Hydroxylamines nitro compounds

Electrochemical detection has matured considerably in recent years and is routinely used by many laboratories, often for a very specific biomedical application. The most popular applications include acetylcholine, serotonin, catecholamines, thiols and disulfides, phenols, aromatic amines, macrocycUc antibiotics, ascorbic acid, nitro compounds, hydroxylamines, and carbohydrates. As the last century concluded, it is fair to say that many applications for which LC-EC would be an obvious choice are now pursued with LC-MS-MS. This only became practical in the 1990s and is clearly a more general method applicable to a wider variety of substances. In a similar fashion, LC-MS-MS has also largely supplanted LC-F for new bioanalytical methods. Nevertheless, there remain a number of key applications for these more traditional detectors known for their selectivity (and therefore excellent detection limits). 

Dissolve 0-5 g. of the substance in 10 ml. of 50 per cent, alcohol, add 0-5 g. of solid ammonium chloride and about 0 -5 g. of zinc powder. Heat the mixture to boiling, and allow the ensuing chemical reaction to proceed for 5 minutes. Filter from the excess of zinc powder, and teat the filtrate with Tollen s reagent Section 111,70, (i). An immediate black or grey precipitate or a silver mirror indicates the presence of a hydroxyl-amine formed by reduction of the nitro compound. Alternatively, the filtrate may be warmed with Fehling s solution, when cuprous oxide will be precipitated if a hydroxylamine is present. Make certain that the original compound does not aflfect the reagent used. 

Nitro compounds and their reduction products. Tertiary nitro compounds (these are generally aromatic) are reduced by zinc and ammonium chloride solution to the corresponding hydroxylamines, which may be detected by their reducing action upon an ammoniacal solution of silver nitrate or Tollen s reagent ... 

Electrolytic reductions generally caimot compete economically with chemical reductions of nitro compounds to amines, but they have been appHed in some specific reactions, such as the preparation of aminophenols (qv) from aromatic nitro compounds. For example, in the presence of sulfuric acid, cathodic reduction of aromatic nitro compounds with a free para-position leads to -aminophenol [123-30-8] hy rearrangement of the intermediate N-phenyl-hydroxylamine [100-65-2] (61). 

Neta.1 Ama.lga.ms. Alkali metal amalgams function in a manner similar to a mercury cathode in an electrochemical reaction (63). However, it is more difficult to control the reducing power of an amalgam. In the reduction of nitro compounds with an NH4(Hg) amalgam, a variety of products are possible. Aliphatic nitro compounds are reduced to the hydroxylamines, whereas aromatic nitro compounds can give amino, hydra2o, a2o, or a2oxy compounds. 

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Dissolved in alkali, extracted with ether (discarded), then the aqueous phase was acidified with hydroxylamine hydrochloride, and the nitro compound fractionally distd under reduced pressure. [Pearson and Dillon J Am Chem Soc 75 2439 1953.]... 

Transformations of nitro compounds, nitrones, nitrates, hydroxylamines, and amino-A-oxides into heterocycles 98SL939. 

Nitro functions are easily reductively alkylated and a number of alkylated anilines are made industrially starting with the appropriate nitroaromatic in the ketone as solvent. The addition reaction can occur at the hydroxylamine intermediate as well as the aniline. A process step is saved by beginning with the nitro compound. 

Aromatic nitro compounds are hydrogenated very easily aliphatic nitro compounds considerably more slowly. Hydrogenations have been carried out successfully under a wide range of conditions including vapor phase (S9). Usually the goal of reduction is the amine, but at times the reduction is arrested at the intermediate hydroxylamine or oxime stage nitroso compounds never accumulate, although their transient presence may appreciably influence the course of reaction. In practice, nitro compounds often contain other reducible functions that are to be either maintained or reduced as well. 

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). 

Formation of azo-type products might be troublesome. These by-products, arising from reduction of aromatic nitro compounds, usually are assumed to be derived from the coupling of intermediate nitroso and hydroxylamine compounds. The coupling problem is accentuated in reduction of nitroso compounds because of much higher concentrations. It can be alleviated by dropwise addition of the substrate to the hydrogenation and use of acidic media. 

Arylisoxazol-5(4//)-oncs 21 react with benzene-1,2-diamines to yield 4-aryl-l,5-benzodiaze-pinones 22 by elimination of hydroxylamine from the intermediate oximes. Unsymmetrically substituted benzene-1,2-diamines are attacked at the more nucleophilic amino group. Thus, 4-methylbenzene-1,2-diamine gives 7-methylbenzodiazepinones 22f-h, whereas 4-nitrobenzene-1,2-diamine gives 8-nitro compounds 22k-n. The benzodiazepinones are accompanied by minor amounts of 2-methylbenzimidazoles 23. Selected examples are given.275... 

When aromatic nitro compounds are reduced with zinc and water under neutral conditions, hydroxylamines are formed. Among other reagents used for this... 

Nitro compounds have been reduced electrochemically, to hydroxylamines as well as to other products. ... 

Nitroso compounds and hydroxylamines can be reduced to amines by the same reagents that reduce nitro compounds (19-41). One example reduces a hydro-xylamine to the amine with CS2 in acetonitrile. N-Nitroso compounds are similarly reduced to hydrazines ... 

Azoxy compounds can be obtained from nitro compounds with certain reducing agents, notably sodium arsenite, sodium ethoxide, NaTeH, NaBH4—PhTeTePh, and glucose. The most probable mechanism with most reagents is that one molecule of nitro compound is reduced to a nitroso compound and another to a hydroxylamine 119-42), and these combine (12-51). The combination step is rapid compared to the reduction process. Nitroso compounds can be reduced to azoxy compounds with triethyl phosphite or triphenylphosphine or with an alkaline aqueous solution of an alcohol. ... 

We now illustrate the opposite case where the intermediate is in fact a highly undesirable substance, as it presents a health, or even explosion, hazard. The hydrogenation of aromatic nitro compounds, such as the one shown in Fig. 2.6, is industrially important for the production of dyes, whiteners, agrochemicals and pharmaceuticals. The reaction occurs in the presence of a platinum catalyst and proceeds via intermediates, among which the hydroxylamine (-NHOH) species is particularly hazardous, as it is both carcinogenic and explosive. Unfortunately, standard platinum catalysts give rise to high levels of this undesired intermediate. 

Aromatic nitro and nitroso compounds are easily reduced at carbon and mercury electrodes. Other nitro compounds such as nitrate esters, nitramines, and nitrosamines are also typically easily reduced. The complete reduction of a nitro compound consists of three two-electron steps (nitro-nitroso-hydroxylamine-amine). Since most organic oxidations are only two-electron processes, higher sensitivity is typically found for nitro compounds. Several LCEC based determination of nitro compounds have been reported... 

It must be remembered, however, that nitroso, azoxy and azo compounds (which are usually more highly coloured than nitro compounds) may be reduced by zinc powder to the corresponding hydroxylamine, hydrazo and hydrazine compounds respectively, all of which reduce Tollen s reagent in the cold. 

Unprotonated hydroxylamines are not reducible by electron transfer (10) as already mentioned and the electrohydrogenation of nitro compounds at Raney metal electrodes in neutral and basic aqueous alcoholic media gives the corresponding amines as shown by the numerous examples illustrated above. Therefore, in these media, hydroxylamines must be reduced to the amine by an ECH mechanism (eq. [1] followed by eqs. [18] and [19]). 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

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