Synthesis and characterization of sterically and electrostatically shielded pyrrolidine nitroxide radicals

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via Intramolecular 1,3-Dipolar Cycloaddition

“…The difference in aH on these hydrogens occurs due to substituent at the positions 3 or 4 of the ring, which hinders rotation and affects population of conformations of neighbouring geminal ethyl groups, preventing averaging. In agreement to this conclusion, there are no large splittings in the EPR spectrum of 12c and the line width is a bit higher than in the spectra of similar non-spirocyclic 3,4-unsubstituted 2,2-diethyl-pyrrolidine nitroxides [26], implying free rotation of ethyl groups. The initial rates of EPR signal decay were used to obtain the rate constants of the nitroxides reduction by ascorbic acid (Fig.…”

New synthetic route to 2,2,6,6-tetraethylpiperidin-4-one: A key-intermediate towards tetraethyl nitroxides

“…A similar behavior has previously been reported for tetramethyl nitroxides and tetraethyl pyrrolidine nitroxides and was attributed to electrostatic repulsion between the carboxylate and the ascorbate monoanion at physiological pH. 7,9,18 These results suggest that it should be feasible to load cells with high concentrations of compound 20 via incubation with its esterase-hydrolysable derivative 21. Biological assays of the present nitroxides are currently underway.…”

“…16,17 The insertion of ionizable carboxylate groups in the structure affords additional protection through electrostatic repulsion as recently shown with pyrrolidine nitroxides. 18 Nitroxides derived from 2,2,6,6-tetraethylpiperidin-4-one 1, such as compound 2, have been used in vivo, [19][20][21][22] and are also a cornerstone in the synthesis of other tetraethyl nitroxides such as pyrrolidine-and pyrroline-based ones (Scheme 1). 15,[23][24][25][26] However, the presence of bulky ethyl groups in tetraethyl-substituted nitroxides makes them far more difficult to synthesize than their methylsubstituted counterparts.…”

A Simple Method of Synthesis of 3-Carboxy-2,2,5,5-Tetraethylpyrrolidine-1-oxyl and Preparation of Reduction-Resistant Spin Labels and Probes of Pyrrolidine Series

“…It was shown previously that treatment of 3,4-bis-(hydroxymethyl)-2,5,5-triethyl-1-pyrroline N -oxide with ethylmagnesium bromide does not lead to nucleophilic addition onto nitrone group, presumably due to metalation [ 15 ]. In contrast, the reactions of 2,5,5-triethyl-1-pyrroline 1-oxides with less basic vinylmagnesium bromide or allylmagnesium bromide were shown to afford corresponding nitroxides [ 15 , 17 ]. Here, we used even less basic organometallic reagent, i.e., ethynylmagnesium bromide.…”