Synthesis and Application of Stable Nitroxide Free Radicals Fused with Carbocycles and Heterocycles

Abstract

Stable nitroxide free radicals have traditionally been associated with 2,2,6,6- tetramethylpiperidine-1-oxyl (TEMPO) or its 4-substituted derivatives as relatively inexpensive and readily accessible compounds with limited possibilities for further chemical modification. Over the past two decades, there has been a resurgence of interest in stable free radicals with proper functionalization tuned for various applications. The objective of this review is to present recent results with synthetic methodologies to achieve stable nitroxide free radicals fused with aromatic carbocycles and heterocycles. There are two main approaches for accessing stable nitroxide free radicals fused with arenes, e.g., isoindoline- like nitroxides: further functionalization and oxidation of phthalimide or inventive functionalization of pyrroline nitroxide key compounds. The latter also offers the constructions of versatile heterocyclic scaffolds (furan, pyrrole, thiophene, 1,2-thiazole, selenophene, pyrazole, pyrimidine, pyridine, pyridazine, 1,5-benzothiazepine) that are fused with pyrroline or tetrahydropyridine nitroxide rings. The possible applications of these new stable nitroxide free radicals, such as covalent spin labels and noncovalent spin probes of proteins and nucleic acids, profluorescent probes, building blocks for construction of dual active drugs and electroactive materials, and substances for controlled free radical polymerization, are discussed.

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

“…Among various types of organic radicals, nitroxyl radicals (NRs) are the most stable, most robust, and best-studied class of paramagnetic species. In addition to numerous publications on their synthesis and properties [1][2][3][4][5][6][7][8][9], more and more reports include numerous examples of their use. Thus, NRs are actively employed as oxidants and as trapping reagents in synthetic chemistry [10], as ligands in metal complex catalysis [11], as agents in nitroxide-mediated radical polymerization [12], as molecular spin probes [13], and spin labels [14] and in many other applications [15,16].…”