1 -Hydroxy-3-imidazoline-3-oxide

The only example of ring-chain tautomerism of imidazoles is 1-hydroxy-4 -imidazoline-3-oxide (69MI86 78MI2, pp. 155,182). 

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). 

A strictly dehned region of chemical shifts of C2, C4, and C5 atoms in A-oxides of 4A-imidazoles allows to dehne clearly the position of the A-oxide oxygen atom (102). Chemical shifts of the a-C nitrone group in a-N-, O-, and S-substituted nitrones are located in the region of 137 to 150 ppm (388, 413). On the basis of 13C NMR analysis of 3-imidazoline-3-oxide derivatives, the position of tautomeric equilibria in amino-, hydroxy-, and mercapto- nitrones has been estimated. It is shown that tautomeric equilibria in OH- and SH-derivatives are shifted toward the oxo and thioxo forms (approximately 95%), while amino derivatives remain as amino nitrones (413). In the compounds with an intracyclic amino group, an aminonitrone (A) - A-hydroxyaminoimino (B) tautomeric equilibrium was observed (Scheme 2.76), depending on both, the nature of the solvent and the character of the substituent in position 2 of the heterocycle (414). 

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. 

Reduction of nitrone groups to hydroxylamines occurs readily with sodium borohydride (201). In particular, the action of NaBHj on l-hydroxy-3-imidazoline-3-oxides (268) leads to 1,3-dihydroxyimidazolidines (269), which on subsequent treatment with hydroxylamine hydrochloride afford 1,2-bishydroxyl-amines (270) (Scheme 2.99) (478). 

It was found (616) that the course of the heterogeneous reaction of 1-hydroxy-5,5- dimethyl-2,4- diphenyl-3-imidazoline-3-oxide with PhLi depends on the crystalline phase of the starting compound, which can be obtained, predominantly, in cyclic or open chain tautomeric forms. 

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. 

On the basis of UV measurements it has been shown that l-hydroxy-2-imidazolines exist in equilibrium with 2-imidazoline 3-oxides (76CHE1280). 

When l-hydroxy-3-imidazoline 3-oxides (263) are treated with HCl they dehydrate forming imidazole 3-oxides (Scheme 153) (73CHE1175). Reduction of 4//-imidazole N-oxides with borohydride leads to either 1-hydroxy-imidazolines or -imidazolidines, depending on the position of the oxide function. Under the same conditions 4//-imidazole 1,3-dioxides give 1,3-dihydroxyimidazolidines (76CHE1280). The 4iT-imidazole AT-oxides are prepared by heating 5,5-disubstituted l-acyloxy-3-imidazoline 3-oxides in vacuo. 

H(14)1313, 90JOC1772). Substituents also affect the equilibrium between l-hydroxy-3-imidazoline 3-oxides and the open-chain hydroxyiminonitrones electron-withdrawing groups in the... 

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. 

Interaction of 1,2-hydroxylaminooximes with diacetyl resulted in 1-hydroxy derivatives of 3-imidazoline-3-oxides (9a,c) with a carbonyl... 

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-... 

The presence of the reactive nitrone group in the molecule of the 3-imidazoline-3-oxide heterocyle is responsible for the course of reactions of 1,3-bipolar addition. The interaction of 1-hydroxy-2,2,5,5-tetramethyl-... 

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)-... 

Treatment of l-hydroxy-3-imidazoline-3-oxides (6a,c) with Grignard reagent opens the cycle and forms 1,2-iV-t rt-butylhydroxylaminooximes (38a,c). Oxidation of the latter leads to acyclic stable nitroxides (39a,c)... 

Polarization of the C=N bond also causes electrophilic substitution of the alkyl group hydrogen in the a-position. Interaction of 1-hydroxy-3-imidazoline-3-oxide (6a) with aromatic aldehydes in the presence of bases, similar to the case observed for heterocyclic iV-oxides (Ochiai, 1967 Katritzky and Lagowski, 1971 Hansen and Boyd, 1970), leads to l-hydroxy-4-arylvinyl-3-imidazoline-3-oxides (41), oxidation of which generates nitroxides 42. The action of an equimolar amount of amyl nitrite on l-hydroxy-4-methyl- and l-hydroxy-4-ethyl-3-imidazoline-3-oxides... 

Numerous derivatives of imidazoline nitroxides with various functional groups have been obtained in the investigations of reactions of 4-alkyl-halide- and 4-alkyl-dihalide-3-imidazoline-3-oxides. The interaction of compounds 7a,b with an equimolar quantity of iV-bromo- and N-chloro-succinimide leads to 4-bromomethyl-, 4-a-bromoethyl-, and 4-a-chloro-ethyl-3-imidazoline-3 oxides (64a,b) (Kutikova and Volodarsky, 1973 Grigor ev and Volodarsky, 1975). With the addition of excess iV-succinimide halide 4-dibromomethyl-, 4-dichloromethyl-, and 4-a,a-dichloroethyl-3-imidazoline-3-oxides (65a,b) are formed (Grigor ev and Volodarsky, 1974 Grigor ev et a/., 1975 Mitasov et ai, 1978). Nitroxides 64 and 65 are reduced by zinc to diamagnetic 1-hydroxy-derivatives 66 and 67. 

The reaction of 4-diIialoalkyl derivatives with primary amines, depending on the conditions, leads to different products. The interaction of 1-hydroxy-4-dibromomethyl-3-imidazoline-3-oxide (67a, X = Br) with pri-... 

Figure 2. Raman spectra of 1-hydroxy-2,2,4,5,5-pentamethyl-3-imidazoline-3-oxide (6a) and 2,2,4,5,5-pentamethyl-3-imidazoline-3-oxide-l-oxyl (7a) in the solid state. Curve A, 6a spectrum in the region of 1000-1700 cm curve B, the spectrum of 7a curve C, the spectrum of 7a labeled by in position 1 ( N abundance is 95 %).

Dissociation of molecular ions of l-hydroxy-3-imidazoline-3-oxides (6) (Scheme 4) and of corresponding nitroxides (7) (Scheme 5) proceeds in a more complicated manner (Ivanovskaja et al, 1979). 

Pentamethyl-3-imidazoline-3-oxide-l-oxyl (7a). l-Hydroxy-2,2,4,5,5-pentamethyl-3-imidazoline-3-oxide (6a) (10 g, 58 mmoles) is rubbed with Mn02 (20 g, 230 mmoles) and intermixed in benzene (200 ml) until the solution acquires an intensive yellow color (for about 30 min). The solution is decanted, 150 ml of benzene is added to the residue, and the solution is intermixed again till it acquires an intensive yellow color (for about 30 min). Then the solution is decanted. This operation is repeated two or three more times until the coloring of the benzene solution ceases. The combined filtrates are evaporated under reduced pressure. The yellow oil that remains after the evaporation of the benzene is crystallized. The yield of 7a is 9 g (90%), m.p. 103-104°C (from hexane-benzene mixture, 1 1). UV (ethanol), Anm (Ig e) 234 (4.07). IR (in KBr), vem- 1601 (C=N), 1294 (N+—O ), 1250, 1170. 

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