Effective 2,6-substitution of piperidine nitroxyl radical by carbonyl compound

Nitroxyl radicals (nitroxides) with unpaired electron are widely used as antioxidants, contrast agents, and spin probes. Although piperidine nitroxyl radicals have many applications, these are mainly tetramethylpiperidine compounds, and only a few reports consider the substitution of N-O surround as a reaction site, such as 2,2,6,6-tetrasubstituted piperidine nitroxyl radicals. Our results revealed that the 2,6-position of the 2,2,6,6-tetramethylpiperidin-4-one compound was substituted by cyclohexyl groups to produce 2,2,6,6-tetrasubstituted piperidin-4-one derivatives under mild reaction conditions. An interesting result was obtained by using ¹⁵N-labeled NH₄Cl instead of ¹⁴NH₄Cl: it gave ¹⁵N-labeled 2,2,6,6-tetrasubstituted piperidin-4-one-1-oxyls with a high ¹⁵N content. In conclusion, the new method for the synthesis of nitroxyl radicals readily yields 2,2,6,6-tetrasubstituted piperidin-4-one under mild conditions.