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

Abstract

This work reports the design and synthesis of a series of 5membered 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 Nhydroxyglutarimide 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.

Organic Synthesis Using Nitroxides

“…For larger rings, β-scission is less efficient and the cyclic ketone is preferably formed from O radicals of type 165 . Suppression of alkoxyl radical fragmentation can also be achieved upon adding a better H donor such as N -hydroxysaccharin, resulting in a higher selectivity toward ketone formation. , Alkyl-conjugated , and perfluoroalkyl-conjugated NHPI derivatives were introduced to increase their solubility, allowing the oxidation to be conducted under neat conditions or in trifluorotoluene, which shows a higher O 2 solubility. Interestingly, when using HNO 3 in combination with O 2 for oxidation of NHPI to PINO, reaction of cyclohexane provides adipic acid in 45% isolated yield at 50% conversion …”