Hydroxylamines, addition rearrangement

The Beckmann rearrangement of oximes to produce amides is promoted by perrhenate ions under phase-transfer catalytic conditions, in the presence of trifluoro-methanesulphonic acid in nitromethane [6]. Under these conditions, the rearrangement reaction is frequently accompanied by the solvolysis of the oxime to the ketone. This can be obviated by the addition of hydroxylamine hydrochloride. No reaction occurs in the absence of the ammonium catalyst or with the O-acetyl oximes. 

The new metabolite from Red Sea marine invertebrates, Asmarine B (169), presents a hydroxylamine functional group (equation 50). When treated with acetic anhydride at room temperature the Asmarine B (169) underwent an unexpected [3,3]-sigmatropic rearrangement to give 170. After 1,6-addition of methanol and concomitant loss of acetic acid 170 produced the pyrimidine 171. ... 

A new semipinacol rearrangement mediated by Sn(IV) was proposed by Bates and to explain the formation of 579 from 578 (equation 256). As stated by the authors, the mechanism of formation of 579 most likely involves an intermediate hydroxylamine 580 (equation 257). Nucleophilic addition of the hydroxylamine to the ketonic carbonyl leads to 581, which may undergo a tin-mediated pinacol-type rearrangement with preferred migration of the phenyl substituent to produce amide 582. 

The Beckmann rearrangement is used in a similar way to produce the lactam 32, an intermediate in the synthesis of swainsonine 33. Stereoselective addition of dichloroketene to the enol ether 30 gave one isomer ( 95 5) of cyclobutanone 31. Beckmann rearrangement with a sulfonated hydroxylamine and dechlorination gave the lactam 32 in 34% yield over five steps7 from a precursor of 30. Note that the m-alkene 30 gives the trans cyclobutanone selectively. 

Stannous chloride-mediated reductive cyclisation-rearrangement of the nitro-ketone 269 (obtained from the nitro-acid, 268) gave the dibenzothiazepine derivative 270 in good overall yield mechanistically it was proposed that a hydroxylamine intermediate leads to the rearrangement after intramolecular nucleophilic addition to the ketone [02JOC8662]. 

The addition of allylamine to the benzaldehyde nitrone 17 gave mainly the //wi.v-3,6-disubs tituted 1,2,5-oxadiazinane 20 via the cyclization of the ci.y-unsaturated hydroxylamine 18 to give the pyrrolidine A-oxide 19, and a final rearrangement step77. The product 20 was relatively sensitive to chromatographic purification, but could be converted to the more stable A -Boc and iV-(4-ni-trobenzoyl) derivatives (X-ray). 

Blechert has developed an interesting synthesis of 2-substituted indoles which involves the conjugate addition of V-phenylhydroxylamine salts (or V-phenylnitrones) to electron-deficient allenes, followed by carbanion-accelerated hetero-Cc rearrangement of the Michael adduct. For exanple, addition of the hydroxylamine salt (46) to the allenyl sulfone (47) produces the anion (48), which undergoes rapid 3.3-sigmatropic rearrangement to afford the -keto sulfone (49). Cyclization to the indole proceeds smoothly upon exposure to formic acid (Scheme 3). 

The reduction of 0-acyl oximes to 0-acylhydroxylamines also is accomplished under mild conditions with pyridine-BHs/HCl, NaBHsCN/HCl, and NaBHsCN/AcOH in a similar fashion as with other oxime derivatives. In addition, BH3 (1 equiv.) and the combination of EtsSiH/TFA also effects efficient reduction. With the former reagent, rearrangement to N-acylhydroxylamines has been observed (equation 3). Representative examples of 0-acyl oxime reductions are presented in Table 12. The related derivatives nitrones are also reduced by LAH, or NaBHsCN/H to hydroxylamines (equation 4).202... 

Such a procedure adapted from Gross and Morell (1966) and Blumenfeld and Gallop (1962) is as follows. Visser et al. (1971) treated 2.5 to 10 mg of a modified elastase with 1 N NHjOH-HCl, adjusted to pH 9 by addition of sodium hydroxide, for 2 hr at 25°C. The excess hydroxylamine was removed either by dialysis or by precipitation of the protein at pH 3.0. The protein was then dissolved, brought to pH 8.0 by addition of NaOH and treated with an equal volume of a 1 % solution of l-fluoro-2,4-dinitrobenzene in ethanol. The pH of the solution was maintained at 8 by the continuous addition of NaOH. The reaction is complete when no additional alkali must be added for 5 min. The mixture is then extracted three times with ether and the aqueous phase subjected to the conditions of the Lossen rearrangement (i.e. heating to 100°C under alkaline condition (0.1 N NaOH) for 10 min). Acid hydrolysis followed by amino acid analysis permits the identification of either diaminopropionic or diaminobutyric acid which would result from either aspartate or glutamate modification, respectively. Diaminopropionic and diaminobutyric acids may be estimated on the short column of the amino acid analyzer. Diaminopropionic acid emerges with histidine. (Color values do not seem to be available.)... 

Using this pulse sequence to estimate the nature of derivatization of Suwannee River fulvic acid with N-enriched hydroxylamine to leam more about the carbonyl functionality of fulvic acid, Thom et al.(76) obtained signals for the primary products as oximes. Additional signals of secondary products arising from Beckmann rearrangements of the initial oxime derivatives were identified as nitriles, secondary amides and lactams. The bands assigned to hydroxamic acid result from a reaction of esters with NH2OH and are evidence for the presence of esters in the fulvic acid. 

The addition of diazoacetic ester to phosphinylallenes gives phosphinylpyraz-oles. Hydroxylamine adds to vinylphosphonates, and the products (96) rearrange under acid conditions. Alkyl diallylphosphinates undergo prototropic isomerization when treated with t-butoxide ion. ... 

Disubstituted nitroxides constitute a well-known class of rather stable free radicals. N,N-disubstituted anions of organometallic hydroxylamines have just one additional electron more than the corresponding nitroxide. Oxidation of the rearranged anions of silyl or germylhydroxyl amines, electrolytically or with oxygen, produces solutions of organometal nitroxides (30). Examples are shown in Eqs. (19)-(21). These nitroxides are stable in dilute solution for several days at room temperature. 

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