N-substituted Hydroxylamines Research Articles

An approach to carbapenems from α,β-unsaturated sugar lactones

Conjugate addition-rearrangement of N-substituted hydroxylamines to α,β-unsaturated D-lactones provides a short and effective route to 3-substituted isoxazolidin-5-ones. These compounds were converted into 4-substituted azetidin-2-ones via a two-step procedure involving hydrogenolysis of the NO bond followed by cyclization of the resulting β-amino acids. N-Benzyl-4-(3′-acetoxy-2′-tert-butyldimethylsiloxypropyl)azetidin-2-one ( 37) was transformed into known precursors of carbapenem antibiotics.

Synthesis, chemical, and biological properties of vinylogous hydroxamic acids: dual inhibitors of 5-lipoxygenase and IL-1 biosynthesis.

Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.

Deoxyhydroxyamino analogs of sugars: derivatives of methyl 2,3-dideoxy-2-hydroxyamino-α- d- arabino- and - lyxo-hexopyranosides

N-Substituted hydroxylamines reacted both regio- and stereo-specifically with ethyl 2,3-dideoxy-α- d- glycero-hex-2-enopyranosid-4-ulose ( 1) to give N-substituted ethyl 2,3-dideoxy-2-hydroxyamino-α- d- threo-hexopyranosid-4-uloses ( 2– 7), whereas O-methylhydroxylamine gave a mixture of O-methyloximes ( 8– 10), including the product of both stereospecific conjugate addition and oximation ( 10). Sodium borohydride reduction of ethyl 2,3-dideoxy-2-( N-hydroxy- N-methylamino)- and 2,3-dideoxy-2-( N-hydroxy- N-isopropylamino)α- d- threo-hexopyranosid-4-uloses proceeded stereoselectively, and the major product had the α- d- arabino configuration. The conformations of these compounds were established using n.m.r. spectroscopy and X-ray diffraction for 3 and 19. The major interest of these deoxyhydroxyamino sugars was their easy oxidation into spin-labelled sugar analogs whose conformation could be studied by e.s.r. spectroscopy.

Formation of prostaglandin synthase-iron-nitrosoalkane inhibitory complexes upon in situ oxidation of N-substituted hydroxylamines

Various N-alkylhydroxylamines such as N-hydroxyamphetamine react with prostaglandin synthase (PGHS) from sheep seminal vesicles, with the formation of new complexes characterized by a Soret peak around 421 nm. These complexes are very stable toward O2 or dithionite but are destroyed upon oxidation by Fe(CN)6K3 with regeneration of starting PGHS-FeIII. Their spectral characteristics, chemical properties, and routes of formation (either by direct oxidation of RNHOH or by in situ reduction of RNO2 in the presence of dithionite) are very similar to those previously reported for nitrosoalkane complexes of hemoglobin-, myoglobin-, and cytochrome P-450-FeII. Their FeII-N(O)R structure was completely confirmed in the case of N-hydroxyamphetamine, both by extraction of the heme complex by butanone and by identification to authentic protoporphyrin IX-FeII-N(O)-amphetamine, and by insertion of this authentic complex into apoPGHS. Phenylhydroxylamine also reacts with PGHS-FeIII to give a PGHS-FeII-N(O)Ph complex which is not stable in the presence of dithionite because of its weaker PGHS-FeII-N(O)R bond when compared to PGHS-FeII-nitrosoalkane complexes. The ability of various N-alkylhydroxylamines to form PGHS-FeII-N(O)R complexes greatly depends upon their hydrophobicity. Actually, CH3NHOH and C2H5NHOH are totally inactive whereas about 10 molar excess of N-hydroxyamphetamine and C6H5NHOH already lead to 50% complex formation. This is in favor of an hydrophobic environment of the heme in PGHS. Finally, PGHS engaged in such FeII-nitrosoalkane complexes completely loses its dioxygenase activity, suggesting that N-substituted hydroxylamines or compounds that can be metabolized in vivo to give such hydroxylamines could act as strong PGHS inhibitors.

Intramolekulare Cycloaddition von Nitronen

Intramolecular Cycloaddition of NitronesNitrones 9 and 10, formed by treatment of the corresponding aldehydes with N‐substituted hydroxylamines, are converted into the cis fused bicyclic compounds 11 and 12, respectively. While this intramolecular cycloaddition as a rule occurs at room temperature, the formation of compounds 17/18 and/or 20/21 from the corresponding nitrones needs refluxing in toluene with exception of 17Ca. The N‐aryl‐substituted nitrones 14C/15C form dimers 22C/23C spontanously at room temperature. However, dimerization is reversible; thus 22/23C afford the bicyclic compounds 17/18 and/or 20/21 on heating in toluene via the corresponding nitrone intermediates. — Hydrogenation cleaves isoxazolidine ring of the bicyclic compounds. Thus, 17Ca and 18Ca yield the hexahydrothiepine 27C and oxepane derivatives 28C, respectively, 21Ca gives the tetrahydropyran 30C. Diastereomerically pure 29C arises by prolonged hydrogenation of 17Ca under reinforced conditions via 27C.

ChemInform Abstract: The (3 + 2) Nitrone‐Olefin Cycloaddition Reaction

Early researchers studying the condensation product of carbonyl compounds with N-substituted hydroxylamines elected to coin the term “nitrone” as a combination of the words “nitrogen” and “ketone.” This was done to emphasize the parallel between this newly discovered functionality and the already rich chemistry of the carbonyl group. For example, nitrones are capable of reacting with carbanions of various types, a consequence of the iminium species embedded in the nitrone that renders the functionality susceptible to nucleophilic attack. Thus C-phenyl-N-methylnitrone undergoes a Reformatsky reaction with ethyl bromoacetate in complete analogy with benzaldehyde. The intermediate zinc alkoxide cyclizes to 2-methyl-3-phenylisoxazolidin-5-one, a type of compound that can also be prepared by the related nucleophilic addition of dialkyl malonates to nitrones. This chapter deals with a unique property of nitrones not shared by the corresponding carbonyl compounds, namely, a marked ability to undergo a [3 + 2] cycloaddition reaction in the presence of a dipolarophile. The reactions of nitrones with substituted olefins, both intermolecular and intramolecular are addressed. This process yields isoxazolidines directly, affording products related to those obtained in the Reformatsky reaction but arising by a different reaction mode. The intent of the review presented in this chapter is to provide a thorough understanding of the nitrone–olefin [3 + 2] cycloaddition reaction and to illustrate its power by describing some significant applications to complex synthetic problems. Various aspects have been reviewed. This documentation of the nitrone–olefin cycloaddition reaction begins with the preparation and stability of the nitrone component and is followed by mechanistic considerations. A presentation of the dipolarophile syntheses is beyond the scope of this chapter; however, the tabular survey provides leading references to specific examples. The important concepts of regio- and stereo-selectivities are introduced next. Since the general rules of regiochemistry that apply in the intermolecular version of the reaction are often reversed in the intramolecular version, the latter are dealt with separately. Finally, important applications to the total synthesis of natural products are presented. The versatile utility of the nitrone–olefin cycloaddition reaction in the synthesis of natural products has been the major driving force in the development of this long-neglected chemistry. An in-depth understanding of the key transformations of the isoxazolidines afforded by the reaction will place this chemistry firmly within the arsenal of organic reactions. Keywords: cycloaddition reactions; [3 + 2] reaction; nitrone; olefins; nitrone stability; mechanism; regioselectivity; intermolecular reaction; intramolecular reaction; C-alkenylnitrones; N-alkenylnitrones; natural products; alkaloids; biotin; aldehyde-derived nitrones; ketone-derived nitrones; endocyclic nitrones; exocyclic nitrones; amino glycosides; adaline; nitrogen-free systems; experimental procedures

Synthesis of isoxazolidine derivatives from N-substituted hydroxylamines and ?,?-unsaturated ketones

The reaction of methyl vinyl ketone with N-Phenyl-hydroxylamine leads to a tautomeric mixture of 5-hydroxy-2-phenyl-5-methylisoxazolidine and its linear form, while the reaction with benzohydroxamic acid leads to linear products of addition to the oxygen or nitrogen atoms, depending on the reaction conditions. The first representatives of 5-hydroxyisoxazolidines with the residue of an aliphatic carboxylic acid attached to the nitrogen atom were obtained by acylation of 5-hydroxy-3,3,5-trimethylisoxazolidine.

ChemInform Abstract: N‐Hydroxyisothioureas. Part 2. Addition of N‐Substituted Hydroxylamines to Methyl Thiocyanate.

ChemInformVolume 20, Issue 10 Isocyclic Compounds ChemInform Abstract: N-Hydroxyisothioureas. Part 2. Addition of N-Substituted Hydroxylamines to Methyl Thiocyanate. B. CLEMENT, B. CLEMENT Inst. Pharm. Chem., Univ., D-3550 Marburg/LahnSearch for more papers by this authorS. WISSEL, S. WISSEL Inst. Pharm. Chem., Univ., D-3550 Marburg/LahnSearch for more papers by this author B. CLEMENT, B. CLEMENT Inst. Pharm. Chem., Univ., D-3550 Marburg/LahnSearch for more papers by this authorS. WISSEL, S. WISSEL Inst. Pharm. Chem., Univ., D-3550 Marburg/LahnSearch for more papers by this author First published: March 7, 1989 https://doi.org/10.1002/chin.198910153Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume20, Issue10March 7, 1989 RelatedInformation

Synthesis of enantiomerically pure 2,3-disubstituted isoxazolidin-5-ones

Conjugate addition-rearrangement of N-substituted hydroxylamines to α,β-unsaturated sugar δ-lactones provides a short and effective route to title compounds.

N‐Hydroxyisothioharnstoffe, 2. Mitt. Addition von N‐substituierten Hydroxylaminen an Methylthiocyanat

AbstractN‐Hydroxyisothioureas, Part 2: Addition of N‐Substituted Hydroxylamines to Methylthiocyanate

Synthesis and structure of hydroxyisoxazolidines and derivatives of hydroxylamine and alkenals

The reactions of N-substituted hydroxylamines with alkenals serve as a method for the synthesis of the corresponding 2-substituted 3(5)-hydroxyisoxazolidines. The reaction pathway is determined by the nature of the substituent attached to the nitrogen atom. Ring-chain isomerism has been detected in these newly obtained compounds

One-Pot Synthesis ofN-Substituted Hydroxamic Acids UsingN,N-Dimethylchloromethaniminium Chloride

N,N-dimethylchloromethaniminium chloride formed from dimethylformamide and oxalyl dichloride is an efficient reagent for the synthesis of N-substituted hydroxamic acids from carboxylic acids and N-substituted hydroxylamines in the presence of a base.

Reduction of .alpha.,.beta.-unsaturated nitro compounds with boron hydrides: a new route to N-substituted hydroxylamines

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of .alpha.,.beta.-unsaturated nitro compounds with boron hydrides: a new route to N-substituted hydroxylaminesM. Soubei Mourad, Rajender S. Varma, and George W. KabalkaCite this: J. Org. Chem. 1985, 50, 1, 133–135Publication Date (Print):January 1, 1985Publication History Published online1 May 2002Published inissue 1 January 1985https://doi.org/10.1021/jo00201a030RIGHTS & PERMISSIONSArticle Views936Altmetric-Citations51LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (428 KB) Get e-Alerts Get e-Alerts

A general procedure for the synthesis of isoxazolidin-5-ones

Abstract Conjugate addition of N-substituted hydroxylamines to α,β-unsaturated esters followed by cyclisation of the adducts with lithium bis (trimethylsily)amide provides the first general means of synthesising isoxazolidin-5-ones, the N-benzyl derivatives of which may be hydrogenolised to β-aminoacids.

Nitrone von 2-formylphenylboronsäureestern

Reactions of 2-formylphenylboronic acid with N-substituted hydroxylamines lead to nitrones which undergo partial anhydride formation at the boronic acid group. The crystallized intermediates of variable composition are converted by esterification with catechol or ethylene glycol into stable defined arylboronate complexes with a cyclic B,N-betaine structure.

The reaction of N-mono an N,N-disubstituted hydroxylamines with palladium catalyst

The Palladium catalyzed reactions of N,N-disubstituted and N-substituted hydroxylamines give the corresponding nitrones and azoxy compounds highly efficiently. The former reactions are performed in the presence of alkenes to give the cycloadducts which are valuable intermediates regio and stereoselectively.

Nukleophile Substanzen zur Entgiftung von Phosphorestern

A series of N-substituted hydroxylamine derivatives was synthesized as a potential substitute for calcium hypochlorite. Like calcium hypochlorite, these compounds are highly P(V)-nucleophilic with respect to toxic phosphorus esters.

Ketenimines as intermediates to heterocycles. Part 3. Rearrangement of 3-iminoisoxazolines to 2-imino-oxazolines

N-Substituted hydroxylamines (2) add to 2-benzoyl-N,2-diphenylvinylideneamine (1) and the adducts are easily dehydrated to give the 3-iminoisoxazolines (4). Compounds (4) with 2-aryl substituents rearrange spontaneously to give the 2-imino-oxazolines (5) or (6), but the 2-methyl derivative is more stable and only rearranges on heating. 2-Imino-3-acylaziridines (8) or (9) are assumed to be the intermediates; the expected 2-imino-oxazoline (5b) was isolated among the products during an attempted synthesis of 1,3-diphenyl-2-phenylimino-3-benzoylaziridine (8b) from benzoylphenylcarbene and diphenylcarbodi-imide.

Chelating ion-exchangers containing n-substituted hydroxylamine functional groups: Part 6. Sorption and separation of gold and silver by a polyhydroxamic acid

The sorption and desorption characteristics of gold and silver on a polyhydroxamic acid chelating resin are described. Gold is quantitatively sorbed from 0.5 M nitric acid or neutral solutions, and readily eluted with 0.5% ( w v ) potassium cyanide solution. Silver is removed from 0.05 M nitric acid or neutral solutions, and can be eluted with the cyanide solution or with 0.5 M nitric acid. Gold can be quantitatively separated from copper, iron and silver; gold and silver are sorbed from dilute cyanide solutions. Tests with river water and other eluting systems are reported.

Rapid catalytic transfer reduction of aromatic nitro compounds to hydroxylamines

A general method has been developed for the rapid, metal-catalysed transfer reduction of nitro compounds to N-substituted hydroxylamines.