Reduction of nitro-groups

Nitropyridazines are reduced catalytically either over platinum, Raney nickel or palladium-charcoal catalyst. When an N-oxide function is present, palladium-charcoal in neutral solution is used in order to obtain the corresponding amino N-oxide. On the other hand, when hydrogenation is carried out in aqueous or alcoholic hydrochloric acid and palladium-charcoal or Raney nickel are used for the reduction of the nitro group, deoxygenation of the N- oxide takes place simultaneously. Halonitropyridazines and their N- oxides are reduced, dehalogenated and deoxygenated to aminopyridazines or to aminopyridazine N- oxides under analogous conditions. 

Hydroxyaminopyridazine 1-oxides are usually formed by catalytic hydrogenation of the corresponding nitro derivatives over palladium-charcoal in methanol, provided that the reaction is stopped after absorption of two moles of hydrogen. 3-Hydroxyaminopyridazine 1-oxide and 6-amino-4-hydroxyamino-3-methoxypyridazine 1-oxide are prepared in this way, while 5-hydroxyamino-3-methylpyridazine 2-oxide and 5-hydroxyamino-6-methoxy-3-methylpyridazine 2-oxide are obtained by chemical reduction of the corresponding nitro compounds with phenylhydrazine. 

Reduction of nitroaminopyridazines yields the corresponding aminopyridazines. Reductive cleavage of hydrazinopyridazines to give amino compounds is of practical significance in cases when halogen atoms are resistant to ammonolysis. Many substituted 3,4-diamino-, 4,5-diamino- and 3,5-diamino-pyridazines can be prepared in this way. 

Reduction of nitro groups to amines may occur under either aerobic or anaerobic conditions  

The complete sequence of reduction products was produced from 2,6-dinitrotoluene by Salmonella typhimurium strain TA 98 (Sayama et al. 1992)—2-nitroso-6-nitrotoluene, 2-hydroxylamino-6-nitrotoluene, and 2-amino-6-nitrotoluene. 

Reduction of nitroarenes has been demonstrated in species of Clostridium and Eubacte-rium, and was associated with the reduction in the mutagenic activity of 1-nitropyrene, and 

Anaerobic extracts of Clostridium acetobutylicum reduced 2,4,6-trinitrotoluene to 

Clostridium bifermentans reduced 2,4,6-trinitrotoluene to 2,4,6-triaminotoluene, and a metabolite was formed by reaction of one of the amino groups with methylglyoxal (Lewis et al. 1996). 

Aromatic nitro compounds are often straightforward to synthesise, and their reduction gives easy access to aromatic amines. A variety of reducing agents for conversion of nitro aromatics to amines have been used in microwave conditions, for example, metal powders (e.g., Zn, Fe, Sn) or other compounds that are easy to oxidise (e.g., SnCl2, hydrazine 

Compared to conventional methods, the microwave-assisted approach has a major advantage in requiring a very short reaction time. The method is technically simple and allows for the use of less hazardous reagents (e.g., KOH substituting the conventionally used NaOEt). Still, the reaction lacks from a drawback of being performed in a two-step sequence, with necessary isolation of the intermediate hydrazone. 

A further extension of the Huang-Minlon modification of the Wolff—Kishner reduction using similar conditions has also been reported66. 

Bose reported the dehalo genation of bromoanthracene, bromonaphthalene and several bromobenzenes under microwave-assisted hydrogen transfer conditions (ammonium formate, 10% Pd/C, ethylene glycol). An application of this reaction is the synthesis of several (3-lactams and isoquinoline derivatives14. 

Microwave heating was also successfully used in the preparation of more efficient catalysts for hydrodehalogenation reactions, although in these cases, the actual dehalo-genations with hydrogen gas were performed in a flow reactor under thermal conditions. 

FIGURE 13.35 Use of the different directing effects of the nitro and amino groups in synthesis. 

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This compound can be converted to l,5-diamino-4,8-dihydroxyanthraquiaone by reduction of nitro groups with sodium sulfide. 

Amino groups are formed by reduction of nitro groups in aryl substituents and behave normally (62JCS1671), but when attached directly to the pyridopyridazine ring they may be removed by acid hydrolysis or treatment with nitrous acid, or replaced by hydrazine. 

Other possibilities are the reduction of nitro groups by applying the sample solutions to adsorbent layers containing zinc dust and then exposing to hydrochloric acid vapors [110] 3,5-Dinitrobenzoates and 2,4-dinitrophenylhydrazones can also be reduced in the same way on tin-containing silica gel phases [111] Cellulose layers are also suitable for such reactions [112] Seiler and Rothweiler have described a method of trans-salting the alkali metal sulfates to alkali metal acetates [113]... 

The NH2 groups can be diazotized and reduced in the presence of thiosulphates and different metal ions. The effect of some metal ions, namely Fe ", Sn, Cu +, and Co on the graft yield of cotton modified with aryl diazonium groups via its reaction with 2,4-dichloro-6-(p-nitroaniline)-5-triazine in the presence of alkali and followed by reduction of nitro group was studied [4]. 

An easy approach to obtain amino-substituted phthalocyanines is the reduction of nitro groups, which are easily introduced into the macrocycle by condensation of the respective phthalonitrile. 

It has been shown that some reductases can mediate the reduction of nitro groups and of the ring to Meisenheimer-type complexes that are analogous to those that have been observed in nitrophenols (which are described later) ... 

Although the possibility of bioremediation of sites contaminated with nitrotoluene waste is clearly possible, important issues should be clearly appreciated. These include (a) additional carbon sources may be necessary to accomplish partial or complete reduction of nitro groups, (b) under aerobic conditions, dimeric azo compounds may be formed as terminal metabolites, and (c) aromatic amines may be incorporated into humic material by covalent bonding and thereby resist further degradation. 

Nitrocycloalkanones can be successfully C-allylated by Pd(0)-catalyzed reaction with various allyl carbonates and 1,3-dienemonoepoxides under neutral conditions, as shown in Eqs. 5.56 and 5.57, respectively.801 The product of Eq. 5.56 is converted into cyclic nitrone via the reduction of nitro group with H2-Pd/C followed by hydrolysis and cyclization.80b... 

Scheme 24 illustrates two examples for reduction of nitro groups as side-chain substituents to amino functions. 

Reduction of carboxylic acids and esters, aldehydes, and nitriles, and the hydro-boration of alkenes with diborane in non-ethereal solvents is highly effective (Table 11.8), but reduction of nitro groups or cleavage of arena-halogen bonds does not occur [1]. However, in spite of the potential advantages, very little use appears to have been made of the procedure. 

Bechamp reduction org chem Reduction of nitro groups to amino groups by the use of ferrous saits or iron and dilute acid. ba shan ri dok-shon ... 

The catalytic reduction of nitro groups is usually achieved using heterogeneous catalysts, although the iridium complex 28 has been shown to be effective for the reduction of p-nitroanisole 29 to the corresponding aniline 30 using isopropanol as the hydrogen donor (Scheme 8) [30]. In the reduction of some nitroarenes, azo compounds (Ar-N=N-Ar) could be formed as by-products or as the major product by variation of the reaction conditions. 

Table 15.3 Reductive and hydrolytic microbiaUy-mediated reactions of synthetic pesticides. R organic moiety Ar aromatic moiety (BoUag and Liu 1990) Reduction of nitro group...

Iron and acetic or dilute hydrochloric acid can be safely used for the reduction of nitro group to an amino group in nitro esters. The problem arises when a nitro ester is to be reduced to a nitro alcohol. Nitro groups are not inert toward the best reagents for the reduction of esters to alcohols, complex hydrides. However the rate of reduction of a nitro group by lithium... 

The LDso values for picric acid after oral dosing of male and female rats were 290 and 200 mg/kg, respectively. Death was due to severe acidosis, with toxic doses of picric acid exceeding the buffering capacity of the blood. In rats, metabolism of picric acid is primarily limited to reduction of nitro groups of the aromatic ring and subsequent conjugation by acetate. 

Nitro-2,3 -bipyridine is reduced to 4-amino-2,3 -bipyridine by iron and acetic acid, and other similar reductions of nitro groups have been reported. 2, 3-Diamino-2,3 -bipyridine on diazotization and heating affords j07,ii62... 

DESIGNING DRUG MOLECULES TO LIT RECEPTORS 92. Reduction of nitro groups... 

The reduction of nitro groups may also be catalyzed by microsomal reductases and gut bacterial enzymes. The reduction passes through several stages to yield the fully reduced primary amine, as illustrated for nitrobenzene (Fig. 4.39). The intermediates are nitrosobenzene and phenylhydroxylamine, which are also reduced in the microsomal system. These intermediates, which may also be produced by the oxidation of aromatic amines (Fig. 4.21), are involved in the toxicity of nitrobenzene to red blood cells after oral administration to rats. The importance of the gut bacterial reductases in this process is illustrated by the drastic reduction in nitrobenzene toxicity in animals devoid of gut bacteria, or when nitrobenzene is given by the intraperitoneal route. 

Reduction of nitro groups. The lithium anion of phthalocyaninecobalt(I), Li[Co(I)Pc], selectively reduces aliphatic and aromatic nitro compounds to primary amines at room temperature in 65 95% yield. Double bonds, nitriles, carhonyl groups, and aryl halides are not reduced. 

Hydrolysis of enamine, kelalization and reduction of nitro group... 

The 4-, 5-, 6- and 7-substituted aminoindoles are usually prepared using standard transformations of substituents introduced at ring closure, with the reduction of nitro groups being the usual method (72HC(25-2)268). 

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