3- Imidazoline 1-oxides, radicals

Xep2 added to a soln. of l-nitroso-2,2,5,5-tetramethyl-4-phenyl-3-imidazoline 3-oxide in methylene chloride in a Teflon-type vessel, and stirred at 20-25° for 20 h 3-nitroso-2,2,4,4-tetramethyl-5-phenyl-5-fluoroimidazolidine 1-oxyl. Y 70%. F.e. and 1,1-difluoro-N-oxide radicals s. I.A. Grigorev et al., Izv. Akad. Nauk SSSR Ser. Khim. 1989, 933-7. 

Thermolysis of a stable radical 4-[(hydroxyimino)nitromethyl]-2,2,5,5-tetra-methyl-3-imidazolin-l-oxyl 13 gives the corresponding spin-labeled nitrile oxide. It was also identified in isoxazolines formed in cycloadditions with olefins (88). 

In electrochemical oxidation of l-hydroxy-3-imidazoline-3-oxides containing one to four H atoms at a-C, one observes in ESR-spectra not only triplet splitting of the nucleus 14N of the nitroxyl group (a v 15-16 G) but also splitting of the neighboring protons (a// 18-20 G), with multiplets corresponding to their number (from doublet to quintet) (101). Unlike spatially hindered hydroxylamines which show reversibility in electrochemical oxidation, hydroxylamines with H at a-C are oxidized irreversibly. Oxidation of hydroxylamines with nitroxyl radical proceeds easily and with quantitative yields (102). In the oxidation of asymmetric polylluorinated hydroxylamines with Mn02, isomeric polyfluorinated nitrones have been obtained (103). 

From a comparative analysis of H NMR spectra of structurally similar pairs of nitroxyl radicals of 3-imidazoline and 3-imidazoline-3-oxide, it was concluded that the nitrone group contributes to a more efficient long-range spin density delocalization in the conjugated n -system of functional groups bonded with atom C-4 (404). 

The result of a study of 15 N NMR spectra of cyclic nitrones of 3-imidazoline-3-oxide and of the corresponding nitroxyl radicals has been reported (422). 

On studying electrochemical properties of l-hydroxy-3-imidazoline-3-oxides and their conversion into nitronyl nitroxyl radicals (NNR), the intermediate production of a nonaromatic radical cation (220) of AH -imidazole-1,3- dioxides (219) (Scheme 2.78) (101) was suggested. 

Unlike the 4H- imidazoles (219), (223), (224) electrochemical oxidation of the nitrone group in 4-R-3-imidazoline-3-oxides (228), (230-232), as in a-PBN and DMPO is of irreversible nature. Therefore, the formation of radical cations... 

The method of optically detected EPR (OD EPR) has been successfully employed to detect short-lived radical anions of cyclic nitrones DMPO and l,2,2,5,5-pentamethyl-3-imidazoline-3-oxide (PMIO) (229, R = H), generated by... 

A detailed analysis of photoisomerization of the nitrone group in the nitroxyl radical 4-phenyl-2,2,5,5-tetramethyl-3-imidazoline-3-oxide-l-oxyl, based on double electron-nuclear resonance methods, has shown that in the absence of oxygen the photochemical reaction occurs without affecting the radical center. The... 

Owing to the existence of two centers for nucleophilic attack (at C2 and C5) in radical cations (220) obtained from the oxidation of 4-H -imidazole-1,3-dioxides (219), the formation of two products of methoxy group addition was observed, namely NNR (221) and NR of 3-imidazoline-3-oxide (222). The ratio of the products depends on the electronic nature of substitutes R1 and R2. Both, the donor character of R1 and acceptor character of R2 facilitate the formation of nitroxyl radicals (222) with the yield of (221) increasing with the inverted effect of the substituents. As was mentioned in Section 2.4, the results of preparative electrochemical oxidative methoxylation of 4H -imidazole-1,3-dioxides are similar to the results of chemical oxidation. 

Oxidative Fluorination of Nitrones to a-Fluorosubstituted Nitroxyl Radicals Formation of nitroxyl radicals by the radical cation route was observed in reactions of various nitrones with xenon difluoride in dry methylene chloride (520, 523). In this reaction, more than 40 nitrones, including 4H -imidazole N,N -dioxides (219), 4H -imidazole TV-oxides (223) and (224), 2H -imidazole N -oxides (225), 2H -imidazole TV,TV-dioxides (226), 3,3,5,5-tetramethylpyrroline N -oxide (TMPO), derivatives of 3-imidazoline-3-oxides (231) and (232), have been examined. ESR spectra of nitroxyl radicals containing one or two fluorine atoms at a-C have been registered (Scheme 2.108) (523). In the case of... 

Chiral 2-imidazoline dianions undergo one-electron oxidation in the presence of TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxy) to form a radical anion that is either trapped stereoselectively by TEMPO or undergoes dimerization. Oxidation of bis-diazene oxides leads to novel (9-stabilized 4N/3e radical cations and 4N/2e dications. These were detected by ESR spectroscopy and cyclic voltammetry. B3LYR/6-31G calculations confirmed the nature of the 4N/3e and 4N/2e systems. ... 

Oxidation gives stable radicals (442) which form cycloadducts with dipolarophiles (e.g. 443) (85TL4801). Radicals formed from 3-imidazoline 1-oxides or l-hydroxy-3-imidazolines can be formylated on nitrogen under Vilsmeier conditions and exocyclically brominated or chlorinated by NBS or NCS on a 4-methyl group. 

A pair of Ullman s nitronyl nitroxide radicals carrying m- and p-ethynylphenyl groups at position 2 of the imidazoline ring (7 and 8) are quite stable at room temperature under air and the unpaired electrons withstand the catalyzed polymerization conditions (see Section 11.4.3) [6]. The terminal ethynyl groups are not susceptible to Pb02 in benzene/metha-nol at room temperature, which is used for the oxidation of the bis(hydroxylamine)s to the nitronyl nitroxides [6, 7]. Fremy s salt gives the best result for the oxidation of the hydroxyl-amine 14 carrying a terminal 1,3-butadiyne moiety [9]. 

Dianions derived from chiral imidazolines have been reported to undergo selective one-electron oxidation reactions followed by stereoselective radical coupling. ... 

Imidazolidine and imidazoline derivatives were formed when dialdose derivatives reacted with 2,3-bis(hydroxylamino)-2,3-dimethylbutane (Scheme 60) oxidation of these derivatives afforded stable free radicals that were examined by e.s.r. spectroscopy. Several oxazole and thiazolidine derivatives having C-5 and C-6 of 3-0-benzyl-l,2-0-isopropylidene-jS-L-idofuranose as part of the heterocyclic ring, and a new class of bicyclic thiazolidine derivative (172) have been prepared by the reactions shown in Scheme 61. The bis(l,3,4-oxadia-zole) derivative (173) has been prepared by condensative cyclization of 2,3,4,5-tetra-O-acetylgalactaric acid bis(benzoylhydrazide) with triethyl orthoformate in p-dioxan. Other heterocyclic derivatives are referred to in Chapters 14 and 15. 

Ferric chloride-photosensitized oxidations of several alcohols (e.g. ethanol, cyclohexanol, and 2-methylpropan-2-oI) have been conducted in the cavity of an e.s.r. spectrometer at temperatures between —150 and — 196°C. Except for rigid glasses of 2-methylpropan-2-ol, all the photolysed alcohols investigated yielded free-radicals detectable by the spectrometer alcohols in rigid glasses should provide better models for cellulose in the solid state than alcohols in solution. Free radicals formed on y-irradiation of single crystals of trehalose and sucrose, on oxidation of some carbohydrate imidazolines (see Scheme 60), and on treatment of L-ascorbic acid with hydrazine in oxygenated alkaline solution have been examined by e.s.r. spectroscopy. 

The formation of l-hydroxy-3-imidazolines proceeds under mild weakly alkaline or weakly acidic conditions, in contrast to the strongly acidic media usually employed for obtaining precursors of doxyl radicals (Keana, 1978). l-Hydroxy-3-imidazolines are easily oxidized to nitroxides by molecular oxygen, Pb02, Mn02, etc. 

The presence in the molecule of imidazoline nitroxides of an additional nitrogen atom or of an N-oxide group in combination with functional groups in position 4 of the heterocycle allows com-plexation, chelation, and cyclometalation without participation of the radical center. This made it possible to investigate for the first time the magnetic resonance spectra of multispin systems. 

Oxidation of 1-hydroxy derivatives (6a-g) with lead dioxide in nonpolar organic solvents leads smoothly to nitroxides, namely 2,2,5,5-tetra-alkyl-3-imidazoline-3-oxide-l-oxyls (7a-g) (Volodarsky and Kutikova, 1971). In the crystalline state radicals 7 can be stored for a long time without decomposition. Both radical precursors 6 and the radicals themselves enter into various substitution, condensation, and other reactions. 

For generating 3-imidazoline derivatives containing no N-oxide oxygen, 1,2-hydroxylaminoketones were employed, which are formed in the acidic hydrolysis of 1,2-hydroxylaminooximes (Volodarsky and Sevastyanova, 1971), The interaction of 1,2-hydroxylaminoketones with ketones and ammonia under mild conditions (in some cases at 20°C) leads to the formation of l-hydroxy-4-aryl- and l-hydroxy-4-alkyl-2,2,5,5-tetraalkyl-3-imidazolines (12) (Sevastyanova and Volodarsky, 1972 Volodarsky and Sevastyanova, 1973). Compounds 12 are colorless crystalline substances that have lower melting points and are more readily soluble in organic solvents than 3-imidazoline-3-oxides 6. When stored or recrystallized in air, they become partially oxidized to radicals. Oxi-... 

Interaction of 3-imidazoline-3-oxide nitroxides with Grignard reagent proceeds with the involvement of the radical center and leads to reduction products 6a,c and methoxy derivatives 35a,c. Meanwhile, in the interaction of methylmagnesium iodide with the methoxy derivatives 1,3-addition to the nitrone group occurs, and 1-methoxy-3-hydroxy-4-alkyl (aryl)-... 

Hence, polarization of the C=N bond of imidazolinium nitroxyl salts provides easy and unique addition of nucleophilic agents (i.e., cyanide ion, Grignard reagent, and hydride ion) with the formation of imidazolidine nitroxides, whereas the radical center participates when, in reactions of this type, as in the case of 3-imidazoline-3-oxides, the functional group becomes transformed and the heterocycle is opened. 

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