Hydroxylamin derivatives

CHR) , formed, e g. from the reaction of diazomethane and alcohols or hydroxylamine derivatives in the presence of boron compounds or with metal compounds. Poly-methylene is formally the same as polyethene and the properties of the various polymers depend upon the degree of polymerization and the stereochemistry. 

The imonium salt (199), obtained from ynamines and phosgeneimonium chloVide, underwent ready reaction with monosubstituted hydrazines to give the 3,5-bis(dimethyl-amino)pyrazole (200) (68T4217, 69T3453). Similarly, the adduct (201), resulting from the addition of phosgene to ynamines, likewise reacted with sym-disubstituted hydrazines to give pyrazoles (202). With hydroxylamine derivatives the isoxazolinone (203) was obtained. 

Because of the great range of structures containing cyclic hydroxamic acid functions it is difficult to give a concise summary of the available synthetic methods. Nevertheless, the vast majority of published syntheses depend on condensation reactions involving only familiar processes of acylation or alkylation of hydroxylamine derivatives. The principles of such syntheses are outlined in a number of typical examples in Section III, A but no attempt has been made to cover all reported cases. 

Menthylhydroxylamine may be used to form hydroxylamine derivatives for the determination of carbohydrates [20]. 

More recently, Tardella and co-workers reported that treatment of 2-trifluorome-thyl acrylate 36 (Scheme 3.12) with the anion generated from nosyloxycarbamate 37 gave rise to aziridine-2-carboxylate 38 in 96% yield and 72% de with undetermined stereochemistry [40]. Aza-MIRC (Michael-initiated ring closure) was used to account for this transformation. A number of other hydroxylamine derivatives have been employed successfully in this type of aziridination reaction, includ-... 

Sulphoxides may be reduced by heating in weakly basic ethanol with one of a range of hydrazine or hydroxylamine derivatives . The process has been patented both for simple sulphoxides and for more complex molecules such as a-methylsulphinylacetophenone, PhCOCHjSOMe, although the yield for this reduction was only 48%. 

Use of nitrous acid to liberate a free keto-acid from its semicarbazone caused formation of hydrogen azide which was co-extracted into ether with the product. Addition of silver nitrate to precipitate the silver salt of the acid also precipitated silver azide, which later exploded on scraping from a sintered disc. The possibility of formation of free hydrogen azide from interaction of nitrous acid and hydrazine or hydroxylamine derivatives is stressed. 

Reactions of 2,3-dioxo-l,2,3,5,6,7-hexahydropyrido[l,2,3-carboxylic acids and the homologous acetic and propionic acids, prepared by basic hydrolysis of the corresponding ester, with amines, 28% NH4OH, and hydroxylamine derivatives in the presence of l-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and hydroxybenztria-zole <1995BML1527>, 1995BML1533>, and in the presence of NEt3 and A, A -bis(2-oxo-3-oxazolidinyl)phosphinic... 

Polarographic reduction of l-methyl-5-nitroimidazole (97 R = Me, R2 = H) has been shown to proceed in two distinct steps, probably via the hydroxylamine derivative (102), to give the amino compound (96 R = Me, R2 = H) (62CR2603). 

O -Benzoyloximcs are nicely reduced to <9-benzoyl hydroxy lamincs with EtsSiH/TFA (Eq. 328) 550,551 <9-Acetyl oximes arc reduced with Et3SiH/TMSOTf in moderate to high yields.552 The diethylphosphatoimine 88 is reduced to the hydroxylamine derivative.553... 

Another type of spin traps, which have been recommended for the detection of superoxide, are the derivatives of hydroxylamine. In 1982, Rosen et al. [25] showed that superoxide is able to oxidize the hydroxylamine derivative 2-ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazoli-dine (OXANOH) to corresponding free radical 2-ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazolidinoxyl (OXANO). Although this radical is very stable and easily identified by its ESR spectrum, it is also easily reduced by ascorbic acid and other reductants. Furthermore, OXANOH and other hydroxylamines are oxidized by dioxygen in the presence of transition metal ions to form superoxide, and therefore, superoxide detection must be carried out in the presence of chelators. 

Later on, other hydroxylamine derivatives such as 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine (TEMPONEH) and l-hydroxy-3-carboxy-pyrrolidine (CP-3) have been used for superoxide detection [26]. It was found that these spin traps react with both superoxide and peroxynitrite and that they might be applied for quantification of these reactive species [27]. The CP-3 radical is less predisposed to reduction by ascorbic acid and therefore is probably more suitable for superoxide detection in biological systems. 

Unfortunately, due to the above shortcomings of hydroxylamine derivatives as spin traps, the uncertainties of the mechanism of their reactions with superoxide are added. Although it is supposed that nitroxide radicals are formed by oxidation with superoxide (Reaction (6)), this reaction cannot be an elemental stage because superoxide cannot abstract a hydrogen atom. 

Aromatic amines 4 are metabolised in vivo by cytochrome P450 mediated oxidation to phenolic and hydroxylamine derivatives 5 and 6. Phase II conjugation of the latter with PAPS or acyl transferase results in formation of the sulfuric or acetic acid esters 7. Nitrogen conjugation to give the A-acetyl analogues is also possible (Scheme l).54 65... 

Acyl nitroso compounds (3, Scheme 7.2) contain a nitroso group (-N=0) directly attached to a carbonyl carbon. Oxidation of an N-acyl hydroxylamine derivative provides the most direct method for the preparation of acyl C-nitroso compounds [10]. Treatment of hydroxamic acids, N-hydroxy carbamates or N-hydroxyureas with sodium periodate or tetra-alkyl ammonium periodate salts results in the formation of the corresponding acyl nitroso species (Scheme 7.2) [11-14]. Other oxidants including the Dess-Martin periodinane and both ruthenium (II) and iridium (I) based species efficiently convert N-acyl hydroxylamines to the corresponding acyl nitroso compounds [15-18]. The Swern oxidation also provides a useful alternative procedure for the oxidative preparation of acyl nitroso species [19]. Horseradish peroxidase (HRP) catalyzed oxidation of N-hydroxyurea with hydrogen peroxide forms an acyl nitroso species, which can be trapped with 1, 3-cyclohexanone, giving evidence of the formation of these species with enzymatic oxidants [20]. 

Another preparation employed the condensation of hydroxylamine with a substituted thiourea 239. In this example (Equation 30), no oxidation was required, since the central nitrogen atom is already in a higher oxidation state via its hydroxylamine derivative 240. Nucleophilic attack of the pyridine nitrogen atom resulted in ring closure, affording 241 accompanied by decarboxylation <2003S1649>. 

In addition to the tert-butyl enol ethers mentioned above (15% yield), the action of KOtBu on l-iodo-4-methylcyclohexene in DM SO furnished the dimers 85 and tri-mers of 81 in 30 and -25% yield (Scheme 6.24). As in the case of 6 (see Scheme 6.10), the formation of oligomers of 81 was completely suppressed on performance of this reaction in the presence of (tBu)2NO, whereas theenol ethers (86 and its 5-methyl isomer, with the former originating in part and the latter totally from 4-methylcydohex-yne) were observed as in the reaction in the absence of the stable radical. Instead of the dimers 85 and the trimers of 81, a mixture of the hydroxylamine derivatives 87 was isolated in 38% yield. These findings indicate that 81 has no diradical character, in contrast to its immediate dimer 84, which is hence trapped quantitatively by (tBu)2NO [61]. 

Any rational approach to the study of antidotes for nerve-gas poisoning must take this firm attachment into account. It has been observed that, in experiments in vitro, the D.F.P.-poisoned heart recovers to an appreciable extent in the presence of hydroxylamine. With this experiment in mind I. B. Wilson1 has examined the action of hydroxylamine derivatives and has had considerable success with nictonic hydroxamic acid meth-iodide (IV). The reaction envisaged here is a nucleophilic attack... 

Reaction of hydroxylamine derivatives with sulfinyl chlorides yields sulfonamides as the final reaction product. Study of this reaction (Bouma and Engberts, 1976) indicates that it proceeds by the mechanism shown in (146),... 

From the discussion of the Marcus theory above and equations (20) and (21), we see that the experimental data needed to judge the feasibility of ET steps involving spin traps and spin adducts are the redox potentials and A values of the ST +/ST and ST/ST - couples, as well as those for hydroxylamine derivatives related to the operation of reactions (4) or (5). The electroactivity of the spin adducts themselves is also of interest since it must somehow be related to their lifetimes in a redox-active environment. Moreover, the excited-state redox potentials (of ST /ST and ST,+/ST ) are also necessary for the understanding of photo-ET processes of spin traps. 

Another unnatural amino acid (28), the (3-diketone, has also been genetically incorporated and used in vitro to label proteins with hydroxylamine derivatives of biotin or fluorescent dyes, thereby increasing the number of unique chemical handles that can be genetically incorporated into proteins in vivo. 

Hydroxylamine derivatives are ambident nucleophiles. For example, N-benzylhy-droxylamine functions as an N-nucleophile in the Ir-catalyzed allylic substitution, while N-Boc-hydroxylamine yields mixtures of the N- and O-substituted products in Ir- as well as Pd-catalyzed allylic substitutions. Accordingly, either O- or N,0-protected hydroxylamine derivatives need to be used as nucleophiles [63]. 

Scheme 9.30 Allylic substitutions with a hydroxylamine derivative as nucleophile.

A few other hydroxylamine derivatives were tested with cinnamyl diethyl phosphate as substrate (Scheme 9.30, Ar= Ph) and Cs(OH)-H20 as base [39]. The addition of a base was necessary in the case of N,0-dibenzoylhydroxylainine, whereas the reaction with N, O-dibenzylhydroxylamine proceeded without base. The corresponding amide N-benzoylbenzylamine did not undergo the reaction. 

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