Derivatives of Fluorene. IV. Raney Nickel-Hydrazine Hydrate Reduction of Various Mono- and Dinitrofluorene Derivatives; Some New 9-Substituted Fluorenes¹

Abstract

A Raney nickel-hydrazine hydrate method for reducing aromatic nitro groups has been extended to fluorene derivatives including those having >0=0, >C=C<, NHCOCF3 and other functional groups, and dinitro compounds. For the less soluble substances, certain specific directions must be followed, but most yields were 90% or higher and the first crop out of the reaction mixture was of good quality. A nitro compound with an azomethine linkage gave a product with both functions reduced. Some new substances are described.The convenient steam bath reduction, in excellent yields, of some aromatic nitro compounds to amines with Raney nickel and hydrazine hydrate in ethanol was reported by Balcom and Furst.2 3Since then, a few reports8•4 have appeared in which this method has been tried on one or two nitro compounds with good results, after failure or poor results with other methods. This work is presented because there have been several recent reports of reduction of nitrated derivatives of fluorene in poor yield or by methods more tedious than this, because we have found this reaction, with few exceptions, thoroughly satisfactory, and because in certain of the procedures, notably with dinitro compounds and fluorenone derivatives, simple but necessary precautions must be observed.It was found,5 and confirmed,2 that without a catalyst nitro compounds did not undergo reduction at room temperature. Some can be reduced to the amine in refluxing alcohol by hydrazine hydrate alone5•6 but yields are often low and the reaction is slow. Higher temperatures often lead to side reactions. Recently, reduction with palladized charcoal and hydrazine hydrate was reported.7 Yields,

Hypoxia-Selective, Enzymatic Conversion of 6-Nitroquinoline into a Fluorescent Helicene: Pyrido[3,2-f]quinolino[6,5-c]cinnoline 3-Oxide

“…38,39 Indeed, the LC/MS spectra of the 19.4 min product matched that of an authentic sample of 3 prepared via reduction of 1 by hydrazine hydrate in the presence of Raney nickel (Figures 2E and F). 40,41 Importantly, 3 displayed no fluorescence in aqueous buffer and, therefore, could not account for the fluorescence generated by the hypoxic metabolism of 1 . Accordingly, we turned our attention to the product eluting near 15 min in the LC/MS.…”

Hydrazine as a Reducing Agent for Organic Compounds (Catalytic Hydrazine Reductions)

“…Without catalysts, 4,4'-dinitrodiphenyl sulfide is smoothly reduced to the diamine with no thioether cleavage (127,152). Fletcher and Namkung (63) confirmed that, in the main, carbonyls are unaffected by this procedure. However, an almost quantitative reduction of 2-nitrofluorenone to its amine was obtained with a side product of 3% 2-aminofluorenol.…”

“…Catalysts can 143),Pd-CaC03(l%) (31), Ni (69,82,128,165), or Cu (101). It appears that the rate of reduction of these intermediates is such that azobenzene (XXX), while it can be isolated, tends to go to hydrazobenzene (XXXI) (19,31,35,44,63,82,106,127) in high yields regardless of the catalyst used; even Ru-C will catalyze this reaction (143). Azo dyes like methyl orange and methyl red are easily reduced to the hydrazo in the presence of Cu (106).…”

Enzymatic Conversion of 6-Nitroquinoline to the Fluorophore 6-Aminoquinoline Selectively under Hypoxic Conditions

“…This compound can be envisioned to arise from the condensation of 6-nitroso and 6-hydroxylamino intermediates generated in the reductive metabolism of 1. 57,58 Indeed, LC-MS of an authentic sample of 3 prepared by reduction of 1 with hydrazine hydrate in the presence of Raney nickel 54,59,60 matched the 13 min metabolite generated in the hypoxic metabolism of 1. 59,60 Compound 3 is not fluorescent in aqueous buffered solution 54 indicating that this product did not contribute to the fluorescence observed in Figure 1.…”

“…A second, relatively minor product eluting around 13 min produced an [M + H] + at m / z 301 consistent with the compound 6,6′-azoxyquinoline ( 3 , Scheme ). This compound can be envisioned to arise from the condensation of 6-nitroso and 6-hydroxylamino intermediates generated in the reductive metabolism of 1 . , Indeed, LC-MS of an authentic sample of 3 prepared by reduction of 1 with hydrazine hydrate in the presence of Raney nickel ,, matched the 13 min metabolite generated in the hypoxic metabolism of 1 . , Compound 3 is not fluorescent in aqueous buffered solution indicating that this product did not contribute to the fluorescence observed in Figure . We note that the azoxy compound 3 was observed using thin-layer chromatography prior to concentration of the reaction mixtures.…”