Reaction of sterically hindered 1-hydroxy-3-imidazoline 3-oxides with phenyllithium

The reaction of 3-imidazoline 3-oxide derivatives with phenyllithium followed by oxidation affords nitroxyl radicals of the 2-imidazoline or 2-imidazoline 3-oxide series depending on the nature of the substituent in position 2 of the heterocycle.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 292–294, February, 1994.     

Synthesis and some reactions of sterically hindered 3-imidazoline 3-oxides

Sterically hindered 3-imidazoline 3-oxides were obtained by condensation of -amino oximes with ketones. It is shown that the reaction of these compounds with electrophilic agents takes place at both the nitrone grouping and the amino group. The oxidation of the products makes it possible to obtain stable nitroxyl radicals.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 103–109, January, 1979.     

Synthesis of 2H-imidazole 1-oxides and stable nitroxyl radicals based on them

2H-Imidazole 1-oxides containing an aldonitrone group in the heterocyclic ring are obtained by the condensation of hydroximinomethyl ketones with ketones and ammonium acetate. Their oxidation with lead dioxide in methanol gives stable nitroxyl radicals — 5,5-dimethoxy-3-imidazoline-1-oxyls.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2113–2121, September, 1991.     

Polymers having stable radicals. II. Synthesis of nitroxyl polymers from 4-methacryloyl derivatives of 1-hydroxy-2,2,6,6-tetramethylpiperidine

Polymers having stable pendant . radicals were synthesized through their precursor polymers by oxidizing them in air or by H₂O₂–Na₂WO₄. Hydrochlorides and sulfates of 4-methacryloylamino- and 4-methacryloyloxy-1-hydroxy-2,2,6,6-tetramethylpiperidines were synthesized as precursor monomers and polymerized by using α,α′-azobisisobutyronitrile under appropriate conditions to precursor polymers of high molecular weight: poly-4-methacryloylamino-/oxy-1-hydroxy-2,2,6,6-tetramethylpiperidinehydrochlorides and sulfates. The precursor polymers were converted to polymers having nitroxyl stable radicals, i.e., poly-4-methacryloylamino-/oxy-2,2,6,6-tetramethylpiperidine-1-oxyls, by oxidation in air or with H₂O₂–Na₂WO₄ without any main-chain scission. The structure of the resultant stable radical polymers was determined by infrared, ultraviolet, and ESR spectroscopy. Based on the results of spectroscopic analysis and Kjeldahl analysis, the transformation from precursors to nitroxyl stable radical polymers was found to be quantitative. Investigations on the applicability of polymeric nitroxyl radicals to oxidation-reduction reactions were attempted by means of polarography; the reduction half-wave potential was found to be ?1.16 V for the mercury pool.     

Syntheses of 2-acetyl-3-hydroxy-1-n-propylpyrrole from isomaltol and 1-n-alkyl-3-hydroxy-2-methyl-4-pyridones from maltol

2-Acetyl-3-hydroxyfuran (2) reacts with n-propylamine affording 2-acetyl-3-hydroxy-1-n-propylpyrrole (3) in 63% yield. The transformation of 2-methyl-3-hydroxy-4-pyrone (4) into 1-n-alkyl-3-hydroxy-2-methyl-4-pyridones is achieved by benzylation of the 3-hydroxyl group whereupon the product reacts with ammonia and the corresponding pyridone is obtained. The pyridone is alkylated with alkyl bromides and after hydrobromic acid in acetic acid cleavage of the 3-position ether function, 1-n-alkyl-3-hydroxy-2-methyl-4-pyridones are obtained in 48% overall yield.     

Reaction of 1,2-hydroxylaminooximes with 1,2-diketones. Conversion of 2-acyl-1-hydroxy-3-imidazoline 3-oxides to pyrazine 1,4-dioxides

The reaction of acyclic primary and secondary 1,2-hydroxylaminooximes with aliphatic, alkylaromatic, and alkylheteroaromatic 1,2-diketones, depending on the structure of the starting compounds and the reaction conditions, gives derivatives of pyrazine 1,4-dioxide, 2-acyl-1-hydroxy-3-imidazoline 3-oxide, or mixtures thereof. 2-Acyl-1-hydroxy-3-imidazoline 3-oxides have been converted to pyrazine 1,4-dioxides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 331–338, March, 1986.     

Oxidative coupling of alkynes mediated by nitroxyl radicals under Sonogashira conditions and Pd-free catalytic approach to stable radicals of 3-imidazoline family with triple bonds

In the presence of Pd catalyst, 3-imidazoline nitroxyl radicals promote oxidative coupling (dimerization) of terminal alkynes even in the absence of Cu(II) additives. On the other hand, the Pd-free CuI-PPh₃-K₂CO₃-DMF catalytic system leads to the efficient cross-coupling of 1-hydroxy-4-[2-(p-iodophenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-3-oxide with terminal aryl- and hetarylacetylenes with the formation of 4-[2-(aryl/hetarylethynyl)phenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-3-oxide-1-oxyls in 70-75% yields.     

13C NMR Spectra of cyclic nitrones. 1. 2-substituted 4-methyl- and 4-phenyl-1-hydroxy-5,5-dimethyl-3-imidazoline 3-oxides

The introduction of an N-oxide oxygen atom into azomethines leads to an upfield shift of the signals for the carbon atom of the G=N group in the ¹³C NMR spectra by 30–33 ppm. This is consistent with the increase in the electron density on this atom. The signal of the nitrone carbon atom is observed in the region of 140–147 ppm, depending on the nature of the substituent at the C(₂) atom of the 3-imidazoline 3-oxide ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 247–251, February, 1985.     

Synthesis of bipyrazoles and pyrazoloisoxazoles from 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one

Phenylhydrazine or hydrazine react with 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one ( 1 ) to give 4-acetoacetyl-3-methylpyrazolin-5-ones 4 . The synthesis of bipyrazoles and pyrazoloisoxazoles from 4 are reported.     

Reaction of 4H- and 2H-imidazole oxides with organolithium compounds,a novel route to stable nitroxyl radicals of the 2(3)-imidazoline series

Reactions of 4H and 2H-imidazole oxides with phenyl- and methyilithium followed by oxidation afford stable nitroxyl radicals — derivatives of 2- and 3-imidazolines including otherwise inaccessible sterically hindered radicals of the latter group. An unusual reaction, the formation of 2-azabutadiene derivatives after NO elimination in the dark, has been observed for pentaphenyl- and 5-methyltetraphenyl-3-imidazoline-1-oxyls.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 933–936, May, 1993.     

Synthetic and mechanistic aspects of cross-coupling of nitroxyl radicals of 3-imidazoline series with terminal alkynes

Practical synthetic approaches to the new class of acetylenic derivatives of 3-imidazolyl-3-oxide-1-oxyls, including biradicals, were developed through cross-coupling reactions of 3-imidazolyl halides with either terminal alkynes or their copper salts. The presence of nitroxyl functional group as an internal oxidant leads to a competition between the formation of cross-coupling products and the products of oxidative homocoupling. The balance in this competition can be shifted toward the cross-coupling products through the combination of factors that includes nature of the catalyst, reactivity of the halides, and reaction conditions.     

Synthesis and properties of sterically hindered hydroxystyrlpyridines

A number of new sterically hindered hydroxystyrylpyridines were synthesized, and their antioxidative activity as a function of structure was studied. The antitumorigenic characteristics of three of the synthesized compounds are given.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1660–1664, December, 1971.The authors thank L. S. Vasil'eva, R. F. D'yachkovskaya, and N. A. Zakharova for their assistance in this research.     

The thermal reaction of sterically hindered nitroxyl radicals with allylic and benzylic substrates: experimental and computational evidence for divergent mechanisms

The reaction of stable sterically hindered nitroxyl radicals with benzylic and allylic substrates was investigated. An allyloxyamine derivative was obtained by the reaction of 2 molar equiv of a nitroxyl radical with an unactivated alkene. Experimental and computational evidence is consistent with a low-energy pathway involving addition of the nitroxyl radical to the double bond followed by H-atom abstraction from the intermediate by another equivalent of nitroxyl radical.     

Synthesis of nitroxyl radicals — Derivatives of 5,5-dimethoxy-3-imidazoline-3-oxide-1-oxyl from 2H-imidazole 1,3-dioxides

2H-Imidazole 1,3-dioxides containing an aldonitrone fragment in the heterocyclic ring are obtained by the oxidation of 5-unsubstituted 1-hydroxy-3-imidazoline 3-oxides. Their further oxidation by lead dioxide in methanol leads to the formation of stable nitroxyl radicals — 5,5-dimethoxy-3-imidazoline-3-oxide-1-oxyls.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2122–2126, September, 1991.