Syntheses and Study of a Pyrroline Nitroxide Condensed Phospholene Oxide and a Pyrroline Nitroxide Attached Diphenylphosphine

The reaction of a diene nitroxide precursor with dichlorophenylphosphine in a McCormac procedure afforded 1,1,3,3-tetramethyl-5-phenyl-1,2,3,4,5,6-hexahydrophospholo[3,4-c]pyrrole-5-oxide-2-oxyl. Lithiation of the protected 3-iodo-pyrroline nitroxide followed by treatment with chlorodiphenylphosphine after deprotection afforded (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine oxide, and after reduction, (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine was realized, which was also supported by X-ray single crystal diffraction measurements. This pyrroline diphenylphosphine derivative was converted to hexadecylphosphonium salt, which is an analogue of antineoplastic agent, MITO-CP.     

Polymerization of styrene in the presence of nitroxide radicals of the dihydroimidazole series

2,2,5,5-Tetramethyl-4-phenyl-2,5-dihydroimidazole-1-oxyl and 2,2,5,5-tetramethyl-4-phenyl-2,5-dihydroimidazole-3-oxide-1-oxyl have been used as regulators of chain growth in the free-radical polymerization of styrene. It has been shown that the compounds of the dihydroimidazole series function as new living polymerization agents and allow the synthesis of polymers with low polydispersity coefficients and desired molecular masses.     

Nitroxyl radicals of the imidazoline series as agents of pseudoliving polymerization of styrene

Radical polymerization of styrene in the presence of 2,2,4,5,5-pentamethyl-2,5-dihydro- Imidazol-1-oxyl, 2,2-diethyl-4,5,5-trimethyl-2,5-dihydroimidazol-1-oxyl, 2,2,5,5-tetramethyl- 4-phenyl-2,5-dihydroimidazol-1-oxyl, 2,2,5-trimethyl-4,5-diphenyl-2,5-dihydroimidazol- 1-oxyl, and 2-methyl-2,3-diphenyl-1,4-diazaspiro[4.5]deca-3-en-1-oxyl was studied. Effect of substituents in the nitroxyl radical and the nature of initiator on the features of “pseudoliving” polymerization and the molecular-weight characteristics of polystyrene synthesized were considered. Nitroxyl radicals of imidazoline series, like TEMPO and its derivatives, allow one to regulate polymerization of styrene and obtain polymers with relatively low values of polydispersity index.     

Synthesis and properties of the first representatives of terminal acetylenes in 3-imidazoline-1-oxyl 3-oxide series

Method for the synthesis of m-and p-isomers of 4-[2-(ethynylphenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxides by the cross-coupling of 4-[2-(3-iodophenyl)vinyl]-and 4-[2-(4-iodophenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxides with (trimethylsilyl)acetylene followed by desilylation was elaborated. The reactions at the CH-fragment of the ethynyl group were performed. The Mannich reaction proceeds with the loss of a spin label, whereas the oxidative homocoupling, with its retention. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2051–2054, October, 2007.     

Indirect electrochemical oxidation of piperidin-4-ones mediated by sodium halide-base system

Indirect electrochemical oxidation of 1-N-subsituted piperidin-4-ones in methanol in an undivided cell in the presence of sodium iodide/sodium methoxide system leads to the corresponding α-hydroxyketals in 50-80% substance yield (50-65% current yield). 2,2,6,6-Tetramethylpiperidin-4-one under the same conditions forms a mixture of methyl 2,2,5,5-tetramethyl-3-pyrrolidinecarboxylate and methyl 2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole-3-carboxylate in 70% substance yield (60-70% current yield) via electrochemically induced Favorskii rearrangement.     

Reaction of amides of 3-imidazoline and 3-imidazoline-3-oxide derivatives with sodium hypobromite

Conclusions The reaction of 2,2,5,5-tetramethyl-3-imidazoline-1-oxyl-4-carboxamide with sodium hypobromite leads to 4-amino-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl. 2,2,5,5-Tetramethyl-3-imidazoline-3-oxide-1-oxyl-4-carboxamide under the same conditions gives 3-hydroxy-2,2,5,5-tetramethylimidazolidin-4-one-1-oxyl.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 228–231, January, 1979.     

Synthesis of block copolymers from polyvinyl chloride prepared in the presence of nitroxyl radicals of the imidazoline series

Specific features of radical polymerization of vinyl chloride in the presence of nitroxyl radicals of the imidazoline series (2-methyl-2,3-diphenyl-1,4-diazaspiro[4,5]dec-3-ene-1-oxyl, 2,2,5,5-tetramethyl-4-phenyl-2,5-dihydroimidazole-1-oxyl, 2,2,5-trimethyl-4,5-diphenyl-2,5-dihydroimidazole-1-oxyl) were studied. The possibility of preparing vinyl chloride-styrene block copolymers in the presence of these nitroxyl radicals was demonstrated, suggesting the occurrence of the polymerization by the reversible inhibition mechanism. The molecular-mass characteristics and the glass transition points of the synthesized samples were determined.     

The effect of the nature of the substituent at the nitrogen atom on transformations of 3-bromo-2,2,6,6-tetramethyl-4-piperidinone and its 1-hydroxy and 1-oxyl derivatives under conditions of the Favorsky rearrangement

3-Bromo-2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl reacts with NH₄OH to give 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl, a product of the Favorsky rearrangement. 3-Bromo-2,2,6,6-tetramethyl-4-piperidinone is transformed under these conditions into a bicyclic amino ketone, while its 1-hydroxy derivative affords acyclic nitrosoenone. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1189–1191, June, 1997.     

Synthesis and structure of products of hydroxylamine acylation with 3-carboxy-2,2,5,5-tetramethylpyrrolinoxyl derivatives

The reaction of NH₂OH with the derivatives of 2,2,5,5-tetramethylpyrrolin-1-oxyl-3-carboxylic acid in all events led to the formation of a mixture of the corresponding nitroxylhydroxamic acid with a stable O-acylhydroxylamine. The ratio between the products depends on the nature of the acylating agent and under the studied conditions varies from ∼5.5: 1 to 1: 3 indicating the comparable nucleophilicity in this reaction of N and O atoms in the hydroxylamine. The most active chloride of the mentioned acid alongside the indicated products afforded in a considerable yield N,O-diacylhydroxylamine and the triacylated hydroxylamine, 3-{[(2,2,5,5-tetramethyl-1-oxylopyrrolin-3-yl)carbonyloxyimino][(2,2,5,5-tetramethyl-1-oxylopyrrolin-3-yl)carbonyloxy]-methyl}-2,2,5,5-tetramethylpyrrolin-1-oxyl. The structure of both latter compounds was established by XRD analysis.     

XPS spectra of free nitroxyl radicals and their electronic structure

The N(1s) and O(1s) XPS spectra of stable nitroxyl radicals and molecules with a related heterocycle structure: 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxyphenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxy-3-nitrophenyl)-4,5-dihydro-1Himidazole-3-oxide-1-oxyl, and 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide were studied. The possibility to apply X-ray electron spectra for investigation of the charge electron and spin density distribution on free radical atoms and at their coordination by a metal is considered.     

Stable nitroxyl radicals with triple bonds: 4-acetylenyl-3-imidazoline-3-oxide-1-oxyls

Cross-coupling reaction of 1-hydroxy-2,2,5,5-tetramethyl-4-[2-(p-iodophenyl)vinyl]-3-imidazoline-3-oxide with copper(I) salts of 1-aryl(hetaryl)alkynes leads to the corresponding 2,2,5,5-tetramethyl-4-[2-(p-aryl(hetaryl)ethynylphenyl)vinyl]-3-imidazoline-3-oxide-1-oxyls in high yields.     

Synthesis and EPR investigation of nitroxyl derivatives of fullerenes C<Subscript>60</Subscript> and C<Subscript>70</Subscript>

Nitroxide derivatives of C₆₀ and C₇₀ were obtained by [3+2] cycloaddition of 4-(4-azidophenyl)-2,2,5,5-tetramethyl-3-oxy-2,5-dihydroimidazol-1-oxyl to fullerenes. The products were isolated by TLC and studied by EPR and optical spectroscopy. Molecular rotation of the adducts was shown to slow down on successive addition of the nitroxides, rotational correlation times depending nearly linearly on the number of the nitroxides added. Investigation of photochemical stability of nitroxide derivatives of C₆₀ and C₇₀ in benzene-ethanol medium reveal that the dissolved oxygen quenches efficiently the excitation of nitroxide (λ = 250–400 nm). In the absence of oxygen photoexcitation converts nitroxides to diamagnetic products, presumably, hydroxylamines formed through the interaction with the solvent.     

Crystal Structures of Ni(II) and Co(II) cis-Octahedral Complexes with 3-Imidazoline Nitroxide

NiL₂Bipy·1.5EtOH, CoL₂Bipy·1.5EtOH, and CoL₂Phen·0.5EtOH mixed-ligand complexes with a fixed cis` position of paramagnetic ligands (L = 4-(3',3',3'-trifluoro-2'-oxopropylidene)-2,2,5,5-tetramethyl-3-imidazolidine-1-oxyl) have been synthesized and studied by X-ray crystallography.     

Synthesis of 2,2,5,5-tetramethyl-3-imidazoline-1-oxyl

Condensation of -(hydroxylamino)-2-methylpropanal with acetone and ammonia afforded 2,2,5,5-tetramethyl-3-imidazoline-1-oxyl, the first member of a series of stable nitroxyl radicals which are derivatives of 3-imidazoline. It was shown that 2,2,5,5-tetramethyl-2, 5-dihydropyrazine-1,4-dioxide can reversibly add two molecules of water or ammonia to the nitrone groups.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 931–933, May, 1993.     

First acetylenic derivatives of stable 3-imidazoline nitroxides

The Stephens-Castro reaction of copper(I) salts of 1-aryl(hetaryl)alkynes with 2,2,5,5-tetramethyl-4-[2-(4-iodophenyl)-vinyl]imidazoline-3-oxide-1-ol proved to be a general method for the preparation of 2,2,5,5-tetramethyl-4-[2-(p-aryl(hetaryl)ethynylphenyl)]vinyl-3-imidazoline-3-oxide-1-oxyles.     

Synthesis of a paramagnetic boronic acid as a useful synthetic building block and carbohydrate affinity spin probe

A paramagnetic boronic acid was synthesized by lithiation of 1-acetoxy-3-bromo-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole followed by treatment with trimethyl borate. This paramagnetic boronic acid proved to be a useful starting compound in Suzuki cross-coupling reactions and it exhibited affinity toward fructose and inulin.     

Synthesis and properties of nicotinic acid derivatives containing a 2,2,6,6- tetramethylpiperidine 1-oxyl residue

N¹-(Nicotinoyl)-N²-4-(2,2,6,6-tetramethyl-4-hydroxypiperidine-1-oxyl)hydraxine was obtained by condensation of nicotinoyl hydrazide with 2,2,6,6-tetramethyl-4-oxopiperidine 1-oxyl. Acylation of 2,2,6,6-tetramethyl-4-hydroxypiperidine 1-oxyl with nicotinoyl chloride gives nicotinic acid 2,2,6,6-tetramethyl-1-oxyl 4-piperidyl ester. A spin-labeled analog of nicotinamide was obtained by condensation of nicotinoyl azide with 4-amino-2,2,6,6-tetramethylpiperidine 1-oxyl. The synthesis of 1-N-(-D-ribofuranoside)-3'-N[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)pyridinecarboxamide from 2,2,6,6-tetramethyl-4-nicotinoylaminopiperidine 1-oxyl and 2,3,5-tri-O-benzoyl--D-ribofuranosyl bromide proceeds without damage to the iminoxyl radical. The preparation of the corresponding spin-labeled nucleotide is hindered by destruction of the iminoxyl radical during ion-exchange chromatography.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 352–355, March, 1976.     

Magnetic resonance studies of imidazoline nitroxides and their photochemical transformations

ESR, ¹H and ¹³C NMR, ENDOR and TRIPLE resonance have been employed to study photochemical reactions of 2,2,5,5-tetramethyl-4-phenyl-3-imidazoline-3-oxide-1-oxyl and to determine the electronic structures of the initial and final radicals. The light-induced isomerization of a phenyl nitron group to an oxaziridine group has been shown to proceed without involving the radical centre.     

Interaction of chlorine dioxide with nitroxyl radicals

The formation of charge transfer complexes between chlorine dioxide and nitroxyl radicals (2,2,6,6-tetramethylpiperidin-1-oxyl, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-oxo-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-methoxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-acetylamido-2,2,6,6-tetramethylpiperidin-1-oxyl, 2,2,5,5-tetramethyl-4-phenyl-3-imidazolin-1-oxyl, and bis(4-methoxyphenyl) nitroxide) in acetone, acetonitrile, n-heptane, diethyl ether, carbon tetrachloride, toluene, and dichloromethane was found by spectrophotometry at –60—+20 °C. The thermodynamic parameters of complex formation were determined. The radical structure affects its complex formation ability. The charge transfer complex is transformed into the corresponding oxoammonium salt.     

Syntheses and structures of azol-1-yl derivatives of nitronyl and imino nitroxides

2-(Pyrazol-1-yl)-, 2-(imidazol-1-yl)-, 2-([1,2,4]triazol-1-yl)-, and 2-(benzotriazol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl were prepared by reactions of 2-bromo-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NIT-Br) with the corresponding sodium azolides. In prepared 2-(azol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyls, the NIT-N_Het bond is readily hydrolyzed. Reduction of imidazole-3-oxide-1-oxyls leads to corresponding 2-(azol-1-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyls, which are much more stable against hydrolysis. The structures of spin-labeled imidazoles, [1,2,4]triazoles and benzotriazoles are confirmed by X-ray analysis, showing that the paramagnetic molecules form packings with motifs from centrosymmetric dimers to topologically linear chains.