Iodine-Catalyzed Radical C-H Amination of Nonaromatic Imidazole Oxides: Access to Cyclic α-Aminonitrones.

A straightforward cross-dehydrogenative coupling approach to incorporate alicyclic amino residues into the structure of model cyclic aldonitrones, 2H-imidazole oxides, is reported. The elaborated C(sp2)-H functionalization is achieved by employing cyclic amines in the presence of the I2-tert-butyl hydroperoxide (TBHP) reagent system. As a result, a series of 19 novel heterocyclic derivatives were obtained in yields of up to 97%. A mechanistic study involving electron paramagnetic resonance spectroscopic experiments allowed the radical nature of the reaction to be confirmed. In particular, the envisioned mechanistic rationale comprises N-iodination of a cyclic amine, followed by N-I bond homolysis of the resulting intermediate and subsequent amination of the nitrone moiety via the newly generated nitrogen-centered radical.

Magnetically Manipulable Ionic Liquid Crystals Incorporating Neutral Radicals.

Invited for this month's cover are the collaborating groups of Dr. Yoshiaki Uchida from Osaka University, Japan, Prof. Rui Tamura and Prof. Masahito Sugiyama from Kyoto University, Japan and Dr. Dmitrii G. Mazhukin from Novosibirsk State University, Russia. The cover picture depicts a contrast between localized spins and conductive ions in the newly-synthesized ionic liquid crystalline (ILC) nitroxide radicals. The ILC droplet of the new compounds is magnetically manipulable. More information can be found in the Full Paper by Yoshiaki Uchida, Rui Tamura, and co-workers.

Magnetically Manipulable Ionic Liquid Crystals Incorporating Neutral Radical Moiety.

With a view to fabricating a new remote input-output system by applying functional ionic liquid crystalline (ILC) materials, we have developed novel ILC compounds containing a nitroxide radical unit in the organic cations, which show an enantiotropic smectic A (SmA) phase. We have implemented the magnetic manipulation of a droplet of one of the ILC compounds on the basis of the intermolecular magnetic interactions between radical moieties. This ILC monoradical compound shows a 55 % larger increase in paramagnetic susceptibility at the solid-to-LC melting point in the first heating process than the non-ionic LC monoradical compounds. It is most likely owing to the nanosegregation of strongly bonded ionic and non-ionic moieties. The increased molar magnetic susceptibility is preserved not only in the SmA phase but also in the isotropic liquid and solid phases during the first cooling process.

Stable Bicyclic Functionalized Nitroxides: The Synthesis of Derivatives of Aza-nortropinone-5-Methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octene 8-oxyls.

In recent decades, bicyclic nitroxyl radicals have caught chemists' attention as selective catalysts for the oxidation of alcohols and amines and as additives and mediators in directed C-H oxidative transformations. In this regard, the design and development of synthetic approaches to new functional bicyclic nitroxides is a relevant and important issue. It has been reported that imidazo[1,2-b]isoxazoles formed during the condensation of acetylacetone with 2-hydroxyaminooximes having a secondary hydroxyamino group are recyclized under mild basic catalyzed conditions to 8-hydroxy-5-methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octenes. The latter, containing a sterically hindered cyclic N-hydroxy group, upon oxidation with lead dioxide in acetone, virtually quantitatively form stable nitroxyl bicyclic radicals of a new class, which are derivatives of both 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TEMPON) and 3-imidazolines.

Spirocyclic Nitroxides as Versatile Tools in Modern Natural Sciences: From Synthesis to Applications. Part I. Old and New Synthetic Approaches to Spirocyclic Nitroxyl Radicals.

Spirocyclic nitroxyl radicals (SNRs) are stable paramagnetics bearing spiro-junction at a-, b-, or g-carbon atom of the nitroxide fragment, which is part of the heterocyclic system. Despite the fact that the first representatives of SNRs were obtained about 50 years ago, the methodology of their synthesis and their usage in chemistry and biochemical applications have begun to develop rapidly only in the last two decades. Due to the presence of spiro-function in the SNRs molecules, the latter have increased stability to various reducing agents (including biogenic ones), while the structures of the biradicals (SNBRs) comprises a rigid spiro-fused core that fixes mutual position and orientation of nitroxide moieties that favors their use in dynamic nuclear polarization (DNP) experiments. This first review on SNRs will give a glance at various strategies for the synthesis of spiro-substituted, mono-, and bis-nitroxides on the base of six-membered (piperidine, 1,2,3,4-tetrahydroquinoline, 9,9'(10H,10H')-spirobiacridine, piperazine, and morpholine) or five-membered (2,5-dihydro-1H-pyrrole, pyrrolidine, 2,5-dihydro-1H-imidazole, 4,5-dihydro-1H-imidazole, imidazolidine, and oxazolidine) heterocyclic cores.

5-Aryl-2-(3,5-dialkyl-4-hydroxyphenyl)-4,4-dimethyl-4H-imidazole 3-Oxides and Their Redox Species: How Antioxidant Activity of 1-Hydroxy-2,5-dihydro-1H-imidazoles Correlates with the Stability of Hybrid Phenoxyl-Nitroxides.

Cyclic nitrones of the imidazole series, containing a sterically hindered phenol group, are promising objects for studying antioxidant activity; on the other hand, they can form persistent hybrid phenoxyl-nitroxyl radicals (HPNs) upon oxidation. Here, a series of 5-aryl-4,4-dimethyl-4H-imidazole 3-oxides was obtained by condensation of aromatic 2-hydroxylaminoketones with 4-formyl-2,6-dialkylphenols followed by oxidation of the initially formed N-hydroxy derivatives. It was shown that the antioxidant activity of both 1-hydroxy-2,5-dihydroimidazoles and 4H-imidazole 3-oxides increases with a decrease in steric volume of the alkyl substituent in the phenol group, while the stability of the corresponding HPNs generated from 4H-imidazole 3-oxides reveals the opposite tendency.

Unique Superparamagnetic-like Behavior Observed in Non-π-delocalized Nitroxide Diradical Compounds Showing Discotic Liquid Crystalline Phase.

A unique superparamagnetic-like behavior and a large "positive magneto-LC effect" were observed in the solid phases and the hexagonal columnar (Colh ) liquid crystalline (LC) phase, respectively, of novel achiral non-π-delocalized nitroxide diradical compounds (R,S)-1, which showed polymorphism in the solid phases (solids I and II). The SQUID magnetization measurement revealed that (1) (R,S)-1 containing a small amount of racemic diastereomers (R*,R*)-1 possessed an unusual and large temperature-independent magnetic susceptibility (χTIM >0) component in the original nanocrystalline solid I that was responsible for the observed superparamagnetic-like behavior under low magnetic fields and did not arise from the contamination by extrinsic magnetic metal or metal ion impurities, besides ordinary temperature-dependent paramagnetic susceptibility (χpara >0) and temperature-independent diamagnetic susceptibility (χdia <0) components, (2) a large increase in molar magnetic susceptibility (χM ) (positive magneto-LC effect) that occurred at the solid I-to-liquid crystal transition upon heating was preserved as an additional χTIM increase in the resulting polymorphic nanocrystalline solid II by cooling, and (3) such unique magnetic phenomena were induced by thermal processing for (R,S)-1 or by adding a small amount of (R*,R*)-1 to (R,S)-1 as the impurity.

The Suzuki-Miyaura reaction as a tool for modification of phenoxyl-nitroxyl radicals of the 4H-imidazole N-oxide series.

2-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-(4-iodophenyl)-4,4-dimethyl-4H-imidazole 3-oxide reacts with phenylboronic acid and its substituted derivatives in a cross-coupling reaction of the Suzuki-Miyaura type to form 5-biphenyl derivatives of 4H-imidazole-N-oxide. Interaction of the same compound with B2(pin)2 in the presence of PdCl2(PPh3)2 proceeds through the formation of intermediate 1,3,2-dioxoborolane and leads to the product of homocoupling: biphenyl-bis(imidazole). Oxidation of the resultant imidazoles with lead dioxide quantitatively yields stable conjugated phenoxyl-nitroxyl mono- and diradicals, which are of interest as electroactive paramagnetic materials. The crystal structure of the monoradical, 2,6-di-tert-butyl-4-[1-oxido-4-(biphenyl-4-yl)-5,5-dimethyl-1H-imidazole-2(5H)-ylidene]cyclohex-2,5-dienone, its magnetic susceptibility, EPR spectra of the obtained hybrid radicals in solution, and cyclic voltammetry characteristics of 4H-imidazoles were studied.

Chiral all-organic nitroxide biradical liquid crystals showing remarkably large positive magneto-LC effects.

The liquid crystalline chiral nitroxide biradical (S,S,S,S)-3 synthesized has shown much larger 'positive magneto-LC effects' in the chiral nematic (N*) phase than the monoradical (S,S)-1.