Nitroxyl catalytic cycles

The reaction of nitric oxide with superoxide dismutase is a simple reversible equilibrium, whereas the catalytic cycle with superoxide involves a two step sequence. Consequently, superoxide dismutase may be reduced by superoxide and then react with nitric oxide to form nitroxyl anion. Nitroxyl anion may react with molecular oxygen to form peroxynitrite anion (ONOO"). 

Stable organic nitroxyl radicals are of relatively recent use as catalysts in the oxidation of alcohols. Nitroxyl radicals are compounds that contain the A ,A -disubstituted NO-group with one unpaired electron, and their uses have been reviewed.124 The most simple radical of this class is 2,2,6,6-tetramethylpiperidin-l-oxyl (43, TEMPO). It is generally assumed that the active oxidizing species, the oxoammonium salt (44), is formed in a catalytic cycle by a one-electron oxidation of the nitroxyl radical by a primary oxidant [two-electron oxidation of the hydroxylamine (45) is also possible, depending on the primary oxidant] (Scheme 21). 

TEMPO and other organic nitroxyls have been used as catalysts in combination with numerous stoichiometric oxidants, such as sodium hypochlorite [24], PhI(OAc)2 [25], and sodium chlorite [26]. A number of recent studies have shown that NO -based redox cocatalysts enable these reactions to be conducted with O2 as the terminal oxidant [27]. The general catalytic cycle for these aerobic nitroxyl/NO -catalyzed alcohol oxidation reactions is depicted in Scheme 15.6a. A variation of this approach features halides as additives, in which the X2/HX redox couple is believed to mediate the NO2/NO and oxoammonium/hydroxylamine redox couples (Scheme 15.6b). 

Scheme 15.6 General proposed catalytic cycles for (a) NO - and nitroxyl-catalyzed aerobic alcohol oxidation and (b) NOj -, Xj-, and nitroxyl-catalyzed aerobic alcohol oxidation.

The mechanism of the reaction was not studied, but a catalytic cycle similar to that in Scheme 15.6a is likely. Subsequently, there have been numerous other reports of nitroxyl/NOj catalytic systems for aerobic alcohol oxidation [30], including the chemoselective oxidation of primary over secondary ahphatic alcohols [31], and application to the oxidation of hgnin, in which secondary benzyhc alcohols are oxidized in preference to primary aliphatic alcohols [32]. 

When the halide source was omitted from the nitroxyl/hahde/NO catalyst systems, little catalytic activity was observed, indicating that the halide-free nitroxyl/NO catalytic cycle in Scheme 15.6a is not viable under the reported conditions. This outcome may reflect ineffective conversion of the NO source (e.g., a nitrate or a nitrite) into NO/NOj in the absence of a halogen. 

In the biochemical context, it has been well noted that the chemistry of NO (and of its conjugated acid, FINO (i8)) is quite distinct from that of NO (22). Its occurrence in catalytic cycles of NO synthase, nitrite reductase, and nitric oxide reductase (NOR) has been postulated (23). For example, in the multi-iron containing enzyme NOR two NO molecules are converted reductively to nitrous oxide, N2O, with nitroxyl (NO ), and hyponitrite (N202 ) (24) as putative intermediates (23). 

Nitroxyl (HNO/NO ) heme-model complexes ( FeNO , according to the Enemark-Feltham notation) have received special attention due to the intermediacy of nitroxyl-heme adducts in a variety of catalytic processes related to the biogeochemical cycle of nitrogen (104). For example, for the six-electron reduction of nitrite to ammonia that is catalvzed by cytochrome c nitrite reductase (ccNir), a heme FeNO complex is proposed as an intermediate (Scheme 5) (105,106). This intermediate has also been suggested for the reduction of NO to N2O by P450nor (Scheme 6) (107). Then, the isolation of a suitable FeNO heme complex that allows structural and functional characterizations will help to imderstand the reaction mechanism of ccNir and other enz5mies. 

The TMPs behave similarly to the diaryl nitroxyls in rubber (page 58) and catalytically destroy both macroalkyl and macroalkylperoxyl radicals in the cyclical mechanisms described in reactions (3.8) and (3.9). The aminoxyl (nitroxyl) radicals, > N-O, trap macroalkyl radicals formed in the polymer and, to complete the cycle, the macroalkyl hydroxylamines, > N-OP, formed are reoxidised to aminoxyl by per-oxidic species (such as acylperoxyl and acylhydroperoxides) formed in the polymer (Scheme 3.9). 

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