Hydroxylamines from nitro compounds

Aluminum amalgam Hydroxylamines from nitro compounds... 

Reductions with palladium-carbon/hydrazine Hydroxylamines from nitro compounds Hydrazo from azo compounds... 

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. ... 

The earliest and to date most extensively studied class of intramolecular cycloadditions involves unsaturated nitrones.4 These are most readily available from condensation of an unsaturated aldehyde with a hydroxylamine or an unsaturated hydroxylamine with an aldehyde. Another approach is simply to oxidize an unsaturated hydroxylamine. Nitronic esters are nitrones containing an alkoxy substituent attached to the N-atom they can be prepared from nitro compounds. Frequently an unsaturated nitrone can be isolated and purified, although much work has been done with the nitrone generated in situ eventual cyclization can provide three new contiguous chiral centers, often with only one diastereomer actually formed. 

Selective reduction to hydroxylamine can be achieved in a variety of ways the most widely applicable systems utilize zinc and ammonium chloride in an aqueous or alcoholic medium. The overreduction to amines can be prevented by using a two-phase solvent system. Hydroxylamines have also been obtained from nitro compounds using molecular hydrogen and iridium catalysts. A rapid metal-catalyzed transfer reduction of aromatic nitroarenes to N-substituted hydroxylamines has also been developed the method employs palladium and rhodium on charcoal as catalyst and a variety of hydrogen donors such as cyclohexene, hydrazine, formic acid and phosphinic acid. The reduction of nitroarenes to arylhydroxyl-amines can also be achieved using hydrazine in the presence of Raney nickel or iron(III) oxide. ... 

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. 

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). 

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). 

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... 

I.2. Oxidation of Amines Oxidation of primary amines is often viewed as a particularly convenient way to prepare hydroxylamines. However, their direct oxidation usually leads to complex mixtures containing nitroso and nitro compounds and oximes. However, oxidation to nitrones can be performed after their conversion into secondary amines or imines. Sometimes, oxidation of secondary amines rather than direct imine oxidation seems to provide a more useful and convenient way of producing nitrones. In many cases, imines are first reduced to secondary amines which are then treated with oxidants (26). This approach is used as a basis for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b). 

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. 

The rearrangement reaction continues to be of synthetic utility, often involved in industrial processes. Patent references (e.g. Reference 48) refer to the formation of 4-amino phenols. Often the reactant nitro compound is reduced (to the hydroxylamine) in an acid environment so that the two-stage reaction can be accomplished as a one-pot synthesis. 4-Amino phenol itself 45 can be made in high yield directly from nitrobenzene49 and the 4-methoxy aniline derivative 46 similarly from 2-methylnitrobenzene by hydrogenation in MeOH/H2S0450. 

Hydroxylamines can be synthesized from various aliphatic and aromatic nitro compounds by reduction with metals and other one-electron donors, with complex hydrides and other two-electron donors, and by hydrogenation. In all cases the reduction proceeds stepwise and, depending on reaction conditions, can provide both amines and hydroxylamines. 

Historically this reaction developed from the assumption that the formation of azoxy compounds by the reduction of aromatic nitro compounds probably involved the intermediate formation of C-nitroso compounds and hydroxylamines. In the all-aliphatic series, this reaction appears to be quite general. Symmetrically and unsymmetrically substituted azoxy compounds have been prepared by it, the only major problems being the usual ones of developing procedures that afford good yields and of determining the exact position of the azoxy oxygen in unsymmetrically substituted products. 

The reduction of aromatic nitro compounds is believed to proceed to an intermediate mixture of nitroso compounds and substituted hydroxylamines which are not isolated but condense to form an azoxy compound which, in turn, is reduced to an azo compound. Contributing evidence to substantiate this mechanism is that the reduction of a mixture of two aromatic nitro compounds leads to a mixture of azo compounds consistent with that predicted if each of the nitro compounds were reduced to a nitroso compound and a hydroxylamine and these, in turn, reacted with each other in all possible combinations. This observation also implies that the bimolecular reduction of nitro compounds is practical only from the preparative standpoint for the production of symmetrically substituted azo compounds. Spectrophotometric studies of the reaction kinetics of the reduction of variously substituted nitro compounds may, however, uncover reasonable procedures for the synthesis of unsymmetrical azo compounds. 

In some cases in which the Caro s acid oxidation of amines was not satisfactory, the corresponding hydroxylamines have been oxidized with acidified dichromate solutions [42], Both aliphatic and aromatic nitroso compounds have been prepared by this method [17, 42, 82, 90]. Frequently the reaction mixture from the reduction of a nitro compound is treated directly with the oxidizing medium without the isolation of the intermediate hydroxylamine. The method has been called the nitro reduction oxidation technique, [82] a terminology we cannot condone. 

The filtered reaction mixtures from the zinc-ammonium chloride reductions of aromatic nitro compounds have been added to aqueous solutions of ferric chloride. Within 10-15 min the oxidation to nitroso compounds was completed. In the oxidation of nine different hydroxylamines, yields ranged from 30 to 60% [86a, b]. 

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... 

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