Alcohols oxidation with nitroxyl radical

As noted above, the duration of the retarding action of an inhibitor is directly proportional to the / value. In systems with a cyclic chain termination mechanism, the / coefficient depends on the ratio of the rate constants for two reactions, in which the inhibitor is regenerated and irreversibly consumed. In the oxidation of alcohols, aminyl radicals are consumed irreversibly via the reaction with nitroxyl radical formation (see earlier) and via the following reaction [11] ... 

The method uses a simple electrode made of a thin film of sol-gel organosilica doped with nitroxyl radicals deposited on the surface of an indium tin oxide (ITO) electrode. Thus, whereas in water benzyl alcohol is rapidly oxidized to benzoic acid, the use of the hydrophobic sol-gel molecular electrode TEMPO DE affords benzaldehyde only (Figure 1.9), with an unprecedented purity, which is highly desirable for the fragrance and pharmaceutical industries where this aromatic aldehyde is employed in large amounts. 

Organic acids retard the formation of nitroxyl radicals via the reaction of the peroxyl radical with the aminyl radical [10], Apparently, the formation of a hydrogen bond of the >N H0C(0)R type leads to the shielding of nitrogen, which precludes the addition of dioxygen to it, yielding the nitroxyl radical. Thus, the products of the oxidation of alcohols, namely, acids have an influence on the mechanism of the cyclic chain termination. 

Nitroxyl radicals (AmO ) are known to react rapidly with alkyl radicals and efficiently retard the radical polymerization of hydrocarbons [7]. At the same time, only aromatic nitroxyls are capable of reacting with alkylperoxyl radicals [10,39] and in this case the chain termination in the oxidation of saturated hydrocarbons occurs stoichiometrically. However, in the processes of oxidation of alcohols, alkenes, and primary and secondary aliphatic amines in which the chain reaction involves the HOT, >C(0H)02 , and >C(NHR)02 radicals, possessing the... 

Oxidative Animation of Nitrones to a-Amino-Substituted Nitroxyl Radicals Similar to the oxidative methoxylation reaction, oxidative animation of 4H -imidazole TV-oxides, in amine saturated alcohol solutions, give stable nitroxyl (282), nitronyl nitroxyl (283), imino nitroxyl (284) and (285) radicals with the amino group at the a-carbon atom of the nitroxyl group (Scheme 2.107) (520, 521). The observed influence of substituents on the ratio of animation products at C2 and C5 atom is close to the ratio observed in the previously mentioned oxidative methoxylation reaction. It allows us to draw conclusions about the preference of the radical cation reaction route. 

Oxidation of —CHtOH — —CHO (cf., 12,479-480). This oxidation can be effected in high yield with sodium hypochlorite (slight excess) in buffered H20/ CH2C12 with this nitroxyl radical and KBr as the catalysts.1 The oxidation is exothermic, and the temperature should be maintained at 0-15° with a salt-ice bath. Saturated primary alcohols are converted to aldehydes in 88-93% yield yields are lower in the case of unsaturated substrates. Addition of quaternary onium salts permits further oxidation to carboxylic acids. 

A report was concerned with the ability of nitroxyl radicals, such as TEMPO and other related structures, to act as catalysts in the asymmetric oxidation of alcohols. Cyclic voltammetry was used to measure the oxidation potentials of the nitroxyl... 

The oxidation of primary and secondary alcohols by stable organic nitroxyl radicals has been reviewed.111 The kinetics of reactions of alkanes and arenes with peroxynitrous acid suggest the participation of the same active oxidizing species in both gas and aqueous phase HOONO or its decomposition product OONO. 112 The oxidation of the alkaloids reserpine and rescinnamine by nitric acid has been studied.113... 

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). 

The oxidation of alcohols to carbonyl compounds with the stable nitroxyl radical TEMPO (86) as catalyst is a well-known preparative method [134, 135]. Hypochlorite or peracetic acid is usually used as the final oxidizing agent and ca. 1 mol% of catalyst 86 is used. In 1996 Rychnovsky et al. reported the synthesis of the chiral, binaphthyl-derived TEMPO analog 87 [136], Results obtained by use of 0.5-1 mol% of catalyst 87 [136] are listed in Table 10.12. In these oxidation reactions 0.6-0.7 equiv. sodium hypochlorite were used as the final oxidizing agent (plus... 

The nitroxyl-based systems are the most important and widely investigated homogeneous catalysts for the aerobic and non-aerobic oxidation of alcohols [9]. The different mechanisms with persistent (Scheme 1) and nonpersistent (Scheme 2) nitroxyl radicals is reflected in the selectivity of primary alcohol oxidation. Several... 

In an alternative application of asymmetric alcohol oxidation, Rychnovsky has reported the use of the chiral nitroxyl radical 34 (Fig. 12.14) along with bleach, allowing kinetic resolution of secondary alcohols [89]. The best substrates were simple benzylic alcohols, for which S factors (= ks/kR) were in the range 3.9 to 7.1 (Scheme 12.22). Other chiral C2-symmetric nitroxyl radicals reported recently give lower selectivities [90]. 

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). 

A combination of RuCl2(Ph3P)3 and the stable nitroxyl radical, 2,2, 6,6 -tetra-methylpiperidine-N-oxyl (TEMPO) is a remarkably effective catalyst for the aerobic oxidation of a variety of primary and secondary alcohols, giving the corresponding aldehydes and ketones, respectively, with above 99% selectivity [87]. The best results were obtained using 1 mol % of RuCl,(Ph3P)3 and 3 mol % of TEMPO (Eq. 21). 

TEMPO is a commercially available nitroxyl radical-containing reagent that catalyzes the oxidation of primary and secondary alcohols in conjunction with co-oxidants (oxygen, hypochlorite, bromite, hypervalent iodine, or peroxy acids).The catalyst is particularly useful for the oxidation of optically active a-alkoxy- or a-amino alcohols to the corresponding aldehydes without loss of enantiomeric purity. ... 

Early reports of Cu-catalyzed aerobic alcohol oxidation focused on simple homogeneous complexes [11] with nitrogenous ligands, such as 2,2 -bipyridine and 1,10-phenanthroline. However, copper-catalyzed methods that include nitroxyl radical or azodicarboxylate cocatalysts exhibit significant synthetic advantages and have been widely investigated in the literature (Figure 6.1). 

There is extensive history on the use of stoichiometric and catalytic organic nitroxyls for alcohol oxidation, wherein the key step involves a reaction between the alcohol and an JV-oxoammonium salt (Scheme 15.5, featuring TEMPO) [18, 20]. The JV-oxoammonium salt can be formed in situ from the corresponding nitroxyl radical using various oxidants, such as NaOCl or NO2 (Scheme 15.5, top left), or by acid-induced disproportionation of the nitroxyl into N-oxoammonium and hydroxylamine species (Scheme 15.5, bottom left) [21]. Stable Af-oxoammonium salts have also been isolated and used directly as reagents or catalysts for alcohol oxidation [22]. The pH-dependent mechanism of the reaction of the Af-oxoammonium salt with alcohols has been studied... 

The stable, commercially available nitroxyl radical 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) 51 is an excellent catalyst, in conjunction with a co-oxidant, for the oxidation of alcohols. The most popular co-oxidant is buffered sodium hypochlorite (NaOCl). Oxidation of the nitroxyl radical gives the oxoammonium ion 52, which acts as the oxidant for the alcohol to form the carbonyl product. Primary alcohols are oxidized faster than secondary and it is often possible to obtain high chemoselectivity for the former. For example, oxidation of the triol 53 gave the aldehyde 54, with no oxidation of the secondary alcohols (6.44). The use of TEMPO is particularly convenient for the oxidation of primary alcohols in carbohydrates, avoiding the need for protection of the secondary alcohols. 

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