Nitro amine oxides, reduction

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. 

Titanous chloride (titanium trichloride) is applied in aqueous solutions, sometimes in the presence of solvents increasing the miscibility of organic compounds with the aqueous phase [199, 200]. Its applications are reduction of nitro compounds [201] and cleavage of nitrogen-nitrogen bonds [202] but it is also an excellent reagent for deoxygenation of sulfoxides [203] and amine oxides [199] (Procedure 38, p. 214). 

Oxidative cleavage of amines 9-39 Reduction of amides 9-47 Reduction of nitro compounds 9-50 Reduction of nitroso compounds or hydroxylamincs 9-51 Reduction of oximes 9-52 Reduction of azides 9-53 Reduction of isocyanates, isothiocyanates, or N-nitroso compounds 9-55 Reduction of amine oxides 9-59 Reduction of azo, azoxy, or hydrazo compounds... 

Arylhydroxy la mines, whether derived from nitro compounds by reduction or amines by N-hydroxylation, have been shown to be involved in the toxicity of a number of compounds. The possibility of reduction followed by oxidation in a cyclical fashion with the continual production of toxic metabolites has important toxicological implications. 

Deoxygenation of N-oxides reduction of ArNO2. An Mo(IIl) species obtained by reduction of MoC15 with zinc in aqueous THF reduces aromatic N-oxides in 45 65% yield. The reagent also reduces aromatic and heteroaromatic nitro compounds lo amines in 30-70% yield. 

Table 5. //-Hydroxy Amines by Oxidative Photoaddition of A-Nitroso and A-Nitro Amines, Followed by Reduction ...

The Co(bipy)3+ ion is a useful catalyst for a number of borohydride reductions, e.g., organic nitro compounds are reduced smoothly to amines at pH 6.5-7 the true reducing agent is Co(bipy)3+. The oxidation-reduction potential for Co(I)/Co(II) is 0.91 volt (vs. standard calomel electrode in 50% aqueous ethanol) and this should fall between the potentials of the other reactants (709). Catalytic reductions of organic halogen compounds may be achieved (436), and the system is reactive to small molecules such as NgO (38). 

The utility of reductive amination with NaBHsCN in synthesis is contained in reviews and successful applications have been compiled through 1978. Table 7 provides a variety of examples taken from more recent accounts and chosen to illustrate the versatility and compatibility of the process with diverse structural types and chemoselectivity demands. Thus, esters (entries 2-4, 8-12), amides (entries 3, 6-9, 12), nitro groups (entry 13), alkenes (entry 2), cyclopropyl groups (entry 2), organometallics (entry 5), amine oxides (entry 14) and various heterocyclic rings (entries 1, 3, 5-10) all survive intact. Entry 6 illustrates that deuterium can be conveniently inserted via the readily available NaBDjCN, and entry 15 demonstrates that double reductive amination with diones can be utilized to afford cyclic amines. 

The following paragraphs describe the methods of forming azo compounds in which an N-N bond is created (for preparation by coupling see the Section on Preparation of the C-N bond by replacement .) These methods can be classified as (a) oxidative junction of amines (b) oxidation of hydrazo compounds (c) disproportionation of hydrazo compounds (d) action of hypochlorite on iV,jV -diarylsulfamides (e) condensation of nitroso compounds with amines (f) reaction of nitro compounds with amines (g) reduction of nitro and nitroso compounds and (h) reaction of JV-arylhydroxylamines with sulfinylimines. 

B. Reduction The enzymology of reduction is not as well as characterized as for oxidation but, for example, reductive reactions can be catalyzed by cytochrome P-450 and P-450 reductase and soluble enzymes such as DT-diaphorase (EC 1.6.99.2) Many compounds including azo-and nitro-compounds, epoxides, heterocycles and halogenated hydrocarbons Sources of reducing equivalents for the reactions include NAD PH and NADH. Chemical groups modified include nitro, nitroso, tertiary amine oxide, hydroxylamine, azo, quinone, nitroso, alkylhalide... 

Since the latter are useful sources of pyridine derivatives, methods for their deoxygenation have been much studied. These compounds lack the oxidizing properties found with some amine oxides. Polarographic studies show that in acid media pyridine 1-oxide has a much lower reduction potential than oxides of tertiary amines with exocyclic nitrogen atoms -. The half-wave potentials are not useful guides to the abilities of the N-O bonds in pyridine oxides to take part in oxygen transfer reactions, and in 4-nitropyridine 1-oxide the nitro group is reduced first . 

Azo-compounds can be obtained by reduction of nitro-compounds, or by oxidation of hydrazo-compounds. They are usually prepared, however, by reacting a phenol or amine with a diazonium salt. The coupling usually takes place in the position para to the hydroxyl or amino group, but if this position is occupied it goes to the ortho position, e.g. 

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. 

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