Oxidation aminoxyl radicals

In atmospheric chemistry, reactions between pure nitric oxide and a range of activated alkenes have been examined. However, no addition products were observed." Only in the presence of NO2 was addition to give jS-nitroalkyl radicals, followed by trapping to /3-nitronitroso compounds, observed. These final products can also trap other radicals to give aminoxyl radicals. 

Besides this hydrogen atom transfer (HAT) route, the aminoxyl radical may also take part in oxidation procedures where, through a preliminary monoelectronic step, it is converted into an oxoammonium ion (R2N=0+), or variations of this route. Examples of... 

It is appropriate to summarize here relevant data of both the aminoxyl radicals and their precursors that are useful for the ensuing discussion. Hydroxylamine (H2NOH) is the precursor of the archetypal aminoxyl radical (HaNO ). Upon one-electron oxidation of H2NOH by a suitable oxidant, e.g. Ce, the formation of H2NO (plus one proton) has been documented by the first step being the formation of the transient radical... 

The Fremy s salt (nitrosodisulfonate), whose properties as a selective oxidant have been reviewed , and bis(trifluoromethyl)aminoxyl radical, (CF3)2N—O" which has been... 

Persistent or moderately stable aminoxyl radicals (1, in Scheme 6) lend themselves to one-electron oxidation to yield an oxoammonium ion (4) at a redox potential that depends on the structure of the hydroxylamine precursor Calculation methods have... 

SCHEME 6. Oxidation of an alcohol by the oxoammonium ion 4 derived from an aminoxyl radical 1... 

TABLE 3. Redox data for the monoelectronic oxidation of aminoxyl radicals... 

Table 1 shows that iV-hydroxyphthalimide (HPI) presents features almost opposite to those of TEMPO. In fact, the dissociation energy of the NO—H bond in HPI (88 kcal moR ) , accessible through EPR measurements" , is much higher than that of the corresponding NO—H bond in the hydroxylamine moiety of TEMPO (viz. TEMPOH, 69 kcalmoR ) . TEMPO is a persistent aminoxyl radical , whereas the aminoxyl radical of HPI, dubbed PINO (phthaUmide-N-qxyl)", is not stable but endowed with a half-life of ca 8000 s in AcOH solution at 25 °C . By using an oxidant such as a Pb(OAc)4 , or a Co(III) salt " " , HPI can be oxidized into PINO, and the H-abstraction reactivity of the latter subsequently exploited in the catalytic oxidation of appropriate H-donor substrates (RH) (Scheme 7). 

More recently, the soundness of the electrochemical approach for the generation of PINO from HPI has been confirmed by using cyclic voltammetry at a rotating disk electrode. Anodic oxidation had been also employed for the generation of the aminoxyl radical from hydroxamic acids. ... 

Another transient aminoxyl radical has been generated , and employed in H-abstraction reactivity determinations" . Precursor 1-hydroxybenzotriazole (HBT, Table 2) has been oxidized by cyclic voltammetry (CV) to the corresponding >N—O species, dubbed BTNO (Scheme 9). A redox potential comparable to that of the HPI —PINO oxidation, i.e. E° 1.08 V/NHE, has been obtained in 0.01 M sodium acetate buffered solution at pH 4.7, containing 4% MeCN". Oxidation of HBT by either Pb(OAc)4 in AcOH, or cerium(IV) ammonium nitrate (CAN E° 1.35 V/NHE) in MeCN, has been monitored by spectrophotometry , providing a broad UV-Vis absorption band with A-max at 474 nm and e = 1840 M cm. As in the case of PINO from HPI, the absorption spectrum of aminoxyl radical BTNO is not stable, but decays faster (half-life of 110 s at [HBT] = 0.5 mM) than that of PINO . An EPR spectrum consistent with the structure of BTNO was obtained from equimolar amounts of CAN and HBT in MeCN solution . Finally, laser flash photolysis (LFP) of an Ar-saturated MeCN solution of dicumyl peroxide and HBT at 355 nm gave rise to a species whose absorption spectrum, recorded 1.4 ms after the laser pulse, had the same absorption maximum (ca 474 nm) of the spectrum recorded by conventional spectrophotometry (Scheme 9)59- 54... 

Another facet of the reactivity of aminoxyl radicals has been brought to attention by recent studies of the oxidation of substrates endowed with low redox potential. Some aminoxyl radicals, depending on the reduction potential value of the couple >N—O / >N—O, can behave as moderate one-electron abstractor towards substrates endowed with appropriate oxidation potential. This rather unprecedented reactivity feature, outlined in Scheme 10, has been substantiated by the oxidation of aniline or phenol derivatives, whose redox potential is conveniently located in the 0.4-1.0 V/NHE range ". 

As opposed to such a consistent body of evidence in favour of the H-abstraction route with aminoxyl radical intermediates, the reactivity features of the oxoammonium ion , as a derivative of the aminoxyl radical (TEMPO), are somewhat baffling (Section III.E). In spite of the many studies from the literature, a lack of uniformity emerges whenever the Hammett and KIE parameters are investigated and compared. The possible interplay of different mechanistic routes has been suggested, and more experimental work is needed before satisfactory conclusions can be drawn. Certainly, this does not undermine the synthetic value of the procedure, as we will see below, even though care must be exerted when comparing results obtained by the use of different primary oxidants. 

Following the discussion on the reactivity features of exemplary aminoxyl radicals, it is now time to deal with applications of those concepts to valuable oxidative... 

Minisci and coworkers followed Ishii s procedure, and implemented it in the oxidation of benzyhc alcohols to benzaldehydes in almost quantitative yields" (Table 12). A,Af-dimethylbenzylamines were converted into aldehydes in good yields, by using catalytic amounts of either HPI or A-hydroxysuccinimide (HSI) for the formation of the corresponding aminoxyl radical intermediates. Because the attempted oxidation of primary and secondary amines caused the degradation of catalyst HPI, protection of the amino group in those substrates by acetylation was considered. This led one to develop... 

In conclnsion, TEMPO is an aminoxyl radical very valnable for synthetic pnrposes, not jnst as snch bnt in its oxidized form, most likely the TEMPO-oxoammoninm ion. Many recipes are available (Table 13), which allow synthetic transformations endowed with high efficiency and mild operating conditions. One needs to search and choose the one recipe that most likely fits the specihc needs, withont indnlging too mnch in mechanistic considerations that are perhaps still far from a fnlly exhanstive assessment. 

Primary benzylic alcohols are oxidized to aldehydes in good yields without overoxidation (entry 1) lowering the pH from 5 to 3.5 increases the conversion, for reasons not fnUy understood yet (entry 2) . The aminoxyl radical is an electrophilic species" ... 

The aminoxyl radicals lend themselves to synthetically interesting procedures of oxidation, both in the radical form itself and in the oxoammonium form (from TEMPO). Major advantages appear to be the mild operating conditions, the range of substrates susceptible to transformation and the selectivity in the oxidation of specific structural motifs. 

A new catalytic system consisting of a persistent macrocyclic aminoxyl radical and the couple Mn(N03)2-Co(NC>3)2 for the aerobic oxidation of alcohols to carbonyl compounds has been developed. The rate-determining step has been identified by studying the effect of substituents on the oxidation of benzyl alcohol. The chemistry of aminoxyl, amidoxyl, and imidoxyl radicals has been discussed.265... 

The nitroxyl radical TEMPO (18a) is an active catalyst for the selective oxidation of alcohols, with hypochlorite as the oxidant. The actual oxidizing species is the oxoaminium ion (18b), which in the alcohol oxidation (I in the structure) is reduced to the hydroxylamine (18c). A catalytic amount of bromide is used to generate BrO , which is capable of reoxidizing the hydroxylamine or the aminoxyl radical (18a) to the oxoaminium stage (408). 

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