Mechanistic Insight Into Aerobic Oxidation Of Alcohol Mediated By Cu/TEMPO Biomimetic Catalyst In Aqueous Solution

The alcohol oxidation to the corresponding aldehydes or ketones is one of the most important reactions in organic synthesis,and its intermediates and products have a wide range of applications in the synthesis.Galactose oxidase?GOase?can directly oxidize primary alcohol to aldehyde by using oxygen in the air under mild reaction conditions,and GOase has high catalytic activity for primary alcohol.Therefore,the biomimetic catalytic system that mimics GOase has become a research hotspot in chemistry and bionics.TEMPO?2,2,6,6-tetramethylpiperidine oxide?is a stable nitrogen oxide and has a wide range of applications in chemistry and biology.Oxygen as the oxidant,and water as the solvent are better choices in Cu/TEMPO Catalytic systems.Similar systems mainly focus on the selection of experimental materials and the optimization of experimental conditions.Although the mechanism is given,there is no detailed mechanism study.Based on the above ideas,quantum chemical methods?such as density generalization?are proposed.Functional theory)Study on the reaction mechanism of Cu^?-TEMPO biomimetic catalytic system in aqueous solution,and hope to guide the design and synthesis of new biomimetic catalysts.as follows:1.Density functional theory?DFT?calculations have been performed to investigate alcohol oxidation to acetophenone catalyzed by the Cu^?/L-Proline-2,2,6,6-tetramethylpiperidinyloxy?TEMPO?catalyst system.Seven possible pathways?paths A-F?are presented.Our calculations show that two pathways?path A and path B?are the potential mechanisms.Furthermore,by comparing with experimental observation,it is found that path A—in which substrate alcohol provides the proton to^-OtBu to produce HOtBu followed by the oxidation of substrate directly to product acetophenone by O₂—is favored in the absence of TEMPO.Correspondingly,path B is likely to be favored when TEMPO is involved.?n path B,the O–O bond cleavage of Cu^?–OOH to Cu^?–OH species occurs,followed by acetophenone formation assisted by ligand?L?^2-.?t is also found that the cooperation of ligand?L?^2-and TEMPO plays an important role in assisting the formation of the product acetophenone in path B.2.The catalytic mechanism for the aerobic alcohol oxidation in the alkaline water solution catalyzed by a Cu^?/2,2,6,6-tetramethylpiperidinyl-1-oxy?TEMPO?catalyst system,([?L?Cu^??Hen??H₂O?]?H₃L:3-?5-Chloro-2-hydroxy-3-sulfophenylhydrazo?pentane-2,4-dione;en:Ethylenediamine?,is presented by density functional theory?DFT?calculations.Four pathways?path A,path B,path C and path D?are presented.Our calculations demonstrate that path A is the favourable pathway and zwitterionic property of the catalyst is not likely affect the efficiency of alcohol oxidation.?n path A,the catalytic cycle consists of catalyst activation,substrate oxidation and catalyst regeneration parts.The calculated turn-over frequency(TOF=3.89 h^-1)is in line with the experimental result(TOF=5.40 h^-1).?t is also found that the H atom migrates from alkoxide to the oxygen atom of TEMPO in the TOF determining transition state?TDTS?.3.Density functional theory is used to study the catalytic oxidation of alcohol to aldehyde system by Cu^??pytl-?-CD?/TEMPO catalyst system.Combined with experiments,there are three stages of catalyst activation,substrate oxidation and catalyst regeneration.?n the catalyst activation step,four possible pathways?paths A-D?are presented.During the catalyst activation,Path B and Path C are excluded due to the high energy barriers.Thus,path A and path D proposed by our group are found to be the favorateroutes and Path D is supposed to be the main route.Then,the substrate oxidation part occurs.The hydrogen atoms on the alcohol are transferred to TEMPO.At this time,the product is obtained.O₂ assisted catalyst regeneration process.TEMPO replaces the H₂O₂regeneration active catalyst to complete the catalyst cycle.