Hydroxylamine as intermediate

Nitroaromatic Reduction Nitroaromatics constitute an important class of potential environmental contaminants, because of their wide use in agrochemicals, textile dyes, munitions, and other classes of industrial chemicals. Reduction of nitroaromatics produces amines, throngh a series of electron transfer reactions with nitroso and hydroxylamines as intermediates (Fig. 13.1). Compared to the parent nitroaromatic compound, all intermediates typically reduce readily (Larson and Weber 1994). 

For the assimilatory pathway it was proposed (Meyer and Schultze, 1894) that the reduction of nitrite to ammonia proceeded by three steps, each step involving the transfer of two electrons with the production of hyponitrite and hydroxylamine as intermediates. Although belief in this three step reductive pathway was maintained for 60 years, current evidence shows that nitrite is reduced to ammonia by the enzyme nitrite reductase according to this scheme. 

From aliphatic 2-nitroalkanols, readily accessible via the Henry reaction,i3i the reduction by aluminum amalgam also gives hydroxylamines as intermediates, further reduced to amino alcohols.i mildly basic conditions permit the acylation of the amino group, and the amino alcohols can be conveniently isolated as the N-acetyl or benzoyl derivatives. 

Controlled hydrogenation over Ni or the electrochemical reduction of o -nitrobenzo itriles produced 3-amino-2,l-benzisoxazoles either as the major product or by-product, depending in part on the reaction media and ratio of reactants (72BSF2365, 65CB1562). Reduction of o-nitrobenzonitrile gave either 3-amino-2,l-benzisoxazole or 2-aminobenzonitrile. The benzisoxazole is presumed to arise via an intermediate hydroxylamine. The electrochemical reduction of o-nitrobenzonitrile at acid pH produced the hydroxylamine as the primary product. Reduction at neutral pH gave the amino-2,1-benzisoxazole and the hydroxylamine (72BSF2365). 

This presumably forms oxime, 120, on reaction with hydroxylamine that intermediate is not isolated as it cyclizes spontaneously to the isoxazole, 121. Acylation of the isoxazole with the sulfonyl chloride, 88, affords sulfisoxazole (98) after removal of the acetyl group. 

A second mechanism involving as intermediate step a stable hydroxylamine ether (isopropyl I-ether) is also a possibility (reaction (15)). In a second step the ether would undergo cleavage by the acylperoxy radical with formation of isobutyric acid and acetone and liberation of the nitroxide (reaction (16)) ... 

As can be seen from the preceding discussion, the existence of nitroso compounds as intermediates in the electrochemical reduction of nitro compounds is mostly inferential nitroso compounds are easier to reduce than nitro compounds. Hence, they should be reduced as quickly as they are formed and would not be expected to be isolable. However, nitroso compounds have occasionally been isolated in unusual structural cases54 and the nitrosobenzene radical anion has been identified by ESR spectroscopy in at least one instance64. It is possible to prepare nitroso compounds by a two-step sequence one reduces the nitro compound electrochemically to the hydroxylamine, then electrochemi-cally oxidizes the hydroxylamine to the nitroso compound65. 

Bonner, F. T., Dzelzkalns, L. S., and Bonucci, J. A. (1978). Properties of nitroxyl as intermediate in the nitric oxide-hydroxylamine reaction and in trioxodinitrate decomposition. Inorg. Chem. 17, 2487-2494. 

An iron-catalyzed reaction of an a,P-unsaturated oxime such as 68 with a P-oxo ester also gave pyridine derivatives such as nicotinic acid 69 [99]. Under the reaction conditions (150-160 °C, without solvent) first Michael adducts such as intermediate 70 are presumably formed, which further condense via intermediate 71. This method is not restricted to a centric symmetry in the substitution pattern, which is an advantage compared with the Hantzsch synthesis. Moreover, the method starts with hydroxylamine being two oxidation stages above ammonia therefore, no oxidation in the final stage from dihydro- to pyridine is necessary (Scheme 8.31). 

While osmium is the metal of choice for the AA, there has been a recent report of the copper]I)-catalyzed intramolecular aminohydroxylation starting from hydroxylamines [27], The mechanism of this reaction is distinctively different, involving radicals as intermediates. 

In his last years, Dr. Isbell became convinced of the importance of saccharide peroxides as reaction products, and not merely as intermediates. He pointed to the structural similarity that exists between hydrazines, hydroxylamines, and peroxides and suggested that a missing group, saccharide peroxides, might be prepared by nucleophilic substitution using suitably protected glycosyl halides and aryl peroxides, as shown in the scheme below. 

Hydroxylamines are commonly postulated as intermediates in diese oxidations, but dey are rarely isolated or detected. Two examples of reactions in which products at the hydroxylamine oxidation level can be isolated bodi involve peroxides. Oxidation of alkylamines (2 R = Bu, Me and niCH2) with arenesul-fonyl peroxides bearing an electron-wididrawing group gave die arenesulfonyloxyamines in good yields (Scheme 6). A similar reaction of primary amines wi dibenzoyl peroxide gave benzoyloxyamines. ... 

While the. V-hydroxypyrrolidine 1 was obtained as a mixture of isomers, the /V-hydroxypipc-ridine 2 was obtained predominantly as the trans-isomer. However, these intermediates were not isolated and the observed ratio of trans- and d.v-l-acetyl-2,5-dimethylpyrrolidine does not necessarily reflect the composition of the intermediate cyclic hydroxylamine as the cyclic imine is probably formed as the initial step in the reduction. 

Since hydroxylamines, as well as their precursor oxime derivatives, are reduced by diborane to amines, the reaction has been extended by reducing the initially formed hydroxylamine intermediates (57) to amines (58). Thus excess borane reduces nitroalkenes (56) to amines (58) in the presence of a catalytic amount of sodium borohydride (equation 32). 

Bengtsson studied the kinetics of the reduction of V(V) in perchloric acid solutions and concluded that a complex is formed as an intermediate with hydrazine or hydroxylamine as the reductant. 

With some reducing agents, especially with aromatic nitro compounds, the reduction can be stopped at an intermediate stage, and hydroxylamines (19-46), hydrazobenzenes, azobenzenes (19-80), and azoxybenzenes (19-79) can be obtained in this manner. However, nitroso compounds, which are often postulated as intermediates, are too reactive to be isolated, if indeed they are intermediates. Reduction by metals in mineral acids cannot be stopped, but always produces the amine. 

In 1996 the worldwide capacity caprolactam capacity was ca. 4400 10 t. Over 90% of plants operate with hydroxylamine as an intermediate. The hydroxylamine capacities are not recorded separately, but in total must be at least 1 10 t/a (calculated on the basis of NH2OH), assuming 100% synthesis yield, in order to provide this caprolactam capacity. 

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