8- Nitroquinoline reduction

An important example is the reduction of nitroquinoline N-oxide. This proceeds via the hydroxylamine, which is an extremely carcinogenic metabolite, probably the ultimate carcinogen (Fig. 4.40). 

Isoxazole rings were annelated onto 5-nitroquinoline and isoquinoline-based o-nitrobenzyl-p-tolylsulfones by treatment with potassium phenoxide, which acted as both base and reductant (Equation (42)) <95H(40)187>. In the cases of quinolines as starting materials, product benzisoxazoles (75) both with and without phenoxy substitution were obtained, but in the case of an isoquinoline starting material no phenoxy-substituted product was generated. The reaction is thought to proceed via a nitrosobenzylsulfone carbanion intermediate, and can be applied to nitronaphthalenes but not to less active nitrobenzenes. 

An important use of the traditional Skraup synthesis is to make 6-methoxy-8-nitroquinoline from an aromatic amine with only one free ortho position, glycerol, the usual concentrated sulfuric acid, and the oxidant arsenic pentoxide. Though the reported procedure uses 588 grams of As2Os, which might disconcert many chemists, it works well and the product can be turned into other quinolines by reduction of the nitro group, diazotization, and nucleophilic substitution (Chapter 23). 

Low valent species of transition metals (Groups IVB, VB and VIB) have found widespread use in the reduction of nitro compounds. Chromium(II) chloride, titanium(III) chloride and vanadium(II) sulfate readily reduce aromatic nitro compounds to arylamines. Chromium(II) chloride also reduces nitrobenzene and nitroquinoline to the corresponding amines in excellent yields. ... 

The nitro group of 4-nitropyridine-N-oxide (1) was hydrogenated preferentially over palladium in neutral medium -2 but in acid the N-oxide was also reduced (Eqn. 19.1).2 Hydrogenation of 1 or 4-nitroquinoline-N-oxide over Raney nickel at elevated temperatures and pressures resulted in the reduction of both the nitro group and the N-oxide.3.4 Hydrogenation of 2-nitropyridine-N-oxide gave only 2-aminopyridine.5... 

Heald repeated the same reduction of 6-nitroquinoline (147) at a higher temperature and isolated 1-ethyl-l,2-dihydro-6-nitroquinoline (148), the product of reductive alkylation. With quinoline and NBH in carboxylic acids the Aralkyl-1,2,3,4-tetrahydroquinoline 149 is obtained. Use of sodium cyanoborohydride gives reduction but no alkylation (150). In the presence of acetone, l-isopropyl-l,2,3,4-tetrahydroquinoline (151) is the predominant compound. Quinoline W-oxides undergo deoxygenation, and some ring reduction with NBH. ... 

Replacement, after first formulation]. Note, however,... and formulas < 1)—(2) Note, however, that under the same conditions 6-nitroquinoline (1) affords (2) and (3), while reduction of 2-nitronaphthalene yields (4) and (5).lb... 

Quinones such as the anti-cancer drug adriamycin can undergo one-electron reduction catalysed by NADPH cytochrome P-450 reductase. The semiquinone product may be oxidized back to the quinone with the concomitant production of superoxide anion radical, giving rise to redox cycling and potential cytotoxicity (see Chapter 6). An important example is the reduction of nitroquinoline N-oxide. This proceeds via the hydroxylamine, which is an extremely carcinogenic metabolite, probably the ultimate carcinogen (figure 4,391. 

Scheme 8. In fact, when placed in the reaction medium in the dark, (23) gives a product distribution similar to that observed in the photochemical reaction. In contrast with reduction in alcohols, the quantum yield in aqueous HC1 drops rapidly with decreasing HC1 concentration ( = 0.11 in 12moll-1 HC1, but = 0.012 in 6 mol l-1 HC1 48 whereas in 50% aqueous propan-2-ol, is constant at >0.1 mol l-1 HQ 47). Both this dependence of quantum yield on acidity and some radical scavenging observed when phenol or anisole (chlorine atom traps) are present are in accord with the mechanism outlined in Scheme 8. Cu and Testa49 have found that the 313 nm irradiation of protonated 5-nitroquinoline...

The problem of nitration with aqueous nitric acid was reviewed by Hanson and associates [8]. They confirmed the idea of nitracidium ion being a nitrating agent and pointed out that attention should be paid to the presence of nitrous acid in the system, as nitration with dilate nitric acid can proceed through the nitrosation by nitrous acid formed as the result of oxidation—reduction. T. Urbahski and Kutkiewicz [9] (Vol. I, p. 85) found that 8-hydroxyquinoline can be nitrated by boiling with 0.5% nitric acid to yield 5,7-dinitro-8-hydroxyquino-line. It was also found that 8-hydroxy-5-nitroquinoline yielded the same dinitro derivative. 

In fig 2 is displayed the first derivative of the sampled voltammograms derived from single and double potential step chronoamperometric measurements for the reduction of 4-nitroquinoline-N- oxide on a T1 upd platinum electrode. The reduction of heterocyclic nitro compounds follows an E.C.E. mechanism. 

However in the case of 4-nitroquinoline -N- oxide the chemical step is fast relative to the rate of mass transport in the time scales of our experiment and the electrochemical reaction is controlled by diffusion. The product of the first reduction step of p-nitroquinoline -N- oxide undergoes very rapidly a chemical change to form R-NO which is further reduced to form R-NHOH. Single step chronovoltammetry gives no direct evidence for the existence of this reaction. 

Aliphatic and aromatic nitro compounds are reduced at relatively positive potentials via the hydroxylamines to the corresponding amines. The carcinogenic 4-nitroquinoline-/V-oxide is determined by DPP in the presence of 4-hydroxyam-inoquinoline-/V-oxide and 4-aminoquinoline-/V-oxide via the reduction of the nitro group [79]. Nitrazepam, parathion, nitrofurantoin, and the ni-troimidazoles in blood plasma or urine are also determined via the reduction of the respective nitro groups. 

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