Design And Mechanistic Investigations Of N-Hydroxyimides As Organocatalysts For Aerobic Oxidation

The green selective oxofunctionalization of hydrocarbons into organic chemicals via organic catalysis under aerobic conditions has received worldwide attentions in recent decades. Among the numerous developed catalytic systems, catalysis with N-hydroxyphthalimide (NHPI) and its analogues becomes one of the most promising reactions due to their excellent behaviors under mild conditions, which are of special interest for industrial applications. Although this catalytic system has been developed for many years, there are still many problems that need to be further addressed in detail. Therefore, this work concentrates on the catalytic efficiencies and rational design of these kinds of catalysts using density functional theory (DFT) based on relevant experimental phenomenon.Firstly, metal-free mechanistic insight into the NHPI-catalyzed selective aerobic oxidation of β-isophorone (β-IP) has been studied via theoretical calculations, where β-IP is a valuable raw material for preparing vitamin E, carotenoids, and so on. It appears that the discrepancies in the C-H bond strengths of α/β-IP can mainly account for the different selectivity of oxygen-containing products in their oxidation. Besides, phthalimide-N-oxyl radical (PINO·), generated from ts precursor NHPI, is more reactive than peroxyl radical (ROO·), which effectively accelerates IP activation and subsequently produces considerable ROO·. The rapid equilibrium reaction between ROO· and NHPI favorably yields considerable hydroperoxide (ROOH) and recycle reactive PINO·. Moreover, the a-H decomposition of ROOH by radicals is proven to be the rapid dissociation route and also the competitive way to form KIP and hydrogen radical (HO·), which is the reason why ROOH cannot be directly detected and only catalytic amounts of NHPI is enough. The strong exothermicity of these processes, combined with that from the hydrogen abstraction by co-yielded hot HO·, leads to the formation of water, a-IP, and4-hydroxyisophorone (HIP).Then, the advantages and disadvantages of known highly efficient N-hydroxyimides (A-D) and four newly designed model organocatalysts (E-H) were investigated. Besides, their potentials in the catalytic oxidation of toluene were also addressed, followed by discussing the design rule for more efficient catalysts. Our calculations show that, for the same type of catalysts, increasing the numbers of intramolecular conjugated N-O or N-hydroxyimide groups in the same π systems, or including N atoms in the π system can obviously improve their O-H bond energies, enhance their electron affinities, thereby decrease their barrier and endothermic enthalpy changes in their key hydrogen-abstraction reactions, ultimately increase the degree and opportunity in activating substrates. Evidently, the catalytic reactivity of newly designed catalysts (E-H) is better than that of known catalysts (A-D), therefore, they have potential usage for aerobic oxidation of less activated substrates. Besides, N-hydroxynaphthalimide (NHNI),N,N’,N"-trihydroxyisocyanuric acid (THICA), and catalyst G are unsuitable for solvent-free catalysis due to their coexistent planar and gauche conformers, which is also the partial reason why THICA has poor reactivity at room temperature and NHNI needs high temperature. Catalyst G may also be utilized for aerobic oxidation under high temperature, as its structure is similar to that of NHNI. In addition, atomization enthalpies (ΔaHe298.15K) of-1487.3±1.4kcal/mol and enthalpies of formation (≡fHθ298.15K) of-120.9±1.4kcal/mol are recommended for THICA.Lastly, a series of representative N-hydroxyimide organocatalysts were selected to study the key factors in governing the inconsistence of their actual catalytic efficiencies and intrinsic reactivity. Theoretically, organocatalysts with electron-withdrawing substituents are more energetically feasible in their H-abstraction reactions than that of electron-donating cases, but their actual catalytic performances are not as high as one can expect due to their stronger acidicities and more favorable capability of hydrogen-bonding interactions with certain solvents. Such effects are quite significant for the substituents in cationic and anionic forms. Besides, the catalytic performances of catalysts with substituents in conjugated acidic-basic pairs can be adjusted to optimal states by certain solvents with proton-acceptor/donor properties. In addition, the orders of1:1H-bonding strength between solvents with NHPI and its analogues can be used to reasonably select solvents and predict their catalytic efficiencies before experiments. Furthermore, we rationalize the large underestimation of their experimental O-H bond dissociation energy theoretically due to this H-bonding character, and also confirm the experimental views towards the preference of hydrogen atom transfer mechanism in their key C-H activation steps.[n addition, the electron affinities of nitroxyl radicals are found to be good indicatives for assessing or predicting their abilities in biological important electron-transfer reactions.In summary, the mechanism of NHPI-catalyzed selective aerobic oxidation of β-1P, design rule for more efficient organocatalysts, and the key factors in governing their catalytic efficiencies have been systematically explored by DFT methods, which are of great help for understanding of the selective oxidation processes for similar substrates (e.g. cyclohexene, cholesterol, and a-pinene) catalyzed by NHPI or its analogues, and selecting or developing suitable catalysts for the aerobic oxidation of certain substrates.