Lipophilic N-Hydroxyimide Derivatives: Design, Synthesis, and Application to Aerobic Alkane Oxidation Under Neat Conditions

This work reports the design and synthesis of a series of 5-membered and 6-membered N-hydroxyimides flanked by lipophilic alkyl groups adjacent to carbonyl groups, aiming to endow lipophilicity and tolerance toward ring opening degradation. Their solubility in cyclohexane was 5-20 times higher than those of unsubstituted N-hydroxyphthalimide (NHPI) and even 3-10 times higher than a formerly known lipophilic NHPI analog bearing a long alkyl ester. UV-Vis spectroscopy determined the rate constants of first-order decay of N-oxyls, which revealed enhanced stability of 3,5-di-tert-butyl-NHPI and N-hydroxyglutarimide flanked by spiro-cyclohexanes compared with that of NHPI. Their bond dissociation energies were assessed by EPR spectroscopy and DFT calculation, suggesting these lipophilic N-hydroxyimides catalyzed aerobic cyclohexane oxidation under neat conditions with up to 60 turnovers, which is the highest among hitherto reported reactions under neat conditions.

Automated summary

This study reports the design and synthesis of a series of lipophilic N-hydroxyimides with enhanced solubility, stability, and reactivity compared to unsubstituted N-hydroxyphthalimide. These compounds displayed higher solubility in cyclohexane and exhibited improved stability and activity in oxidation reactions under neat conditions.