CC1127>. 

Aromatic hydroxylamines are generally prepared by chemical reduction or selective hydrogenation of aromatic nitrocompounds by using metal catalysts promoted with dimethylsulfoxide. However, such methods of synthesis are characterized by difficult products purification and low yields /1,2/. The low cost production of arylhydroxylamines can be of great practical interest because these compounds can undergo rearrangement to yield a variety of important chemicals 111. 

Before references] Aromatic hydroxylamines are oxidized in 70—90% yield oh being heated with the reagent in ether.14 Yields are lower with aliphatic hydroxy amines. 

The 3-hydroxylaminophenol mutase from cells of R. eutropha JMP134 grown with 3-nitrophenol as N-source has been purified (Schenzle et al. 1999), and is able to catalyze the rearrangement of a number of substituted aromatic hydroxylamines, and the formation of both 2- and 4-hydroxyphenol from hydroxylaminobenzene that is formally comparable to the classic Bamberger rearrangement. 

Aromatic hydroxylamines and hydrosg l-amides are good substrates for some sulfotransferases and yield unstable sulfate esters... 

Due to high redox potential (the polarographic reduction potentials of nitroso compounds are 0.2-0.8 V higher than those of parent nitroaromatics [56]), nitrosobenzenes may be also reduced by NAD(P)H, GSH, and other reductants non-enzymatically [55,57], Alternatively, aromatic hydroxylamines may be formed during the N-hydroxylation of amines by cytochrome P-450 [58],... 

Aromatic hydroxylamines can modify DNA either directly or via formation of an O-acetylated intermediate. The acetylated intermediate can be transformed to a strongly electrophilic nitrenium ion (ArNH+) capable of modifying guanine bases with the formation of N-(deoxyguanosin-8-yl)-NHAr adducts. However, the formation of TNT adducts with DNA in mammalian cells has not been reported. On the other hand, NHOH-DNT may undergo the transition metal-catalyzed redox cycling, which may cause the DNA oxidative damage [62] ... 

Hydroxyamino groups are reduced to amino groups, in principle, by the same methods as are used for the oxime group. Aromatic hydroxylamines, which can rearrange to aminophenols in an acid medium, are advantageously reduced by aluminum amalgam.116... 

Many other polyamines are known. Among these are a 4-aminobutylcadaverine isolated from root nodules of the adzuki bean and very long partially aromatic hydroxylamine derivatives from venom of common funnel-web spiders (structures at top of page). Cationic polypeptides called silaffins, with masses of 3 kDa, apparently initiate the growth of the silica cell walls of diatoms (Box 4-B). These peptides contain polyamines consisting of 6 to 11 repeated N-methylpropylamine imits covalently attached to lysine residues and also many phosphoserines. ... 

The most common reactions of acylation are in fact acetylations of xenobiotics containing a primary amino group. The cofactor of acetylation is acetylcoenzyme A (acetyl-S-CoA), the reaction being catalysed by a variety of A-acetyltransferases. Arylamine Af-acetyltransferases (NAT-1 and -2) are the most important enzyme, but aromatic-hydroxylamine O-acetyltransferase and N-hydroxyarylamine >-acetyltransferase are also involved in the acetylation of some aromatic amines and hydroxyl-amines. 

Nitroaromatics R—NO2 Ketones —CO— Reduction Aromatic hydroxylamines Amines, aromatic R—NH2... 

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