Hydroxylamine ethers

Eor antioxidant activity, the reaction of aminyl radicals with peroxy radicals is very beneficial. The nitroxyl radicals formed in this reaction are extremely effective oxidation inhibitors. Nitroxides function by trapping chain-propagating alkyl radicals to give hydroxylamine ethers. These ethers, in turn, quench chain propagating peroxy radicals and in the process regenerate the original nitroxides. The cycHc nature of this process accounts for the superlative antioxidant activity of nitroxides (see Antioxidants). Thus, antioxidant activity improves with an increase in stabiUty of the aminyl and nitroxyl radicals. Consequendy, commercial DPA antioxidants are alkylated in the ortho and para positions to prevent undesirable coupling reactions. 

A second mechanism involving as intermediate step a stable hydroxylamine ether (isopropyl I-ether) is also a possibility (reaction (15)). In a second step the ether would undergo cleavage by the acylperoxy radical with formation of isobutyric acid and acetone and liberation of the nitroxide (reaction (16)) ... 

The aUcoxylamines have a >N—O—C substrucmre and may be considered O-substituted hydroxylamine ethers. The simplest example of these species is MeONH2 with a gas phase enthalpy of formation of —25.1 kJmol which was discussed in a previous section. Consider now the perfluorinated species (CF3)2N0CF2CF20N(CF3)2 and its synthesis shown in equation 9. 

Additionally, we posit thermoneutrality for equation 11 in order to to derive the enthalpy of formation of the bis hydrocarbon hydroxylamine ether of —73 kJmol . ... 

The hydroxyquinoline (39-2) provides the starting material for a quinolone that incorporates a hydrazine function. Reaction of (39-2) with 2,4-dintrophenyl O-hydroxylamine ether (41-1) in the presence of potassium carbonate leads to a scission of the weak N-O hydroxylamine bond by the transient anion from the quinolone the excellent leaving character of 2,4-dinitrophenoxide adds the driving force for the overall reaction, resulting in alkylation on nitrogen to form the hydrazine (41-2). The primary amine is then converted to the formamide (41-3) by reaction with the mixed acetic-formic anhydride. Alkylation of that intermediate with methyl iodide followed by removal of the formamide affords the monomethylated derivative (41-4). Chlorine at the 7 position is then displaced by A-methylpiperazine and the product saponified. There is thus obtained amifloxacin (41-6) [48]. 

A rational extension of ortho-tolyl benzamide metalation [68], part of the broadly encompassing lateral metalation protocol [69] that can be DoM-connected, is the DreM equivalent, 154 —> 155 (Scheme 41), which provides a general regioselective route to 9-phenanthrols (156, 157, 158) [70] and may be extended to diaryl nitriles, hydroxylamine ethers, and hy-drazones 160, which provide the corresponding 9-amino derivatives 161 of similar generality 162-165 (Scheme 42), as may also be applied in natural product synthesis [71]. Further opportunities for DoM-cross-coupling and reduction/oxidation chemistry (159) have also been demonstrated [70a]. 

Reduction of oxime ethers and esters to hydroxylamine ethers and esters... 

Hindered nitroxyl radicals recombine with active alkyl radicals tOggivg hydroxylamine ethers. The rate of this reaction amounts to 10 10 L/mol. sec. i.e., nitroxyls are efficient acceptors of alkyl radicals they also react vigorously with hydroxyl radicals (37-38). 

Hydroxylamine ethers are poorer inhibitors than commonly used phenols and aromatic amines (rate constant for their reaction with Me2CNC00 radical in chlorobenzene at 65° is 1-20 L/mol. sec.)... 

Under thermal conditions, hydroxylamine ethers can reversibly decompose (Reaction 15). The radicals formed disproportionate to eliminate olefins and yield hydroxylamine (Reaction 16). In the presence of sufficiently effective acceptors of alkyl radicals (e.g., oxygen), the reaction rate of peroxy radical formation is much higher than that of hydroxylamine formation. Thus, in the process of polymer photooxidation, nitroxyl radicals regenerate and can break multiple oxidative chains. 

Analysis of reaction rate constants in model systems shows that at room temperature, the main reaction leading to regeneration of nitroxyl radicals is their interaction with peroxide radicals, (Reaction 11) and at elevated temperatures (more than 80°) the main reaction is that of hydroxylamine ether decomposition (Reaction 15) (53). 

Scheme 7. Reactions of hydroxylamines and hydroxylamine ethers in polymer stabilization.

Hindered amines have been found to function as radical scavengers (21) and to interact with species such as hydroperoxides (22.23). One key feature in the mechanism is the regenerative nature of this class of compounds, where the parent secondary amine is first converted to an active radical scavenger, the nitroxide radical, which then can undergo reactions leading to hydroxylamine and hydroxylamine ether. These species can then be reconverted to the nitroxide by (21)... 

G.A. Kovtun, A.L. Aleksandrov, and V.A. Golubev, Interaction of peroxide radicals with hydroxylamine ethers, Izv. Akad. Nauk. SSSR Ser. Kim. 1974, 2197. 

Another explanation of the UV protection mechanism of HALS involves the hydroxylamine ethers (XXIX) formed in Reaction 1.96. There is indirect evidence that (XXIX) can react very quickly with peroxy radicals, thereby regenerating nitroxyl radicals (Reaction 1.97). Reaction 1.96 and Reaction 1.97, which constitute the Denisov cycle, result in an overall slowdown of the usual chain oxidation Reaction 1.80 and Reaction 1.81. 

The hydroperoxides associated with HALS may undergo photolysis producing hydroxy and alkoxy radicals in close proximity to the amines. The radicals may then abstract a hydrogen atom from the amine and form hydroxylamine and hydroxylamine ethers (Reaction 1.103) ... 

Many studies have been made to identify the mechanism(s) by which HALS provide such effective UV stabilisation, and these have been reviewed [149-151]. Most authors agree that the >NH moiety is not, in fact, the stabilising species, but that >NO stable radicals and >NOR hydroxylamine ethers formed during photo-oxidation are the true antioxidant species. These are constantly regenerated the nitroxyl scavenging alkyl radicals and the hydroxylamine ethers intercepting hydroperoxy radicals and hydroperoxides. Hydroxylamines may also be formed, which are efficient photostabilisers in their own right. 

Tertiary hydroxylamine ethers, the main constituent in degraded polypropylene, lead preferentially to the formation of alkyl peroxides [Eq. (90c)j. 

In contrast to this behavior, HA(L)S derivatives show a more gradual deterioration of mechanical properties keeping some mechanical stability particularly at lower aging tempera-ttrres. This effect can be explained by a continuous oxidation of HA(L)S-based N-H functions into the N-0 radical by means of peroxy radicals and peracids (Figure 14). The total concentration of N-O radicals in polyolefins at low and moderate temperatures is higher than at elevated temperatures. In addition, intermediately formed hydroxylamine ethers are able to react quickly with peroxy radicals and peracids, which prevents the acceleration of oxidation processes at low temperatures. Scheme 6 gives an overview about various reactions of HA(L)S with hydroperoxides and peroxides. 

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