Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls.

chemistry Medicinal and pharmaceutical chemistry Nano- and molecular-scale electronics Nano-biomaterials and bioscience Nanomagnetics Nanomaterials, thin films and nanointerfaces Nanomedicine Nanometrology and nanomechanics Nano-optics Nanopatterning, self-assembly and nanofabrication Nanostructures for energy and sensing applications Natural products chemistry Organo main group chemistry Other nanotechnology (unclassified) Other organic chemistry (unclassified) Photochemistry and photovoltaics Physical organic chemistry Supramolecular chemistry Rotational correlation time is a key parameter for Organic Radical Contrast Agents (ORCA) for MRI. Design of polycyclic systems with incorporated nitroxide moieties in which rotation of the radical separately from the framework is impossible is one of the ways to improve properties of ORCA. Feasibility of the synthesis of rigid 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2-c][1,2,3]triazole and 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2-b]pyrazole ring systems with incorporated nitroxide moiety from 2-alkynyl-substituted pyrrolidine nitroxides was studied. These nitroxides have been prepared via intramolecular Huisgen cycloaddition or intramolecular alkylation in 2-pyrazolyl derivativatives prepared by Michael addition-cyclocondensation of corresponding alkynones with hydrazine. The reduction kinetics by ascorbate showed that the formation of the rigid tricyclic framework does not lead to a significant increase in stability of the radical center to chemical reduction.

Nitroxide, Annulated tricyclic system, Pyrrolidine, Triazole, Pyrazole. When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information: Gulman, M.; Polienko, Y.; Trakhininа, S.; Gatilov, Y.; Rybalova, T.; Dobrynin, S.; Kirilyuk, I. Beilstein Arch. 2025, 202565. doi:10.3762/bxiv.2025.65.v1 Citation data can be downloaded as file using the "Download" button or used for copy/paste from the text window below. Citation data in RIS format can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Zotero. © 2025 Gulman et al.; licensee Beilstein-Institut. This is an open access work licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-archives.org/xiv/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this work could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material.