A screening method for a cu-tempo catalytic system

Abstract

The application relates to a screening method of a Cu-TEMPO catalytic system, which comprises the following steps: (1) calculating a full potential energy surface and confirming an optimal reaction path; (2) establishing a base source thermodynamic volcano relationship diagram and evaluating the catalytic efficiency of the base source; and (3) constructing a ligand prediction model and evaluating the reaction activity of the ligand. On the basis of determining the optimal reaction path, a thermodynamic volcano relationship diagram is drawn to evaluate the performance of the base source, chemical descriptors are selected as input variables of the ligand prediction model, and a ligand prediction model is constructed by using multiple linear regression analysis. The screening method can quickly and accurately screen suitable base sources and ligands, and the screening method is verified by chemical experiments, thereby providing guidance for the design of Cu-TEMPO reaction base sources and ligands and providing an effective approach for the combination of theoretical calculation and experimental research.

Description

Technical Field

[0001] This invention relates to a quantum chemical calculation method, specifically a method for screening the base source and ligands of a Cu-TEMPO catalytic system. Background Technology

[0002] In the field of industrial chemical synthesis, oxidation reactions play a crucial role, involving the oxidation of organic substrates into corresponding organic products. Of particular note is the oxidation of benzyl alcohol to benzaldehyde, a reaction with broad application prospects. Benzaldehyde, as an important organic synthesis intermediate, is widely used in pharmaceuticals, fragrances, dyes, and chemicals. Traditionally, the domestic industrial production of benzaldehyde typically employs the toluene chlorination hydrolysis method, but this method requires large amounts of acid, alkali, and chlorine, leading to the emission of corrosive gases and organic waste, and the product contains chlorine; therefore, it is rarely used now. To develop new benzaldehyde production processes, extensive research has been conducted both domestically and internationally, including gas-phase or liquid-phase oxidation methods using toluene as a raw material, simple electrolytic oxidation methods, manganese trioxide heterogeneous oxidation methods, oxidation methods in supercritical (near) critical fluids, biomimetic catalytic oxidation methods, benzyl alcohol oxidation methods, and benzoic acid reduction methods. Notably, the direct oxidation method of benzyl alcohol, due to its simplicity and environmental friendliness, has promising application prospects. In the field of organic synthesis, the oxidation of alcohols to aldehydes or ketones is a fundamental transformation process. With increasing environmental awareness, catalytic oxidation has become a feasible and promising method. For many years, researchers have been striving to find and develop efficient molecular oxygen catalytic processes. Traditional alcohol oxidation typically requires the use of stoichiometric oxidants and catalysts (often toxic). For example, oxidants used in traditional methods, such as MnO2 and chromite, are not only expensive but also generate large amounts of waste and toxic gases. Therefore, utilizing air or oxygen as the sole oxidant for alcohol oxidation is an inevitable trend towards green oxidation, as the only byproduct is water, which does not pollute the environment.

[0003] Currently, the oxygen-induced oxidation of alcohols mediated by the Cu-based / TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidinoxy) catalytic system has been extensively studied. This homogeneous catalyst combination, consisting of copper salt and TEMPO, has proven to be a highly efficient and practical catalyst for alcohol oxidation reactions.

[0004] Existing literature reports that the reaction time using the NMI (N-methylimidazole) system is relatively long and easily affected by temperature, reducing reaction efficiency. On the other hand, although the reaction time using the DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) system is shorter, its selectivity needs further improvement and it is also easily affected by temperature. The inventors' prior patent CN114582431B (A method for studying and analyzing the reaction mechanism of catalytic oxidation of (bipy)CuⅡ-TEMPO / organic base catalytic system) analyzed the catalytic oxidation reaction mechanism and optimal reaction path of NMI and DBU. However, this patent only simply analyzed the reaction path of the base source NMI and DBU. However, multiple base sources and multiple ligands may be combined to produce many technical solutions. How to quickly screen out the optimal ligand and base source through the optimal reaction path to achieve high reaction efficiency remains an urgent technical problem to be solved.

[0005] Furthermore, the influence of ligands on the Cu-based / TEMPO catalytic reaction needs further consideration, and technical issues such as how to effectively control catalyst activity through ligand regulation remain to be addressed. Given these challenges and issues, it is necessary to improve the mechanistic analysis of the Cu-based / TEMPO catalytic system, further screen suitable base sources and ligands, and optimize reaction conditions to achieve a more efficient and environmentally friendly benzyl alcohol oxidation process.

[0006] To address these issues, we conducted oxidation experiments of benzyl alcohol to benzaldehyde using density functional theory calculations and experimental verification on base sources and ligands with excellent theoretical calculation results. By combining theoretical simulations with experimental synthesis, we achieved a more efficient and environmentally friendly benzyl alcohol oxidation process. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides a screening method for Cu-TEMPO catalytic systems, comprising the following steps: (1) calculating the full potential energy surface and confirming the optimal reaction pathway; (2) Establish a thermodynamic volcanic relationship diagram of the alkali source and evaluate the catalytic efficiency of the alkali source; (3) Construct a ligand prediction model and evaluate ligand reactivity.

[0008] The screening method further includes: (4) Chemical experiment verification.

[0009] Step (1) involves calculating the full potential energy surface and confirming the optimal reaction path using the following methods: 1.1 Perform geometric optimization on all structures and calculate frequencies; 1) All calculations were performed using the Gaussian 09 program; 2) Benzyl alcohol was selected as the reactant model, and the SMD solvation model was used, with acetonitrile (dielectric constant 35.688) as the reaction solvent. Geometric optimization and frequency calculations were performed on all structures at the B3LYP-D3(BJ) / def2svp / SMD(acetonitrile) level to determine the structures of the intermediate (TDI) and transition state (TDTS).

[0010] 1.2 Calculate the single-point energy (Electronic Energy) of all intermediates and transition states; The single-point energies of all intermediates (TDI) and transition states (TDTS) were calculated at a higher computational level M06 / 6-311+G(d,p) / SMD(acetonitrile) to further determine the energies.

[0011] 1.3 The calculation results were subjected to entropy correction using Shermo correction; 1.4 The accuracy of determining the transition state using intrinsic reaction coordinate theory (IRC); The intrinsic reaction coordinate theory (IRC) yields a minimum energy path for determining the accuracy of the transition state.

[0012] 1.5 Use the span energy model to calculate δE (energy span of the reaction path) and confirm the optimal reaction path.

[0013] 1.6 TOF Calculation The overall Gibbs free energy curve was analyzed using an energy span model. The conversion efficiency ("TOF") was calculated using the AUTOOF program. The TOF value of the catalyst was calculated using the following formula to verify the accuracy of this analytical method: (I) Where: K b is Boltzmann constant, h is Planck constant, R is ideal gas constant, T is reaction temperature, is the energy span of the reaction path, and the RDZ region refers to the region between the rate-determining intermediate (TDI) and the rate-determining transition state (TDTS), which corresponds to the experimental kinetic analysis results.

[0014] This application performed detailed calculations on the reaction processes corresponding to 16 base sources. The results showed that changing the base source would alter the structure of the key intermediates and key transition states in the reaction mechanism. Therefore, based on the overall cycle path, the true key intermediates and key transition states involved in the reactions of the 16 base sources were obtained (as shown in Table 1).

[0015] Table 1. Predictions and accurate TDI and TDTS for 16 types of alkalis .

[0016] In one embodiment of the present invention, based on the inventor's prior patent CN114582431B, the optimal path for the alkali source DBU and NMI can be determined to be the dual-core Path BI. Further path calculations for 19 different alkali sources show that the optimal path is the dual-core Path BI.

[0017] Step (2), establishing the thermodynamic volcano relationship diagram of the alkali source, is based on the mechanism calculation results of step (1), selecting the optimal reaction path, and constructing the linear proportional relationship and thermodynamic volcano relationship diagram. Specifically, it includes the following methods: 2.1 Determine the intermediate descriptor; When screening catalysts for a specific reaction, intermediate descriptors should be determined, which are intermediates that can exhibit a linear relationship with other intermediates.

[0018] First, determine the ΔG of each intermediate. RRS If a linear proportional relationship exists between them, then select the intermediate whose ΔG is linearly proportional to the other intermediates. RRS As an intermediate descriptor, the determined intermediate descriptor can then be used as the independent variable in a linear proportional relationship to represent the free energy change (ΔG) of other intermediates. RRS The dependent variable is (see Equation 1-14 for details).

[0019] In one embodiment, we choose the free energy ΔG of intermediate 10. RRS (10) As an intermediate descriptor, it is used to predict the free energy (ΔG) of other intermediates. RRS The specific method is as follows.

[0020] Based on step (1), the optimal reaction route is Path BI ( Figure 1 Assuming the reactants are in a reference state, a linear proportional relationship can be derived: G(TEMPO)=G(R)=G(TEMPOH)=G(O2)=G(PhCH2OH)=0kcal / mol (Equation 1) The energy of the formed product PhCHO corresponds to the energy of the overall reaction as follows: △G(PhCHO) = -27 kcal / mol (Equation 2) Based on the above assumptions, the free energy (ΔG) of the intermediate descriptor relative to the rest state is obtained. RRS The following linear proportional relationship exists between ) and the remaining intermediates (e.g. Figure 2 (as shown) △G RRS(3) = 0.6△G RRS (10) + 21.1 kcal / mol (Equation 3) △G RRS (4) = 0.6△G RRS (10) + 21.9 kcal / mol (Equation 4) △G RRS (5) = 0.6△G RRS (10) -4.7 kcal / mol (Equation 5) △G RRS (10)=△G RRS (10) (Equation 6) △G RRS (11)=△G RRS (10) + 1 kcal / mol (Equation 7) △G RRS (12) = 0.7△G RRS (10) -4.7 kcal / mol (Equation 8) △G RRS (18) = 0.6△G RRS (10)-7kcal / mol (Equation 9) △G RRS (19) = 0.6△G RRS (10)-4kcal / mol (Equation 10) △G RRS (7) = 0.6△G RRS (10)-5kcal / mol (Equation 11) △G RRS (8) = 0.6△G RRS (10) -5.7 kcal / mol (Equation 12) △G RRS (9) = 0.6△G RRS (10) + 3.8 kcal / mol (Equation 13) △G RRS (3) = 0.6△G RRS (10) -5.8 kcal / mol (Equation 14) like Figure 2 It can be seen that intermediate 10 has a good correlation with the other intermediates (R0). 2 =0.95 / 0.97), meaning that there is a good correlation between key intermediate 10 and other intermediates, and a linear proportional relationship exists. Therefore, the free energy ΔG of intermediate 10 can be selected. RRS (10) is used as an intermediate descriptor to describe the predicted values ​​of the remaining intermediates.

[0021] 2.2 Calculate the theoretical reaction free energy and plot the linear relationship between the theoretical reaction free energy and the reaction free energy. Before establishing the thermodynamic volcanic relationship diagram of the alkali source, it is necessary to calculate the theoretical reaction free energy and draw a linear proportional relationship diagram of the theoretical reaction free energy. Figure 3 After obtaining the linear proportional relationship between the intermediate descriptor and other intermediates in section 2.1, the theoretical reaction free energy (Equations 17-38) can be obtained from these linear proportional relationships.

[0022] In one embodiment of the present invention, after establishing a linear proportional relationship between key intermediates, the theoretical reaction free energy (AK) in the dual-core PathB-I reaction pathway is calculated as follows: 1) Reaction A The theoretical reaction free energy ΔG theo Given by Equation 17: -△G theo (A) = -[△G RRS (4)-△G RRS (3)] ​​(Equation 17) Take △G from equation 4 RRS (4) Take △G from equation 3 RRS (3) can be obtained as follows: -△G theo (A) = -[0.6△G RRS (10) + 21.9 kcal / mol - (0.6 ΔG RRS (10) + 21.1 kcal / mol) = -0.8 kcal / mol (Equation 18) 2) Reaction B The theoretical reaction free energy ΔG theo Equation 19 gives -△G theo (B) = -[△G RRS (5N)-△G RRS (4)] (Equation 19) Take △G from equation 5 RRS (5N), take △G from equation 4 RRS (4) can be obtained as follows: -△G theo (B) = -[0.6△G RRS (10)-4.7kcal / mol-(0.6ΔG RRS(10) + 21.9 kcal / mol) =26.6 kcal / mol (Equation 20) 3) Reaction C The theoretical reaction free energy ΔG theo Equation 21 gives -△G theo (C) = -[△G RRS (10)+PhCHO-△G RRS (5)] (Equation 21) Take △G from equation 6 RRS (10), take △G from equation 5 RRS (5N) can be obtained as follows: -△G theo (C) = -[△G RRS (10) -27-(0.6△G RRS (10) -4.7 kcal / mol =-0.4△G RRS (10) + 22.3 kcal / mol (Equation 22) 4) Reaction D The theoretical reaction free energy ΔG theo Equation 23 gives -△G theo (D) = -[△G RRS (11)-△G RRS (10)-△G RRS (10)] (Equation 23) Take ΔG from equation 7 RRS (11), take △G from equation 6 RRS (10) can be obtained as follows: -△G theo (D) = -[△G RRS (10) + 1 kcal / mol - ΔG RRS (10) -△G RRS (10) =△G RRS (10)-1kcal / mol (Equation 24) 5) Reaction E The theoretical reaction free energy ΔG theo Given by Equation 25 -△G theo (E) = -[△GRRS (12)-△G RRS (11)] (Equation 25) Take △G from equation 8 RRS (12), take △G from equation 7 RRS (11) can be obtained as follows: -△G theo (E) = -[0.7△G RRS (10) -4.7 kcal / mol -(△G RRS (10) + 1 kcal / mol)] =0.3△G RRS (10) + 5.7 kcal / mol (Equation 26) 6) Reaction F The theoretical reaction free energy ΔG theo Equation 27 gives -△G theo (F) = -[△G RRS (18)-△G RRS (12)] (Equation 27) Take △G from equation 9 RRS (18), take △G from equation 8 RRS (12) can be obtained as follows: -△G theo (F) = -[0.6△G RRS (10)-7kcal / mol-(0.7△G RRS (10)-4.7kcal / mol)] =0.1△G RRS (10) + 2.3 kcal / mol (Equation 28) 7) Reaction G The theoretical reaction free energy ΔG theo Equation 29 gives -△G theo (G) = -[△G RRS (19)-△G RRS (18)] (Equation 29) Take △G from equation 10 RRS (19), take △G from equation 9 RRS (18) can be obtained as follows: -△G theo (G) = -[0.6△G RRS (10)-4kcal / mol-(0.6△G RRS(10)-7kcal / mol)] =-3kcal / mol (Equation 30) 8) Reaction H The theoretical reaction free energy ΔG theo Equation 31 gives -△G theo (H)=-[△G RRS (7)+△G RRS (10)-△G RRS (19)] (Equation 31) Take ΔG from equation 11 RRS (7) Take △G from equation 10 RRS (19), take △G from equation 6 RRS (10) can be obtained as follows: -△G theo (H) = -[0.6△G RRS (10)-5kcal / mol+ΔG RRS (10) -(0.6△G RRS( 10)-4kcal / mol =-△G RRS (10) + 1 kcal / mol (Equation 32) 9) Reaction I The theoretical reaction free energy ΔG theo Given by Equation 33 -△G theo (I)=-[△G RRS (8)-△G RRS (7)] (Equation 33) Take ΔG from equation 12 RRS (8), take △G from equation 11 RRS (7) can be obtained as follows: -△G theo (I) = -[0.6△G RRS (10) -5.7 kcal / mol -(0.6 ΔG RRS (10)-5kcal / mol)] =0.7 kcal / mol (Equation 34) 10) Reaction J The theoretical reaction free energy ΔG theo Given by equation 35 -△Gtheo (J)=-[△G RRS (9)-△G RRS (8)] (Equation 35) Take △G from equation 13 RRS (9), take △G from equation 12 RRS (8) can be obtained as follows: -△G theo (J)=-[0.6△G RRS (10) + 3.8 kcal / mol - (0.6 ΔG) RRS (10) -5.7 kcal / mol =-9.5kcal / mol (Equation 36) 11) Reaction K The theoretical reaction free energy ΔG theo Given by equation 37 -△G theo (K)=-[△G RRS (3)-△G RRS (9)] (Equation 37) Take ΔG from equation 14 RRS (3) Take △G from equation 13 RRS (9) can be obtained as follows: -△G theo (K)=-[0.6△G RRS (10)-5.8kcal / mol-(0.6ΔG RRS (10) - 5.8 kcal / mol)] = 9.6 kcal / mol (Equation 38) The theoretical reaction free energy (-ΔG) of reaction AK was obtained from equation 17-38. theo (A)~-△G theo (K)), will -△G theo (A)~-△G theo (K) plotted on the linear proportional relationship of theoretical reaction free energy Figure 3 In the equation (RxnA-RxnK), ΔG(Rxn) represents the energy absorbed (or released) in each step of the catalytic cycle corresponding to different base sources, for example, ΔG(RxnA)=ΔG RRS (4 碱 )-△G RRS (3 碱 ), where △G RRS (4 碱() represents the free energy of intermediate 4 corresponding to different base sources, and the rest are similar). Since the slopes in the proportional relationships of intermediates 3-5 and 18-3 are equal (equations 3-5 and 9-14), therefore in Figure 3 In the process, the continuous elementary reactions (A, B, G, IK) between these intermediates form a horizontal line (because reaction H is a mono- and binuclear transition process and it depends on the descriptor intermediate ΔG). RRS (10), therefore reaction H is not a horizontal line), meaning the reaction free energy is independent of the catalyst selectivity of these steps. Reactions D, H, and C depend on the descriptor intermediate ΔG. RRS (10) appears as an oblique line.

[0023] 2.3 Establishing the thermodynamic volcano relationship diagram of the alkali source: Based on the linear proportional relationship diagram of the theoretical reaction free energy, establish the thermodynamic volcano relationship diagram of the alkali source.

[0024] Figure 3 The graph shows the relationship obtained from the linear scaling relationship with ΔG. RRS (10) is the theoretical reaction free energy (AK) for the descriptor, but the thermodynamic volcano relation is defined based on ΔG(pds) (Equation II) of the potential determining step: △G(pds) = max[△G(RxnA),△G(RxnB),△G(RxnC), △G(RxnD),△G(RxnE),△G(RxnF),△G(RxnG), △G(RxnH),△G(RxnI),△G(RxnJ),△G(RxnK)] (Equation II) Wherein, △G(RxnA)~△G(RxnK) are the free energies of the relevant reactions A~K: △G(RxnA) is the free energy of reaction A, △G(RxnB) is the free energy of reaction B, △G(RxnC) is the free energy of reaction C, △G(RxnD) is the free energy of reaction D, △G(RxnE) is the free energy of reaction E, △G(RxnF) is the free energy of reaction F, △G(RxnG) is the free energy of reaction G, △G(RxnH) is the free energy of reaction H, △G(RxnI) is the free energy of reaction I, △G(RxnJ) is the free energy of reaction J, and △G(RxnK) is the free energy of reaction K.

[0025] Based on the value of the intermediate descriptor, the reaction line of the AK reaction process can be taken to obtain the preliminary shape of the alkali source volcano relationship diagram. After excluding potential rate-determining factors that are unlikely to be the catalyst reaction, the thermodynamic volcano relationship diagram of the catalyst reaction can be obtained.

[0026] Regardless of the descriptor △G RRS (10) How to choose the value, the potential rate-determining steps are all determined by the reaction line (AK, with the minimum -ΔG(pds) value). Figure 3 ) Determined. For Figure 3 Observations revealed that when △G RRS (10) When the value is below -10 kcal / mol, the straight line corresponding to reaction D is at its lowest, and when ΔG RRS (10) When the value is between -10 kcal / mol and 10 kcal / mol, the straight line corresponding to reaction J is the lowest, and when ΔG RRS When the value of (10) is greater than 10 kcal / mol, the straight line corresponding to reaction H is at its lowest. Taking the above reaction line (the straight line corresponding to the above reaction process), the preliminary shape of the alkali source volcano relationship diagram can be obtained. However, based on experimental and theoretical calculations, for this catalytic reaction, the proton transfer process under mononuclear conditions (reaction J) is faster than the proton transfer process under binuclear conditions (reaction G) and requires a lower activation energy. Therefore, reaction J is unlikely to be a potential rate-determining factor for this catalytic reaction, and this potential rate-determining step needs to be removed. This makes reaction G a plateau region of the thermodynamic volcano relationship diagram ( Figure 4 ).

[0027] Figure 4 To obtain the linear proportional relationship between the theoretical reaction free energy ( Figure 3 The volcano plot of the base source thermodynamics for this reaction is obtained from [reference needed]. We can understand the volcano plot by starting with the meaning of the variables represented by its axes. The base source thermodynamic volcano plot can use any quantity related to the activity of the candidate catalyst as a descriptor (i.e., the x-axis). This includes, but is not limited to, the energy of the reaction step or the free energy of the intermediate relative to the rest state. In this thermodynamic volcano plot, we chose the magnitude of the interaction between the base source and the substrate, i.e., the free energy of reaction E, ΔG(RxnE), as the x-axis. The region of each base source in the volcano plot is determined solely by the value of ΔG(RxnE). The y-axis of the base source thermodynamic volcano plot represents the energy (ΔG(pds)) required to complete the most thermodynamically challenging reaction step in the catalytic cycle.

[0028] Put our calculated alkali source into Figure 4 From the thermodynamic volcano relationship diagram, we can obtain a thermodynamic volcano relationship diagram that allows us to intuitively determine the activity of different alkali sources. Figure 5 ).exist Figure 5In the thermodynamic volcano diagrams for different base sources, the three regions divided by the dashed lines correspond to different reaction steps, which are the most difficult steps to complete in the catalytic cycle. According to the Sabatier principle, the left-hand diagonal line in region I of the thermodynamic volcano diagram represents an excessively strong interaction between the base source and the substrate (commonly referred to as the strong binding side). For base sources appearing on the left diagonal line, the base source is closely bound to the bipyridine moiety, resulting in intermediate 10 being too stable. Therefore, energy must be consumed to bind O2 to generate the binuclear intermediate (10→11). The right-hand diagonal line in region III of the thermodynamic volcano diagram represents an excessively weak interaction between the base source and the substrate (commonly referred to as the weak binding side). In this case, the base source tends to bind to both ligands, making it difficult for the bipyridine ligand to bind to the base source alone. Energy is required to generate intermediates 10 and 7. Base sources appearing at the plateau of the thermodynamic volcano diagram, i.e., in region II, cannot bind any catalytic cycle intermediates well, nor can they bind ligands well, thus possessing the best thermodynamic attraction.

[0029] observe Figure 5 The thermodynamic volcano relationship diagram shows that most alkali sources are concentrated near the highest peak of the volcano relationship diagram. The alkali sources with better yields obtained in the experiment (such as DBU, DBN, Q, N, etc.) all appear at the highest peak of the volcano, which is consistent with the conclusion of the chemical experiment. However, the catalytic efficiency of alkali sources A (benzimidazole) and K (2,5,6,7-tetrahydro-3H-pyrrolo[1,2-a]imidazole) is generally low.

[0030] To further verify the universality of the volcano plot we revealed, we carefully selected five additional common base sources for computational simulation and verification experiments. These base sources cover different chemical properties and structural features, aiming to comprehensively evaluate the accuracy of the volcano plot in predicting catalytic efficiency. They are C: 6,7-dihydro-5H-pyrrole[1,2-A]imidazole, DABCO: triethylenediamine, DMAP: 4-dimethylaminopyridine, MTBD: 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, and EDA: ethylenediamine, corresponding to verification example 4 (EDA). We adopted a method combining experiments and theoretical calculations to comprehensively analyze the performance of these new base sources in catalytic reactions.

[0031] The results show that the catalytic efficiencies corresponding to the positions of these new base sources on the volcano map are consistent with our experimental findings. This discovery not only validates the universality of the volcano map but also provides us with a powerful tool for predicting and optimizing the design of future catalysts. This method allows us to more accurately identify highly efficient base sources, thus providing more efficient and economical solutions for related catalytic processes.

[0032] In summary, our study not only successfully validated the volcano relationship diagram as an effective tool for predicting catalytic efficiency, but also opened up new avenues for future exploration in catalyst design and application.

[0033] The method for constructing the ligand prediction model in step (3) includes the following steps: 3.1 Screening the ligand training set and calculating the reaction energy barrier Changing the structure of the ligands can affect the reactivity of this reaction. The Cu-TEMPO-catalyzed aerobic oxidation of benzyl alcohol is influenced by different types of ligand effects, including steric hindrance, charge transfer, bond order, and buried volume, among other factors. Therefore, we attempt to predict the activation rate of the ligands in this reaction by constructing a mathematical equation.

[0034] We calculated and analyzed the reaction barriers of four different types of bidentate ligands (NN ligand, NO ligand, NS ligand, and OO ligand), and screened out 23 ligands. Figure 6 () as a training set to study the factors affecting the activation rate of ligands.

[0035] The 23 ligands are: A0: 2,2'-bipyridine, A2: 6-bromo-2,2'-bipyridine, A5: 5,5'-dimethyl-2,2-bipyridine, A6: 4,4'-dimethyl-2,2'-bipyridine, A9: 2,2'-bipyridine-4,4'-dicarboxylic acid, A11: 6-bromo-2-pyridin-2-ylquinoline-4-carboxylic acid, A21: 5-bromo-2,2'-bipyridine, B3: 2-pyridin-2-propanol, B5: 1-isoquinoline methanol, B6: N-furanmethylene-2,4-dimethylamine, B10: isoquinoline-1-phenylmethanol, B11: 2-Furan-3-pyridin-3-quinazolin-4-one, C1: N-(2-thienomethyl)-p-benzylamine, C3: 2-(thieno-2-yl)-4H-benzo[D][1,3]oxazin-4-one, C5: N-[(5-bromo-2-thieno)methylene]-N-(4-methoxyphenyl)amine, C10: Ethyl 4-{[(5-methyl-2-thieno)methylene]amine}benzoate, C12: N-(2,5-dimethylphenyl)-1- [5-(2-ethyl)thiophenol]methylimine, C18: N-[(5-bromo-2-thiophene)methylene]-N-[4-(6-methyl-1,3-benzothiophene-2-hydro)phenyl]amine, C19: (trans)-(5-chloro-2-(((3-methylthiophene-2-hydro)methylene)amino)phenyl)(phenyl)methyl ketone, D1: tetrahydrofurfuryl alcohol, D3: methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate, D4: ethyl 2-cyclohexanone carboxylate.

[0036] 3.2 Determine the parameters describing the ligand effect and construct predictive models for the reactivity of ligands with different structures. Effective molecular descriptors were selected, and a predictive model of their correlation with reactivity was constructed using multiple linear regression analysis. The molecular descriptors included CDA net electron transfer and Becke spin configuration (Becke...). spinpop ) and LUMO energy (E LUMO ).

[0037] Detailed analysis of the calculated transition state structure's energy and electronic parameters not only reveals the factors influencing reactivity but also identifies suitable parameters as descriptors to describe ligand effects based on the aforementioned patterns. We use the LUMO energy (E0) LUMO ), ligand charge transfer analysis (CDA) and Becke spin configuration (Becke spinpop A mathematical prediction model using three parameters to predict the reactivity of ligands with different structures is developed. By combining the calculated reaction energy barrier with the three descriptors, formula (III) is obtained using a multiple linear regression equation, and δE is calculated. 预测 Screening for suitable ligands.

[0038] δE 预测 =0.89×CDA+0.58×Becke spinpop -0.42×E LUMO (III) Specifically, this application screened 50 ligands, among which δE 预测 The lower the value, the higher the reactivity of the ligand. Calculated according to the formula in this application, δE... 预测 Ligands in the range of 2-8 exhibit better activity, with δE being more preferred. 预测 The numerical range is 2-5.

[0039] The method for chemical experimental verification in step (4) is as follows: An oxygen balloon method was used to ensure oxygen-enriched conditions for screening ligands and base sources. The solvent environment of the reaction system was strictly controlled throughout the experiment. At the start of the reaction, benzyl alcohol was added dropwise and thoroughly mixed, followed by the sequential addition of copper trifluoromethanesulfonate, the ligand, TEMPO, and the base source. The reaction was carried out under magnetic stirring. The yield of the product benzaldehyde was analyzed by GC-MS using the internal standard method.

[0040] The solvent is acetonitrile, and the amount used is 2-5 ml; The concentration of benzyl alcohol is 0.1-1 mmol; The molar amounts of copper trifluoromethanesulfonate, ligand, TEMPO, and alkali source added are 3-8%, 3-8%, 3-8%, and 5-15% of the amount of benzyl alcohol added, respectively.

[0041] More preferably, the molar amounts of copper trifluoromethanesulfonate, ligand, TEMPO, and alkali source added are 5%, 5%, 5%, and 10% of the amount of benzyl alcohol added, respectively.

[0042] The beneficial effects of this invention are: 1. This invention first determines the optimal reaction path through dual verification, then obtains the linear proportional relationship of the theoretical reaction free energy through intermediate descriptors, and establishes a thermodynamic volcano relationship diagram of the alkali source, which can predict the catalytic efficiency of different alkali sources; at the same time, this invention develops a ligand prediction model and uses a linear regression equation of molecular descriptors, which can be used to accurately evaluate the reactivity of different ligands.

[0043] 2. The Cu-TEMPO catalytic system screening method of this application can quickly, accurately, and with high throughput screen suitable bases and ligands, with little difference from experimental results, and has guiding significance for catalytic oxidation systems. Attached Figure Description

[0044] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0045] Figure 1 The dominant pathway for DBU / NMI: Path B_Ⅰ of the dual-core reaction mechanism; Figure 2 This represents the linear scaling relationship between intermediates in Embodiment 1 of the present invention; Figure 3 This is a linear proportional relationship diagram of Embodiment 1 of the present invention; Figure 4 A thermodynamic volcanic relationship diagram of the alkali source DBU was established for Example 1 of the present invention; Figure 5 This is a two-dimensional thermodynamic volcano diagram showing the relationship between different base sources in the homogeneous oxidation reaction of benzyl alcohol catalyzed by the present invention; Figure 6 Reaction energy barrier diagrams calculated for different ligands of Cu-TEMPO catalyst; Figure 7 This is a GC-MS chromatogram showing the peak positions of benzaldehyde. Figure 8 for Figure 7 The peak shown is the mass spectrum of benzaldehyde. Detailed Implementation

[0046] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0047] Example 1 A method for screening base sources and ligands in a Cu-TEMPO catalytic system includes the following steps: Step (1) Calculate the total potential energy surface of the alkali source and confirm the optimal reaction pathway: 1.1 Perform geometric optimization on all structures and calculate frequencies; 1) All calculations were performed using the Gaussian 09 program; 2) Benzyl alcohol was selected as the reactant model, and the SMD solvation model was used, with acetonitrile (dielectric constant 35.688) as the reaction solvent. Geometric optimization and frequency calculations were performed on all structures at the B3LYP-D3(BJ) / def2svp / SMD(acetonitrile) level to determine the structures of the intermediate (TDI) and transition state (TDTS).

[0048] 1.2 Calculate the single-point energy (Electronic Energy) of all intermediates and transition states; The single-point energies of all intermediates (TDI) and transition states (TDTS) were calculated at a higher computational level M06 / 6-311+G(d,p) / SMD(acetonitrile) to further determine the energies.

[0049] 1.3 The calculation results were entropy corrected using Shermo correction; 1.4 The accuracy of determining the transition state using intrinsic reaction coordinate theory (IRC); The intrinsic reaction coordinate theory (IRC) yields a minimum energy path for determining the accuracy of the transition state.

[0050] 1.5 Use the span energy model to calculate δE (energy span of the reaction path).

[0051] 1.6 TOF Calculation The overall Gibbs free energy curve was analyzed using an energy span model. The conversion efficiency ("TOF") was calculated using the AUTOOF program. The TOF value of the catalyst was calculated using the following formula to verify the accuracy of this analytical method: (I) Where: K b Here, is Boltzmann's constant, h is Planck's constant, R is the ideal gas constant, T is the reaction temperature, is the energy span of the reaction path, and the RDZ region refers to the region between the intermediate (TDI) and the rate-determining transition state (TDTS). This region corresponds to the experimental kinetic analysis results, confirming the optimal path as the dual-core Path BI (…). Figure 1 ).

[0052] (2) Establish a thermodynamic volcanic relationship diagram of the alkali source and evaluate the catalytic efficiency of the alkali source. 2.1 Determine the intermediate descriptor The intermediate descriptor refers to an intermediate that exhibits a linear relationship with other intermediates. Based on the optimal reaction path of DBU (Path BI), it can be seen that intermediate 10 has a good correlation (R0) with the other intermediates. 2 =0.95 / 0.97), meaning that there is a good correlation between key intermediate 10 and other intermediates, and a linear proportional relationship exists. Therefore, the free energy ΔG of intermediate 10 can be selected. RRS (10) As an intermediate descriptor, it describes the predicted value of the remaining intermediates, that is, by calculating ΔG RRS (10) The free energy (ΔG) of each intermediate obtained RRS The specific calculation process is as follows: The calculations are based on the assumption that the reactants are in a reference state, from which a linear proportional relationship can be derived: G(TEMPO)=G(R)=G(TEMPOH)=G(O2)=G(PhCH2OH)=0kcal / mol (S1) The energy of the formed product PhCHO corresponds to the energy of the overall reaction as follows: △G(PhCHO)=-27kcal / mol (S2) Based on the above assumptions, the key intermediate was obtained relative to the static state (ΔG). RRS The following proportional relationships are given: △G RRS (3) = 0.6△G RRS (10) + 21.1 kcal / mol (Equation 3) △G RRS (4) = 0.6△G RRS (10) + 21.9 kcal / mol (Equation 4) △G RRS (5) = 0.6△G RRS (10) -4.7 kcal / mol (Equation 5) △G RRS (10)=△G RRS(10) (Equation 6) △G RRS (11)=△G RRS (10) + 1 kcal / mol (Equation 7) △G RRS (12) = 0.7△G RRS (10) -4.7 kcal / mol (Equation 8) △G RRS (18) = 0.6△G RRS (10)-7kcal / mol (Equation 9) △G RRS (19) = 0.6△G RRS (10)-4kcal / mol (Equation 10) △G RRS (7) = 0.6△G RRS (10)-5kcal / mol (Equation 11) △G RRS (8) = 0.6△G RRS (10) -5.7 kcal / mol (Equation 12) △G RRS (9) = 0.6△G RRS (10) + 3.8 kcal / mol (Equation 13) △G RRS (3) = 0.6△G RRS (10) -5.8 kcal / mol (Equation 14) As shown in the linear formula above and Figure 2 It can be seen that intermediate 10 has a good correlation with the other intermediates (R0). 2 =0.95 / 0.97), which means that intermediate 10 has a good correlation with other intermediates and there is a linear proportional relationship.

[0053] 2.2 Calculate the theoretical reaction free energy and plot the linear relationship between the theoretical reaction free energy and the reaction free energy. After obtaining the linear proportional relationship between the intermediate descriptor and other intermediates in section 2.1, the theoretical reaction free energy (Equations 17-38) can be obtained through these linear proportional relationships, as follows: After establishing a linear relationship between the key intermediates, the theoretical reaction free energy (AK) in the reaction pathway is calculated as follows: 1) Reaction A The theoretical reaction free energy ΔG theo Given by Equation 17: -△G theo (A) = -[△G RRS (4)-△G RRS (3)] ​​(Equation 17) Take △G from equation 4 RRS (4) Take △G from equation 3 RRS (3) can be obtained as follows: -△G theo (A) = -[0.6△G RRS (10) + 21.9 kcal / mol - (0.6 ΔG RRS (10) + 21.1 kcal / mol) =-0.8kcal / mol (Equation 18) 2) Reaction B The theoretical reaction free energy ΔG theo Equation 19 gives -△G theo (B) = -[△G RRS (5N)-△G RRS (4)] (Equation 19) Take △G from equation 5 RRS (5N), take △G from equation 4 RRS (4) can be obtained as follows: -△G theo (B) = -[0.6△G RRS (10)-4.7kcal / mol-(0.6ΔG RRS (10) + 21.9 kcal / mol) =26.6 kcal / mol (Equation 20) 3) Reaction C The theoretical reaction free energy ΔG theo Equation 21 gives -△G theo (C) = -[△G RRS (10)+PhCHO-△G RRS (5)] (Equation 21) Take △G from equation 6 RRS (10), take △G from equation 5 RRS (5N) can be obtained as follows: -△G theo (C) = -[△G RRS (10) -27-(0.6△GRRS (10) -4.7 kcal / mol =-0.4△G RRS (10) + 22.3 kcal / mol (Equation 22) 4) Reaction D The theoretical reaction free energy ΔG theo Equation 23 gives -△G theo (D) = -[△G RRS (11)-△G RRS (10)-△G RRS (10)] (Equation 23) Take ΔG from equation 7 RRS (11), take △G from equation 6 RRS (10) can be obtained as follows: -△G theo (D) = -[△G RRS (10) + 1 kcal / mol - Δ GRRS (10) -△ GRRS (10) =△G RRS (10)-1kcal / mol (Equation 24) 5) Reaction E The theoretical reaction free energy ΔG theo Given by Equation 25 -△G theo (E) = -[△G RRS (12)-△G RRS (11)] (Equation 25) Take △G from equation 8 RRS (12), take △G from equation 7 RRS (11) can be obtained as follows: -△G theo (E) = -[0.7△G RRS (10) -4.7 kcal / mol -(△G RRS (10) + 1 kcal / mol)] =0.3△G RRS (10) + 5.7 kcal / mol (Equation 26) 6) Reaction F The theoretical reaction free energy ΔG theoEquation 27 gives -△G theo (F) = -[△G RRS (18)-△G RRS (12)] (Equation 27) Take △G from equation 9 RRS (18), take △G from equation 8 RRS (12) can be obtained as follows: -△G theo (F) = -[0.6△G RRS (10)-7kcal / mol-(0.7△G RRS (10)-4.7kcal / mol)] =0.1△G RRS (10) + 2.3 kcal / mol (Equation 28) 7) Reaction G The theoretical reaction free energy ΔG theo Equation 29 gives -△G theo (G) = -[△G RRS (19)-△G RRS (18)] (Equation 29) Take △G from equation 10 RRS (19), take △G from equation 9 RRS (18) can be obtained as follows: -△G theo (G) = -[0.6△ RRS (10)-4kcal / mol-(0.6△G RRS (10)-7kcal / mol)] =-3kcal / mol (Equation 30) 8) Reaction H The theoretical reaction free energy ΔG theo Equation 31 gives -△G theo (H)=-[△G RRS (7)+△G RRS (10)-△G RRS (19)] (Equation 31) Take ΔG from equation 11 RRS (7) Take △G from equation 10 RRS (19), take △G from equation 6 RRS (10) can be obtained as follows: -△Gtheo (G) = -[0.6△G RRS (10)-5kcal / mol+ΔG RRS (10) -(0.6△G RRS (10)-4kcal / mol =-△G RRS (10) + 1 kcal / mol (Equation 32) 9) Reaction I The theoretical reaction free energy ΔG theo Given by Equation 33 -△G theo (I)=-[△G RRS (8)-△G RRS (7)] (Equation 33) Take ΔG from equation 12 RRS (8), take △G from equation 11 RRS (7) can be obtained as follows: -△G theo (I) = -[0.6△G RRS (10) -5.7 kcal / mol -(0.6 ΔG RRS (10)-5kcal / mol)] =0.7 kcal / mol (Equation 34) 10) Reaction J The theoretical reaction free energy ΔG theo Given by equation 35 -△G theo (J)=-[△G RRS (9)-△G RRS (8)] (Equation 35) Take △G from equation 13 RRS (9), take △G from equation 12 RRS (8) can be obtained as follows: -△G theo (J)=-[0.6△G RRS (10) + 3.8 kcal / mol - (0.6 ΔG) RRS (10) -5.7 kcal / mol =-9.5kcal / mol (Equation 36) 11) Reaction K The theoretical reaction free energy ΔG theoGiven by equation 37 -△G theo (K)=-[△G RRS (3)-△G RRS (9)] (Equation 37) Take ΔG from equation 14 RRS (3) Take △G from equation 13 RRS (9) can be obtained as follows: -△G theo (K)=-[0.6△G RRS (10)-5.8kcal / mol-(0.6ΔG RRS (10)-5.8kcal / mol)] =9.6 kcal / mol (Equation 38) 2.3 Establishing the thermodynamic volcano relationship diagram of the alkali source: Based on the linear proportional relationship diagram of the theoretical reaction free energy, establish the thermodynamic volcano relationship diagram of the alkali source.

[0054] The y-axis of the thermodynamic volcanic relationship diagram of the alkali source represents the potential rate-determining step Δ. G ( pds The value is determined by equation (II). The x-axis of the thermodynamic volcano plot of the alkali source shows the magnitude of the interaction between the alkali source and the substrate, which is equivalent to the energy of RxnE.

[0055] △G(pds) = max[△G(RxnA),△G(RxnB),△G(RxnC) △G(RxnD),△G(RxnE),△G(RxnF),△G(RxnG), △G(RxnH),△G(RxnI),△G(RxnJ),△G(RxnK)] (II) Wherein, △G(RxnA)~△G(RxnK) are the free energies of the relevant reactions A~K: △G(RxnA) is the free energy of reaction A, △G(RxnB) is the free energy of reaction B, △G(RxnC) is the free energy of reaction C, △G(RxnD) is the free energy of reaction D, △G(RxnE) is the free energy of reaction E, △G(RxnF) is the free energy of reaction F, △G(RxnG) is the free energy of reaction G, △G(RxnH) is the free energy of reaction H, △G(RxnI) is the free energy of reaction I, △G(RxnJ) is the free energy of reaction J, and △G(RxnK) is the free energy of reaction K.

[0056] Based on the value of the intermediate descriptor, the reaction line of the AK reaction process can be taken to obtain the preliminary shape of the volcano diagram. After excluding potential rate-determining factors that are unlikely to be the catalyst for the reaction, the thermodynamic volcano diagram of the catalytic reaction can be obtained.

[0057] like Figure 3 As shown, when △G RRS (10) When the value is below -10 kcal / mol, the straight line corresponding to reaction D is at its lowest, and when ΔG RRS When the value of (10) is between -10 kcal / mol and 10 kcal / mol, the straight line corresponding to reaction J is the lowest. When ΔG RRS When the value of (10) is greater than 10 kcal / mol, the straight line corresponding to reaction H is at its lowest. Taking the above reaction line, the preliminary shape of the volcano relationship diagram can be obtained. However, based on experimental and theoretical calculations, for this catalytic reaction, the proton transfer process under mononuclear conditions (reaction J) is faster than the proton transfer process under binuclear conditions (reaction G) and requires a lower activation energy. Therefore, reaction J is unlikely to be a potential rate-determining factor for this catalytic reaction, and this potential rate-determining step needs to be removed. This makes reaction G the plateau region of the volcano relationship diagram ( Figure 4 ).

[0058] Depend on Figure 3 From the linear proportional relationship diagram, a two-dimensional thermodynamic volcano diagram of the copper-catalyzed homogeneous oxidation reaction of benzyl alcohol can be obtained (e.g., Figure 4 The simplest way to understand the thermodynamic volcano diagram is to start with the meaning of the variables represented by the axes. The x-axis represents the magnitude of the interaction between the base source and the substrate, equivalent to the energy RxnE. The region of each base source in the volcano diagram is determined solely by the value of ΔG(RxnE). The y-axis of the volcano diagram represents the energy required to complete the thermodynamically most difficult reaction step in the catalytic cycle (potential determining step). It is important to note that the potential rate-determining step defined here is not the same as the rate-determining step. Determining the rate-determining step requires calculating the transition barrier in the catalytic cycle.

[0059] like Figure 5 As shown, the left slope of the thermodynamic volcano relationship diagram indicates that the interaction between the catalyst and the substrate is too strong (usually known as the strong binding side), while the right slope indicates that the interaction between the catalyst and the substrate is too weak (known as the weak binding side). The thermodynamically optimal candidate appears near the highest point of the volcano.

[0060] In the thermodynamic volcano diagram, the dashed vertical lines represent different reaction steps. For base sources located in region I, the process of generating the binuclear intermediate requires the most energy thermodynamically challenging step. Base sources located in region II, however, exhibit an "ideal equilibrium" thermodynamic distribution, where the interaction between the substrate and the base source is neither too weak nor too strong, consistent with Sabatier's concept of an ideal catalyst. The width of the plateau regions in the thermodynamic volcano diagram represents the binding energy they span (6 kcal / mol), while their height corresponds to the energy required for the TEMPOH proton transfer process in the dual-catalyst regeneration process.

[0061] Alkali sources located in volcanoes or at higher locations on volcanoes (with larger -ΔG(pds) values) are the most attractive. For these alkali sources, the energy (RxnG) required to complete the TEMPOH proton transfer process during catalyst regeneration is the most challenging in the catalytic cycle, meaning that RxnG is the potential rate-determining step (pds).

[0062] Figure 5 The volcano relationship diagram shows that most alkali sources are concentrated near the highest peak of the volcano relationship diagram. The alkali sources with better yields obtained in the experiment (such as DBU, DBN, Q, N, etc.) all appear at the highest peak of the volcano, which is consistent with the conclusion of the chemical experiment. However, the catalytic efficiency of alkali sources A (benzimidazole) and K (2,5,6,7-tetrahydro-3H-pyrrolo[1,2-a]imidazole) is generally low.

[0063] To further verify the universality of the volcano plot we revealed, we carefully selected five additional common base sources for computational simulation and verification experiments. These base sources cover different chemical properties and structural features, aiming to comprehensively evaluate the accuracy of the volcano plot in predicting catalytic efficiency. They are C: 6,7-dihydro-5H-pyrrole[1,2-A]imidazole, DABCO: triethylenediamine, DMAP: 4-dimethylaminopyridine, MTBD: 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, and EDA: ethylenediamine, corresponding to verification example 4 (EDA). We adopted a method combining experiments and theoretical calculations to comprehensively analyze the performance of these new base sources in catalytic reactions.

[0064] The results show that the catalytic efficiencies corresponding to the positions of these new base sources on the volcano map are consistent with our experimental findings. This discovery not only validates the universality of the volcano map but also provides us with a powerful tool for predicting and optimizing the design of future catalysts. This method allows us to more accurately identify highly efficient base sources, thus providing more efficient and economical solutions for related catalytic processes.

[0065] In summary, our study not only successfully validated the volcano relationship diagram as an effective tool for predicting catalytic efficiency, but also opened up new avenues for future exploration in catalyst design and application.

[0066] (3) Construct a ligand prediction model and evaluate ligand reactivity; 3.1 Screening the ligand training set and calculating the reaction energy barrier Reaction barriers were calculated and analyzed for four different types of bidentate ligands (NN ligand, NO ligand, NS ligand, and OO ligand), and 23 ligands were selected. Figure 6 () as a training set to study the factors affecting the activation rate of ligands.

[0067] 3.2 Determine the parameters describing the ligand effect and construct predictive models for the reactivity of ligands with different structures. Effective molecular descriptors were selected, and a predictive model of their correlation with reactivity was constructed using multiple linear regression analysis. The molecular descriptors included CDA net electron transfer and Becke spin configuration (Becke...). spinpop ) and LUMO energy (E LUMO ).

[0068] Detailed analysis of the calculated transition state structure's energy and electronic parameters not only reveals the factors influencing reactivity but also identifies suitable parameters as descriptors to describe ligand effects based on the aforementioned patterns. We use the LUMO energy (E0) LUMO ), ligand charge transfer analysis (CDA) and Becke spin configuration (Becke spinpop A mathematical prediction model using three parameters to predict the reactivity of ligands with different structures is developed. By combining the calculated reaction energy barrier with the three descriptors, formula (III) is obtained using a multiple linear regression equation, and δE is calculated. 预测 Screening for suitable ligands.

[0069] δE 预测 =0.89×CDA+0.58×Becke spinpop -0.42×E LUMO (III) δE is calculated according to formula (2). 预测 The lower the value, the higher the ligand reaction efficiency. Among the 50 ligands studied, the results showed that 20 ligands had reaction barriers lower than 2,2'-bipyridine (17.4) (see...). Figure 6 ).

[0070] (4) Chemical experimental verification 1) Alkali source: Twenty-one alkali sources were studied and calculated according to steps 2.1-2.3. The activity of these alkali sources was derived from the analysis of thermodynamic volcano diagrams. The alkali sources located in the high-activity region of the thermodynamic volcano diagrams are: benzimidazole (A), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 2,3,5,6,7,8-hexahydroimidazo[1,2-a]pyridine (G), 5,6,7,8-tetrahydroimidazo[1,5-a]pyridine (H), 2,5,6,7-tetrahydro-3H-pyrrolo[1,2-a]imidazole (K), 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (L), and 1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyrimidine (M). Imidazolo[1,2-a]pyridine (N), N-methylimidazolium (NMI), 1,5,6,7,8,8a-hexahydroimidazo[1,5-a]pyridine (P), imidazo[1,5-a]pyridine (Q), 3a,4,5,6,7,7a-hexahydro-1H-benzo[d]imidazolium (R), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), ethylenediamine (EDA), 6,7-dihydro-5H-pyrrole[1,2-A]imidazolium (C), triethylenediamine (DABCO), 4-dimethylaminopyridine (DMAP), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD).

[0071] For experimental verification, we purchased 13 readily available base sources, including benzimidazole (A), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), ethylenediamine (EDA), 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine (L), imidazo[1,2-a]pyridine (N), and N... 1,5,7-Methylimidazolium (NMI), imidazo[1,5-a]pyridine (Q), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 6,7-dihydro-5H-pyrrole[1,2-A]imidazolium (C), triethylenediamine (DABCO), 4-dimethylaminopyridine (DMAP), and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD). These base sources correspond to validation examples 1-13, and the experimental results are shown in Table 2.

[0072] Verification Example 1 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile; (S2) Use a magnetic stirrer to mix the mixed solution in (S1) thoroughly; (S3) Add 0.025 mmol of copper trifluoromethanesulfonate to the well mixed solution obtained in step (S2), stir with a magnetic stirrer for 3 minutes, and the solution will turn a light blue color. (S4) Add 0.025 mmol of 0.025 mmol of 2,2'-bipyridine to the mixed solution obtained in step (S3), and stir with a magnetic stirrer for 5 minutes. The solution changes from light blue to sky blue. (S5) Add 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO) to the mixed solution obtained in step (S4), and stir with a magnetic stirrer for 2 minutes. The solution changes from sky blue to light green. (S6) Add 0.05 mmol of benzimide (A) to the mixed solution obtained in step (S5) and stir with a magnetic stirrer for 2 minutes; (S7) Place the mixed solution obtained in step (S6) under an oxygen-enriched atmosphere (oxygen balloon); (S8) Based on step (S7), place the mixture at room temperature (temperature 27±2℃) and stir for 24 hours; (S9) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 94%.

[0073] Figure 7 This is a gas chromatogram of benzaldehyde elution peaks in the diluted reaction solution under GC-MS, with a retention time of 5.568 min. Figure 8 for Figure 7 The mass spectrum showing the peaks can be confirmed as benzaldehyde by searching a mass spectrometry database.

[0074] Verification Example 2 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and mix them well using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 0.5 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 92%.

[0075] Verification Example 3 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine (bipy), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and mix them well using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 0.5 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 99%.

[0076] Verification Example 4 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of ethylenediamine (EDA). Use a magnetic stirrer to mix them well. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 93%.

[0077] Verification Example 5 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of 5,6,7,8-tetrahydroimidazolo[1,2-a]pyridine (L) and mix them well using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 97%.

[0078] Verification Example 6 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of imidazo[1,2-a]pyridine (N). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 94%.

[0079] Verification Example 7 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of N-methylimidazolium (NMI). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 93%.

[0080] Verification Example 8 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of imidazo[1,5-a]pyridine (Q). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 99%.

[0081] Verification Example 9 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and mix them well using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 0.5 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 93%.

[0082] Verification Example 10 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine (bipy), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of 6,7-dihydro-5H-pyrrole[1,2-A]imidazole (C). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 0.5 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 98%.

[0083] Verification Example 11 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of triethylenediamine (DABCO). Use a magnetic stirrer to mix them well. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 0.5 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 95%.

[0084] Verification Example 12 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine, 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of 4-dimethylaminopyridine (DMAP). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 0.5 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 96%.

[0085] Verification Example 13 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine (bipy), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) and mix them well using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 0.5 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 95%.

[0086] Table 2 Experimental data for different base source systems with bipy ligand. .

[0087] As shown in Table 2, we observed that DBU, TBD, and DBN have similar basic structures. This was demonstrated in our experiments by their ability to efficiently complete the reaction in a relatively short time. Therefore, we set the reaction time for DBU, TBD, and DBN to 30 minutes, while the reaction time for other base sources was kept at 24 hours.

[0088] Experimental data revealed the following findings: Under a 24-hour reaction time, all alkali source systems exhibited yields similar to or higher than the NMI (93% yield) reported in the original literature, as shown in Validation Example 7. This is consistent with the predictions of the highly active region in the thermodynamic volcano relationship diagram of the computational simulation. Notably, when benzimidazole (A) and ethylenediamine (EDA) were used as alkali sources, the yields were 93% and 94%, respectively, as shown in Validation Examples 1 and 4. Considering that their cost is only half that of NMI, these two alkali sources offer significant cost-effectiveness in large-scale production, making them a more economical and efficient alternative to NMI.

[0089] Under a reaction time of 30 minutes, DBN (Validation Example 3) demonstrated superior efficiency, achieving a yield of 99%, which is 7 percentage points higher than the 92% yield of DBU (Validation Example 2) recorded in the reference. This significant improvement not only highlights DBN's superior efficiency but also its outstanding performance in increasing yield. Considering these significant advantages, DBN has the potential to completely replace DBU and NMI as a base source, driving the system towards even higher efficiency and yield.

[0090] We found that benzimidazole (A) and ethylenediamine (EDA), when used as base sources, cost only half that of NMI, yet provide comparable or even higher yields (93% and 94%, respectively), demonstrating their economic efficiency and high effectiveness. DBN, as a base source, exhibited remarkable performance, achieving a yield of up to 99% within 30 minutes, significantly better than the 24-hour reaction time required for base sources such as NMI, benzimidazole (A), and ethylenediamine (EDA), thus substantially improving reaction efficiency.

[0091] DBN significantly improves production efficiency while increasing yield, and boasts advantages such as simple operation and mild reaction conditions. These advantages make DBN a superior alkali source choice, demonstrating strong potential for industrial applications.

[0092] The experiment verified that the alkaline sources with good activity obtained from the calculation, namely the plateau region in the thermodynamic volcanic relationship diagram, all showed good yields in the experiment. This not only confirmed the effectiveness of the screening method used, but also demonstrated its feasibility and efficiency in practical applications, providing guidance for alkaline source screening in practical applications.

[0093] 2) Ligands: Fifty ligands were studied according to steps 3.1-3.2, and the results showed that 20 ligands had reaction barriers lower than 2,2'-bipyridine (17.4) (see...). Figure 6 To verify the experimental results, we purchased five commercially available ligands: methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate (D3), ethyl 2-cyclohexanone carboxylate (D4), 4-(thiophene-2-yl)-2,3-dihydro-1H-1,5-benzodiazepine (C6), tetrahydrofurfuryl alcohol (D1), 6-bromo-2,2'-bipyridine (A2), and 2,2'-bipyridine (A0). These ligands correspond to validation examples 14-19, and the experimental results are shown in Table 3.

[0094] Verification Example 14 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate (D3), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of N-methylimidazolium (NMI). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 98%.

[0095] Verification Example 15 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of ethyl 2-cyclohexanone carboxylate (D4), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of N-methylimidazole (NMI). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 96%.

[0096] Verification Example 16 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 4-(thiophene-2-yl)-2,3-dihydro-1H-1,5-benzodiazepine (C6), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of N-methylimidazolium (NMI). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 97%.

[0097] Verification Example 17 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of tetrahydrofurfuryl alcohol (D1), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of N-methylimidazolium (NMI). Use a magnetic stirrer to mix them well. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 94%.

[0098] Verification Example 18 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 6-bromo-2,2'-bipyridine (A2), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of N-methylimidazolium (NMI). Mix each mixture thoroughly using a magnetic stirrer. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 96%.

[0099] Verification Example 19 (S1) Add 52 μL (0.5 mmol) of benzyl alcohol to a 10 mL reaction tube containing 2.5 mL of acetonitrile and mix well. Then add 0.025 mmol of copper trifluoromethanesulfonate, 0.025 mmol of 2,2'-bipyridine (A0), 0.025 mmol of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), and 0.05 mmol of N-methylimidazolium (NMI). Use a magnetic stirrer to mix them well. (S2) Place the mixed solution obtained in step (S1) in an oxygen-enriched atmosphere (oxygen balloon) and stir at room temperature (temperature 27±2℃) for 24 hours; (S3) After the reaction was completed, the product was diluted with an appropriate amount of acetonitrile and then subjected to qualitative and quantitative analysis by GC-MS. The yield of benzaldehyde was 93%.

[0100] Experimental data (Table 3) show that the yield of benzaldehyde in systems with ligands whose reaction energy barrier is lower than that of 2,2'-bipyridine (A0) is greater than or equal to that of the 2,2'-bipyridine (A0) system.

[0101] Experimental data verified the following conclusions from the calculations: ligands with lower reaction energy barriers than 2,2'-bipyridine (A0) did indeed exhibit higher benzaldehyde yields in the experiment than those in the 2,2'-bipyridine (A0) system. This not only confirms the effectiveness of the screening method used, but also demonstrates its feasibility and efficiency in practical applications, providing guidance and a reference basis for ligand selection in practical applications.

[0102] Table 3 Experimental data under different ligand systems with N-methylimidazole (NMI) as the base source. .

[0103] In summary, the screening method developed in this invention first determines the linear free energy ratio of intermediates. Then, based on this ratio, it calculates the free energy changes of different base sources and the stability of steady-state intermediates during the reaction, constructing a thermodynamic volcano diagram of the relationship between reaction free energy and steady-state intermediate stability to evaluate the catalytic efficiency of different base sources. Furthermore, by analyzing the reaction patterns of different ligands, chemical descriptors (including catalyst LUMO energy, charge decomposition analysis, and Becke spin population) are selected as input variables for the prediction model. A prediction model is constructed using multiple linear regression analysis, which can be used to predict the reaction efficiency of different ligands. The screening method of this invention can quickly and accurately screen suitable base sources and ligands, and has been verified through chemical experiments. This provides guidance for the design of base sources and ligands for the Cu-TEMPO reaction and offers an effective approach to combining theoretical calculations with experimental research.

[0104] The above-described embodiments are merely specific implementations of the present invention, used to illustrate the technical solutions of the present invention, and are not intended to limit it. The scope of protection of the present invention is not limited thereto. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that any person skilled in the art can still modify or easily conceive of changes to the technical solutions described in the foregoing embodiments within the scope of the technology disclosed in the present invention, or make equivalent substitutions for some of the technical features; and these modifications, changes, or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention, and should all be covered within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of protection of the claims.

Claims

1. A method for screening Cu-TEMPO catalytic systems, characterized in that, Includes the following steps: (1) Calculate the total potential energy surface and confirm the optimal reaction path; (2) Establish a thermodynamic volcanic relationship diagram of the alkali source and evaluate the catalytic efficiency of the alkali source; (3) Construct a ligand prediction model and evaluate ligand reactivity; Step (1) includes the following method: 1.1 Perform geometric optimization on all structures and calculate frequencies; 1) All calculations were performed using the Gaussian 09 program; 2) Benzyl alcohol was selected as the reactant model, and the SMD solvation model was used, with acetonitrile as the reaction solvent. At the B3LYP-D3(BJ) / def2svp / SMD level, the geometry of all structures was optimized and the frequencies were calculated to determine the structures of intermediate TDI and transition state TDTS. 1.2 Calculate the single-point energy of all intermediates and transition states; 1.3 The calculation results are subjected to Shermo correction for entropy correction; 1.4 The accuracy of determining the transition state using intrinsic reaction coordinate theory (IRC); 1.5 The energy span δE of the reaction path was calculated using the span energy model to confirm the optimal reaction path; 1.6 TOF calculation verification; Step (2) includes the following methods: 2.1 Identify key intermediate descriptors; The intermediate descriptor refers to an intermediate that can have a linear relationship with other intermediates; 2.2 Calculate the theoretical reaction free energy and plot the linear proportional relationship between the theoretical reaction free energy; 2.3 Establishing the thermodynamic volcano relationship diagram of the alkali source: Based on the linear proportional relationship diagram of the theoretical reaction free energy, establish the thermodynamic volcano relationship diagram of the alkali source; Furthermore, the method for constructing the ligand prediction model in step (3) includes: 3.1 Screening the ligand training set and calculating the reaction energy barrier; 3.2 Determine the parameters describing the ligand effect and construct a predictive model for the reactivity of ligands with different structures.

2. The method according to claim 1, characterized in that, The optimal reaction pathway is the dual-core Path BI; the intermediate descriptor is the free energy ΔG of intermediate 10. RRS (10); The theoretical reaction free energy of AK in the reaction pathway is calculated as follows: 1) Reaction A ； -△G theo (A)=-0.8kcal / mol 2) Reaction B ； -△G theo (B)=26.6kcal / mol 3) Reaction C ； -△G theo (C)=-0.4△G RRS (10)+22.3kcal / mol 4) Reaction D ； -△G theo (D)=△G RRS (10)-1kcal / mol 5) Reaction E ； -△G theo (E)=0.3△G RRS (10)+5.7kcal / mol 6) Reaction F ； -△G theo (F)=0.1△G RRS (10)+2.3kcal / mol 7) Reaction G ； -△G theo (G)=-3kcal / mol 8) Reaction H ； -△G theo (H)=-△G RRS (10)+1kcal / mol 9) Reaction I ； -△G theo (I)=0.7kcal / mol 10) Reaction J ； -△G theo (J)=-9.5kcal / mol 11) Reaction K ； -△G theo (K)=9.6kcal / mol。 3. The method according to claim 2, characterized in that, The y-axis of the thermodynamic volcano relationship diagram of the alkali source represents the potential rate-determining step ΔG(pds), which is determined by equation (II); the x-axis of the thermodynamic volcano relationship diagram of the alkali source shows the magnitude of the interaction between the alkali source and the substrate; the alkali source located at the highest peak of the volcano is a thermodynamically attractive alkali source; Potential velocity-determining steps ΔG(pds) = max[ΔG(RxnA), ΔG(RxnB), ΔG(RxnC)] △G(RxnD),△G(RxnE),△G(RxnF),△G(RxnG), △G(RxnH),△G(RxnI),△G(RxnJ),△G(RxnK)] (II) Where △G(RxnA)~△G(RxnK) are the free energies of the relevant reactions A~K.

4. The method according to claim 1, characterized in that, The ligands are NN ligands, NO ligands, NS ligands, and OO ligands.

5. The method according to claim 1, characterized in that, Effective molecular descriptors were selected, and a predictive model for ligand reactivity was constructed using multiple linear regression analysis; the molecular descriptors were CDA net electron transfer and Becke spin configuration. spinpop and LUMO energy E LUMO .

6. The method according to claim 5, characterized in that, Formula (III) is obtained using the multiple linear regression equation, and δE is calculated. 预测 ,δE 预测 Suitable ligands were screened within the range of 2-8; δE 预测 =0.55×CDA+0.35×Becke spinpop +0.07×E LUMO (III)。 7. The method according to claim 1, characterized in that, It also includes step (4) chemical experiment verification: Cu-TEMPO catalyzes the aerobic oxidation reaction of benzyl alcohol, ensuring oxygen-rich conditions. Benzyl alcohol is added dropwise at the beginning of the reaction, and after thorough mixing, copper trifluoromethanesulfonate, ligand, TEMPO and base source are added in sequence. The solvent is acetonitrile, and the amount used is 2-5 ml; The concentration of benzyl alcohol is 0.1-1 mmol; The molar amounts of copper trifluoromethanesulfonate, ligand, TEMPO, and alkali source added are 3-8%, 3-8%, 3-8%, and 5-15% of the amount of benzyl alcohol added, respectively.

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