3317-61-1

Hazards Identification

GHS Hazard Statements:

Not Classified
Reported as not meeting GHS hazard criteria by 2 of 2 companies. For more detailed information, please visit ECHA C&L website.

Hazards Summary:

May cause irritation; [Sigma-Aldrich MSDS]

Usage

Uses

Used in Biological Systems:
5,5-DIMETHYL-1-PYRROLINE N-OXIDE is used as a spin trap agent for detecting free radicals in electron paramagnetic resonance (EPR) based reactions. It is particularly effective in characterizing O-, N-, S-, and C-centered radicals, allowing for a better understanding of their roles in various biological processes.
Used in Chemical Synthesis:
5,5-DIMETHYL-1-PYRROLINE N-OXIDE is used as a free-radical spin-trapping agent or an electrophilic component during the synthesis of pyrrolidine derivatives. Its reactivity and stability make it a valuable component in the development of new chemical compounds.
Used in Cycloaddition Processes:
In addition to its role as a spin trap and reagent in chemical synthesis, 5,5-DIMETHYL-1-PYRROLINE N-OXIDE can also be considered as a 1,3-dipole in cycloaddition processes. This further expands its utility in the creation of complex molecular structures.

Preparation

To a three-necked round bottom flask equipped with a condenser, addi-tion funnel, thermometer, and mechanical stirrer and containing 300 ml. 95% ethanol precooled to 2°C is added, all at once, 14.5 g (0.1 mole) 4-methyl-4-nitropentanol, and 13.1 g (1.2 mole) zinc dust. With rapid agita-tion, the glacial acetic acid (24.0 g, 0.4 mole) is added dropwise over a 1-hr period while maintaining the reaction temperature below 15°C. The mix-ture is stirred vigorously for 2 hr and then stored in the refrigerator for 2 days, at approximately 1°C. Then the zinc acetate is filtered and rinsed with 100 ml of ethanol. The combined ethanol factions are rotoevapo-rated to give the crude nitrone. The crude nitrone is dissolved in a 200 ml portion of dichloromethane and the latter washed two times with saturated sodium bicarbonate solution. The organic layer is dried over sodium sul-fate and the solvent rotoevaporated, to give 10.7 (94% yield) of the crude nitrone. The product was purified by double distillation (b.p. 53°C, 0.1 Torr), to give 6.8 g (60%) of the pure nitrone as a white hygroscopic solid. The H1 NMR (400 MH CDC13, Me4Si) is 6.80 (t, 2H, methylene bound to quaternary C, J = 7.2Hg), 1.43 (s, 6H, methyl), C13NMr (100 MH2, CDC13, Me4 Si) 5=132.4 (Vinyl), 73.5 (quaternary), 34.1 (Allyl), 25.3 (methylene bound to quaternary C), 24.4 (methyls).

Biological Activity

Water soluble nitric oxide spin trap; allows the measurement of oxygen-centered free radicals in biological systems at room temperature using electron spin resonance (ESR). Has a high reaction rate constant for superoxide and hydroxyl radicals, and distinguishes simultaneously among a variety of important biologically generated free radicals.

References

1) Nishizawa et al. (2004), Hydroxyl radical generation caused by the reaction of singlet oxygen with the spin trap DMPO, increases significantly in the presence of biological reductants; Mol. Pharmacol., 6 597 2) Shi et al. (2005), Evaluation of spin trapping agents and trapping conditions for detection of cell-generated reactive oxygen species; Arch. Biochem. Biophys., 437 59 3) Clement et al. (2005), Assignment of the EPR spectrum of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) superoxide spin adduct; J. Org. Chem., 70 1198 4) Gomez-Mejiba et al. (2009), Immuno-spin trapping of protein and DNA radicals: ‘tagging’ free radicals to locate and understand the redox process; Free Rad. Biol. Med., 42 530

InChI:InChI=1/C6H11NO/c1-6(2)4-3-5-7(6)8/h5H,3-4H2,1-2H3

Upstream product

• 61856-91-5 5,5-dimethyl-1-pyrroline-2-carboxylic acid 1-oxide 
• 57620-49-2 4-methyl-4-nitropentanal 
• 57620-56-1 2-(3-methyl-3-nitrobutyl)-[1,3]dioxolane 
• 55482-04-7 2,2-dimethyl-5-hydroperoxy-1-pyrrolidinyloxyl 

Downstream Products

• 4567-18-4 2,5,5-trimethylpyrroline N-oxide 
• 127034-79-1 (3aR,8aS,8bS)-6,6-Dimethyl-2-phenyl-hexahydro-dipyrrolo[1,2-b;3',4'-d]isoxazole-1,3-dione 
• 127034-79-1 (3aR,8aR,8bS)-6,6-Dimethyl-2-phenyl-hexahydro-dipyrrolo[1,2-b;3',4'-d]isoxazole-1,3-dione 
• 55482-03-6 5,5-dimethyl-2-hydroxypyrrolidino-1-oxyl 
• 40936-17-2 DMPO/CH₂OH 
• 94556-98-6 C₂₄H₄₆NO 
• 112672-95-4 (2R,3R,3aR)-6,6-Dimethyl-3-nitro-2-phenyl-hexahydro-pyrrolo[1,2-b]isoxazole 
• 112672-95-4 (2R,3S,3aR)-6,6-Dimethyl-3-nitro-2-phenyl-hexahydro-pyrrolo[1,2-b]isoxazole 
• 131480-25-6 cis-6,6-dimethyl-2-diphenylthiophosphinylhexahydropyrrolo<1,2-b>isoxazole 
• 131480-26-7 cis-6,6-dimethyl-3-diphenylthiophosphinylhexahydropyrrolo<1,2-b>isoxazole 
• 40936-05-8 2,5,5-trimethylpyrrolidine-1-oxyl 
• 100655-75-2 <2,2-dimethyl-5-(p-nitrophenyl)-1-pyrrolidinyl>oxy radical 
• 143140-42-5 (1R^*,2S^*,3a'R^*)-2-benzyltetrahydro-6',6'-dimethylspiroisoxazole> 
• 143140-42-5 (1S^*,2R^*,3a'R^*)-2-benzyltetrahydro-6',6'-dimethylspiroisoxazole> 

Relevant academic research and scientific papers

NMR and EPR studies of the reaction of nucleophilic addition of (bi) sulfite to the nitrone spin trap DMPO

The reaction of the nitrone spin trap 5,5-dimethylpyrroline-N-oxide (DMPO) with sodium (bi)sulfite in aqueous solutions was investigated using NMR and EPR techniques. Reversible nucleophilic addition of (bi)sulfite anions to the double bond of DMPO was observed, resulting in the formation of the hydroxylamine derivative 1-hydroxy-5,5-dimethylpyrrolidine-2-sulfonic acid, with characteristic 1H and 13C NMR spectra. The reaction mechanism was suggested and corresponding equilibrium constants determined. The mild oxidation of the hydroxylamine results in the formation of an EPR-detected spectrum identical with that for the DMPO adduct with sulfur trioxide anion radical. The latter demonstrates that a non-radical addition reaction of (bi)sulfite with DMPO may contribute to the EPR detection of SO3 -? radical. This possibility must be taken into account in spin trapping analysis of sulfite radical. Copyright

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

Sterically shielded nitroxides of the pyrrolidine series have shown the highest resistance to reduction. Here we report the synthesis of new pyrrolidine nitroxides from 5,5-dialkyl-1-pyrroline N-oxides via the introduction of a pent-4-enyl group to the nitrone carbon followed by an intramolecular 1,3-dipolar cycloaddition reaction and isoxazolidine ring opening. The kinetics of reduction of the new nitroxides with ascorbate were studied and compared to those of previously published (1S,2R,3′S,4′S,5′S,2″R)-dispiro[(2-hydroxymethyl)cyclopentan-1,2′-(3′,4′-di-tert-butoxy)pyrrolidine-5′,1″-(2″-hydroxymethyl)cyclopentane]-1′-oxyl (1).

COMPOSITIONS COMPRISING A NITRONE COMPOUND FOR USE IN TREATING UVEITIS

Ophthalmic pharmaceutical compositions containing a pharmaceutically acceptable ophthalmic carrier and an inflammation-treating amount of a nitrone compound are disclosed. Also disclosed are methods for treating ocular inflammation conditions, such as uveitis, using pharmaceutical compositions.

Decay of the Hydroperoxyl Spin Adduct of 5-Diethoxyphosphoryl-5-methyl-1-pyrroline N-Oxide: an EPR Kinetic Study

The decay kinetics of the hydroperoxyl spin adduct of both 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO), a new β-phosphorylated cyclic nitrone and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) were studied in various media by EPR spectroscopy.In organic solvents, both first- and second-order processes were shown to contribute to the decay of the two spin adducts.However, in aqueous solution the DMPO-hydroperoxyl spin adduct decay was pure first-order.The half-lives of the two spin adducts were determined in every medium tested and the DEPMPO-hydroperoxyl spin adduct was shown to be significantly more persistent (from five times in organic solvents to 30 times in a pH 5.6 buffer) than the DMPO-hydroperoxyl spin adduct.

Acylation of Aldo 1-Pyrroline 1-Oxides (4,5-Dihydro-3H-pyrrole 1-Oxides) and the Oxidation of the Resulting 3-Acyloxy-1-pyrrolines (3-Acyloxy-4,5-dihydro-3H-pyrroles)

5,5-Dimethyl-1-pyrroline 1-oxide (DMPO), when treated with NaH (1 mol) followed by ethyl chloroformate, benzoyl chloride, pivaloyl chloride or 2-bromoisobutyryl bromide gave the corresponding 3-acyloxy-1-pyrrolines.With NaH (2-4 mol) followed by benzoyl chloride or 2-bromoisobutyryl bromide, DMPO gave the corresponding 2-(3'-acyloxy-1'-pyrrolin-3'-yl)-3-acyloxypyrrolidines.Acylation of the 3-phenyl and 3-methyl DMPOs also gave the corresponding 3-acyloxy-1-pyrrolines.Oxidation of the 3-acyloxy-1-pyrrolines with m-CPBA gave the correspondong oxaziridines in good yield.These oxaziridines were resistant to ring opening by acid hydrolysis, photolysis and thermolysis.

Cycloaddition Reaction of 2,2-Dimethyl-3,4-dihydro-2H-pyrrole N-Oxide With Unsaturated Sugar Lactones and Esters

Intermolecular asymmetric 1,3-dipolar cycloaddition of 2,2-dimethyl-3,4-dihydro-2H-pyrrole N-oxide with optically active α,β-unsaturated esters 1,2 gave the diastereomers 8,9,10 and with sugar lactones 3 and 6 gave stereoselectively the cycloadduct 11 and 12.The stereochemistry of the products has been established using high field nmr techniques.The major adducts 11 and 12 arise from an exo transition state and anti-approach, indicating the dominance of steric factors over secondary orbital interactions.

SYNTHESIS OF SOME SUBSTITUTED PYRROLINE-1-OXIDES BY CATALYTIC HYDROGENATION OF ALIPHATIC GAMMA-NITROVCARBONYL COMPOUNDS

Various pyrroline-1-oxides were prepared by the catalytic hydrogenation of appropriately substituted gamma-nitrocarbonyl compounds.Initially the reaction affords a mixture of the nitrone and the corresponding hydroxilamine, but copper(II)-catalyzed aerial oxidation readily converts the hydroxylamine to the desired cyclic nitrone.This method was found to be more convenient than the zinc-ammonium chloride reduction and the corresponding yields were comparable.

ADDITION 1-3 D'HYDROSILANES ET STANNANES SUR DIVERSES NITRONES : RADICAUX NITROXYDES α-METALLES R3M-C-N.-O ET O- ET C-METALLA-HYDROXYLAMINES R3M-O-N-C-H ET R3M-C-N-OH

Free radical 1,3-addition of silanes or stannanes to various nitrones generally leads to corresponding O-organometallohydroxylamines.The α-metallonitroxide radicals =-M-C-N.-O, obtained by trapping silyl or stannyl-centred radicals with an appropriate nitrone, have been characterised by e.s.r. spectroscopy.The O-stannylhydroxylamines are generally sufficiently stable to be isolated by distillation under vacuum.The less stable O-germyl or O-silylhydroxylamines decompose readily upon heating or by photolysis by competing intra- and intermolecular processes.Under special conditions favouring the formation of silylanions (MeNO2, NEt3), a competitive 1,3-dipolar addition of phenyldichloro- or trichlorosilane with the nitrone leads to the unstable C-metallohydroxylamine =-M-C-N-OH .