α‑Phenyl‑N‑cyclohexyl Nitrones: Preparation and Use as Spin-Traps

• Published in: Journal of organic chemistry Vol. 82; no. 1; pp. 135 - 142
• Main Authors: Durand, Grégory, Rosselin, Marie, Klein, Pierre-André, Zéamari, Kamal, Choteau, Fanny, Tuccio, Béatrice
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.01.2017
• Subjects: Chemical Sciences
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b02262

Two bifunctional α-phenyl-N-cyclohexyl nitrones were synthesized with the expectation that the cyclohexyl ring will impart lipophilicity to the molecule, high reactivity to the nitronyl group, and stability to the spin adducts formed. The synthesis of the acid nitrone 4 and its corresponding tert-butyl ester 3 was initiated by a Michael reaction to introduce the cyclohexyl ring. A Zn/AcOH-mediated reduction of the nitro functionality followed by condensation onto benzaldehyde generated the nitronyl function. In agreement with their high lipophilicity values, nitrone 3 was insoluble in water, while nitrone 4 exhibited a poor water solubility. It was determined that the presence of the cyclohexyl ring did not affect either the reduction or oxidation potentials of the nitronyl group in comparison to the classical α-phenyl-N-tert-butylnitrone (PBN). The spin trapping ability of 3 and 4 was investigated by EPR for oxygen- and carbon-centered radicals. In most cases, the nitrones gave rise to a standard six-line EPR spectrum whose values were in agreement with the literature, accompanied by a minor second species. In DMSO, the half-lives of nitrone 3 and 4–OOH adducts were double that of PBN, suggesting that the stabilization comes from the cyclohexyl ring and/or the electronic effect of the carboxylic acid.