Theoretical Design of Multi‐Nitroxyl Organocatalysts with Enhanced Reactivity for Aerobic Oxidation

Higher catalytic performances of N,N′,N′′‐trihydroxyisocyanuric acid (THICA), N,N‐dihydroxypyromellitimide (NDHPI), and N‐hydroxynaphthalimide (NHNI) than that of N‐hydroxyphthalimide (NHPI) have been demonstrated recently in aerobic oxidation. Herein, the rational design of reactive multi‐nitroxyl organocatalysts has been addressed theoretically by using systematic analysis of some important properties and catalytic activities of yet‐to‐be‐synthesized catalysts. Our results show that 1) NHNI and its analogue, similar to THICA, unlike NHPI and others, are unsuitable for solvent‐ or mediator‐free catalysis due to their strong intramolecular hydrogen‐bonding interactions; 2) increasing the reactive hydroxyimide groups on the same aromatic ring, or doped N atoms or ionic‐pair groups onto the aromatic ring, can improve catalytic reactivity, whereas appropriate enlargement of conjugated aromatic systems results in unchanged activity; 3) the newly designed catalysts are more active than NHPI and NHNI and have catalytic activities comparable to NDHPI and THICA; 4) the ionic‐pair supported case is suggested to be a very active catalyst, even towards inert propane, and can be used as a novel model catalyst for further improvements. The present work will be helpful in designing reactive hydroxyimide organocatalysts.