Hydroxylamines cyclic

Katsuki, S., Arnold, W., Mittal, C. K., and Murad, F. (1977a). Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. /. Cyclic Nucleotide Res. 3, 23-35. 

Lactones, which may be regarded as cyclic or inner esters, react similarly. Anhydrides of carboxylic acids also react with hydroxylamine to form hydroxamic acids ... 

Cyclic a-cyanoketones, when treated with hydroxylamine, yielded 3-amino-4,5,6,7-tetrahydro-2,1-benzisoxazole. This compound could also be obtained by sodium or potassium cyanide interaction with chlorocyclohexanone oxime (Scheme 187) (67AHC(8)277, 66Bail25>. 

Only one cyclic hydroxamic acid which contains the pyrido[2,3-d]-pyrimidine ring system has been reported.This is 2-methyl-3-hydroxypyrido[2,3-d]pyrimidin-4(3i/)-one (21) which was prepared by the action of acetic anhydride on 2-aminonieotinhydroxamic acid (20) or from ethyl 2-aeetamidonicotinate (22) and hydroxylamine. In view of the known antibacterial activity of certain cyclic hydroxamic acids further work on these compounds would be of interest. 

The name hydroxamic acid was first used by Losseii in 1869, in the case of oxalohj droxamic acid, obtained from diethyl oxalate and hydroxylamine. Where this grouping forms part of the main cyclic system, however, the compound is named as a derivative of this system. In this review, 2 and 3 would be named as 1-hydroxy-2-pyrrolidone and l-hydroxy-2-pyridone, respectively. 

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. 

Acyl derivatives of cyclic hydroxamic acids, like all 0-acyI derivatives of hydroxylamine, show infrared absorption because of the acjd carbonyl at characteristically high frequencies, generally near 1800 The range of frequencies is similar to that found for... 

The benzodiazepine jV-oxide 4 is converted into the cyclic hydroxylamine 9 by the action of lithium aluminum hydride, while catalytic hydrogenation in the presence of platinum gives the tetrahydrobenzodiazepine 10.219... 

Monoalkylamines give only the cyclic products, i.e. lV-alkyltetrahydro-l,4-thiazin-l-oxides 542 (equation 341), while dialkylamines afford the mono- and diaddition products (equation 342)633. Hydroxylamine undergoes double addition to substituted divinyl sulphoxides 543 to give thiazine 1-oxides 544634 (equation 343). 

A high yield synthesis involving formal oxidation of a sulphoxide to a sulphoximine has been reported183 using O-mesitylenesulphonyl hydroxylamine (NH2OMes) (equation 67). The reaction is successful for a wide range of sulphoxides including dialkyl, diaryl and cyclic species. 

A similar strategy has been used to prepare pyrimidines, as well as pyra-zoles and isoxazoles by reacting the enamine intermediate with a variety of bidentate nucleophiles [78]. Microwave irradiation of a cyclic 1,3-diketone 49 and acetal 45 in water generated the corresponding enaminoketone 50 in situ which reacted with amidines, substituted hydrazines or hydroxylamine in only 2 min in a one-pot process to give 4-acylpyrimidines, pyrazoles or isoxazoles, respectively (Scheme 20). 

In the above-mentioned reactions with hydrazine and hydroxylamine, the actual reducing species is diimide (NH=NH), which is formed from N2H4 by the oxidizing agent and from NH2OH by the ethyl acetate.The rate of this reaction has been studied.Although both the syn and anti forms of diimide are produced, only the syn form reduces the double bond, at least in part by a cyclic mechanism ... 

A somewhat unusual sequence to generate azepanones 80 involved the intramolecular addition of hydroxylamines to alkynes 76 to form cyclic nitrones 77. A vinyl magnesium bromide addition at low temperatures and a reduction with TiCls followed by N-Boc protection led to the azepane 78. Double bond bromination and subsequent RUO4 oxidation gave the lactam 79. Several further steps allowed the generation of the lactam structure 80 proposed for d,/-aca-cialactam, but the spectral data of the synthetic material differed from that of the natural product (Scheme 16)] [23 a, b]. 

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... 

The reaction of 2-chloro-4,5-dihydroimidazole 347 with hydroxylamine-O-sulfonic acid gives 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate 348, which reacts with aldehydes and cyclic ketones to give the imidazo[l,2-f] fused 4,5-dihydro-l,2,4-oxadiazoles 350 (Scheme 58). Mechanistically, the reaction may be explained by the reaction of an imidazoline NH with the carbonyl followed by intramolecular electrophilic amination of the anionic oxygen present in the resultant intermediate 349 and elimination of the sulfate group <2003JOC4791>. 

Oxidation of cyclic and acyclic hydroxylamines with yellow mercuric oxide appears to proceed with high regioselectivity (109-115). Regioselectivity is determined by the electronic nature of the substituents (116). The oxidative regioselectivity of Mn02 is comparable to that of HgO, but due to its lower toxicity, it has been proposed to use Mn02 rather than HgO (Table 2.2) (117). 

Oxidation with m-CPBA of monocyclic isoxazolidines (56) without H at a-C gives a tautomeric mixture of acyclic nitrones (57) and six-membered cyclic hydroxylamines (58), with their proportion depending on the substituents... 

To undertake oxidation of both cyclic and acyclic hydroxylamines to nitrones, an electrochemical oxidative system has been developed, where WC>42-/WC>52-are used as cathodic redox mediators and Br /Br2 or I—/I2 as anodic redox mediators (129-131). 

Another synthetic approach for generating sugar-containing nitrones is by initial treatment of sugars with unsubstituted hydroxylamine. The resulting cyclic hydroxylamine of the tautomeric mixture (68a) and of the open chain oxime (68b) react with aldehydes to give the corresponding nitrones (69) (Scheme 2.24) (216-220). 

Enantio-pure five-membered cyclic nitrones (154) and (155) were formed in a one-pot synthesis from the corresponding lactols (152) and (153) as the result of their reactions with unsubstituted hydroxylamine and by (a) subsequent treatment with MsCl and NaOH (Scheme 2.55) (310a) or by (b) subsequent treatment with TBDMSC1,12, TPP, imidazole, and tetrabutylammonium fluoride (TBAF) (310b). 

High diastereoselectivity occurs in the addition of lithiated methoxyallene to chiral cyclic nitrones. The hydroxylamines obtained can be easily transformed into derivatives of 1,2-oxazine hydroxylamine, which are products of a novel [3 + 3] cyclization reaction (Scheme 2.182) (646, 647). 

The general method, that has been widely used for the synthesis of perhydropyrrolo[1,2-6]isoxazoles, is based on a cycloaddition reaction of cyclic nitrones with dipolarophiles. The nitrone is easily available by oxidation of the corresponding hydroxylamine with mercuric chloride. The cycloaddition of nitrone to dipolarophiles is highly regioselective and stereoselective and have been often applied in the total synthesis of natural products <20010L1367, 2004BML3967, 2005JOC3157>. As one representative example of dipolar cycloaddition, reaction... 

Following a similar approach, the first bis(triorganosilyl) diazene 402 that is stable at room temperature could be obtained.410 Thus, the reaction of (/-Bu2MeSi)HNNH(SiMe/-Bu2) 403, an analog of 399, with 2 equiv. of BuLi has provided (/-Bu2MeSi)LiNNLi(SiMe/-Bu2) 404, whose oxidation with bromine has led to the formation of the diazene /-Bu2MeSiNNSiMe/-Bu2 402 (Scheme 58). Recently, the stepwise synthesis of cyclic and open-chain silyl hydro-xylamines has been reported by Klingebiel < / /.411 14 For hypervalent silyl hydroxylamines, see Section 6.8. 

The mechanism of the global 4-electron electrochemical reduction of aromatic nitro compounds to hydroxylamines in aqueous medium shown in reaction 37 was investigated by polarography and cyclic voltametry. The nitro group is converted first to a dihy-droxylamine, that on dehydration yields a nitroso group the latter is further reduced to a... 

Electrosyntheses of heterocycles from nitroso derivatives prepared in a batch cell according to Scheme 34 need two conditions. The first one is a good stability of the hydroxylamine intermediate and the second one is a very fast cyclization of the nitroso compound to avoid the formation of an azoxy compound by condensation of the generated nitroso and the hydroxylamine. Electroanalytical studies using cyclic voltammetry can give information on the rate of cyclization. 

A bond between nitrogen and oxygen was hydrogenolyzed in a cyclic derivative of hydroxylamine, 2-methyl-6-[ -pyridyl]-l,2-oxazine, which on treatment with zinc dust in acetic acid gave, on ring cleavage, 84.5% of 1-hydroxy-4-methylamino-1 -[ -pyridyl]butane [739]. 

This enzyme [EC 1.14.13.25] catalyzes the reaction of methane with NAD(P)H and dioxygen to produce methanol, NAD(P), and water. This enzyme is reported to exhibit a broad specificity. Many alkanes can be hydrox-ylated and alkenes are converted into the corresponding epoxides. Carbon monoxide is oxidized to carbon dioxide, ammonia is oxidized to hydroxylamine, and some aromatic compounds and cyclic alkanes can also be hy-droxylated, albeit not as efficiently. 

A seemingly complex heterocycle which on close examination is in fact a latentiated derivative of a salicylic acid shows antiinflammatory activity. It might be speculated that this compound could quite easily undergo metabolic transformation to a salicylate and that this product is in fact the active drug. Condensation of acid 134 with hydroxylamine leads to the hydroxamic acid 135. Reaction of that with the ethyl acetal from 4-chlorobutyraldehyde then leads to the cyclic carbinolamine derivative 136. Treatment... 

The common name caprolactam comes from the original name for the Ce carboxylic acid, caproic acid. Caprolactam is the cyclic amide (lactam) of 6-aminocaproic acid. Its manufacture is from cyclohexanone, made usually from cyclohexane (58%), but also available from phenol (42%). Some of the cyclohexanol in cyclohexanone/cyclohexanol mixtures can be converted to cyclohexanone by a ZnO catalyst at 400°C. Then the cyclohexanone is converted into the oxime with hydroxylamine. The oxime undergoes a very famous acid-catalyzed reaction called the Beckmann rearrangement to give caprolactam. Sulfuric acid at 100-120°C is common but phosphoric acid is also used, since after treatment with ammonia the by-product becomes... 

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