Nitrone Formation Research Articles

Synthesis and bioorthogonal coupling chemistry of a novel cyclopentenone-containing unnatural tyrosine analogue

Herein we report the synthesis of a novel amino acid with orthogonal functionality to the natural amino acid side chains. Tyrosine was O-alkylated with a cyclic 5-membered α,β-unsaturated ketone ring ( 5). We have established that this amino acid analogue can undergo cycloaddition reactions in aqueous media with in situ generated nitrones. Nitrone formation occurred by micellar catalysis can undergo aqueous 1,3-dipolar cycloaddition reactions with the unnatural Tyr. We also performed a linear free energy analysis of the one pot bioconjugation reaction in water using cyclopentenone as a model for the Tyr analogue and seven different aryl nitrones. We found that the Hammett ρ value was −0.94, suggesting that the reaction occurs in a concerted fashion with a slight positive charge buildup in the transition state. The Hammett ρ value also suggests that the bioconjugation reaction is tolerant of different substituents and thus may be useful for introducing novel functionality into peptides and proteins containing the Tyr analogue 5. The aqueous 1,3-dipolar cycloaddition reactions, that use nitrones to trap the O-alkylated Tyr 5, establish a novel strategy for rapid, water compatible bioconjugation reactions.

Solvent‐Free Nucleophilic Addition of N‐Alkylhydroxylamines to Substituted Nitroolefins: Formation of Nitrones by a Tandem process

Nucleophilic addition of 1‐methyl‐2‐arylethylhydroxylamine to substituted β‐nitrostyrene under solvent‐free conditions has led to unexpected nitrones via a tandem process involving 1,4‐addition and elimination.

Kinetic study of oxidation of N‐(α‐methylbenzylidene) anilines by dimethyldioxirane

AbstractA kinetic study of the oxidation of substituted N‐(α‐methylbenzylidene) anilines by dimethyldioxirane was investigated using a UV/VIS spectrophotometer. Oxaziridines and nitrones were formed as intermediates, and in the excess of dimethyldioxirane corresponding carbonyl compounds, nitrosobenzene or nitrobenzene, were formed quantitatively. The kinetic data were used in the equation for the formation of oxaziridines and nitrones as an intermediate and further oxidation to the corresponding acetophenones and nitrosobenzene. Hammett ρ values were determined for compounds p‐substituted on the aromatic ring attached to the carbon atom of the imino group, and it was found that these substituents have very little effect on the oxidation reaction. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 492–497, 2007

Selective Synthesis of Allylated Oxime Ethers and Nitrones Based on Palladium‐Catalyzed Allylic Substitution of Oximes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Selective Synthesis of Allylated Oxime Ethers and Nitrones Based on Palladium-Catalyzed Allylic Substitution of Oximes

[reaction: see text] The viability of oximes as nucleophiles in transition-metal-catalyzed allylic substitution was examined. The oxygen atom of oxime acted as a reactive nucleophile in the reaction of a pi-allyl palladium complex. In the presence of Pd(PPh3)4, the allylic substitution of oximes with allylic carbonate afforded the linear O-allylated oxime ethers selectively without a base. In contrast, the palladium-catalyzed reaction with allylic acetate proceeded smoothly in the presence of K2CO3 or Et2Zn as a base. Selective formation of nitrones was achieved by using palladium(II) catalyst. In the presence of Pd(cod)Cl2, the allylic substitution of oximes with allylic acetate afforded the N-allylated nitrones under solvent-free conditions, as a result of the reaction with the nitrogen atom of oximes.

The absence of nitrone form in re-determined crystal structure of 2-hydroxyimino-3-methyl-4-nitro-2,5-dihydrothiophene 1,1-dioxide

Crystal and molecular structures of 2-hydroxyimino-3-methyl-4-nitro-2,5-dihydrothiophene-1,1-dioxide C5H6N2O5S (I) have been re-determined by single crystal X-ray diffraction analysis. The structure of I (space group P212121, a = 6.124(1) A, b = 9.205(2) A, c = 14.884(3) A, Z = 4) was solved by the direct method and refined anisotropically in the full-matrix approximation to R = 0.064 using all 1756 measured independent reflections (automated diffractometer CAD-4, λCuKα, anomalous scattering taken into account). This study proves that the compound I contains a disordered group H-O-N=C, but not the isomeric nitrone group O←N(H)=C, as it has been concluded by the workers who pioneered single crystal X-ray diffraction study of I and erroneously took the second low-occupied oxygen position of the disordered hydroxyimine group for H at N atom.

Water Exclusion Reaction in Aqueous Media: Nitrone Formation and Cycloaddition in a Single Pot.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Water exclusion reaction in aqueous media: nitrone formation and cycloaddition in a single pot.

[reaction: see text] The formation of nitrone (a water exclusion reaction) in aqueous media using surfactant and subsequent cycloaddition in the same pot, a new example of green chemistry, is reported. The control of regioselectivity favors the formation of trans-5-substituted isoxazolidine. This work not only may lead to an environmentally benign system but also will provide a new aspect of reactions in water.

A Convenient Synthesis of Iminosugar‐C‐glycosides via Organometallic Addition to N‐Benzyl‐N‐glycosylhydroxylamines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Absence of the Nitrone Form among the Refined Crystal Structures of 1-Methoxy- and 1-(2-Chloro-ethyl)oxy-2-hydroximino-3-methyl-4-nitro-3-phospholene-1-oxides

Crystal structure refinement has been performed by XRD for 1-methoxy- and 1-(2-chloroethyl)oxy-2-hydroximino-3-methyl-4-nitro-3-phospholene-1-oxides (I) C6H9N2O5P, Z=8, space group P21/c, and (II) C7H10ClN2O5P, Z=4, space group P21/c. Disordering of independent molecules I and I' in the crystal structure of I and of molecule II in the crystal structure of II has been found. Full-matrix least-squares refinement of I and II was performed anisotropically (isotropically for H) to R=0.052 (I) and 0.034 (II) for all 4377 (I) and 2533 (II) independent reflections (CAD-4 automatic diffractometer, λMoKα). The authors of the first XRD analysis of crystals I and II made the wrong conclusion that compounds I and II exist in crystal in NH-nitrone form; i.e., that they contain an O←N(H)=C nitrone isomer group instead of an H−O−N=C oxime group. As shown in this study, compounds I and II exist in ordinary oxime form. The authors of the first XRD analysis failed to notice the disordering of molecules I, I', and II, and they erroneously took the second, low-occupied oxygen sites of the disordered oxime groups for the H atoms at N atoms.

A convenient synthesis of iminosugar- C-glycosides via organometallic addition to N-benzyl- N-glycosylhydroxylamines

N-Benzyl- N-glycosylhydroxylamines were prepared in very good yield via condensation of furanoses and pyranoses with N-benzylhydroxylamine at 110°C for 30 min under solvent-free conditions. These anomeric sugar-hydroxylamines exist in equilibrium with the open-chain nitrone form. In fact upon treatment with various organometallic reagents, the corresponding adducts were obtained with good to high diastereoselectivity. These adducts were converted into iminosugar- C-glycosides by reductive dehydroxylation and intramolecular cyclization.

Crystal and Molecular Structure of 4-Nitro-2-oximino-3-phenylamino-3-thiolene-1,1-dioxide

The present publication reports the results of X-ray diffraction (XRD) analysis of 4-nitro-2-oximino-3-phenylamino-3-thiolene-1,1-dioxide crystals (I). The synthesis and the useful properties of this class of compounds are reviewed in [1]. It is noteworthy that previously [2] an X-ray structure analysis has been performed for another compound from this class, 3-methyl-4-nitro-2-oximino-3-thiolene-1,1-dioxide (II), which was assumed to exist in nitrone form. The XRD data for compound I disprove this assumption.

TBAT‐Mediated Nitrone Formation of ω‐Mesyloxy‐O‐tert‐butyldiphenylsilyloximes: Facile Synthesis of Cyclic Nitrones from Hemiacetals.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective addition of ketene silyl acetals to nitrones catalyzed by chiral titanium complexes. Synthesis of optically active beta-amino acids.

A chiral titanium complex, Ti(O-i-Pr)(4)/BINOL/tert-butylcatechol, catalyzes enantioselective addition reaction of ketene silyl acetals to nitrones to give optically active beta-amino acid derivatives which are biologically active compounds and useful synthetic intermediates of natural products and pharmaceuticals such as beta-lactam antibiotics. The combined process of catalytic oxidation of secondary amines and enantioselective carbon-carbon bond formation of nitrones thus obtained with ketene silyl acetals provides a useful two-step method for the synthesis of optically active beta-amino acid derivatives and related nitrogen compounds.

TBAT-Mediated Nitrone Formation of ω-Mesyloxy-O-tert-butyldiphenylsilyl-oximes: Facile Synthesis of Cyclic Nitrones from Hemiacetals

Chiral and cyclic nitrones were synthesized by TBAT-mediated desilylative cyclization of ω-mesyloxy-O-tert-butyldiphenylsilyloximes, readily prepared from sugar derivatives by a consecutive treatment with O-tert-butyldiphenylsilylhydroxyl­amine and with mesyl chloride. The method was applied to sequential nitrone formation and intramolecular cycloaddition.

ChemInform Abstract: X=Y—ZH Systems as Potential 1,3‐Dipoles. Part 51. Halogen‐Induced Inter‐ and Intra‐Molecular Formation of Nitrones from Oximes and Alkenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: X=Y—ZH Systems as Potential 1,3‐Dipoles. Part 50. Phenylselenyl Halide Induced Formation of Cyclic Nitrones from Alkenyl Oximes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

XY–ZH Systems as potential 1,3-dipoles. Part 51: Halogen-induced inter- and intra-molecular formation of nitrones from oximes and alkenes

Oximes possessing γ- and δ-alkenyl substituents are cyclised by N-bromo- or N-iodosuccinimide, iodine or ICl to the corresponding cyclic nitrones or their dimeric H-bonded hydroiodide salts in good yield; facially specific cycloaddition of these nitrones, and others derived by cyclisation of δ,δ-bis(alkenyl) ketoximes or by iodine induced addition of acetaldoxime to cyclohexene, furnish isoxazolidines.

Novel Five/Five- and Six/Five-Membered Bicyclic Nitroso Acetals from High-Pressure-Promoted Cyclisation Reactions ofp-Methoxybenzyl Vinyl Ether, 1-Nitro-2-heteroaryl Ethenes, and Mono- and Di-Substituted Olefins

At 15 kbar the 1-nitro-2-heteroarylethenes 2a−c reacted in a one-pot three-component cycloaddition with p-methoxybenzyl vinyl ether (1) and methyl acrylate to yield novel heteroaromatic-substituted six/five-membered bicyclic nitroso acetals. In the reaction of 3-[(E)-2-nitroeth-1-enyl]pyridine (2 equiv.) and 1 a competition between the formation of the tandem [4 + 2]/[3 + 2] cycloadducts and the formation of a novel five-membered cyclic nitronate was observed. The ratio of product formation was strongly pressure and solvent dependent. A mechanistic explanation for the formation of the novel five-membered cyclic nitronate has been proposed. 1-Nitro-4-[(E)-2-nitroeth-1-enyl]benzene (2d) reacted with 1 in the same manner as 2a in accordance with the proposed mechanism. The five-membered cyclic nitronate reacted as an 1,3-dipole in a high-pressure promoted [3 + 2] cycloaddition with both electron-rich and electron-poor olefins and yielded a novel class of pyridyl-substituted five/five-membered bicyclic nitroso acetals.

XY–ZH Systems as Potential 1,3-Dipoles. Part 50: Phenylselenyl Halide Induced Formation of Cyclic Nitrones from Alkenyl Oximes

Oximes possessing γ-, δ or ω-alkenyl substituents are cyclised by phenylselenyl bromide, or by phenylselenyl chloride and an appropriate silver salt to the corresponding cyclic nitrones; the seleno nitrones undergo facially specific cycloaddition reactions with N-methylmaleimide; bis(alk-γ,δ-enyl) ketones undergo regiospecific cyclisation and stereospecific intramolecular cycloaddition to furnish spirocyclic products.