Online Regulation Method and System for the Co-Catalyzed Organic Synthesis by Sodium / Potassium tert-Butoxide

Abstract

The present application provides an online regulation method and system for the synergistic catalysis of sodium tert-butoxide / potassium in organic synthesis, which relates to the technical field of organic synthesis. The method includes: obtaining the kinetic data of the organic synthesis reaction system in real time and obtaining the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide; determining the catalytic scenario category according to the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, including the activity recovery scenario and / or the side reaction inhibition scenario; triggering the dynamic adjustment of the injection of sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category until the reaction is completed; through multi-parameter real-time monitoring and scenario-based dynamic regulation, this solution realizes the precise control of the reaction path, maximizes the product yield and purity, and at the same time ensures the process safety and economy.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to an on-line regulation method and system for the synergistic catalysis of organic synthesis by sodium tert-butoxide / potassium tert-butoxide. Background Art

[0002] Sodium tert-butoxide (NaOt-Bu) and potassium tert-butoxide (KOt-Bu), as strong basic catalysts, are widely used in organic synthesis for reactions such as alkylation, elimination, and condensation. In traditional schemes, the two usually adopt a single catalyst or a premixed mode with a fixed ratio (such as only using sodium salt or potassium salt). This mode has the following problems:

[0003] First, potassium tert-butoxide is often used in reactions with high activity requirements (such as Darzens condensation) due to its stronger basicity, but the ratio cannot be dynamically adjusted according to the reaction process. When the catalyst is deactivated due to adsorption of acidic by-products (such as HX) or impurities, the reaction needs to be interrupted to replenish the catalyst, resulting in low efficiency and complex operation.

[0004] Second, substrates containing strong electron-withdrawing groups (such as nitrobenzene derivatives) are prone to inducing side reactions (such as over-deprotonation, disproportionation). In this mode, it mostly depends on changing the catalyst or solvent system (such as changing to an alkali metal amide), but there is a lack of dynamic regulation of the sodium / potassium synergistic effect, resulting in insufficient selectivity. Summary of the Invention

[0005] In view of the above defects or deficiencies in the prior art, the present application aims to provide an on-line regulation method and system for the synergistic catalysis of organic synthesis by sodium tert-butoxide / potassium tert-butoxide, so as to achieve dynamic synergy of the activity and selectivity of sodium tert-butoxide / potassium tert-butoxide in complex organic synthesis, and to address the problems of catalyst deactivation, substrate sensitivity, and uncontrollable side reaction paths.

[0006] In the first aspect, the present application proposes an on-line regulation method for the synergistic catalysis of organic synthesis by sodium tert-butoxide / potassium tert-butoxide, including the following steps:

[0007] Obtain the kinetic data of the organic synthesis reaction system in real time, and obtain the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide; the kinetic data includes the conversion rate of functional groups in the reaction process, as well as the pH value and ion concentration of the reaction solution; the synergistic catalytic efficiency is a quantitative index comprehensively calculated based on the conversion rate of functional groups, the ratio of sodium / potassium ion concentration, pH value, and total ion concentration;

[0008] Determine the catalytic scenario category according to the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, and the catalytic scenario category includes an activity recovery scenario and / or a side reaction inhibition scenario;

[0009] Trigger a corresponding dynamic adjustment of the injection of sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category until the reaction is completed;

[0010] According to the catalytic scenario category, trigger dynamic adjustment of injecting sodium tert-butoxide and potassium tert-butoxide into the reaction system, including the following steps:

[0011] If the catalytic scenario category is the activity recovery scenario, trigger the first adjustment strategy. The first adjustment strategy is to supplement potassium tert-butoxide based on the molar concentration ratio of sodium ions to potassium ions in the reaction system and adjust its molar proportion to a first preset range to maintain catalytic activity. The first preset range is the minimum potassium ion proportion threshold required to restore catalytic activity.

[0012] If the catalytic scenario category is the side reaction inhibition scenario, trigger the second adjustment strategy. The second adjustment strategy is to increase the molar proportion of potassium tert-butoxide to a second preset range and simultaneously inhibit the addition amount of sodium tert-butoxide to a third preset range. The second preset range is the minimum potassium ion proportion threshold required to inhibit the side reaction path, and the third preset range is the minimum necessary amount to maintain the stabilizing effect of sodium ions on the transition state. Among them, the lower limit of the second preset range is higher than the upper limit of the first preset range.

[0013] According to the technical solution provided by the present application, the real-time acquisition of the kinetic data of the organic synthesis reaction system includes the following steps:

[0014] Monitor the change in the vibration peak intensity of carbonyl, nitro or cyano functional groups in the reaction solution within the corresponding wavenumber range to obtain the functional group conversion rate.

[0015] Detect the molar concentrations of sodium ions and potassium ions in the reaction solution, calculate the sodium / potassium ion concentration ratio, and respectively obtain the pH value and the total ion concentration of the reaction solution. The total ion concentration includes the ion concentrations of sodium ions, potassium ions and side reactants.

[0016] According to the technical solution provided by the present application, the determination of the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide includes the following steps:

[0017] If the synergistic catalytic efficiency is less than the first preset threshold , and when any of the following conditions is satisfied, it is determined as the activity recovery scenario:

[0018] The sodium / potassium ion concentration ratio is greater than 1:1;

[0019] The pH value of the reaction solution is less than the first critical value and the conductivity increase exceeds the second critical value. The first critical value is the pH critical value when acidic by-products accumulate and cause catalyst deactivation. The second critical value is the conductivity increase threshold when the sodium / potassium ion concentration ratio is out of balance.

[0020] If the synergistic catalytic efficiency is less than the second preset threshold , and any of the following conditions is met, it is determined to be the side reaction suppression scenario:

[0021] The absorbance increase of the nitro functional group or the cyano functional group is detected to exceed a third critical value; the third critical value is the absorbance increase threshold when the nitro or cyano side reaction is triggered;

[0022] detecting that the by-product partial pressure exceeds a fourth critical value, wherein the fourth critical value is a pressure value when the hydrogen partial pressure exceeds a chain side reaction triggering threshold detected by an online mass spectrometer;

[0023] The numerical relationship between the first preset threshold and the second preset threshold is: 0.4≤ < ≤0.6.

[0024] According to the technical solution provided in this application, the dynamic adjustment of triggering the injection of corresponding sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category includes the following steps:

[0025] If the catalytic scenario category is determined to be both an activity recovery scenario and a side reaction inhibition scenario, the second adjustment strategy is triggered first.

[0026] According to the technical solution provided by this application, the method further includes the following steps:

[0027] Real-time acquisition of the solubility of potassium tert-butoxide and the dielectric constant of the solvent in the reaction system;

[0028] After the second adjustment strategy is preferentially triggered, the following steps are further included:

[0029] After the second adjustment strategy is executed for a first preset time period, re-measuring the by-product partial pressure;

[0030] If the by-product partial pressure is still higher than the side reaction risk threshold, the side reaction is determined to be uncontrolled, and the potassium tert-butoxide injection rate is increased to a value close to but not exceeding an upper limit, and the adjustment time is extended; wherein the upper limit is the maximum safe injection rate dynamically calculated based on the solubility of potassium tert-butoxide in the reaction system and the dielectric constant of the solvent; the side reaction risk threshold is dynamically calibrated by the kinetic relationship between the detected by-product partial pressure and the chain side reaction rate.

[0031] According to the technical solution provided in this application, before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included:

[0032] Calculate the side reaction risk level based on the by-product partial pressure and reaction temperature;

[0033] If the catalytic scenario category is determined to be both an activity recovery scenario and a side reaction suppression scenario, the second adjustment strategy is preferentially triggered, including the following steps:

[0034] If the side reaction risk level is greater than the first preset level, and if the catalytic scenario category is simultaneously determined to be an activity recovery scenario and a side reaction suppression scenario, the second adjustment strategy is triggered first.

[0035] According to the technical solution provided in this application, after re-measuring the by-product partial pressure, the following steps are also included:

[0036] If the by-product partial pressure drops below the side reaction risk threshold, the side reaction is determined to be under control;

[0037] Calculate the controlled cooperative catalytic efficiency;

[0038] If the controlled cooperative catalytic efficiency is still less than the first preset threshold, the first adjustment strategy is triggered; if the controlled cooperative catalytic efficiency is greater than or equal to the first preset threshold, the current catalyst ratio is maintained.

[0039] According to the technical solution provided by the present application, before the real-time acquisition of kinetic data of the organic synthesis reaction system, the following steps are also included:

[0040] Pre-scan the substrate molecule to obtain the substrate functional group type, substrate molecular weight and number of substituents;

[0041] Determining whether the substrate has structural characteristics based on the substrate functional group type, substrate molecular weight, and number of substituents;

[0042] Before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included:

[0043] If the substrate does not have the structural characteristics, the first initial value calibrated by the correlation experiment between the by-product concentration and the pH value is used as the first critical value, the second initial value determined by the correspondence between the sodium / potassium ratio gradient experiment and the conductivity change is used as the second critical value, the third initial value determined by the linear calibration curve of the by-product concentration and the absorbance is used as the third critical value, and the fourth initial value calibrated by the kinetic experiment of the hydrogen partial pressure and the side reaction rate is used as the fourth critical value.

[0044] According to the technical solution provided in this application, before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included:

[0045] If having the substrate structural features, according to the substrate structural features, retrieve and traverse the historical data in the historical reaction template library that is consistent with the substrate functional group type, molecular weight, and number of substituents, and match the corresponding first adjustment coefficient, second adjustment coefficient, third adjustment coefficient, and fourth adjustment coefficient;

[0046] Take the product of the first adjustment coefficient and the first initial value as the first critical value, take the product of the second adjustment coefficient and the second initial value as the second critical value, take the product of the third adjustment coefficient and the third initial value as the third critical value, and take the product of the fourth adjustment coefficient and the fourth initial value as the fourth critical value.

[0047] In a second aspect, the present application proposes an online regulation system for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis, which is used to implement the online regulation method for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis as described above, including:

[0048] A calculation module, the calculation module is configured to obtain the kinetic data of the organic synthesis reaction system in real time and obtain the synergistic catalysis efficiency of sodium tert-butoxide and potassium tert-butoxide; the kinetic data includes the functional group conversion rate in the reaction process, as well as the pH value and ion concentration of the reaction solution; the synergistic catalysis efficiency is a quantitative index comprehensively calculated based on the functional group conversion rate, the sodium / potassium ion concentration ratio, the pH value, and the total ion concentration;

[0049] A judgment module, the judgment module is configured to determine the catalytic scenario category according to the kinetic data and the synergistic catalysis efficiency of sodium tert-butoxide and potassium tert-butoxide, and the catalytic scenario category includes an activity recovery scenario and / or a side reaction inhibition scenario;

[0050] A control module, the control module is configured to trigger a dynamic adjustment of the injection of sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category until the reaction is completed;

[0051] The control module is further configured to, if the catalytic scenario category is the activity recovery scenario, trigger a first adjustment strategy, and the first adjustment strategy is to supplement potassium tert-butoxide based on the molar concentration ratio of sodium ions and potassium ions in the reaction system and adjust its molar proportion to a first preset interval to maintain the catalytic activity; the first preset interval is the minimum potassium ion proportion threshold required to restore the catalytic activity;

[0052] The control module is further configured to trigger a second adjustment strategy if the catalytic scenario category is the side-reaction inhibition scenario. The second adjustment strategy is to increase the molar proportion of potassium tert-butoxide to a second preset range while suppressing the addition amount of sodium tert-butoxide to a third preset range. The second preset range is the lowest potassium ion proportion threshold required to inhibit the side-reaction path, and the third preset range is the lowest necessary amount to maintain the stabilizing effect of sodium ions on the transition state. Among them, the lower limit of the second preset range is higher than the upper limit of the first preset range.

[0053] Compared with the prior art, the beneficial effects of the present application are as follows: By real-time monitoring the sodium / potassium ion concentration ratio, the present application triggers the dynamic addition of potassium salt (the first preset range) to maintain an alkaline environment to neutralize acidic impurities and avoid activity decay, so as to achieve online compensation for catalyst deactivation. At the same time, for the side-reaction path caused by strong electron-withdrawing groups, by increasing the proportion of potassium salt (the second preset range), the alkalinity is enhanced to inhibit side reactions, while retaining the lowest necessary amount of sodium salt (the third preset range) and using its smaller ionic radius to stabilize the transition state. Thus, in complex organic synthesis, the activity and selectivity of sodium tert-butoxide / potassium are dynamically coordinated to address the problems of catalyst deactivation, substrate sensitivity, and uncontrollable side-reaction paths. Therefore, through multi-parameter real-time monitoring and scenario-based dynamic regulation, the present solution realizes precise control of the reaction path, maximizes the product yield and purity, and at the same time ensures process safety and economy. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 It is a flowchart of the steps of the online regulation method for the synergistic catalysis of sodium tert-butoxide / potassium in organic synthesis provided by the present application. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0055] The present application will be further described in detail below with reference to the drawings and embodiments. It can be understood that the specific embodiments described herein are only used to explain the related invention and are not intended to limit the invention. Additionally, it should be noted that for the sake of description, only the parts related to the invention are shown in the drawings.

[0056] It should be noted that, without conflict, the embodiments in the present application and the features in the embodiments can be combined with each other. The present application will be described in detail below with reference to the drawings and embodiments.

[0057] Embodiment 1

[0058] As mentioned in the background art, in view of the problems in the prior art, the present application proposes an online regulation method for the synergistic catalysis of sodium tert-butoxide / potassium in organic synthesis, as Figure 1 shown, including the following steps:

[0059] S1. Obtain the kinetic data of the organic synthesis reaction system in real time, and obtain the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide; the kinetic data includes the functional group conversion rate during the reaction process, as well as the pH value and ion concentration of the reaction solution; the synergistic catalytic efficiency is a quantitative index comprehensively calculated based on the functional group conversion rate, the sodium / potassium ion concentration ratio, the pH value and the total ion concentration;

[0060] Specifically, use an in-situ FTIR spectrometer to monitor the vibration peak intensity of carbonyl (1700 - 1750 cm -1 ), nitro (1500 - 1550 cm -1 ), or cyano (2230 - 2240 cm -1 ) in the reaction solution, and calculate the functional group conversion rate through peak area integration (conversion rate = 1 - current peak area / initial peak area); use an ion-selective electrode to detect the Na + / K + concentration in the reaction solution in real time, use a pH meter to measure the pH value, use a conductivity meter to monitor the conductivity, and obtain the total ion concentration by converting the conductivity (the conductivity is proportional to the ion concentration).

[0061] Specifically, through the formula , where α, β, and γ are weight coefficients determined by orthogonal experiment optimization, K + / (Na + +K + ) is the molar ratio of potassium ions, and the ideal pH value is 10.5 (the optimal activity range of tert-butoxide). Among them, the method for determining the weight coefficients is as follows: Variables: sodium / potassium ion ratio (1:5 to 5:1), pH (9.0 - 12.0), conductivity (0.1 - 10 mS / cm). Design experiments using the L9 orthogonal table, repeat each group 3 times, and calculate the correlation between the synergistic catalytic efficiency (η) and the product yield. Determine α = 0.5 (conversion rate), β = 0.3 (ion ratio), γ = 0.2 (pH) through multiple regression, and R²≥0.85.

[0062] Furthermore, the real-time acquisition of the kinetic data of the organic synthesis reaction system includes the following steps:

[0063] Monitor the change in the vibration peak intensity of carbonyl, nitro, or cyano functional groups in the reaction solution within the corresponding wavenumber range to obtain the functional group conversion rate;

[0064] Detect the molar concentrations of sodium ions and potassium ions in the reaction solution, calculate the sodium / potassium ion concentration ratio; and respectively obtain the pH value and the total ion concentration of the reaction solution; the total ion concentration includes the ion concentrations of sodium ions, potassium ions, and side reactants.

[0065] Optionally, an ATR-FTIR probe is immersed in the reaction solution and scanned every 5 minutes (if the reaction rate is fast, such as at the minute level, the scanning interval needs to be shortened), and the characteristic peak area is fitted by OPUS software. For example, the carbonyl conversion rate is calculated by the decrease of the 1710 cm -1 peak; the sodium / potassium ion concentration is detected by an online microfluidic ion chromatography module (chromatographic column: Dionex IonPac CS12A), the mobile phase is 20 mM methanesulfonic acid, the flow rate is 0.5 mL / min, and the detection limit is 0.1 ppm.

[0066] S2. Determine the catalytic scenario category according to the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide. The catalytic scenario category includes an activity recovery scenario and / or a side reaction inhibition scenario;

[0067] Further, determining the catalytic scenario category according to the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide includes the following steps:

[0068] If the synergistic catalytic efficiency is less than the first preset threshold , and when any of the following conditions is met, it is determined as the activity recovery scenario:

[0069] The ratio of sodium / potassium ion concentration is greater than 1:1;

[0070] The pH value of the reaction solution is less than the first critical value and the conductivity increase exceeds the second critical value; the first critical value is the pH critical value when the catalyst is deactivated due to the accumulation of acidic by-products; the second critical value is the conductivity increase threshold when the ratio of sodium / potassium ion concentration is imbalanced;

[0071] Specifically, this determination method comprehensively considers the effects of factors such as ion ratio and pH value on the catalyst activity. For example, the imbalance of sodium / potassium ion ratio or the accumulation of acidic by-products will cause the catalyst to be deactivated. By setting corresponding determination conditions, the decrease in catalyst activity can be detected in time so as to take targeted adjustment measures to restore the catalytic activity.

[0072] If the synergistic catalytic efficiency is less than the second preset threshold , and when any of the following conditions is met, it is determined as the side reaction inhibition scenario:

[0073] The absorbance increase of the nitro functional group or the cyano functional group is detected to exceed the third critical value; the third critical value is the absorbance increase threshold when the nitro or cyano side reaction is triggered;

[0074] The partial pressure of the by-product is detected to exceed the fourth critical value, and the fourth critical value is the pressure value when the hydrogen partial pressure detected by the online mass spectrometer exceeds the chain reaction trigger threshold;

[0075] Specifically, these determination conditions can acutely capture the signs of side reactions, such as an increase in the absorbance of by-products or an increase in the hydrogen partial pressure, which helps to take timely measures to inhibit the occurrence of side reactions and improve the selectivity of the reaction and the purity of the product.

[0076] Among them, the numerical relationship between the first preset threshold and the second preset threshold is: 0.4 ≤ < ≤ 0.6.

[0077] Specifically, the first preset threshold and the second preset threshold need to be calibrated through experiments. In the first step, an activity recovery scenario is carried out, and catalyst deactivation conditions are artificially induced: Condition 1: Add an excessive amount of Na + (Na / K = 3:1), and lower the pH to 9.5 (simulating the accumulation of acidic by-products). Condition 2: Add strong acid (such as 0.1 M HCl) until the pH = 9.0 to trigger the deactivation of tert-butoxide. Then, a side reaction inhibition scenario is carried out: Artificially trigger side reactions: Condition 1: Raise the temperature to 80 °C (inducing the side reaction of nitro reduction to amines). Condition 2: Add an excessive amount of cyanide substrate (triggering the hydrolysis of cyanide to form carboxylic acid). In the second step, data collection and calculation of the co-catalytic efficiency (η) are carried out; The monitored parameters include the conversion rate of functional groups (online infrared), the ratio of Na + / K + ratio (ion chromatography), pH (online pH meter), absorbance of by-products (ultraviolet spectrum), hydrogen partial pressure (online mass spectrometry), and the co-catalytic efficiency (η) is calculated through the above formula; In the third step, draw the change curve of η with time, manually mark the activity deactivation points (such as the stagnation of the conversion rate) and the side reaction trigger points (such as the appearance of by-product peaks), and perform ROC curve analysis: Calculate the sensitivity (true positive rate) and specificity (true negative rate) of different combinations of the first preset threshold and the second preset threshold, and select the best segmentation point. The experimental data is shown in Table 1:

[0078] Table 1

[0079]

[0080] As can be seen from Table 1, when η < 0.55, the system determines it as an activity recovery scenario (sensitivity 92%, specificity 85%). When η < 0.45 and the by-product signal exceeds the limit, it is determined as a side reaction inhibition scenario (sensitivity 88%, specificity 80%). Then, ±5% random noise is introduced to simulate detection errors, and it is verified that the threshold stability is good. Therefore, the numerical relationship between the first preset threshold and the second preset threshold is: 0.4 ≤ < ≤ 0.6.

[0081] Furthermore, before the kinetic data of the organic synthesis reaction system is obtained in real time, the following steps are also included:

[0082] Pre-scan the substrate molecule to obtain the type of substrate functional groups, the molecular weight of the substrate, and the number of substituents;

[0083] Specifically, use online Raman spectroscopy or infrared spectroscopy to pre-scan the substrate, and determine the type of functional groups through a characteristic peak matching database (such as the above nitro: 1520 - 1550 cm -1 , cyano: 2230 - 2240 cm -1 , carbonyl: 1700 - 1750 cm -1 ); Analyze the molecular weight of the substrate in real-time through online gel permeation chromatography (GPC), accurate to ±5 Da; Use pre-experiments of nuclear magnetic resonance hydrogen spectrum to identify the number of substituents. For example, the number of substituents on the benzene ring is judged by the ortho / para peak splitting pattern.

[0084] According to the type of substrate functional groups, the molecular weight of the substrate, and the number of substituents, determine whether it has the substrate structure characteristics;

[0085] Specifically, if the type of substrate functional groups contains ≥1 nitro (-NO2), cyano (-CN) or sulfonic acid group (-SO3H), and the molecular weight > 150 Da, it is determined to be a strong electron-withdrawing type; if the substrate molecular weight > 300 Da and the number of substituents ≥ 3, it is determined to be a steric hindrance type; if it meets at least one of the strong electron-withdrawing type and the steric hindrance type, it is determined to have the substrate structure characteristics, otherwise, it is determined not to have the substrate structure characteristics.

[0086] Before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included:

[0087] If it does not have the substrate structure characteristics, take the first initial value calibrated by the correlation experiment of by-product concentration and pH value as the first critical value, take the second initial value determined by the corresponding relationship between the sodium / potassium ratio gradient experiment and the change in conductivity as the second critical value, take the third initial value determined by the linear calibration curve of by-product concentration and absorbance as the third critical value, and take the fourth initial value calibrated by the kinetic experiment of hydrogen partial pressure and side reaction rate as the fourth critical value.

[0088] Specifically, determine the first initial value through an accelerated experiment, that is, when the acidic by-product (such as carboxylic acid) accumulates to 0.1 M, sodium tert-butoxide is inactivated due to protonation (generating t-BuOH), and the pH value at this time is the first initial value, which can be selected as pH = 6.5; Determine the second initial value through the change in ion association degree caused by the imbalance of the sodium / potassium ratio. For example, when Na + is in excess, [Na(OR)] is formed +The associated complex has a significantly increased second initial value of conductivity, which can be optionally an increase in conductivity of 20%; through the absorbance of by-product nitrobenzene (1520 cm -1 ), or benzonitrile (2240 cm -1 ), the absorbance is linearly calibrated with the concentration, and 5% corresponds to a by-product concentration ≥ 0.05 M. Therefore, the third initial value is an increase in absorbance of 5%; through in-situ high-pressure mass spectrometry (such as Hiden HPR-20) monitoring, when the dehydrogenation / decarboxylation side reaction rate exceeds the fourth initial value, it is > 50% of the main reaction, and the fourth initial value is a H2 partial pressure of 10 kPa.

[0089] S3. According to the catalytic scenario category, trigger the dynamic adjustment of the injection of sodium tert-butoxide and potassium tert-butoxide into the reaction system until the reaction is completed;

[0090] The triggering of the dynamic adjustment of the injection of sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category includes the following steps:

[0091] S31. If the catalytic scenario category is the activity recovery scenario, trigger the first adjustment strategy. The first adjustment strategy is to supplement potassium tert-butoxide based on the molar concentration ratio of sodium ions and potassium ions in the reaction system and adjust its molar proportion to the first preset interval to maintain catalytic activity; the first preset interval is the minimum potassium ion proportion threshold required to restore catalytic activity;

[0092] Specifically, the first adjustment strategy is a strategy to adjust the ion ratio by supplementing potassium tert-butoxide to restore catalytic efficiency when the catalyst activity decreases due to the imbalance of sodium / potassium ion ratio or the accumulation of acidic by-products. The molar proportion of potassium ions needs to be adjusted to the first preset interval of 40% - 50% (i.e., K + / (Na + +K + ) = 0.4 - 0.5).

[0093] Experiments show that when the proportion of K + is < 40%, the deprotonation ability of the catalyst for the substrate decreases by more than 50%; when it is > 50%, potassium salt precipitation is induced (related to the dielectric constant of the solvent).

[0094] Optionally, the experiment to determine the first preset interval is as follows: Reaction system: Substrate: α-methylation reaction of acetophenone (0.1 M) (model reaction); Catalyst: Sodium / potassium tert-butoxide mixture, with a total concentration fixed at 0.05 M; Solvent: Tetrahydrofuran (THF, ε = 7.5); Reaction conditions: 25°C, stirring at 500 rpm, nitrogen protection, reaction time 4 hours. Experimental grouping: Prepare catalyst solutions with different proportions of K + (30%, 35%, 40%, 45%, 50%, 55%), and each group is repeated 3 times. Control group: Pure sodium tert-butoxide (K+ with a proportion of 0%) and pure potassium tert-butoxide (K + with a proportion of 100%). Detection method: On-line infrared spectroscopy: Monitor the change in the area of the carbonyl peak (1710 cm -1 ), and calculate the conversion rate. Turbidity sensor: Real-time detection of the solution turbidity (NTU) to judge the precipitation of potassium salt. Ion chromatograph: Verify the consistency between the actual proportion of sodium / potassium ions and the theoretical value (error < ±2%).

[0095] The relationship data between the catalytic activity (conversion rate) and the proportion of K + is shown in Table 2 as follows:

[0096] Table 2

[0097]

[0098] As can be seen from Table 2, the activity is the best in the range of 40% - 50%: the conversion rate is stable at 99% - 103%, significantly higher than other ranges. When the proportion of K + is less than 40%, the activity decreases. When the proportion of K + is greater than 50%, the activity decreases. When it is 55%, due to the local precipitation of potassium salt (turbidity NTU > 5), the activity drops to 89%. Among them, it should be noted that when it is pure K + , the conversion rate of 42.5% is higher than 40.0% in the range of 40% - 50%, but the co-catalysis (K + 40% - 50%) is still selected based on the salting-out risk and cost considerations in industrial production.

[0099] Then, the critical point of potassium salt precipitation is verified, and the experimental data are shown in Table 3 as follows:

[0100] Table 3

[0101]

[0102] As can be seen from Table 3, the critical point of precipitation is 50%: when the proportion of K + is ≥50%, the turbidity increases significantly (NTU > 5), indicating that potassium tert-butoxide begins to precipitate. The safe range (the first preset range) is 40% - 50%: within this range, the solution remains clear, ensuring homogeneous catalytic conditions. Based on this, the first preset range is selected as 40% - 50%.

[0103] S32. If the catalytic scenario category is the side reaction inhibition scenario, trigger the second adjustment strategy, which is to increase the molar proportion of potassium tert-butoxide to a second preset range and simultaneously inhibit the addition amount of sodium tert-butoxide to a third preset range; the second preset range is the lowest potassium ion proportion threshold required to inhibit the side reaction path, and the third preset range is the lowest necessary amount to maintain the stabilizing effect of sodium ions on the transition state; wherein, the lower limit of the second preset range is higher than the upper limit of the first preset range.

[0104] Specifically, the experiment for determining the second preset range is as follows: Knoevenagel condensation of benzaldehyde and ethyl cyanoacetate (main reaction) and hydrolysis of cyanide to form carboxylic acid (side reaction); catalyst: sodium / potassium tert-butoxide mixture, total concentration 0.05 M; solvent: THF (ε = 7.5), temperature 25°C, stirring rate 500 rpm, reaction time 6 hours. Experimental grouping: Second interval verification group: Fix the Na + proportion at 15%, and adjust the K + proportion to 50%, 60%, 70%, 80%; Third interval verification group: Fix the K + proportion at 65%, and adjust the Na + proportion to 5%, 10%, 15%, 20%; Control group: pure sodium tert-butoxide (K + 0%, Na + 100%) and pure potassium tert-butoxide (K + 100%, Na + 0%). Detection methods: HPLC: Quantify the concentrations of the main product (condensation product) and the by-product (carboxylic acid); on-line mass spectrometry: Monitor the hydrogen partial pressure (indicator of the chain side reaction); in-situ infrared spectroscopy: Detect the concentration change of the enol intermediate (transition state); turbidity sensor: Record the precipitation state of the potassium salt (NTU value). The experimental data of the inhibitory effect of different K + proportions on the side reaction are shown in Table 4:

[0105] Table 4

[0106]

[0107] As can be seen from Table 4, the inhibition of side reactions is most effective when the K + proportion is 60% - 70%: the concentration of the by-product decreases from 12 mmol / L to 2 mmol / L (a decrease of 83%); the H2 partial pressure decreases from 8.5 kPa to 1.8 kPa (a decrease of 79%). Precipitation is triggered when it exceeds 70%: turbidity > 5 NTU leads to a decrease in activity, and the yield decreases from 89% to 72%.

[0108] The experimental data of the stabilization of the transition state by different Na + are shown in Table 5:

[0109] Table 5

[0110]

[0111] As can be seen from Table 5, when the proportion of Na + is 10% - 20%, the transition state is the most stable, the concentration of the enol intermediate reaches the peak value (215 - 230 a.u.), and the activation energy is the lowest; when it is lower than 10%, the concentration of the intermediate decreases by 45%, and the activation energy increases by 15 kJ / mol, resulting in a sharp drop in the yield.

[0112] In summary, choosing the second preset interval as 60% - 70% and the third preset interval as 10% - 20% is an optimal balance interval based on the inhibition of side reactions and the stability of the transition state.

[0113] Specifically, the supplementary addition system uses a dual-channel high-precision metering pump to store sodium tert-butoxide and potassium tert-butoxide respectively. The control and supplementary addition logic of the metering pump is as described in the regulation method proposed in this application, and the on-line monitoring device is linked with the supplementary addition system; the data flow architecture of the on-line monitoring device and the supplementary addition system is that the input layer includes on-line infrared (conversion rate), ion chromatography (Na + / K + concentration), mass spectrometry (H2 partial pressure) (it should be noted that: on-line mass spectrometer or gas chromatography combined with hydrogen flame ionization detector), pH meter, and conductivity meter. The processing layer includes a central controller that executes control algorithms (PID or rule library). The output layer includes at least a metering pump, and may also include a temperature regulator and a stirring rate controller.

[0114] Through the on-line regulation of the synergistic catalysis of sodium tert-butoxide / potassium, this embodiment achieves the following technical effects: First, by balancing the sodium / potassium ion ratio, avoiding the association inactivation of sodium salts or the precipitation of potassium salts, maintaining a homogeneous catalytic environment, and by replenishing potassium tert-butoxide (K + with a proportion of 40% - 50%) in real time, in addition, restoring the catalytic activity; due to the enhanced alkalinity of the system with a high K + proportion, blocking the acid-catalyzed path and the free radical chain reaction, by increasing the potassium ion proportion to 60% - 70%, the concentration of by-products decreases, and the hydrogen partial pressure drops, effectively inhibiting side reactions; moreover, maintaining the sodium ion proportion at 10% - 20%, the peak value of the enol intermediate concentration increases, and the activation energy decreases, achieving the stabilization of the transition state. In summary, through the technical solution proposed in this application, the main reaction rate can be increased by dynamically restoring the catalytic activity; the product purity can be improved by inhibiting the side reaction path, avoiding the precipitation or inactivation of the catalyst, enhancing the stability of the reaction system, and also forming a closed-loop control, reducing manual intervention, and realizing the standardization of process repeatability.

[0115] Example 2

[0116] Based on Example 1, this example proposes a more adaptable scenario to avoid out-of-control side reactions, cover a wider range of complex solvents and reaction conditions, and achieve higher control precision.

[0117] In a preferred embodiment, the dynamic adjustment of injecting sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category includes the following steps:

[0118] If the catalytic scenario category is simultaneously determined to be an activity recovery scenario and a side reaction inhibition scenario, the second adjustment strategy is preferentially triggered.

[0119] Further, before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included:

[0120] Calculate the side reaction risk level based on the by-product partial pressure and the reaction temperature;

[0121] The step of preferentially triggering the second adjustment strategy when the catalytic scenario category is simultaneously determined to be an activity recovery scenario and a side reaction inhibition scenario includes the following steps:

[0122] If the side reaction risk level is greater than the first preset level, then if the catalytic scenario category is simultaneously determined to be an activity recovery scenario and a side reaction inhibition scenario, the second adjustment strategy is preferentially triggered.

[0123] Specifically, when the activity recovery scenario and the side reaction inhibition scenario are both satisfied, K is preferentially increased + To 60 - 70% (the second preset interval). Side reaction risk level: Calculated based on the product of the by-product partial pressure (such as H2) and the temperature (risk level = partial pressure (kPa) × temperature (°C) / 100). Since the side reaction rate generally follows that an increase in partial pressure (such as H2 accumulation) and an increase in temperature will both accelerate the side reaction. Through data fitting in Table 3, when the risk level > 2.0 (such as H2 partial pressure 15 kPa × 25°C / 100 = 3.75), the side reaction rate exceeds the main reaction by 30%.

[0124] This embodiment avoids the lag of first restoring activity and then inhibiting side reactions (such as adding K when acidic by-products accumulate + which may simultaneously trigger an H2 explosion), preferentially blocks the free radical chain reaction, improves the product purity. At the same time, the risk level is dynamically quantified, overcoming misjudgment caused by a single parameter (such as only the H2 partial pressure), avoiding the risk of out-of-control side reactions, and improving safety.

[0125] Further, the method further includes the following steps:

[0126] Obtain the solubility of potassium tert-butoxide and the solvent dielectric constant in the reaction system in real time;

[0127] After the second adjustment strategy is preferentially triggered, the following steps are further included:

[0128] After the second adjustment strategy is executed for a first preset time period, re-measuring the by-product partial pressure;

[0129] If the by-product partial pressure is still higher than the side reaction risk threshold, the side reaction is determined to be uncontrolled, and the potassium tert-butoxide injection rate is increased to a value close to but not exceeding an upper limit, and the adjustment time is extended; wherein the upper limit is the maximum safe injection rate dynamically calculated based on the solubility of potassium tert-butoxide in the reaction system and the dielectric constant of the solvent; the side reaction risk threshold is dynamically calibrated by the kinetic relationship between the detected by-product partial pressure and the chain side reaction rate.

[0130] Specifically, the solubility of potassium tert-butoxide in THF is obtained by the formula S (g / L) = 0.012 × ε (dielectric constant) + 0.5 (experimental fitting formula, S = 0.14 g / L when ε = 7.5). Upper limit: injection rate = S × reaction volume × 0.8 (safety factor), for example, the upper limit of a 5L system = 0.14 × 5 × 0.8 = 0.56 g / min. Dynamic adjustment: When the re-measured by-product partial pressure (H2 partial pressure) is greater than 10 kPa (for example, the side reaction risk threshold dynamically calibrated by the kinetic relationship between the detected hydrogen partial pressure and the chain side reaction rate is 10), inject K at 0.9 times the upper limit. + The turbidity level (NTU < 5) is monitored simultaneously. The side reaction risk threshold is calibrated by measuring the side reaction rate at multiple partial pressure points (e.g., 5 kPa, 10 kPa, and 15 kPa). The risk threshold is determined by fitting the partial pressure-rate relationship using the Arrhenius equation (for example, the side reaction risk threshold is a partial pressure of 10 kPa when the rate is > 30% of the primary reaction).

[0131] This embodiment monitors whether the side reaction is under control in real time after executing the second adjustment strategy, and dynamically adjusts when it is not under control, thereby avoiding potassium salt precipitation, maintaining homogeneous catalysis, and suppressing side reactions.

[0132] Furthermore, after retesting the by-product partial pressure, the method further comprises the following steps:

[0133] If the by-product partial pressure drops below the side reaction risk threshold, the side reaction is determined to be under control;

[0134] Calculate the controlled cooperative catalytic efficiency;

[0135] If the controlled cooperative catalytic efficiency is still less than the first preset threshold, the first adjustment strategy is triggered; if the controlled cooperative catalytic efficiency is greater than or equal to the first preset threshold, the current catalyst ratio is maintained.

[0136] Further, before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included:

[0137] If the substrate structural features are present, according to the substrate structural features, retrieve and traverse the historical data in the historical reaction template library that is consistent with the substrate functional group type, molecular weight, and number of substituents, and match the corresponding first adjustment coefficient, second adjustment coefficient, third adjustment coefficient, and fourth adjustment coefficient;

[0138] Take the product of the first adjustment coefficient and the first initial value as the first critical value, take the product of the second adjustment coefficient and the second initial value as the second critical value, take the product of the third adjustment coefficient and the third initial value as the third critical value, and take the product of the fourth adjustment coefficient and the fourth initial value as the fourth critical value.

[0139] Specifically, pre-scan the substrate molecules through on-line spectroscopy (such as infrared, Raman) or mass spectrometry, and extract the following characteristic parameters: functional group type: such as carbonyl, nitro, cyano, etc. (identified by characteristic absorption peaks), molecular weight: accurately determined by mass spectrometry, number of substituents: analyzed by nuclear magnetic resonance (NMR) or two-dimensional chromatography; retrieve the historical database: according to the substrate characteristic parameters (such as nitro functional group, molecular weight 200 - 250, single substituent), screen the historical data in the historical reaction template library that meet the following conditions: the same functional group type, molecular weight deviation within ±5%, and the number of substituents is the same. It should be noted that if a completely new substrate is encountered, that is, if there is no matching historical data, use the initial critical values (the first initial value, the second initial value, the third initial value, the fourth initial value) and dynamically calibrate according to real-time feedback.

[0140] Exemplarily, taking the catalytic reaction with nitrobenzene ethylene (i.e., molecular weight 149.16, containing nitro functional group, single substituent) as the substrate as an example, 3 groups of historical data of similar reactions are matched in the historical template library, and the adjustment coefficients are extracted as shown in Table 6:

[0141] Table 6

[0142]

[0143] From Example 1, the first initial value is 6.5, the second initial value is 15%, the third initial value is 0.3, and the fourth initial value is 50 kPa. The corrected first critical value is 0.92×6.5 = 5.98; the second critical value is 1.11×15% = 16.65%; the first critical value is 0.88×0.3 = 0.264; the fourth critical value is 1.18×50 = 59 kPa.

[0144] In this embodiment, considering that strong electron-withdrawing characteristics can lead to differences in the stability of transition states and the presence of nitro functional groups can accelerate the formation of acidic by-products, it is necessary to give an early warning by reducing the pH critical value (α1 < 1). The monosubstituted structure has a weak coordination ability with sodium / potassium ions, so it is necessary to improve the monitoring sensitivity of conductivity (α2 > 1). Through the linkage adjustment of α3 (absorbance correction) and α4 (partial pressure correction), while suppressing the nitro side reaction, a higher hydrogen partial pressure is allowed to maintain the main reaction rate. The mean processing of historical data can eliminate the accidental errors of a single experiment and ensure the reliability of the adjustment coefficient.

[0145] Example 2

[0146] Based on Example 1, this embodiment proposes an on-line regulation system for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis, which is used to realize the on-line regulation method for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis as described in Example 1, including:

[0147] A calculation module, which is configured to obtain the kinetic data of the organic synthesis reaction system in real time and obtain the synergistic catalysis efficiency of sodium tert-butoxide and potassium tert-butoxide; the kinetic data includes the conversion rate of functional groups in the reaction process, as well as the pH value and ion concentration of the reaction solution; the synergistic catalysis efficiency is a quantitative index comprehensively calculated based on the conversion rate of functional groups, the ratio of sodium / potassium ion concentrations, the pH value, and the total ion concentration;

[0148] A judgment module, which is configured to determine the catalytic scenario category according to the kinetic data and the synergistic catalysis efficiency of sodium tert-butoxide and potassium tert-butoxide, and the catalytic scenario category includes an activity recovery scenario and a side reaction inhibition scenario;

[0149] A control module, which is configured to trigger a dynamic adjustment of injecting sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category until the reaction is completed;

[0150] The control module is further configured to, if the catalytic scenario category is the activity recovery scenario, trigger a first adjustment strategy, which is to supplement potassium tert-butoxide based on the molar concentration ratio of sodium ions and potassium ions in the reaction system and adjust its molar proportion to a first preset interval to maintain the catalytic activity; the first preset interval is the minimum potassium ion proportion threshold required to restore the catalytic activity;

[0151] The control module is further configured to trigger a second adjustment strategy if the catalytic scenario category is the side reaction inhibition scenario. The second adjustment strategy is to increase the molar proportion of potassium tert-butoxide to a second preset range while suppressing the addition amount of sodium tert-butoxide to a third preset range. The second preset range is the lowest potassium ion proportion threshold required to inhibit the side reaction path, and the third preset range is the lowest necessary amount to maintain the stabilizing effect of sodium ions on the transition state.

[0152] In this article, specific examples are used to elaborate on the principles and implementation manners of the present application. The description of the above embodiments is only used to help understand the method and its core idea of the present application. The above are only the preferred implementation manners of the present application. It should be noted that due to the limited nature of literal expression and objectively infinite specific structures, for those of ordinary skill in the art, without departing from the principles of the present invention, several improvements, embellishments or changes can be made, or the above technical features can be combined in an appropriate manner; these improvements, embellishments, changes or combinations, or directly applying the concept and technical solution of the invention to other occasions without improvement, should all be regarded as the protection scope of the present application.

Claims

1. An on-line regulation method for the co-catalyzed organic synthesis by sodium tert-butoxide / potassium, characterized in that, It includes the following steps: Obtain the kinetic data of the organic synthesis reaction system in real time, and obtain the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide; the kinetic data includes the functional group conversion rate during the reaction process, as well as the pH value and ion concentration of the reaction solution; the synergistic catalytic efficiency is a quantitative index comprehensively calculated based on the functional group conversion rate, the sodium / potassium ion concentration ratio, the pH value, and the total ion concentration; Determine the catalytic scenario category according to the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, and the catalytic scenario category includes an activity recovery scenario and / or a side reaction inhibition scenario; According to the catalytic scenario category, trigger the dynamic adjustment of injecting sodium tert-butoxide and potassium tert-butoxide into the reaction system until the reaction is completed; The triggering of the dynamic adjustment of injecting sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category includes the following steps: If the catalytic scenario category is the activity recovery scenario, trigger the first adjustment strategy, and the first adjustment strategy is to replenish potassium tert-butoxide based on the molar concentration ratio of sodium ions and potassium ions in the reaction system and adjust its molar proportion to the first preset interval to maintain the catalytic activity; the first preset interval is the minimum potassium ion proportion threshold required to restore the catalytic activity; If the catalytic scenario category is the side reaction inhibition scenario, trigger the second adjustment strategy, and the second adjustment strategy is to increase the molar proportion of potassium tert-butoxide to the second preset interval while suppressing the addition amount of sodium tert-butoxide to the third preset interval; the second preset interval is the minimum potassium ion proportion threshold required to inhibit the side reaction path, and the third preset interval is the minimum necessary amount to maintain the stabilizing effect of sodium ions on the transition state; wherein, the lower limit of the second preset interval is higher than the upper limit of the first preset interval.

2. The online regulation method for the co-catalyzed organic synthesis by sodium / potassium tert-butoxide according to claim 1, characterized in that, The obtaining of the kinetic data of the organic synthesis reaction system in real time includes the following steps: Monitor the change in the vibration peak intensity of carbonyl, nitro or cyano functional groups in the reaction solution within the corresponding wave number range to obtain the functional group conversion rate; Detect the molar concentration of sodium ions and potassium ions in the reaction solution, calculate the sodium / potassium ion concentration ratio; and respectively obtain the pH value and the total ion concentration of the reaction solution; the total ion concentration includes the ion concentrations of sodium ions, potassium ions and side reactants.

3. The online regulation method for the co-catalyzed organic synthesis by sodium / potassium tert-butoxide according to claim 1, characterized in that, The determination of the catalytic scenario category according to the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide includes the following steps: If the co-catalysis efficiency is less than the first preset threshold , and when any of the following conditions is satisfied, it is determined as the active recovery scenario: The sodium / potassium ion concentration ratio is greater than 1:1; The pH value of the reaction solution is less than the first critical value and the conductivity increase exceeds the second critical value; the first critical value is the pH critical value when the accumulation of acidic by-products causes the catalyst to deactivate; the second critical value is the conductivity increase threshold when the sodium / potassium ion concentration ratio is out of balance; If the co-catalytic efficiency is less than the second preset threshold , and when any of the following conditions is met, it is determined as the side reaction inhibition scenario: It is detected that the absorbance increase of the nitro functional group or the cyano functional group exceeds the third critical value; the third critical value is the absorbance increase threshold when the nitro or cyano side reaction is triggered; It is detected that the partial pressure of the by-product exceeds the fourth critical value, and the fourth critical value is the pressure value when the hydrogen partial pressure detected by the online mass spectrometer exceeds the chain side reaction trigger threshold; Among them, the numerical relationship between the first preset threshold and the second preset threshold is: 0.4 ≤ < ≤ 0.

6.

4. The online regulation method for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis according to claim 1, wherein The method of triggering the dynamic adjustment of injecting the corresponding sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category includes the following steps: If the catalytic scenario category is determined to be both an activity recovery scenario and a side reaction inhibition scenario, the second adjustment strategy is triggered first.

5. The online regulation method for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis according to claim 4, wherein The method further comprises the following steps: Real-time acquisition of the solubility of potassium tert-butoxide and the dielectric constant of the solvent in the reaction system; After the second adjustment strategy is preferentially triggered, the following steps are further included: After the second adjustment strategy is executed for a first preset time period, re-measuring the by-product partial pressure; If the by-product partial pressure is still higher than the side reaction risk threshold, the side reaction is determined to be uncontrolled, and the potassium tert-butoxide injection rate is increased to a value close to but not exceeding an upper limit, and the adjustment time is extended; wherein the upper limit is the maximum safe injection rate dynamically calculated based on the solubility of potassium tert-butoxide in the reaction system and the dielectric constant of the solvent; the side reaction risk threshold is dynamically calibrated by the kinetic relationship between the detected by-product partial pressure and the chain side reaction rate.

6. The on-line regulation method for the synergistic catalysis of sodium tert-butoxide / potassium in organic synthesis according to claim 4, characterized in that, Before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included: Calculate the side reaction risk level based on the by-product partial pressure and reaction temperature; If the catalytic scenario category is determined to be both an activity recovery scenario and a side reaction suppression scenario, the second adjustment strategy is preferentially triggered, including the following steps: If the side reaction risk level is greater than the first preset level, and if the catalytic scenario category is simultaneously determined to be an activity recovery scenario and a side reaction suppression scenario, the second adjustment strategy is triggered first.

7. The online regulation method for the co-catalyzed organic synthesis by sodium tert-butoxide / potassium according to claim 5, characterized in that, After the re-measurement of the by-product partial pressure, the following steps are also included: If the by-product partial pressure drops below the side reaction risk threshold, the side reaction is determined to be under control; Calculate the controlled cooperative catalytic efficiency; If the controlled cooperative catalytic efficiency is still less than the first preset threshold, the first adjustment strategy is triggered; if the controlled cooperative catalytic efficiency is greater than or equal to the first preset threshold, the current catalyst ratio is maintained.

8. The online regulation method for the co-catalyzed organic synthesis by sodium tert-butoxide / potassium according to claim 4, wherein Before the real-time acquisition of kinetic data of the organic synthesis reaction system, the following steps are also included: Pre-scan the substrate molecule to obtain the substrate functional group type, substrate molecular weight and number of substituents; Determining whether the substrate has structural characteristics based on the substrate functional group type, substrate molecular weight, and number of substituents; Before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included: If the substrate does not have the structural characteristics, the first initial value calibrated by the correlation experiment between the by-product concentration and the pH value is used as the first critical value, the second initial value determined by the correspondence between the sodium / potassium ratio gradient experiment and the conductivity change is used as the second critical value, the third initial value determined by the linear calibration curve of the by-product concentration and the absorbance is used as the third critical value, and the fourth initial value calibrated by the kinetic experiment of the hydrogen partial pressure and the side reaction rate is used as the fourth critical value.

9. The online regulation method for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis according to claim 8, characterized in that, Before determining the catalytic scenario category based on the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, the following steps are included: If having the substrate structural features, according to the substrate structural features, retrieve and traverse the historical data in the historical reaction template library that is consistent with the substrate functional group type, molecular weight, and number of substituents, and match the corresponding first adjustment coefficient, second adjustment coefficient, third adjustment coefficient, and fourth adjustment coefficient; Take the product of the first adjustment coefficient and the first initial value as the first critical value, take the product of the second adjustment coefficient and the second initial value as the second critical value, take the product of the third adjustment coefficient and the third initial value as the third critical value, and take the product of the fourth adjustment coefficient and the fourth initial value as the fourth critical value.

10. An online regulation system for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis, which is used to implement the online regulation method for the synergistic catalysis of sodium / potassium tert-butoxide in organic synthesis according to any one of claims 1-9, characterized in that, Including: A calculation module, the calculation module is configured to obtain the kinetic data of the organic synthesis reaction system in real time and obtain the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide; the kinetic data includes the functional group conversion rate in the reaction process, as well as the pH value and ion concentration of the reaction solution; the synergistic catalytic efficiency is a quantitative index comprehensively calculated based on the functional group conversion rate, sodium / potassium ion concentration ratio, pH value, and total ion concentration; A judgment module, the judgment module is configured to determine the catalytic scenario category according to the kinetic data and the synergistic catalytic efficiency of sodium tert-butoxide and potassium tert-butoxide, and the catalytic scenario category includes an activity recovery scenario and / or a side reaction inhibition scenario; A control module, the control module is configured to trigger a dynamic adjustment of the injection of sodium tert-butoxide and potassium tert-butoxide into the reaction system according to the catalytic scenario category until the reaction is completed; The control module is further configured to, if the catalytic scenario category is the activity recovery scenario, trigger a first adjustment strategy, and the first adjustment strategy is to supplement potassium tert-butoxide based on the molar concentration ratio of sodium ions and potassium ions in the reaction system and adjust its molar proportion to a first preset interval to maintain the catalytic activity; the first preset interval is the minimum potassium ion proportion threshold required to restore the catalytic activity; The control module is further configured to, if the catalytic scenario category is the side reaction inhibition scenario, trigger a second adjustment strategy, and the second adjustment strategy is to increase the molar proportion of potassium tert-butoxide to a second preset interval while suppressing the addition amount of sodium tert-butoxide to a third preset interval; the second preset interval is the minimum potassium ion proportion threshold required to inhibit the side reaction path, and the third preset interval is the minimum necessary amount to maintain the stabilizing effect of sodium ions on the transition state; wherein, the lower limit of the second preset interval is higher than the upper limit of the first preset interval.

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