Hydroxylamine, condensation with oxidation

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

Formyl C-glycosides, prepared in three steps via the thiazole-based formy-lation of sugar lactones are readily condensed with hydroxylamine to give the corresponding oximes. The latter are the precursors of glycosyl nitrile oxides via the N-bromosuccinimide method (41). 

Oxidation of primary amines with DMD or other oxidants leads to the formation of a complex mixture of nitroso, oximes, and nitro compounds (76). Utilization of DMD in acetone affords dimethyl nitrone (22). This is likely to be a result of the initial oxidation of primary amine (19) to hydroxylamine (20) with the subsequent condensation of acetone and oxidation of imine (21) (Scheme 2.9) (77). 

Starting material which, upon oxidation with PSP, gave aldehydes. These were in turn condensed with primary hydroxylamines, promoted by polymer-bound acetate, to produce nitrones. The nitrones assembled using either method then underwent 1,3-dipolar cyclo-addition reactions with various alkenes to give the corresponding isoxazolidines (Scheme 2.46 and 2.47). 

Catalytic hydrogenation of iV-(o-nitrophenyl)aminoacetonitriles 192 with palladium(ll) oxide hydrate gives high yields of quinoxaline A -oxides 193 through condensing the reduced hydroxylamine intermediate with nitrile (Equation 31) <2001EJ0987>. 

In a similar reaction, 2-(o-nitrophenyl)ethylamine (100) may be reduced in an ammonia buffer to the hydroxylamine and oxidized to the nitroso derivative, which condenses with the amino group to a dihydrocinnoline.160,161 It is also possible to prepare dihydrobenzo-l,2,3-triazinones on reduction of o-nitrobenzhydrazide, followed by oxidation of the hydroxylamine to a nitroso group, and 3-phenyldihydrobenzo-l,2,3-triazine (101) from N-phenyl-(V-(o-nitrobenzyl)hydrazine (100) in an analogous way161 [Eq. (78)]. 

V,/V-Bis(trifluoromethyl)hydroxylamine (5) is oxidized with potassium permanganate in acetic acid to an interesting free-radical compound, bis(trifluoromethyl)nitroxid-A7-yl(6), a pink-violet gas which condenses to a deep brown-violet liquid.246 Various oxidizing agents are effective in the oxidation of 5 to the corresponding nitroxyl 6.247 The best appears to be cerium(IV) salts either in the solid state or in aqueous acid solution.247 Efficient oxidation processes have been developed using aqueous potassium persulfate solutions, or electrochemical oxidation with cerium(III) nitrate and sodium nitrate in dilute nitric acid.247... 

An iron-catalyzed reaction of an a,P-unsaturated oxime such as 68 with a P-oxo ester also gave pyridine derivatives such as nicotinic acid 69 [99]. Under the reaction conditions (150-160 °C, without solvent) first Michael adducts such as intermediate 70 are presumably formed, which further condense via intermediate 71. This method is not restricted to a centric symmetry in the substitution pattern, which is an advantage compared with the Hantzsch synthesis. Moreover, the method starts with hydroxylamine being two oxidation stages above ammonia therefore, no oxidation in the final stage from dihydro- to pyridine is necessary (Scheme 8.31). 

To produce a 1,2-azole, a 1,3-dicarbonyl-compound needs to be condensed with a unit providing the two heteroatoms - a hydrazine or hydroxylamine. The 1,3-dipolar cycloaddition of nitrile oxides or nitrile imines to alkynes provides an important route to isoxazoles and pyrazoles. 

Hydrogen transfer from hydrazobenzene to benzofuroxan (622) results in azobenzene and o-benzoquinone dioxime (623). Compound (622) reacts with formaldehyde to yield the benzimidazolinone (624). Chlorobenzofuroxan aldehyde condenses with derivatives of hydroxylamine or hydrazine to yield oximes or hydrazones (625 R = OH, OMe, NHPh, NMe2, etc.), which rearrange thermally to indazoles (626). Treatment of 7-methoxy-4-nitro-benzofurazan 1-oxide with aqueous potassium hydroxide affords a mixture of the corresponding 7-hydroxy-compound (627) and the rearranged 5-hydroxy-4-nitrobenzofuroxan (628). ... 

Cyclic nitrone 32 was simply prepared from commercially available phenylglycinol (33). Thus, three-step indirect oxidation of (i )-33 afforded hydroxylamine (7f)-34, which was condensed with glyoxybc acid, and then the resulting nitrone was cycbzed by treatment with dehydrated p-toluenesulfonic acid, giving rise to (R)-32 in 79% yield (three steps) [23a,d]. The enantiomer (S)-32 was also prepared from (5)-33, and the structure was confirmed by X-ray crystallography (Scheme 6.13) [23b]. 

Oxidative reactions of organonitrogen species that do not involve molecular oxygen are rather limited. The only case for which the evidence is at all convincing is the oxidation of arylhydroxylamines to arylnitroso species (Table 2). This reaction resembles the first half of the hydroxylamine oxidoreductase reaction found in nitrifying bacteria. The key difference is that the aryl nitroso compound is stable (although condensation with the arylhydroxy-lamine can occur to produce the azoxy compound, ArN(O)NAr), while the inorganic analog is nitroxyl, HNO, which if released from the enzyme would rapidly dimerize and dehydrate to form N2O. Consequently, HAO does not release the HNO or NO intermediate, but instead oxidizes it to nitrite before any substrate-derived species are released. 

Hydroxylamine sulfate is produced by direct hydrogen reduction of nitric oxide over platinum catalyst in the presence of sulfuric acid. Only 0.9 kg ammonium sulfate is produced per kilogram of caprolactam, but at the expense of hydrogen consumption (11). A concentrated nitric oxide stream is obtained by catalytic oxidation of ammonia with oxygen. Steam is used as a diluent in order to avoid operating within the explosive limits for the system. The oxidation is followed by condensation of the steam. The net reaction is... 

A -Isoxazolines are readily available from the 1,3-dipolar cycloaddition of nitrile -oxides with alkenes and from the condensation reaction of ehones with hydroxylamine. Therefore, methods of conversion of -isoxazolines into isoxazoles are of particular interest and of synthetic importance. 

The most widely employed methods for the synthesis of nitrones are the condensation of carbonyl compounds with A-hydroxylamines5 and the oxidation of A+V-di substituted hydroxylamines.5 9 Practical and reliable methods for the oxidation of more easily available secondary amines have become available only recently.10 11 12 13. These include reactions with stoichiometric oxidants not readily available, such as dimethyldioxirane10 or A-phenylsulfonyl-C-phenyloxaziridine,11 and oxidations with hydrogen peroxide catalyzed by Na2W044 12 or Se02.13 All these methods suffer from limitations in scope and substrate tolerance. For example, oxidations with dimethyldioxirane seem to be limited to arylmethanamines and the above mentioned catalytic oxidations have been reported (and we have experienced as well) to give... 

Nitrones have been generally prepared by the condensation of /V-hydroxylamines with carbonyl compounds (Eq. 8.40).63 There are a number of published procedures, including dehydrogenation of /V,/V-disubstituted hydroxylamines, / -alkylation of imines, and oxidation of secondary amines. Among them, the simplest method is the oxidation of secondary amines with H202 in the presence of catalytic amounts of Na2W04 this method is very useful for the preparation of cyclic nitrones (Eq. 8.41).64... 

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