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

作者：Durand Gregory^*; Rosselin Marie; Klein Pierre Andre; Zeamari Kamal; Choteau Fanny; Tuccio Beatrice

来源：Journal of Organic Chemistry, 2017, 82(1): 135-142.

DOI：10.1021/acs.joc.6b02262

Two bifunctional alpha-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 tent-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 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 alpha-phenyl-N-tert-butylhitrone (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.

• 出版日期2017-1-6