Hydroxylamines and derivatives

Yamamoto RS, Weisburger EK, Korzis J Chronic administration of hydroxylamine and derivatives in mice. Proc Soc Exp Biol Med 124 1217-1220, 1967... 

Hydroxylamines and derivatives Borane-Tetrahydrofuran, 42 Dimethylphenylsilane, 123 Hydroxy nitriles (see also Cyanohydrins) Nickel, 197 Hydroxy selenides... 

Reduction of Oximes, Oxime Ethers and Oxime Esters to Hydroxylamines and Derivatives... 

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). 

The first in this series to be reported was 4-oxoisoxazoline-3,5-dicarboxylic acid diethyl ester, which was formed by the reaction of nitrous acid on diethyl acetonedicarboxylate in 1891. Quilico described a number of syntheses in his 1962 review and the most general include the reaction of hydroxylamine and a-hydroxy-(or acetoxy)- 3-diketones and the conversion of 4-isoxazolediazonium salts to the hydroxy moiety (62HC(17)1, p. 3). Additional syntheses reported were the oxygenation of a 4-boric acid derivative (67JOM(9)l9) and peroxide oxidation of a 4-nitro-2-isoxazoline (Scheme 151) (79ZOR2436). 

Sorm et a/. prepared azacytidine and some of its derivatives in a similar way. The 4-thio derivative was obtained from 2, 3, 5 -tri-0-acetyl- or 2, 3, 5 -tri-0-benzoyl-6-azauridine by treatment with phosphorus pentasulfide this liberated 4-thio-6-azauridine (126) which was identified with 4-thio-6-azauracil on comparing the UV spectra. Treatment with ammonia produced 6-azacytidine (127) treatment with hydrazine, hydroxylamine, and n-butylamine yielded the corresponding derivatives. 

The Preparation of Oxaziranes from Carbonyl Compounds and Derivatives of Hydroxylamine and Chloramine... 

Imine formation from such reagents as hydroxylamine and 2,4-dinitro-phenylhydrazine is sometimes useful because the products of these reactions— oximes and 2,4-dinitrophenylhydrazones (2,4-DNPs), respectively—are often crystalline and easy to handle. Such crystalline derivatives are occasionally prepared as a means of purifying and characterizing liquid ketones or aldehydes. 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

Reaction of porphyrins with nitrones has also been studied and the results obtained showed that this is a versatile approach leading to the synthesis of isoxazolidine fused-chlorins (Scheme 26). For instance, chlorin 74 was successfully prepared from the reaction of the jV-methylnitrone, generated in situ from JV-methyl hydroxylamine and paraformaldehyde, with porphyrin Id . It is important to note that bis-addition also took place, yielding exclusively bacteriochlorin type derivatives 76 and 77 (Figure 6). This result contrasts with those obtained in 1,3-DC reactions with azomethinic ylides where isobacteriochlorins were obtained preferentially. 

Transformation of chiral nitrones into enantiomer enriched a-chiral N -hydroxylamines and their derivatives, has been successfully employed in the enantioselective synthesis of (+ )-(R)- and (—)-(S)-zileuton (216). An expeditious synthesis of thymine polyoxin C (347), based on the stereocontrolled addition of 2-lithiofuran (a masked carboxylate group) to the A-benzyl nitrone derived from methyl 2,3-O-isopropylidene-dialdo-D-ribofuranoside, is described (Scheme 2.151) (194). 

The conjugate addition of activated nitrogen nucleophiles, such as hydroxylamine and hydrazine derivatives, to a,/3-unsaturated bicyclic lactam 284 gave the corresponding /3-amino product 285 in good yield and excellent diastereoselectivity. These products can be manipulated to afford enantiopure /3-aminopyrrolidinones of potential application as conformationally constrained, substituted glutamate templates (Equation 45) <2001J(P1)2997>. 

Over the past decade, the semiconductor manufacturing industry has used hydroxylamine solutions in cleaning formulations to strip process residues from integrated circuit devices. Hydroxylamine and its derivatives are also used in the manufacture of nylon, inks, paints, pharmaceuticals, agrochemicals, and photographic developers. 

In our hands, base-activated phosphoramidite-Ir complexes were not suited for the allylation of hydroxylamine and hydrazine derivatives (R. Weihofen and G. Helmchen, unpublished results). However, interesting results were obtained by Takemoto and coworkers with Pybox type ligands (Scheme 9.30) [40]. Phosphates... 

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