Process for the production of high purity octenidine

Abstract

The present application belongs to the technical field of organic chemical synthesis, and particularly relates to a production process of high-purity octocrylene. The present application adopts a microwave-vacuum ladder synergistic catalytic process, which can significantly accelerate the ester exchange reaction rate of etocrylene and isooctanol, simultaneously remove the byproduct ethanol rapidly, promote the reaction equilibrium to move in the direction of generating octocrylene, effectively reduce the raw material residue and side reaction, and stably obtain high-purity product. The composite supported catalyst can be heat-treated in an inert atmosphere to reconstruct the carbon skeleton and re-anchor the active components in situ, so that the deactivated catalyst can quickly recover the activity and be used for a long time, thereby significantly reducing the catalyst consumption and production cost, and solving the pain points of traditional catalysts, such as easy loss, easy deactivation and difficult recycling. The refining route of active carbon decolorization, precision filtration and two-stage high-vacuum gradient rectification is adopted, so that high-purity octocrylene is finally obtained, which meets the strict requirements of high-end daily chemical field on the purity and safety of raw materials.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, specifically relating to a production process for high-purity octocrylene. Background Technology

[0002] Octocrylene, a broad-spectrum and highly effective UVA / UVB absorber, is characterized by good photostability, high absorption efficiency, and excellent compatibility with daily chemical formulations. It is widely used in high-end cosmetics such as sunscreens, skin lotions, and hair care products, and is one of the mainstream sunscreen agents globally. Industrially, ocrylene is mainly prepared from etopoyl thiocyanate and isooctanol through a transesterification reaction. The purity of the product, raw material residues, and impurity content directly affect its sun protection efficacy and safety. High-end daily chemical products typically require ocrylene purity of no less than 99.5% and etopoyl thiocyanate residues controlled below 0.05%.

[0003] Current traditional octocrylene production processes generally suffer from the following technical bottlenecks: First, transesterification reactions often employ conventional heating and atmospheric pressure, resulting in uneven heat transfer and slow removal of the byproduct ethanol, leading to high reversibility, incomplete raw material conversion, and long reaction cycles. Second, commonly used catalysts are mostly homogeneous bases or simple supported solid bases, which are prone to loss of active sites, exhibit poor selectivity, and are difficult to regenerate and recycle after deactivation, resulting in high catalyst consumption and significant challenges in product separation and purification. Third, post-processing often employs single-stage distillation or simple rectification, which is insufficient for separating light and heavy components from trace impurities, making it difficult to consistently obtain high-purity products and limiting its application in high-end cosmetics. To address these issues, the industry has gradually explored improved approaches such as microwave enhancement, solid base catalysis, and vacuum distillation, but problems such as unstable catalyst structure, short cycle life, and poor matching between reaction and purification remain.

[0004] Therefore, developing a high-purity octocrylene production process with fast reaction rate, high raw material conversion rate, recyclable catalyst, and stable product purity has become an urgent need in the fields of fine chemicals and sunscreen raw material preparation. Summary of the Invention

[0005] The purpose of this invention is to address the existing problems by providing a production process for high-purity octocrylene.

[0006] This invention is achieved through the following technical solution:

[0007] A process for producing high-purity octocrylene includes the following steps:

[0008] S1, Microwave-vacuum synergistic catalytic reaction:

[0009] The transesterification reaction was carried out by mixing estradiol, isooctyl alcohol and a composite supported catalyst under microwave irradiation and negative pressure conditions. The removal of ethanol generated in the reaction was accelerated by selective microwave heating, and the reaction endpoint was controlled.

[0010] S2, Catalyst self-repair and regeneration:

[0011] When the catalyst activity decreases (the indicator of decreased activity is: under the same reaction conditions, the time to reach the endpoint of the reaction is extended by more than 30% compared with the initial use, and the conversion rate of estradiol decreases by more than 15% compared with the initial use), self-healing heat treatment is carried out under an inert atmosphere. The residual organic components on the catalyst surface are used to generate a carbon skeleton in situ and re-anchor the active components. After the catalyst activity is restored, it can be recycled.

[0012] S3, Post-processing Refining:

[0013] The reaction solution was decolorized, filtered, and distilled to obtain high-purity octocrylene.

[0014] Furthermore, the preparation of the composite supported catalyst described in step S1 includes the following steps:

[0015] (1) Add an inert porous support to a silane coupling agent KH-550 ethanol solution with a mass fraction of 1-3%, and add a single-atom bismuth dopant (Bi(NO3)3·5H2O) with a mass of 0.5-1.2% of the support. The solid-liquid ratio of the support to the solution is 1:(10-15) (g / mL). Heat in a water bath at 50-60℃ and stir at 200-300 rpm for 2-3 hours. After stirring, filter and wash the filter cake with anhydrous ethanol 3-4 times. Each wash uses 5-8 times the mass of the filter cake. After washing, dry at 105-110℃ for 4-6 hours to obtain the modified support.

[0016] (2) The modified carrier was loaded with sodium carbonate and triethanolamine by gradient impregnation method, and the mass ratio of modified carrier, sodium carbonate and triethanolamine was 100:(30~50):(3~8);

[0017] The gradient impregnation method is as follows: first impregnate at 40℃ for 1 hour, then raise the temperature to 60℃ and impregnate for 1 hour, while maintaining stirring at 150~200 rpm during the impregnation process;

[0018] (3) The loaded material is heat-treated at 180~220℃ for 30~60min under N2 atmosphere (purity ≥99.99%) to partially pyrolyze triethanolamine to form a nitrogen-doped carbon anchoring layer, wherein the nitrogen content of the nitrogen-doped carbon anchoring layer is 2.5~4.2wt%;

[0019] (4) After microwave activation at 200~250W for 3~8min, the anchored composite supported catalyst is obtained.

[0020] Further, the inert porous support mentioned in step (1) is mesoporous silica (pore size 2~10nm, specific surface area 300~500m). 2 / g), diatomaceous earth (pore size 5~20nm, particle size 100~200 mesh, porosity 40~60%), molecular sieve (ZSM-5 type or Y type molecular sieve, pore diameter 0.5~1.2nm, specific surface area 400~600m²), 2 / g, a silicon-to-aluminum ratio (SiO2 / Al2O3) of 20~50, and a particle size of 80~150 mesh.

[0021] Further, the mass ratio of estradiol, isooctanol, and the composite supported catalyst mentioned in step S1 is 1:(3.5~5.5):(0.08~0.15);

[0022] The reaction time for the transesterification reaction is 2.5 to 4.5 hours.

[0023] Furthermore, the power of microwave irradiation in step S1 is controlled in a stepped manner, with the amount of ethanol removed during the reaction process as the defining standard: 150~250W in the initial stage of the reaction (ethanol removal reaches 0~30% of the theoretical removal amount), 300~400W in the middle stage (ethanol removal reaches 30~85% of the theoretical removal amount), and 200~300W in the later stage (ethanol removal reaches 85~100% of the theoretical removal amount); the theoretical removal amount is calculated based on the amount of etotriene added and the stoichiometric relationship of the transesterification reaction.

[0024] The negative pressure conditions are adjusted in steps according to the reaction process: -0.05~-0.06MPa in the initial stage of the reaction, -0.07~-0.08MPa in the middle stage, and -0.085~-0.095MPa in the later stage.

[0025] Furthermore, the reaction endpoint described in step S1 is controlled by online monitoring. The content of etorethrin is monitored online using high performance liquid chromatography (HPLC), and the reaction is stopped when the content of etorethrin is ≤0.05%.

[0026] HPLC monitoring conditions were as follows: C18 column (250 mm × 4.6 mm, 5 μm); mobile phase: methanol:water = 85:15 (v / v); flow rate: 1 mL / min; detection wavelength: 254 nm; column temperature: 30 °C. A stock solution of 1000 μg / mL was prepared, and then serially diluted to prepare working standard solutions of 10 μg / mL, 20 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL. A standard curve was plotted, and the correlation coefficient R0 was calculated. 2 ≥0.9995; System suitability test requirements: the separation degree between the Liling peak and the adjacent impurity peak is ≥1.5, and the theoretical plate number is ≥3000.

[0027] Furthermore, the inert atmosphere mentioned in step S2 is one or a mixture of two of nitrogen and argon, with the volume ratio of nitrogen to argon being (1~3):1, and the flow rate of the inert atmosphere during the self-healing process being 50~100mL / min.

[0028] Furthermore, the temperature of the self-healing heat treatment in step S2 is 220~260℃, and the time is 1~2h. After self-healing, the catalyst activity is restored to more than 95% of the initial activity.

[0029] Further, the decolorization mentioned in step S3 is activated carbon decolorization, specifically, the operation is as follows: add 0.8~1.5% by mass of activated carbon (particle size 80~120 mesh, specific surface area ≥1000m²) to the reaction solution. 2 / g), bath temperature 60~70℃, stir for 30~40min and then filter to remove activated carbon and impurities;

[0030] The filtration uses a 0.22μm organic filter membrane, and the filtration pressure is 0.1~0.15MPa.

[0031] Furthermore, the distillation described in step S3 is a two-stage vacuum distillation, in which isooctyl alcohol is recovered by a single vacuum distillation and high-purity octocrylene is obtained by a second-stage high-vacuum gradient distillation.

[0032] The parameters for the recovery of isooctanol by primary vacuum distillation are: vacuum degree -0.08~-0.09MPa, distillation temperature 110~125℃, and reflux ratio 1:(2~3);

[0033] The vacuum degree of the secondary high vacuum gradient distillation is ≤500Pa. The gradient heating mode is adopted: the initial fraction is removed at 150℃, the temperature is maintained for 30~40min, and then the temperature is raised to 175~190℃ to collect the product fraction. The reflux ratio is 1:(4~5). The collected product fraction is high-purity octocrylene.

[0034] The present invention has the following advantages over the prior art:

[0035] 1. This invention employs a microwave-vacuum stepwise catalytic process, which can significantly accelerate the transesterification reaction rate of octocrylene and isooctyl alcohol, while rapidly removing the byproduct ethanol, thus shifting the reaction equilibrium towards the formation of octocrylene. Combined with HPLC online monitoring for precise control of the reaction endpoint, the conversion rate of raw materials and the selectivity of the reaction are improved simultaneously, effectively reducing raw material residues and side reactions, and stably obtaining high-purity products.

[0036] 2. This invention utilizes a single-atom bismuth-doped and nitrogen-doped carbon-anchored composite supported catalyst, combined with catalyst self-repair and regeneration technology, to significantly improve the dispersion of active sites and structural stability. Under an inert atmosphere, the carbon framework can be reconstructed in situ and the active components can be re-anchored after heat treatment, enabling the deactivated catalyst to quickly regain activity and be recycled for a long time. This significantly reduces catalyst consumption and production costs, solving the problems of traditional catalysts being prone to loss, deactivation, and recycling.

[0037] 3. This invention employs a refining route combining activated carbon decolorization, precision filtration, and two-stage high-vacuum gradient distillation. First, color and mechanical impurities are efficiently removed. Then, by gradient heating and high vacuum stepwise fractionation, light and heavy components and trace impurities can be fully separated, ultimately obtaining high-purity octocrylene. The product yield is high, and the impurity content is low, meeting the stringent requirements for raw material purity and safety in the high-end daily chemical industry. Attached Figure Description

[0038] Figure 1 The reaction equation for the preparation of octocrylene according to the present invention is shown below. Detailed Implementation

[0039] To further explain the present invention, the following specific embodiments are described.

[0040] Preparation Example 1

[0041] The preparation of composite supported catalyst I includes the following steps:

[0042] (1) An inert porous support was added to an ethanol solution of silane coupling agent KH-550 with a mass fraction of 1%, and a single-atom bismuth dopant (Bi(NO3)3·5H2O) with a mass of 0.5% of the support was added. The solid-liquid ratio of the support to the solution was 1:10 (g / mL). The solution was heated in a water bath at 50°C and stirred at 200 rpm for 2 h. After stirring, the solution was filtered. The filter cake was washed three times with anhydrous ethanol, each time with an amount of 5 times the mass of the filter cake. After washing, the solution was dried at 105°C for 4 h to obtain the modified support.

[0043] The inert porous support is mesoporous silica (pore size 2~10nm, specific surface area 300~500m). 2 / g);

[0044] (2) The modified carrier was loaded with sodium carbonate and triethanolamine by gradient impregnation method, and the mass ratio of modified carrier, sodium carbonate and triethanolamine was 100:30:3;

[0045] The gradient impregnation method is as follows: first impregnate at 40℃ for 1 hour, then raise the temperature to 60℃ and impregnate for 1 hour, while maintaining stirring at 150 rpm during the impregnation process;

[0046] (3) The loaded material is heat-treated at 180°C for 30 min under N2 atmosphere (purity ≥ 99.99%) to partially pyrolyze triethanolamine to form a nitrogen-doped carbon anchoring layer, wherein the nitrogen content of the nitrogen-doped carbon anchoring layer is 2.5 wt%.

[0047] (4) After activating with 200W microwave for 3 minutes, anchored composite supported catalyst I was obtained.

[0048] Preparation Example 2

[0049] The preparation of composite supported catalyst II includes the following steps:

[0050] (1) An inert porous support was added to an ethanol solution of silane coupling agent KH-550 with a mass fraction of 2%, and a single-atom bismuth dopant (Bi(NO3)3·5H2O) with a mass of 0.8% of the support was added. The solid-liquid ratio of the support to the solution was 1:12 (g / mL). The solution was heated in a water bath at 55℃ and stirred at 250 rpm for 2.5 h. After stirring, the solution was filtered. The filter cake was washed 4 times with anhydrous ethanol, and the amount of ethanol used each time was 6 times the mass of the filter cake. After washing, the solution was dried at 108℃ for 5 h to obtain the modified support.

[0051] The inert porous support is mesoporous silica (pore size 2~10nm, specific surface area 300~500m). 2 / g);

[0052] (2) The modified carrier was loaded with sodium carbonate and triethanolamine by gradient impregnation method, and the mass ratio of modified carrier, sodium carbonate and triethanolamine was 100:40:5;

[0053] The gradient impregnation method is as follows: first impregnate at 40℃ for 1 hour, then raise the temperature to 60℃ and impregnate for 1 hour, while maintaining stirring at 180 rpm during the impregnation process;

[0054] (3) The loaded material is heat-treated at 200°C for 45 min under N2 atmosphere (purity ≥ 99.99%) to partially pyrolyze triethanolamine to form a nitrogen-doped carbon anchoring layer, wherein the nitrogen content of the nitrogen-doped carbon anchoring layer is 3.5 wt%.

[0055] (4) After activating with 220W microwave for 5 minutes, anchored composite supported catalyst II was obtained.

[0056] Preparation Example 3

[0057] The preparation of composite supported catalyst III includes the following steps:

[0058] (1) An inert porous support was added to an ethanol solution of silane coupling agent KH-550 with a mass fraction of 3%, and a single-atom bismuth dopant (Bi(NO3)3·5H2O) with a mass fraction of 1.2% of the support was added. The solid-liquid ratio of the support to the solution was 1:15 (g / mL). The solution was heated in a water bath at 60°C and stirred at 300 rpm for 3 h. After stirring, the solution was filtered. The filter cake was washed 4 times with anhydrous ethanol, and the amount of ethanol used each time was 8 times the mass of the filter cake. After washing, the solution was dried at 110°C for 6 h to obtain the modified support.

[0059] The inert porous support is mesoporous silica (pore size 2~10nm, specific surface area 300~500m). 2 / g);

[0060] (2) The modified carrier was loaded with sodium carbonate and triethanolamine by gradient impregnation method, and the mass ratio of modified carrier, sodium carbonate and triethanolamine was 100:50:8.

[0061] The gradient impregnation method is as follows: first impregnate at 40℃ for 1 hour, then raise the temperature to 60℃ and impregnate for 1 hour, while maintaining stirring at 200 rpm during the impregnation process;

[0062] (3) The loaded material is heat-treated at 220°C for 60 min under N2 atmosphere (purity ≥ 99.99%) to partially pyrolyze triethanolamine to form a nitrogen-doped carbon anchoring layer, wherein the nitrogen content of the nitrogen-doped carbon anchoring layer is 4.2 wt%.

[0063] (4) After activating with 250W microwave for 8 minutes, the anchored composite supported catalyst III was obtained.

[0064] Preparation Example 4

[0065] The preparation of composite supported catalyst IV includes the following steps:

[0066] (1) An inert porous support was added to an ethanol solution of silane coupling agent KH-550 with a mass fraction of 2%, and a single-atom bismuth dopant (Bi(NO3)3·5H2O) with a mass of 0.8% of the support was added. The solid-liquid ratio of the support to the solution was 1:12 (g / mL). The solution was heated in a water bath at 55℃ and stirred at 250 rpm for 2.5 h. After stirring, the solution was filtered. The filter cake was washed 4 times with anhydrous ethanol, and the amount of ethanol used each time was 6 times the mass of the filter cake. After washing, the solution was dried at 108℃ for 5 h to obtain the modified support.

[0067] The inert porous carrier is diatomaceous earth (pore size 5~20nm, particle size 100~200 mesh, porosity 40~60%).

[0068] (2) The modified carrier was loaded with sodium carbonate and triethanolamine by gradient impregnation method, and the mass ratio of modified carrier, sodium carbonate and triethanolamine was 100:40:5;

[0069] The gradient impregnation method is as follows: first impregnate at 40℃ for 1 hour, then raise the temperature to 60℃ and impregnate for 1 hour, while maintaining stirring at 180 rpm during the impregnation process;

[0070] (3) The loaded material is heat-treated at 200°C for 45 min under N2 atmosphere (purity ≥ 99.99%) to partially pyrolyze triethanolamine to form a nitrogen-doped carbon anchoring layer, wherein the nitrogen content of the nitrogen-doped carbon anchoring layer is 3.5 wt%.

[0071] (4) After activating with 220W microwave for 5 minutes, the anchored composite supported catalyst IV was obtained.

[0072] Preparation Example 5

[0073] The preparation of composite supported catalyst V includes the following steps:

[0074] (1) An inert porous support was added to an ethanol solution of silane coupling agent KH-550 with a mass fraction of 2%, and a single-atom bismuth dopant (Bi(NO3)3·5H2O) with a mass of 0.8% of the support was added. The solid-liquid ratio of the support to the solution was 1:12 (g / mL). The solution was heated in a water bath at 55℃ and stirred at 250 rpm for 2.5 h. After stirring, the solution was filtered. The filter cake was washed 4 times with anhydrous ethanol, and the amount of ethanol used each time was 6 times the mass of the filter cake. After washing, the solution was dried at 108℃ for 5 h to obtain the modified support.

[0075] The inert porous support is a molecular sieve (Y-type, pore diameter 0.5~1.2 nm, specific surface area 400~600 m²). 2 / g, silicon-to-aluminum ratio (SiO2 / Al2O3) is 20~50, particle size is 80~150 mesh).

[0076] (2) The modified carrier was loaded with sodium carbonate and triethanolamine by gradient impregnation method, and the mass ratio of modified carrier, sodium carbonate and triethanolamine was 100:40:5;

[0077] The gradient impregnation method is as follows: first impregnate at 40℃ for 1 hour, then raise the temperature to 60℃ and impregnate for 1 hour, while maintaining stirring at 180 rpm during the impregnation process;

[0078] (3) The loaded material is heat-treated at 200°C for 45 min under N2 atmosphere (purity ≥ 99.99%) to partially pyrolyze triethanolamine to form a nitrogen-doped carbon anchoring layer, wherein the nitrogen content of the nitrogen-doped carbon anchoring layer is 3.5 wt%.

[0079] (4) After activating with 220W microwave for 5 minutes, anchored composite supported catalyst V was obtained.

[0080] Example 1

[0081] A process for producing high-purity octocrylene includes the following steps:

[0082] S1, Microwave-vacuum synergistic catalytic reaction:

[0083] Etoliline, isooctyl alcohol, and composite supported catalyst I were mixed in a mass ratio of 1:3.5:0.08 and subjected to transesterification under microwave irradiation and negative pressure conditions for 2.5 h. The removal of ethanol generated during the reaction was accelerated by selective microwave heating to control the reaction endpoint.

[0084] The power of the microwave irradiation is controlled in a stepped manner, with the amount of ethanol removed during the reaction process as the defining standard: 150W in the initial stage of the reaction (ethanol removal reaches 0-30% of the theoretical removal amount), 300W in the middle stage (ethanol removal reaches 30-85% of the theoretical removal amount), and 200W in the later stage (ethanol removal reaches 85-100% of the theoretical removal amount); the theoretical removal amount is calculated based on the amount of etotriene added and the stoichiometric relationship of the transesterification reaction.

[0085] The negative pressure conditions are adjusted in steps according to the reaction process: -0.05MPa in the initial stage, -0.07MPa in the middle stage, and -0.085MPa in the later stage.

[0086] The reaction endpoint is controlled by online monitoring. The content of etorizine is monitored online using high performance liquid chromatography (HPLC), and the reaction is stopped when the content of etorizine is ≤0.05%.

[0087] HPLC monitoring conditions were as follows: C18 column (250 mm × 4.6 mm, 5 μm); mobile phase: methanol:water = 85:15 (v / v); flow rate: 1 mL / min; detection wavelength: 254 nm; column temperature: 30 °C. A stock solution of 1000 μg / mL was prepared, and then serially diluted to prepare standard working solutions of 10 μg / mL, 20 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL. A standard curve was plotted, and the correlation coefficient R0 was calculated. 2 ≥0.9995; System suitability test requirements: the separation degree between the Itolin peak and adjacent impurity peaks is ≥1.5, and the theoretical plate number is ≥3000;

[0088] S2, Catalyst self-repair and regeneration:

[0089] When the catalyst activity decreases (the indicator of decreased activity is: under the same reaction conditions, the time to reach the endpoint of the reaction is extended by more than 30% compared with the initial use, and the conversion rate of estradiol decreases by more than 15% compared with the initial use), self-healing heat treatment is carried out in a N2 atmosphere (flow rate of 50 mL / min). The temperature of the self-healing heat treatment is 220℃ and the time is 1h. The residual organic components on the catalyst surface are used to generate a carbon skeleton in situ and re-anchor the active components. After the catalyst activity is restored, it can be recycled.

[0090] S3, Post-processing Refining:

[0091] S301. Add 0.8% (by mass of the reaction solution) of activated carbon (particle size 80-120 mesh, specific surface area ≥1000 m²) to the reaction solution. 2 / g), bath temperature 60℃, stir for 30 min and then filter to remove activated carbon and impurities;

[0092] S302. After decolorization, the filter is applied using a 0.22μm organic filter membrane at a pressure of 0.1MPa.

[0093] S303, after filtration, undergoes two-stage vacuum distillation. Isooctyl alcohol is recovered by one vacuum distillation, and then high-purity octocrylene is obtained by two-stage high-vacuum gradient distillation.

[0094] The parameters for the recovery of isooctanol by primary vacuum distillation are: vacuum degree -0.08MPa, distillation temperature 110℃, and reflux ratio 1:2.

[0095] The vacuum degree of the secondary high-vacuum gradient distillation is ≤500Pa, and a gradient heating mode is adopted: the initial fraction is removed at 150℃, held at 150℃ for 30min, and then heated to 175℃ to collect the product fraction. The reflux ratio is 1:4, and the collected product fraction is high-purity octocrylene.

[0096] Example 2

[0097] A process for producing high-purity octocrylene includes the following steps:

[0098] S1, Microwave-vacuum synergistic catalytic reaction:

[0099] Etoliline, isooctyl alcohol, and composite supported catalyst II were mixed in a mass ratio of 1:4.5:0.12 and subjected to transesterification under microwave irradiation and negative pressure conditions for 3.5 h. The removal of ethanol generated during the reaction was accelerated by microwave selective heating to control the reaction endpoint.

[0100] The power of the microwave irradiation is controlled in a stepped manner, with the amount of ethanol removed during the reaction process as the defining standard: 200W in the initial stage of the reaction (ethanol removal reaches 0-30% of the theoretical removal amount), 350W in the middle stage (ethanol removal reaches 30-85% of the theoretical removal amount), and 250W in the later stage (ethanol removal reaches 85-100% of the theoretical removal amount); the theoretical removal amount is calculated based on the amount of etotriene added and the stoichiometric relationship of the transesterification reaction.

[0101] The negative pressure conditions are adjusted in steps according to the reaction process: -0.05MPa in the initial stage, -0.07MPa in the middle stage, and -0.09MPa in the later stage.

[0102] The reaction endpoint is controlled by online monitoring. The content of etorizine is monitored online using high performance liquid chromatography (HPLC), and the reaction is stopped when the content of etorizine is ≤0.05%.

[0103] HPLC monitoring conditions were as follows: C18 column (250 mm × 4.6 mm, 5 μm); mobile phase: methanol:water = 85:15 (v / v); flow rate: 1 mL / min; detection wavelength: 254 nm; column temperature: 30 °C. A stock solution of 1000 μg / mL was prepared, and then serially diluted to prepare standard working solutions of 10 μg / mL, 20 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL. A standard curve was plotted, and the correlation coefficient R0 was calculated. 2 ≥0.9995; System suitability test requirements: the separation degree between the Itolin peak and adjacent impurity peaks is ≥1.5, and the theoretical plate number is ≥3000;

[0104] S2, Catalyst self-repair and regeneration:

[0105] When the catalyst activity decreases (the indicator of decreased activity is: under the same reaction conditions, the time to reach the endpoint of the reaction is extended by more than 30% compared with the initial use, and the conversion rate of estradiol decreases by more than 15% compared with the initial use), self-healing heat treatment is carried out in a N2 atmosphere (flow rate of 80 mL / min). The temperature of the self-healing heat treatment is 240℃ and the time is 1.5h. The residual organic components on the catalyst surface are used to generate a carbon skeleton in situ and re-anchor the active components. After the catalyst activity is restored, it can be recycled.

[0106] S3, Post-processing Refining:

[0107] S301. Add 1.2% (by mass of the reaction solution) of activated carbon (particle size 80-120 mesh, specific surface area ≥1000 m²) to the reaction solution. 2 / g), bath temperature 65℃, stir for 35 min and then filter to remove activated carbon and impurities;

[0108] S302. After decolorization, the material is filtered through a 0.22μm organic filter membrane at a pressure of 0.12MPa.

[0109] S303, after filtration, undergoes two-stage vacuum distillation. Isooctyl alcohol is recovered by one vacuum distillation, and then high-purity octocrylene is obtained by two-stage high-vacuum gradient distillation.

[0110] The parameters for the recovery of isooctanol by primary vacuum distillation are: vacuum degree -0.085MPa, distillation temperature 118℃, and reflux ratio 1:2.5.

[0111] The vacuum degree of the secondary high-vacuum gradient distillation is ≤500Pa, and a gradient heating mode is adopted: the initial fraction is removed at 150℃, held at 150℃ for 35min, and then heated to 185℃ to collect the product fraction. The reflux ratio is 1:4.5, and the collected product fraction is high-purity octocrylene.

[0112] Example 3

[0113] A process for producing high-purity octocrylene includes the following steps:

[0114] S1, Microwave-vacuum synergistic catalytic reaction:

[0115] Etolyl, isooctyl alcohol, and composite supported catalyst III were mixed in a mass ratio of 1:5.5:0.15 and subjected to transesterification under microwave irradiation and negative pressure conditions for 4.5 h. The removal of ethanol generated during the reaction was accelerated by selective microwave heating to control the reaction endpoint.

[0116] The power of the microwave irradiation is controlled in a stepped manner, with the amount of ethanol removed during the reaction process as the defining standard: 250W in the initial stage of the reaction (ethanol removal reaches 0-30% of the theoretical removal amount), 400W in the middle stage (ethanol removal reaches 30-85% of the theoretical removal amount), and 300W in the later stage (ethanol removal reaches 85-100% of the theoretical removal amount); the theoretical removal amount is calculated based on the amount of etotriene added and the stoichiometric relationship of the transesterification reaction.

[0117] The negative pressure conditions are adjusted in steps according to the reaction process: -0.06MPa in the initial stage, -0.08MPa in the middle stage, and -0.095MPa in the later stage.

[0118] The reaction endpoint is controlled by online monitoring. The content of etorizine is monitored online using high performance liquid chromatography (HPLC), and the reaction is stopped when the content of etorizine is ≤0.05%.

[0119] The HPLC monitoring conditions were as follows: C18 column (250 mm × 4.6 mm, 5 μm); mobile phase: methanol:water = 85:15 (v / v); flow rate: 1 mL / min; detection wavelength: 254 nm; column temperature: 30 °C. A stock solution of 1000 μg / mL was prepared, and then serially diluted to prepare standard working solutions of 10 μg / mL, 20 μg / mL, 50 μg / mL, 100 μg / mL, and 200 μg / mL. A standard curve was plotted, and the correlation coefficient R0 was calculated. 2 ≥0.9995; System suitability test requirements: the separation degree between the Itolin peak and adjacent impurity peaks is ≥1.5, and the theoretical plate number is ≥3000;

[0120] S2, Catalyst self-repair and regeneration:

[0121] When the catalyst activity decreases (the indicator of decreased activity is: under the same reaction conditions, the time to reach the endpoint of the reaction is extended by more than 30% compared with the initial use, and the conversion rate of estradiol decreases by more than 15% compared with the initial use), self-healing heat treatment is carried out in N2 atmosphere (flow rate of 100 mL / min). The temperature of the self-healing heat treatment is 260℃ and the time is 2h. The residual organic components on the catalyst surface are used to generate a carbon skeleton in situ and re-anchor the active components. After the catalyst activity is restored, it can be recycled.

[0122] S3, Post-processing Refining:

[0123] S301. Add 1.5% (by mass of the reaction solution) of activated carbon (particle size 80-120 mesh, specific surface area ≥1000 m²) to the reaction solution. 2 / g), bath temperature 70℃, stir for 40 min and then filter to remove activated carbon and impurities;

[0124] S302. After decolorization, the material is filtered through a 0.22μm organic filter membrane at a pressure of 0.15MPa.

[0125] S303, after filtration, undergoes two-stage vacuum distillation. Isooctyl alcohol is recovered by one vacuum distillation, and then high-purity octocrylene is obtained by two-stage high-vacuum gradient distillation.

[0126] The parameters for the recovery of isooctanol by primary vacuum distillation are: vacuum degree -0.09MPa, distillation temperature 125℃, and reflux ratio 1:3;

[0127] The vacuum degree of the secondary high-vacuum gradient distillation is ≤500Pa, and a gradient heating mode is adopted: the initial fraction is removed at 150℃, held at 150℃ for 40min, and then heated to 190℃ to collect the product fraction. The reflux ratio is 1:5, and the collected product fraction is high-purity octocrylene.

[0128] Example 4

[0129] Compared with Example 2, this embodiment only replaces the composite supported catalyst II with the composite supported catalyst IV prepared by the method of Preparation Example 4, while the other steps and parameters are the same as in Example 2.

[0130] Example 5

[0131] Compared with Example 2, Comparative Example 5 only replaces the composite supported catalyst II with the composite supported catalyst V prepared by the method of Preparation Example 5. The remaining steps and parameters are the same as in Example 2.

[0132] Comparative Example 1

[0133] Compared with Example 2, in Comparative Example 1, the composite supported catalyst II in step S1 is replaced with sodium carbonate, and step S2 is omitted, directly proceeding to step S3. Other steps and parameters are the same as in Example 2.

[0134] Comparative Example 2

[0135] Compared with Example 2, in Comparative Example 2, no single-atom bismuth dopant was added to the composite supported catalyst II in step S1 during the preparation process, and the other steps and parameters were the same as in Example 2.

[0136] Comparative Example 3

[0137] Compared with Example 2, Comparative Example 3 replaces the microwave irradiation and negative pressure conditions in step S1 with conventional oil bath heating (oil bath temperature 115°C) and atmospheric pressure reaction. There is no microwave or step negative pressure, but the other steps and parameters are the same as in Example 2.

[0138] Comparative Example 4

[0139] Compared with Example 2, in Comparative Example 4, the catalyst activity decreased in step S2 but was not self-repaired and was directly reused. Other steps and parameters were the same as in Example 2.

[0140] Comparative Example 5

[0141] Compared with Example 2, Comparative Example 5 replaces the two-stage vacuum distillation in step S3 with single-stage vacuum distillation, without gradient temperature rise or two-stage high vacuum, while other steps and parameters are the same as in Example 2.

[0142] 1. Experimental testing

[0143] (1) Octocrylene purity / Etocriline residue

[0144] High-performance liquid chromatography (HPLC) was used for analysis. The test conditions were as follows: C18 column (250 mm × 4.6 mm, 5 μm), mobile phase methanol:water = 85:15, flow rate 1 mL / min, wavelength 254 nm, and external standard method for quantification.

[0145] (2) Catalyst activity retention rate

[0146] The reaction was repeated 5 times, and the activity retention rate was calculated with the initial reaction rate and conversion rate being 100%.

[0147] (3) Product yield

[0148] Actual product output / theoretical output × 100%.

[0149] (4) Impurity content

[0150] HPLC normalization method: sum of the areas of all impurity peaks except the main peak.

[0151] 2. Experimental Results

[0152] Table 1. Comparison of octocrylene purity, product yield, and etopoline residue in each example and comparative example.

[0153] Example 1 0.038 99.78 88.2 Example 2 0.031 99.82 89.5 Example 3 0.035 99.80 88.7 Example 4 0.041 99.75 87.6 Example 5 0.039 99.76 87.9 Comparative Example 1 0.87 97.62 71.3 Comparative Example 2 0.12 99.34 85.1 Comparative Example 3 0.56 98.41 76.4 Comparative Example 4 0.18 99.08 81.7 Comparative Example 5 0.09 99.25 84.0

[0154] Table 2 Comparison of catalyst activity retention rate, total impurities, and reaction time for each example and comparative example.

[0155] Example 1 95.6 0.22 2.5 Example 2 96.8 0.18 3.5 Example 3 96.2 0.20 4.5 Example 4 94.9 0.25 3.5 Example 5 95.2 0.24 3.5 Comparative Example 1 41.5 2.38 7.5 Comparative Example 2 92.3 0.66 4.5 Comparative Example 3 94.7 1.59 8.0 Comparative Example 4 67.9 0.92 5.5 Comparative Example 5 96.5 0.75 3.6

[0156] As can be seen from Tables 1 and 2 above, the purity and yield of Examples 1-3 are significantly better than those of the comparative examples, and the reaction is more complete, with shorter reaction time, lower total impurities, and higher catalyst activity retention. Example 4 uses diatomaceous earth support, which has a slightly lower specific surface area, resulting in a slight decrease in activity and purity. Example 5 uses molecular sieve support, which has a smaller pore size, resulting in slightly slower mass transfer and slightly lower performance than mesoporous silica.

[0157] Comparative Example 1 used a conventional catalyst with no self-repairing function, resulting in a significant decrease in purity and yield, a marked increase in residues and impurities, and a short catalyst lifetime. Conventional catalysts have few active sites and are easily deactivated. Without self-repairing, active components are rapidly lost, leading to low transesterification conversion and numerous side reactions.

[0158] In Comparative Example 2, the catalyst without single-atom bismuth doping showed decreased purity and yield, prolonged reaction time, and increased impurities. This is because single-atom bismuth acts as a Lewis acid promoter, improving the dispersion of active sites and electronic effects. Without bismuth, catalytic activity and selectivity decrease, the transesterification rate decreases, and incomplete reactions increase.

[0159] Comparative Example 3, using an oil bath and atmospheric pressure without microwave-vacuum synergistic treatment, resulted in a reaction time that was more than doubled, a significant decrease in conversion rate and purity, and a doubling of impurities. Because transesterification is a reversible reaction, selective microwave heating and stepped negative pressure synergistic treatment can rapidly remove ethanol, shifting the equilibrium to the right.

[0160] In Comparative Example 4, the catalyst was not self-repaired and was directly reused. After cycling, the activity retention rate decreased significantly, and the yield and purity also decreased. Because it was not self-repaired, the carbon-covered sites on the catalyst surface and the active components were lost, resulting in a shortened lifespan.

[0161] Comparative Example 5 used single-stage vacuum distillation, resulting in decreased purity and yield, higher impurities, and no significant change in reaction time. This was because the single-stage distillation had insufficient separation, and the light / heavy components were not completely removed.

[0162] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A production process for high-purity octocrylene, characterized in that, Includes the following steps: S1, Microwave-vacuum synergistic catalytic reaction: The transesterification reaction was carried out by mixing estradiol, isooctyl alcohol and a composite supported catalyst under microwave irradiation and negative pressure conditions. The removal of ethanol generated in the reaction was accelerated by selective microwave heating, and the reaction endpoint was controlled. S2, Catalyst self-repair and regeneration: When the catalyst activity decreases, a self-healing heat treatment is performed under an inert atmosphere. The residual organic components on the catalyst surface are used to generate a carbon skeleton in situ and re-anchor the active components. After the catalyst activity is restored, it can be recycled. S3, Post-processing Refining: The reaction solution was decolorized, filtered, and distilled to obtain high-purity octocrylene.

2. The production process according to claim 1, characterized in that, The preparation of the composite supported catalyst described in step S1 includes the following steps: (1) Add an inert porous support to a silane coupling agent KH-550 ethanol solution with a mass fraction of 1-3%, and add a single-atom bismuth dopant (Bi(NO3)3·5H2O) with a mass of 0.5-1.2% of the support. The solid-liquid ratio of the support to the solution is 1:(10-15). Heat in a water bath at 50-60℃ and stir at 200-300 rpm for 2-3 hours. After stirring, filter. Wash the filter cake with anhydrous ethanol 3-4 times. After washing, dry at 105-110℃ for 4-6 hours to obtain the modified support. (2) The modified carrier was loaded with sodium carbonate and triethanolamine by gradient impregnation method, and the mass ratio of modified carrier, sodium carbonate and triethanolamine was 100:(30~50):(3~8); The gradient impregnation method is as follows: first impregnate at 40℃ for 1 hour, then raise the temperature to 60℃ and impregnate for 1 hour, while maintaining stirring at 150~200 rpm during the impregnation process; (3) The loaded material is heat-treated at 180~220℃ for 30~60min under N2 atmosphere; (4) After heat treatment, the catalyst is activated by microwave at 200~250W for 3~8min to obtain the anchored composite supported catalyst.

3. The production process according to claim 2, characterized in that, The inert porous support mentioned in step (1) is one of mesoporous silica, diatomaceous earth, or molecular sieve.

4. The production process according to claim 1, characterized in that, The mass ratio of estradiol, isooctanol, and the composite supported catalyst mentioned in step S1 is 1:(3.5~5.5):(0.08~0.15); The reaction time for the transesterification reaction is 2.5 to 4.5 hours.

5. The production process according to claim 1, characterized in that, The power of microwave irradiation in step S1 is controlled in a stepped manner: 150~250W in the initial stage of the reaction, 300~400W in the middle stage, and 200~300W in the later stage. The negative pressure conditions are adjusted in steps according to the reaction process: -0.05~-0.06MPa in the initial stage of the reaction, -0.07~-0.08MPa in the middle stage, and -0.085~-0.095MPa in the later stage.

6. The production process according to claim 1, characterized in that, The reaction endpoint described in step S1 is controlled by online monitoring. The content of etorethrin is monitored online using high performance liquid chromatography. The reaction is stopped when the content of etorethrin is ≤0.05%.

7. The production process according to claim 1, characterized in that, The inert atmosphere mentioned in step S2 is one or a mixture of two of nitrogen and argon, with the volume ratio of nitrogen to argon being (1~3):

1. The flow rate of the inert atmosphere during the self-healing process is 50~100mL / min.

8. The production process according to claim 1, characterized in that, The temperature of the self-healing heat treatment in step S2 is 220~260℃, and the time is 1~2h.

9. The production process according to claim 1, characterized in that, The decolorization described in step S3 is activated carbon decolorization; The filtration uses a 0.22μm organic filter membrane, and the filtration pressure is 0.1~0.15MPa.

10. The production process according to claim 1, characterized in that, The distillation described in step S3 is a two-stage vacuum distillation, in which isooctyl alcohol is recovered by a first vacuum distillation and then high-purity octocrylene is obtained by a second high-vacuum gradient distillation. The parameters for the recovery of isooctanol by primary vacuum distillation are: vacuum degree -0.08~-0.09MPa, distillation temperature 110~125℃, and reflux ratio 1:(2~3); The vacuum degree of the secondary high vacuum gradient distillation is ≤500Pa. The gradient heating mode is adopted: the initial fraction is removed at 150℃, the temperature is maintained for 30~40min, and then the temperature is raised to 175~190℃ to collect the product fraction. The reflux ratio is 1:(4~5). The collected product fraction is high-purity octocrylene.

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