A two-phase regulated method for the preparation of benzothiophene

Abstract

This invention discloses a two-phase controlled method for preparing benzothiophene, relating to the field of liquid-liquid two-phase reaction process control and organic synthesis technology. The method involves adding thiophene, 2,5-dimethoxytetrahydrofuran, and an acidic ionic liquid catalyst to a reaction vessel to establish a liquid-liquid two-phase reaction system in which the organic and ionic liquid phases coexist. During the reaction, the volume fractions of the two phases and the product distribution coefficient are quantitatively characterized at set measurement intervals. When the volume fractions of the two phases or the product distribution coefficient deviate from the target range, feed control, temperature control, or stirring control are implemented to bring the system back to the target range. The reaction is terminated after the product concentration stability criterion and the distribution coefficient criterion are met, and the benzothiophene product is obtained through phase separation and distillation. This invention can improve the process control capability and product acquisition stability of liquid-liquid two-phase reaction systems and is suitable for the controllable synthesis of benzothiophene.

Description

Technical Field

[0001] This invention relates to the field of liquid-liquid two-phase reaction process control and organic synthesis technology, specifically a two-phase controlled method for preparing benzothiophene. Background Technology

[0002] Benzothiophene, as an important sulfur-containing heterocyclic compound, has high application value in fine chemicals, pharmaceutical intermediates, and functional materials. In the preparation of benzothiophene using a reaction system constructed with thiophene, 2,5-dimethoxytetrahydrofuran, and an acidic ionic liquid catalyst, the system typically exhibits a liquid-liquid two-phase reaction state where an organic phase and an ionic liquid phase coexist. This type of two-phase system not only affects the contact mode between the substrate and the catalyst but also further influences the distribution of the target product in different phases, the degree of reaction progression, and the phase separation and product acquisition after the reaction. Current research on the preparation process of benzothiophene focuses primarily on reaction formulation, catalyst selection, or final product separation, while insufficient attention is paid to the dynamic characterization and closed-loop control of the liquid-liquid two-phase behavior during the reaction. Especially in two-phase systems, relying solely on empirical control methods for feeding, heating, or stirring often makes it difficult to adjust the proportions of the organic and ionic liquid phases and the distribution of the target product in both phases based on the real-time state of the system. This can easily lead to unstable phase contact, deviations from expected target product distribution, and difficulty in accurately determining the timing of reaction termination. Furthermore, in liquid-liquid two-phase reaction systems, the volume fractions of the two phases and the distribution coefficient of the target product typically change dynamically with the progress of the reaction, temperature variations, and component migration. Without corresponding quantitative characterization methods and control mechanisms, it is difficult to maintain the reaction process within a state range conducive to the formation and extraction of the target product, thus affecting product stability and process consistency. Therefore, how to construct a preparation method capable of quantitatively characterizing the liquid-liquid two-phase behavior in the benzothiophene preparation process and executing corresponding control actions when the volume fractions of the two phases and the product distribution coefficient deviate from the target range, thereby achieving closed-loop control of the reaction process and stable product acquisition, has become a pressing technical problem to be solved in this field. Summary of the Invention

[0003] The purpose of this invention is to provide a two-phase controlled method for preparing benzothiophene. By establishing a liquid-liquid two-phase reaction system, periodically quantifying the volume fractions of the two phases and the product distribution coefficient, and implementing control actions when deviating from the target range, a closed-loop control of the two-phase state and stable product acquisition are achieved during the benzothiophene preparation process. This solves the problems of existing technologies where the two-phase reaction process relies on empirical adjustment, the system state fluctuates significantly, and the product acquisition stability is insufficient. To achieve the above objective, this invention provides the following technical solution: A two-phase controlled method for preparing benzothiophene, comprising the following steps: S1, Establishing a two-phase reaction system: Thiophene, 2,5-dimethoxytetrahydrofuran, and an acidic ionic liquid catalyst are added to a reaction vessel to form a liquid-liquid two-phase reaction system in which the organic phase and the ionic liquid phase coexist; S2, Quantitative characterization of two-phase parameters: During the reaction process, the parameters are measured periodically... Periodic measurement of two-phase volume fraction and product distribution coefficient; S3, two-phase control closed loop: setting target range and When measured or When deviating from the target range, execute control actions to make and Return to the target range; S4, Phase separation and product acquisition: After the reaction is completed, the organic phase is separated and subjected to atmospheric or vacuum distillation to obtain the benzothiophene product.

[0004] Preferably, step S1 includes the following sub-steps: S1.1, setting the initial phase ratio: setting the initial two-phase volume fraction. And record the initial ionic liquid phase volume. relative to the initial organic phase volume S1.2 Feeding and Phase Formation: Add acidic ionic liquid catalyst, thiophene, and 2,5-dimethoxytetrahydrofuran to the reactor to form a liquid-liquid two-phase system; S1.3 Stirring Start-up: Control the initial stirring speed. To form a stable two-phase contact interface. Preferably, step S2 includes the following sub-steps: S2.1, setting the measurement period: S2.2, Calculation of volume fraction: at the measurement time Read and : S2.3, Calculation of distribution coefficients: at the measurement time The concentrations of benzothiophene in the organic phase and the ionic liquid phase were measured respectively. and Calculate the allocation coefficient using the following formula. : Preferably, the and The concentration was determined by gas chromatography or high-performance liquid chromatography and converted from peak area; , and The Preferably, the adjustment action of S3 includes phase volume fraction adjustment, and includes the following sub-steps: S3.1, low volume fraction compensation: when At the same time, increase the feed volume of the ionic liquid. and satisfy S3.2, High Volume Fraction Compensation: When At the same time, increase the feed volume of organic substrate. and satisfy S3.3 Update Calculation: After compensation, execute the next measurement time and update. Preferably, the regulating action of S3 includes temperature regulation, and when Adjust the reaction temperature. make Rebound, temperature adjustment range and maintain after temperature adjustment Then perform the next S2 measurement. Preferably, the adjustment action of S3 includes stirring control, specifically the stirring speed. , When deviating from the target range, the stirring speed adjustment amount is limited to [value missing]. Preferably, the termination criterion for the end of the reaction is a product concentration stability criterion, including the following sub-steps: S4.1, Calculation of concentration change: Calculate the concentration change in two consecutive measurements. S4.2 Termination Condition: When the condition is met... The reaction is considered complete at a certain time. Preferably, the phase separation in S4 is triggered by temperature adjustment, specifically by adjusting the reaction system to... and maintain The organic phase is collected after a stable phase interface is formed. Preferably, step S4 uses the distillation pressure used in vacuum distillation. , And the distillation reflux ratio .

[0005] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. By setting up a two-phase reaction system establishment step, this invention limits the initial two-phase volume fraction, initial phase volume, and initial stirring state, thereby achieving the effect of constructing a stable liquid-liquid two-phase contact interface at the beginning of the reaction, providing a clear basis for subsequent two-phase parameter measurement and control.

[0006] 2. By setting up a two-phase parameter quantification characterization step, the present invention continuously measures the volume fraction of the two phases and the product distribution coefficient in a measurement cycle, thereby transforming the two-phase state in the reaction process from empirical judgment to quantifiable characterization, and improving the clarity and repeatability of process monitoring.

[0007] 3. By setting up a two-phase control closed-loop step, the present invention performs feed control, temperature control and stirring control when the volume fraction of the two phases or the product distribution coefficient deviates from the target range, thereby achieving the effect of timely returning the reaction system to the target state range, which is beneficial to improving the stability and controllability of the reaction process.

[0008] 4. By setting a termination criterion based on the change in product concentration and the distribution coefficient, and combining it with temperature-triggered phase separation and distillation product acquisition steps, this invention improves the accuracy of reaction termination determination and the stability of product acquisition, which is beneficial for achieving closed-loop control and continuous implementation of the benzothiophene preparation process. Attached Figure Description

[0009] Figure 1 This is a schematic diagram of the overall process of the two-phase controlled benzothiophene preparation method of the present invention. Figure 2 This is a schematic diagram illustrating the steps involved in establishing the two-phase reaction system of the present invention; Figure 3 This is a schematic diagram of the two-phase parameter quantification characterization steps of the present invention; Figure 4 This is a schematic diagram of the two-phase volume fraction calculation logic of the present invention; Figure 5 This is a schematic diagram illustrating the logic for calculating the allocation coefficients in this invention; Figure 6 This is a schematic diagram of the two-phase control closed-loop steps of the present invention; Figure 7 This is a schematic diagram illustrating the termination criteria and phase separation and product acquisition steps of this invention; Figure 8 This is a schematic diagram of the interface state of the liquid-liquid two-phase reaction system of the present invention; Figure 9 This is a schematic diagram of the morphology of the benzothiophene product of the present invention; Figure 10 This is a schematic diagram of a partial surface structure of the benzothiophene product of the present invention. Detailed Implementation

[0010] 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. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0011] Please see Figures 1 to 10 This invention provides a technical solution: a two-phase controlled method for preparing benzothiophene. The method comprises four main steps: establishing a two-phase reaction system, quantitative characterization of two-phase parameters, closed-loop two-phase control, and phase separation and product acquisition. First, thiophene, 2,5-dimethoxytetrahydrofuran, and an acidic ionic liquid catalyst are added to a reactor to form a liquid-liquid two-phase reaction system where an organic phase and an ionic liquid phase coexist. Then, during the reaction, the volume fractions of the two phases and the product distribution coefficient are quantitatively characterized at set measurement cycles. When the volume fractions of the two phases or the product distribution coefficient deviate from the target range, corresponding control actions are executed to bring the system back to the target range. Finally, after meeting the termination criteria, phase separation is performed, and the obtained organic phase is subjected to atmospheric or vacuum distillation to obtain the benzothiophene product. Thus, this invention forms a complete closed-loop process control consisting of two-phase establishment, two-phase monitoring, two-phase control, and product output. In this invention, steps S1 and S2 together form the basis for subsequent closed-loop control. The purpose of step S1 is to establish a liquid-liquid two-phase reaction system with a clear initial two-phase ratio, initial phase volume, and initial stirring conditions, thus providing a starting benchmark for subsequent state monitoring. The purpose of step S2 is to transform the two-phase state changes during the reaction process into measurable, calculable, and comparable quantitative parameters, namely the two-phase volume fraction and product distribution coefficient. Only after establishing a characterizable two-phase system in step S1 and continuously obtaining the two-phase parameters in step S2 can the deviation judgment and control actions in step S3 have a basis for execution. Therefore, S1 and S2 are not simply preliminary steps, but rather the prerequisite foundation for the "two-phase control closed loop" of this invention.

[0012] I. S1, Establishment of the Two-Phase Reaction System: In this invention, step S1 is the establishment step of the two-phase reaction system. Its function is to: before the reaction begins, by setting the initial two-phase ratio, initial phase volume, and initial stirring state, so that thiophene, 2,5-dimethoxytetrahydrofuran, and the acidic ionic liquid catalyst form a liquid-liquid two-phase reaction system in the reaction vessel that can be used for subsequent quantitative monitoring and closed-loop control. Since the core of this invention is not simply to carry out the reaction, but to characterize and control the dynamic state of the two-phase system, the quality of the establishment of step S1 directly determines the effectiveness of the measurement of the two-phase parameters in the subsequent step S2, and the accuracy of the execution of the control actions in step S3. In one embodiment, step S1 specifically includes the following sub-steps: S1.1, Setting the Initial Phase Ratio: Setting the initial two-phase volume fraction. And record the initial ionic liquid phase volume. relative to the initial organic phase volume Among them, parameters This indicates the percentage of the ionic liquid phase in the total system volume at the start of the reaction; parameter Indicates the initial ionic liquid phase volume; parameter This represents the initial organic phase volume. In this invention, the initial two-phase volume fraction... Its constituent basis is reflected in the following relationship, namely, the initial ionic liquid phase volume. relative to the initial organic phase volume A joint decision. Setting it to 0.10–0.70 is beneficial for forming a system state in the initial stage of the reaction that possesses both a clear two-phase interface and maintains interphase contact. If If the concentration is too low, the proportion of the ionic liquid phase will be too small, which may result in insufficient volume of the catalyst phase, hindering the establishment of subsequent control space; if... If the concentration is too high, the organic phase ratio will be too low, which may weaken the two-phase contact characteristics of the system and affect the distribution of subsequent products in the organic phase. Therefore, this invention addresses this issue by... The constraints ensure that the initial two-phase system possesses both an identifiable basis for phase separation and an operational space for subsequent dynamic control. Furthermore, recording... and The purpose is not only to determine the volume scale of the two phases under the initial conditions, but also to provide initial reference values ​​for the periodic calculation of the volume fraction of the two phases in step S2. In other words, step S1 is not just about completing the feeding action, but about establishing a quantifiable and traceable initial state at the very beginning of the reaction.

[0013] S1.2, Feeding and Phase Formation: An acidic ionic liquid catalyst, thiophene, and 2,5-dimethoxytetrahydrofuran are added to the reactor to form a liquid-liquid two-phase system. The purpose of this step is to ensure that the system exhibits a coexistence of organic and ionic liquid phases at the start of the reaction through the preparation of the substrate and catalyst. "Phase formation" here refers to the formation of a liquid-liquid two-phase structure in the reactor that can be distinguished as an organic phase and an ionic liquid phase, and can maintain interphase contact under stirring. In this invention, the acidic ionic liquid catalyst serves as the main ionic liquid phase, while thiophene and 2,5-dimethoxytetrahydrofuran mainly constitute the organic phase component. By adding the above materials together to the reactor, the system can form a two-phase coexistence structure under initial conditions, rather than forming a single homogeneous system. The significance of this setup is that the volume fraction of the two phases measured in the subsequent S2 step... and product partition coefficient All of these are based on the existence of the liquid-liquid two-phase system. If a clear two-phase system cannot be formed in the initial stage, then the subsequent calculation of two-phase parameters and two-phase closed-loop control will lose their basis for implementation. S1.3, Stirring Start-up: Control the initial stirring speed. This is to form a stable two-phase contact interface. Among them, the parameters... This indicates the initial stirring speed at the start of the reaction. The purpose of setting the stirring speed at the start is to increase the contact between the organic phase and the ionic liquid phase without disrupting the coexisting structure, allowing subsequent reactions and component migrations to proceed under control. Maintaining the rpm range of 60 rpm to 300 rpm helps to enhance interphase contact and mass exchange while preserving the two-phase interface. If If the value is too low, there will be insufficient interphase contact, which is detrimental to the advancement of subsequent reactions and the stability of parameter measurements; if... If the temperature is too high, it may lead to excessively strong interface fluctuations, making it difficult for the two-phase state to stabilize in a short period of time, which is not conducive to the establishment of the initial state. Therefore, this invention addresses this issue by... The limitation allows for the formation of a stable two-phase contact interface in the initial stage of the reaction, characterized by "the existence of two clearly defined phases while maintaining effective contact." In a preferred embodiment of the invention, the output of step S1 is: having clearly defined initial two-phase volume fractions. Initial ionic liquid phase volume Initial organic phase volume and initial stirring speed The output of the liquid-liquid two-phase reaction system will be directly used as the input for step S2, for subsequent periodic measurement and calculation of two-phase parameters. From the perspective of step sequence, step S1 establishes the foundation for two-phase monitoring required by step S2 by setting the initial phase ratio, completing the feeding and phase formation, and initiating initial stirring. In other words, the output of step S1 is not simply a "reaction liquid," but a two-phase reaction system that can be continuously characterized and controlled by subsequent steps. This difference is a key distinction between this invention and conventional empirical operating methods. In summary, step S1, through the initial two-phase volume fraction... Setting, initial ionic liquid phase volume relative to the initial organic phase volume Recording, feeding phase formation and initial stirring speed The control of the system completed the establishment of the liquid-liquid two-phase reaction system, providing a clear, stable and traceable starting basis for the quantitative characterization of the two-phase parameters in the S2 step.

[0014] II. S2, Quantitative Characterization of Two-Phase Parameters: In this invention, step S2 is the quantitative characterization step for two-phase parameters. Its function is to periodically measure and calculate the volume fraction of the two phases and the product distribution coefficient in the liquid-liquid two-phase system according to a set measurement cycle during the reaction process. This transforms the two-phase state changes, which originally relied on empirical observation, into quantitative parameters with clear physical meaning, providing a basis for deviation judgment and control actions in the subsequent step S3. For this invention, step S2 is the key starting point for the true formation of the entire "two-phase control closed loop." Without step S2, the two-phase state can only rely on the operator's experience to judge, making it impossible to clearly determine whether the system deviates from the target range, or to objectively verify whether the control actions are effective. Therefore, the technical significance of step S2 is to further enhance the two-phase process from "observable" to "calculable, comparable, and controllable." In one embodiment, step S2 specifically includes the following sub-steps: S2.1, Measurement Cycle Setting: Measurement cycle... Among them, parameters This indicates the time interval between two consecutive measurements of two-phase parameters. Set the measurement period. The aim is to enable continuous tracking of changes in the volume fractions of the two phases and the product partition coefficients throughout the reaction process, rather than discrete observations at individual moments. This involves measuring the period... A monitoring interval of 1 to 20 minutes is beneficial for balancing monitoring frequency and operational burden. If If the measurement frequency is too high, it may increase the burden of sampling and detection; if... If the time is too long, it may lead to the two-phase states deviating from the target range and not being identified in time, thereby weakening the real-time performance of closed-loop control. Therefore, this invention addresses this issue by... The limitations of this process enable step S2 to possess continuous monitoring capabilities suitable for engineering implementation. S2.2, Volume Fraction Calculation: At the measurement time... Reading the phase volume of ionic liquid Volume of organic phase The volume fraction of the two phases is calculated using the following formula. : Among them, parameters Indicates the first Volume of the ionic liquid phase at the time of measurement; parameters Indicates the first Organic phase volume at the time of measurement; parameters Indicates the first The volume fraction of the two phases at the time of measurement. Using the above formula, the proportion of the ionic liquid phase in the entire two-phase system during the reaction can be quantitatively expressed. This parameter reflects whether the current two-phase ratio is still within a range favorable for reaction progression and product distribution. This is in contrast to the initial two-phase volume fraction in step S1. Correspondingly, Used to describe the dynamic changes of the system during the reaction propulsion process; in this invention, a configuration is provided. The technical objective is not simply to record phase volume changes, but to provide a basis for judging the adjustment actions of "low volume fraction compensation" or "high volume fraction compensation" in the subsequent S3 step. In other words, It is a core parameter that directly participates in closed-loop control determination. S2.3, Allocation coefficient calculation: at the measurement time... The concentrations of benzothiophene in the organic phase were measured respectively. Concentration of benzothiophene in ionic liquid phase And calculate the allocation coefficient according to the following formula. : Among them, parameters Indicates the first The concentration of benzothiophene in the organic phase at the time of the next measurement; parameters Indicates the first The concentration of benzothiophene in the ionic liquid phase at the time of the next measurement; parameters Indicates the first The partition coefficient of benzothiophene in the two-phase system at the next measurement time. In this invention, Used to characterize the distribution of the target product benzothiophene between the organic and ionic liquid phases. This mainly reflects the difference in the ratio of the two phases. It directly reflects the migration and enrichment trend of the target product in the two phases. If A higher concentration indicates that benzothiophene tends to be distributed more in the organic phase; if... A low partition coefficient indicates insufficient enrichment of the target product in the organic phase, which is detrimental to the acquisition of subsequent products. Therefore, the partition coefficient... This is another core parameter in this invention for determining whether the current two-phase system is conducive to product derivation. Further, in a preferred embodiment, the... and The concentration of benzothiophene was determined by gas chromatography or high-performance liquid chromatography, and the concentration was calculated from the peak area. Using chromatographic methods to determine the concentration of benzothiophene in both phases is beneficial for maximizing the partition coefficient. It possesses a repeatable, quantifiable, and traceable detection foundation. This detection method aligns with the "quantitative characterization" emphasized above in this invention, allowing step S2 to move beyond empirical judgment and become a parameter calculation process based on detectable data. In this invention, the target interval is set to satisfy: a lower limit for the two-phase volume fraction. Upper limit of two-phase volume fraction ,and Lower limit of allocation coefficient Among them, parameters and Parameters used to determine the target range for two-phase volume fraction. The minimum control requirements used to determine the allocation coefficients. Setting the above parameters as the target range and minimum threshold signifies that the adjustment action in step S3 can be triggered based on whether it deviates from this range or threshold. In other words, step S2 not only completes the measurement and calculation of the parameters but also establishes the judgment boundary for step S3 regarding "when adjustment is needed." In a preferred embodiment of the invention, the output of step S2 is: at each measurement time... The two-phase volume fraction obtained above With allocation coefficient The data is then compared with a preset target range to determine whether the system needs to enter the control action in step S3. Therefore, the output of step S2 is not simply a data record, but directly serves as the basis for subsequent closed-loop control decisions. From the perspective of step sequence, step S2 uses the liquid-liquid two-phase reaction system established in the preceding step S1 as its input, within a set measurement period... Continuous output and Two types of key parameters. This output reflects the current state of the system on the one hand, and directly triggers the phase volume fraction, temperature, and stirring control in step S3. Therefore, step S2 plays a crucial bridging role in the entire method, transitioning from "system establishment" to "system closed-loop control." In summary, step S2, through measurement cycles... Setting, two-phase volume fraction Calculation and allocation coefficients Calculation and target interval and The establishment of this method completes the quantitative characterization process of the dynamic state of the liquid-liquid two-phase reaction system, providing a clear and executable parameter basis for deviation judgment and control actions in step S3.

[0015] III. S3, Two-Phase Control Closed-Loop: In this invention, step S3 is a two-phase control closed-loop step, the function of which is: when the two-phase volume fraction measured in step S2... or allocation coefficient When the system deviates from the preset target range, corresponding control actions are executed to bring the liquid-liquid two-phase reaction system back to a state range conducive to the formation, migration, and derivation of the target product. This step is the core control step of this invention and a key technical feature that distinguishes it from reaction control relying solely on empirical observation and fixed process conditions. In other words, step S1 establishes a controllable two-phase system, step S2 establishes a foundation of measurable parameters, and step S3 truly achieves a closed-loop transition from "parameter monitoring" to "state control." In this invention, the control objectives based on step S3 include: achieving a certain volume fraction between the two phases. Stay within the target range Within, and make the allocation coefficient Keep no less than Among them, the two-phase volume fraction mainly reflects the proportional relationship between the organic phase and the ionic liquid phase, while the partition coefficient mainly reflects the distribution state of benzothiophene between the organic phase and the ionic liquid phase. The former has a greater influence on the phase structure and interphase contact characteristics of the system, while the latter has a greater influence on whether the target product can preferentially accumulate in the organic phase that is easier to extract later. Therefore, this invention sets corresponding control actions for these two types of parameters to make the control process have a clear direction. In one embodiment, the control actions of step S3 include three types: phase volume fraction control, temperature control, and stirring control. (I) Phase volume fraction control: Phase volume fraction control is used to control the phase volume fraction in the organic phase and the ionic liquid phase. When the target range is deviated from, the phase ratio is restored by adjusting the feed volume of one of the two phases. In one embodiment, the phase volume fraction control in step S3 includes the following sub-steps: S3.1, Low volume fraction compensation: When At the same time, increase the feed volume of the ionic liquid. and satisfy Among them, parameters Indicates the first The increase in ionic liquid feed volume during this adjustment. When Less than This indicates that the proportion of the ionic liquid phase in the overall two-phase system is too low. Without compensation, the volume of the catalyst phase may be insufficient, weakening the subsequent reaction propagation and interphase control space. Therefore, this invention increases the volume fraction of the two phases by adding an ionic liquid phase, bringing the system back to the target range. Controlling the compensation to 0.01 to 0.20 times the current total phase volume helps avoid insufficient compensation that would fail to produce an adjustment effect, or excessive compensation that would cause the system to directly transition from a low volume fraction state to the target range. S3.2, High Volume Fraction Compensation: When At the same time, increase the feed volume of organic substrate. and satisfy , where the parameters Indicates the first The increase in organic substrate feed volume during the next adjustment. When Greater than This indicates that the proportion of the ionic liquid phase in the overall system is too high, while the proportion of the organic phase is relatively insufficient. Without compensation, this could lead to a product distribution state unfavorable to the enrichment of the target product in the organic phase, thus hindering subsequent product extraction. Therefore, this invention dilutes the proportion of the ionic liquid phase by adding an organic substrate phase, thereby... It will fall back to the target range. Maintaining the value within 0.01 to 0.20 times the current total phase volume helps ensure the feasibility of the compensation action and avoids over-adjustment. S3.3, Update Calculation: After performing the above compensation, proceed to the next measurement time and update. The purpose of this step is to achieve a true closed-loop control of phase volume fraction through an "adjustment-remeasurement-rejuvenation" approach. In other words, the adjustment action in S3 does not terminate after a single execution, but rather uses the measurement result at the next moment output by S2 as the basis for verification. If the updated... If the target range has not yet been reached, the corresponding control actions can continue to be executed until the target requirements are met. This logic reflects the closed-loop control characteristic of this invention: "control is triggered by parameter deviation, and the control effect is verified by parameter regression." (II) Temperature Control: Temperature control is used in the allocation coefficient... When the temperature is below the minimum requirement, the phase distribution state is affected by changing the reaction temperature, causing benzothiophene to revert to a distribution state favorable for product acquisition. In one embodiment, when Adjust the reaction temperature. make Rebound, temperature adjustment range and maintain after temperature adjustment The S2 measurement is performed again after 5 to 30 minutes. The parameters are... Indicates the current reaction temperature; parameter Indicates the temperature adjustment range; parameters This indicates the holding time after temperature adjustment. In this invention, when the allocation coefficient... Below This indicates that benzothiophene is not sufficiently enriched in the organic phase, or its retention ratio in the ionic liquid phase is too high, which is not conducive to the subsequent product extraction. Adjusting the reaction temperature can affect the dissolution behavior of components, interphase migration behavior, and partition equilibrium in the system, thereby increasing the partition coefficient. The temperature adjustment range... Maintaining the temperature between 2℃ and 20℃ ensures sufficient temperature regulation without causing abrupt temperature changes in the system; the adjusted holding time... Controlling the temperature change to 5-30 minutes allows the temperature to fully affect the system before the next measurement, preventing misjudgments caused by premature measurement before a new distribution equilibrium is reached. Therefore, this invention incorporates temperature control into closed-loop control logic, providing a clear execution path for adjusting the distribution coefficient. (III) Stirring Control: Stirring control is used in... When the system deviates from the target range, the stirring speed is adjusted to influence the contact state between the two phases and the degree of interface renewal, thereby helping the system return to the target state. In one embodiment, the stirring speed... The speed range is 60 rpm to 300 rpm, and when When the speed deviates from the target range, adjust the stirring speed by [amount]. Limited to 10rpm~80rpm. Among them, the parameters... This indicates the stirring speed during the control phase; parameter This indicates the adjustment amount of the stirring speed relative to the current stirring state. In this invention, the stirring state affects the degree of contact renewal and local mixing state at the two-phase interface, thereby indirectly affecting the stability of the two-phase volume fraction and the product migration process. When When the target range is deviated from, adding only one phase component can sometimes adjust the volume ratio, but if the stirring state is not adjusted simultaneously, the system may find it difficult to establish a new stable phase contact state in a timely manner. Therefore, this invention uses stirring control as an auxiliary means of controlling phase volume fraction. The stirring speed is adjusted by... Maintaining a rpm range of 10 to 80 rpm is beneficial for ensuring continuous system operation while allowing for moderate changes in the interface contact state. If If the value is too small, its effect on correcting the contact state between the two phases of the system will be limited; if... Excessive concentration may cause excessive disturbance to the system interface, which is detrimental to subsequent parameter measurements and stability assessment. In summary, step S3 addresses the parameter deviations in the real-time output of step S2 through three methods: phase volume fraction control, temperature control, and stirring control. Phase volume fraction control primarily corrects the two-phase ratio, temperature control primarily corrects the product distribution, and stirring control primarily assists in restoring stable phase contact conditions. These three methods are not independent but rather work together to "make..." Back Internal, envoy Not less than This shared goal is executed collaboratively. In a preferred embodiment of the invention, the output of step S3 is: after one or more adjustments, the liquid-liquid two-phase reaction system returns to the target range and continues to the next round of measurement in S2 or enters the termination determination stage in S4. Thus, step S3 truly realizes a closed-loop control process from "deviation identification" to "deviation correction". From the perspective of the step connection relationship, step S3 outputs the results of the preceding step S2. and Based on the input, corresponding control actions are executed when the target range or threshold is deviated, and the measurement is repeated in step S2 after control. In other words, S2 and S3 form a continuous, iterative "measurement-judgment-control-remeasurement" closed loop in this invention, rather than a linear, one-time operation. This is the core of the process control logic of this invention. In summary, step S3, through low volume fraction compensation, high volume fraction compensation, temperature control, and stirring control, achieves dynamic closed-loop control of the two-phase ratio and product distribution in the liquid-liquid two-phase reaction system, enabling the reaction process to be continuously maintained within a state range favorable for the formation and derivation of benzothiophene.

[0016] IV. S4, Phase Separation and Product Acquisition: In this invention, step S4 is the phase separation and product acquisition step. Its function is to: based on the two-phase control closed loop formed by S2 and S3, when the system meets the termination criterion for the end of the reaction, the reaction is terminated and an organic phase is obtained through phase separation. Subsequently, the organic phase is subjected to atmospheric or vacuum distillation to obtain the benzothiophene product. This step is not only the closing link of the process control in this invention, but also the result link for the final output of the target product. In other words, the establishment, monitoring, and control of the two phases from S1 to S3 should ultimately be reflected in the result that step S4 can stably obtain an organic phase suitable for separation and obtain the benzothiophene product. In one embodiment, the end of the reaction in step S4 is based on the product concentration stability criterion. The termination criterion includes the following sub-steps: S4.1, Calculation of Concentration Change: Calculate the concentration change in two consecutive measurements. , where the parameters Indicates the first The change in the concentration of benzothiophene in the organic phase relative to the previous measurement time; parameters and These represent the concentrations of benzothiophene in the organic phase at two adjacent measurement times. The purpose of calculating the concentration change is to determine whether the current reaction has reached a stable state by observing the trend of the target product's concentration change in the organic phase. If the concentration change of benzothiophene in the organic phase is very small in continuous measurements, it indicates that the enrichment of the target product in the organic phase has stabilized, and the incremental increase from continued reaction is limited. Therefore, This is an important parameter used in this invention to determine whether the reaction has entered the termination stage. S4.2, Termination Condition: When the condition is met... and The reaction is considered complete at a certain time, where the parameters are... The concentration ranges from 0.001 mol / L to 0.050 mol / L. Among these, the parameters... This represents the termination threshold for the change in benzothiophene concentration in the organic phase. The present invention sets the termination condition to be met simultaneously by two conditions: first, the change in benzothiophene concentration in the organic phase is no greater than... This indicates that the reaction has stabilized; secondly, the distribution coefficient Not less than This indicates that the target product still maintains a favorable partitioning of the organic phase under the current conditions. Only when both conditions are met simultaneously is the current reaction considered to be close to completion and possessing a basis for phase separation that is conducive to product extraction. This termination criterion differs from the endpoint criterion based on substrate conversion rate in Scheme 1. Its core is not to determine whether the substrate has been consumed to a certain extent, but rather to determine whether the concentration change of the target product in the organic phase has stabilized and whether the target product still maintains a favorable partitioning state. This aligns more closely with the technical principle of Scheme 3, which focuses on "process control based on two-phase parameters." In one embodiment of the invention, the phase separation in step S4 is triggered by temperature adjustment, specifically by adjusting the reaction system to the phase separation temperature. The temperature is maintained between 20℃ and 50℃, and the phase separation time is kept constant. The time is 10 min to 60 min, allowing a stable phase interface to form before collecting the organic phase. Among these parameters... This indicates the control temperature that triggers the re-stabilization and separation of the two phases after the reaction is complete. (Parameter) This indicates the time maintained at the stated phase separation temperature. The purpose of triggering phase separation by adjusting the temperature is to allow the liquid-liquid system, after undergoing reaction and multiple rounds of closed-loop regulation, to re-enter a state suitable for interface stability, thereby improving the accuracy and consistency of organic phase collection. Maintaining the temperature between 20℃ and 50℃ helps to balance the system's fluidity and interface stability; Controlling the reaction time to 10-60 minutes allows sufficient time for phase interface formation. By controlling these conditions, phase separation can be successfully completed after the reaction system terminates, and the benzothiophene-containing organic phase can be extracted from the ionic liquid phase. In this invention, after phase separation, the obtained organic phase is collected and subjected to atmospheric or vacuum distillation to obtain the benzothiophene product. Specifically, when vacuum distillation is used, the distillation pressure... The pressure ranges from 5 kPa to 60 kPa, and the distillation reflux ratio is... The value ranges from 0.5 to 10. (Parameter) Indicates the control pressure and parameters of the distillation system. This indicates the ratio between the reflux volume and the produced distillate volume. The purpose of setting up atmospheric or vacuum distillation is to further separate benzothiophene from other components in the organic phase obtained after phase separation, so that the target product is output as a product fraction. The pressure is controlled at 5 kPa to 60 kPa, which allows separation to be completed under relatively mild conditions; Controlling the concentration to 0.5–10 improves the effectiveness of component separation during distillation. Therefore, step S4 in this invention not only terminates the two-phase reaction system but also completes the product extraction process. In a preferred embodiment of this invention, the output of step S4 is benzothiophene. Obtaining this product signifies that the two-phase establishment, two-phase quantification, two-phase closed-loop control, and termination judgment logic constructed in this invention have completed the full transformation from process control to product output. In other words, step S4 is not only the termination step but also the step that ultimately demonstrates the technical effect of the entire method. From the perspective of step connection, step S4 uses the stable two-phase system obtained in the preceding S2 and S3 closed-loop control stages as input, ends the reaction after meeting the termination criterion, obtains the organic phase through temperature-triggered phase separation, and further distills to obtain the benzothiophene product. Therefore, step S4 is the final closing point in the entire method, and its completion marks the completion of the overall closed loop of this invention from two-phase process control to product output. In summary, step S4, through concentration change… Calculation and termination threshold Setting and allocation coefficients and Joint termination determination, phase separation temperature With phase separation time Control of distillation pressure and distillation reflux ratio The control of the two-phase closed-loop regulation completes the final implementation process from phase separation and product acquisition, giving the method of the present invention clear starting conditions, process control logic and product output path.

[0017] Example 1: This example illustrates the specific implementation process of the two-phase controlled benzothiophene preparation method of the present invention. In this example, an acidic ionic liquid catalyst, thiophene, and 2,5-dimethoxytetrahydrofuran are added to a reaction vessel to establish a liquid-liquid two-phase reaction system. The initial ionic liquid phase volume is 96 L, the initial organic phase volume is 204 L, the initial two-phase volume fraction is 0.320, and the initial stirring speed is 150 rpm. During the reaction, the volume of the ionic liquid phase, the volume of the organic phase, the two-phase volume fraction, the concentration of benzothiophene in the organic phase, and the concentration of benzothiophene in the ionic liquid phase are measured in 30-minute intervals, and the distribution coefficient is obtained according to the aforementioned calculation method. In this example, the lower limit of the target range for the two-phase volume fraction is set to 0.20, the upper limit of the target range for the two-phase volume fraction is set to 0.40, and the lower limit of the distribution coefficient is set to 3.0. When the two-phase volume fraction or the distribution coefficient deviates from the target range, corresponding control actions are performed; wherein, temperature control, phase volume fraction compensation, and stirring control are all performed according to the aforementioned scheme. After the termination criterion is met, the reaction system is adjusted to the phase separation temperature and maintained for a certain period of time. The organic phase is collected, and then benzothiophene product is obtained by vacuum distillation. The main process conditions of this embodiment are shown in Table 1. Table 1 Main process conditions of Example 1 To demonstrate the measurement of two-phase parameters and closed-loop control during the reaction process, the detection results and actions performed at each measurement moment were recorded, as shown in Table 2. Table 2: Two-phase parameter measurement and closed-loop control data in Example 1: As shown in Table 2, in measurement sequence 1, the distribution coefficient was below the set lower limit, therefore temperature control was implemented; in measurement sequence 3, the volume fraction of both phases was below the lower limit of the target range, therefore ionic liquid compensation and stirring control were implemented; in measurement sequence 5, the volume fraction of both phases was above the upper limit of the target range, therefore organic substrate compensation and stirring control were implemented. After the above adjustments, the system returned to the target range in subsequent measurements, indicating that the two-phase closed-loop control logic described in this invention can effectively act on the reaction process.

[0018] To illustrate the quantification process of the termination criterion, the change in benzothiophene concentration in the organic phase was calculated, and the results are shown in Table 3. Table 3: Data corresponding to the termination criterion in Example 1: As shown in Table 3, at the measurement point 7 (210 min), the concentration change of benzothiophene in the organic phase was 0.007 mol / L, not greater than 0.010 mol / L, and the partition coefficient was 4.40, not lower than the set lower limit of 3.0. Therefore, 210 min was determined as the reaction endpoint of this embodiment. After the reaction was terminated, the reaction system was adjusted to 35°C and maintained for 25 min to trigger phase separation. The obtained organic phase was collected and subjected to vacuum distillation under the conditions of a distillation pressure of 22 kPa and a distillation reflux ratio of 2.5 to finally obtain the benzothiophene product. The relevant results are shown in Table 4. Table 4 Phase separation and product acquisition data in Example 1: To further verify the stability of the method of the present invention under the same control logic, three batches of parallel verification were conducted under the same process conditions. The results are shown in Table 5. Table 5 Parallel verification results of Example 1: As shown in Table 5, under the same process conditions, this embodiment can stably control the volume fraction of the two phases at termination within the target range and maintain the distribution coefficient at no lower than the set lower limit, while obtaining relatively stable benzothiophene product quality, purity, and yield. This indicates that the method described in this invention, by establishing a quantitative characterization and closed-loop control mechanism for two-phase parameters, can improve the controllability and repeatability of the benzothiophene preparation process. This embodiment illustrates that, through the synergistic design of the establishment, quantitative monitoring, deviation control, and termination determination of the liquid-liquid two-phase reaction system, this invention can continuously maintain a two-phase state favorable to the derivation of benzothiophene during the reaction process and obtain a benzothiophene product with high purity and stable yield after the reaction. Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing benzothiophene with two-phase regulation, characterized in that, Includes the following steps: S1. Establishment of the two-phase reaction system: Thiophene, 2,5-dimethoxytetrahydrofuran and acidic ionic liquid catalyst are added to the reaction vessel to form a liquid-liquid two-phase reaction system in which the organic phase and the ionic liquid phase coexist. S2. Quantitative characterization of two-phase parameters: During the reaction process, measurements are performed over a period of time. Periodically measure the volume fraction of the two phases and the product distribution coefficient; S3, Two-phase control closed loop: Set target range and When measured or When deviating from the target range, execute control actions to make and Return to the target range; S4. Phase separation and product acquisition: After the reaction is completed, the organic phase is separated and subjected to atmospheric or vacuum distillation to obtain the benzothiophene product.

2. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that, S1 includes the following sub-steps: S1.1 Initial Phase Ratio Setting: Set the initial two-phase volume fraction. And record the initial ionic liquid phase volume. relative to the initial organic phase volume ; S1.2 Feeding and Phase Formation: Add acidic ionic liquid catalyst, thiophene and 2,5-dimethoxytetrahydrofuran to the reactor to form a liquid-liquid two-phase system; S1.3, Stirring Start: Control the initial stirring speed To form a stable two-phase contact interface.

3. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that, S2 includes the following sub-steps: S2.1 Measurement cycle setting: ; S2.2, Calculation of volume fraction: at the measurement time Read and : ; S2.3, Calculation of distribution coefficients: at the measurement time The concentrations of benzothiophene in the organic phase and the ionic liquid phase were measured respectively. and Calculate the allocation coefficient using the following formula. : .

4. The method for preparing benzothiophene with two-phase regulation according to claim 3, characterized in that, The and The concentration was determined by gas chromatography or high-performance liquid chromatography and converted from peak area; , and The .

5. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that, The S3 control action includes phase volume fraction control, and includes the following sub-steps: S3.1, Low volume fraction compensation: When At the same time, increase the feed volume of the ionic liquid. and satisfy ; S3.2, High Volume Fraction Compensation: When At the same time, increase the feed volume of organic substrate. and satisfy ; S3.3 Update Calculation: Execute the next measurement time and update after compensation. .

6. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that, The control action of S3 includes temperature control, and when Adjust the reaction temperature. make Rebound, temperature adjustment range and maintain after temperature adjustment Then perform the next S2 measurement.

7. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that... The S3's control actions include stirring control and stirring speed. , When deviating from the target range, the stirring speed adjustment amount is limited to [value missing]. .

8. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that, The termination criterion for the end of the reaction is based on the product concentration stability criterion, including the following sub-steps: S4.1 Calculation of concentration change: Calculated from two consecutive measurements. ; S4.2 Termination Condition: When the condition is met The reaction is considered complete at a certain time. .

9. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that, The phase separation in S4 is triggered by temperature adjustment, specifically by adjusting the reaction system to... and maintain The organic phase is collected after a stable phase interface is formed.

10. The method for preparing benzothiophene with two-phase regulation according to claim 1, characterized in that... The S4 refers to the distillation pressure during vacuum distillation. , And the distillation reflux ratio .

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