Distillation purification apparatus for phenyl chlorothioformate
Patent Information
- Application Number
- CN202522302879.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-30
- Publication Date
- 2026-09-22
- Estimated Expiration
- 2035-10-30
AI Technical Summary
[0004]本实用新型提供一种硫代氯甲酸苯酯的蒸馏提纯装置，用以解决现有薄膜蒸发器易挂料影响分离效率、提纯效果不佳、产品外观易变色和纯度稳定性不足的问题
1）提纯效果显著：采用刮板蒸馏器的高效成膜技术，配合真空环境，可有效脱除PTCF中的低沸点溶剂、杂质和高沸点残渣，实现溶剂、产品和杂质的同步分离，产品纯度提升至99.0%以上，提纯效果佳，外观稳定为均匀浅黄色，满足高端医药中间体的品质要求。
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Figure CN224777429U_ABST
Abstract
Description
Technical Field
[0001] This utility model relates to the field of chemical product separation technology, and in particular to a distillation and purification apparatus for phenyl thiochloroformate. Background Technology
[0002] Phenyl thiocarbamate (PTCF), with the chemical formula C7H5ClOS, CAS number 1005-56-7, and a molecular weight of 172.63, is a yellow to yellowish-green liquid at room temperature with a boiling point of 81-83℃. It is mainly used in the preparation of bicyclic thymidine analogs, the thiocarbonylation reaction of unprotected thymidine nucleosides, and the synthesis of phenoxy-thiocarbonyl esters of protected ribonucleosides. It is also a key intermediate in the synthesis of high-end prostate cancer treatment drugs such as apalutamide. Therefore, its product quality directly affects the performance of downstream pharmaceutical products. Currently, in the industrial production of PTCF, the reaction product system contains low-boiling-point low-polarity solvents, low-boiling-point impurities (phenol, phenyl chlorocarbamate, etc., with a total content ≤0.5%), and high-boiling-point impurities (diphenyl carbonate), requiring purification through distillation. Existing technologies often use thin-film evaporators for distillation purification, but the following drawbacks have been found during use: First, the thin-film evaporator has insufficient control over the uniformity of the film formation of the material, which can easily lead to incomplete removal of low-boiling-point impurities. Some products may have an orange-red appearance due to residual trace amounts of colored impurities. Second, it has limited adaptability to high-viscosity materials, and long-term operation is prone to material adhering to the wall, which affects separation efficiency and product purity stability. Third, the vacuum level is limited, making it difficult to meet the requirements of PTCF fine purification for deep separation of low-boiling-point substances.
[0003] Therefore, there is an urgent need for a targeted distillation and purification device to address the shortcomings of existing equipment and ensure the appearance quality and purity stability of PTCF products. Utility Model Content
[0004] This invention provides a distillation and purification apparatus for phenyl thiochloroformate, which solves the problems of existing thin-film evaporators being prone to material buildup affecting separation efficiency, poor purification effect, easy discoloration of product appearance, and insufficient purity stability.
[0005] This invention provides a distillation and purification apparatus for phenyl thiochloroformate, comprising: a scraped plate still; a feed inlet at the top of the scraped plate still connected to the outlet of a pretreatment unit; the pretreatment unit is used to preheat the crude PTCF material and feed it into the scraped plate still; a gas phase outlet is provided at the top of the scraped plate still, and the gas phase outlet is connected to a condensation unit, which is used to recover low-boiling-point solvents and impurities to a pre-fraction collection tank; a finished product outlet is provided in the middle of the scraped plate still, and the finished product outlet is connected to a finished product collection tank through a third condenser; a residue outlet is provided at the bottom of the scraped plate still, and the residue outlet is connected to a high-boiling-point residue collection tank; a vacuum pump is connected to the top of the pre-fraction collection tank and the finished product collection tank, respectively, and the vacuum pump is used to maintain the vacuum environment of the entire apparatus.
[0006] Furthermore, the pretreatment unit includes a jacketed heating device, the inlet of which is connected to the crude product tank via a crude product discharge pump, the outlet of which is connected to a feed pump, and the inlet of the scraped plate still is connected to the outlet of the feed pump via an insulated conveying pipe.
[0007] Furthermore, the outer wall of the insulated conveying pipeline is equipped with an electric heat tracing device; the jacketed heating device is a jacketed heat exchanger that uses steam heating; and a first temperature sensor is installed at the outlet of the jacketed heating device.
[0008] Furthermore, the condensation unit includes a first condenser and a second condenser arranged in series. The gas phase outlet of the scraped still is connected to the input end of the first condenser, the gas phase outlet of the first condenser is connected to the input end of the second condenser, and the liquid phase outlet of the first condenser and the output end of the second condenser are respectively connected to the pre-distillate collection tank.
[0009] Furthermore, the first condenser is a shell-and-tube condenser, and the condensing medium is a chilled brine at -10 to 0°C; the second condenser is a plate condenser, and the condensing medium is a low-temperature ethylene glycol solution at -30 to -20°C.
[0010] Furthermore, the scraped plate still includes an inner cylinder and a heat exchange jacket surrounding the inner cylinder. The inner cylinder is equipped with a scraping film mechanism. The scraping film mechanism includes a motor, which is fixedly connected to the top of the scraped plate still. The output shaft of the motor is fixedly connected to a rotating shaft that extends into the inner cylinder. Multiple scrapers are evenly distributed on the rotating shaft. The gap between the scrapers and the inner wall of the inner cylinder is 0.5~2mm. A liquid distributor is provided above the scrapers.
[0011] Furthermore, the heat exchange jacket of the scraped still is heated by steam; the scrapers are made of polytetrafluoroethylene or Hastelloy, and the shape of the scrapers is triangular or trapezoidal.
[0012] Furthermore, the finished product outlet of the scraped plate still is located at 1 / 3 to 1 / 2 of the height of the inner cylinder, and a second temperature sensor and a solenoid valve are installed at the finished product outlet, with the second temperature sensor and the solenoid valve interlocked.
[0013] Furthermore, both the finished product collection tank and the pre-distillate collection tank are equipped with nitrogen protection devices.
[0014] The distillation and purification apparatus for phenyl thiochloroformate provided by this utility model has the following advantages and beneficial effects: 1) Significant purification effect: The efficient film-forming technology of the scraped plate still, combined with the vacuum environment, can effectively remove low-boiling-point solvents, impurities and high-boiling-point residues from PTCF, achieving simultaneous separation of solvent, product and impurities. The product purity is increased to over 99.0%, with excellent purification effect and a stable, uniform light yellow appearance, meeting the quality requirements of high-end pharmaceutical intermediates.
[0015] 2) High production efficiency: The uniform thin film formed by the rotating scraper in the scraper still can significantly improve the heat transfer coefficient. The appropriate film thickness helps to improve the heat transfer efficiency, evaporation efficiency and separation effect of the equipment. Combined with a two-stage condensation recovery system and a vacuum environment, the distillation cycle is shortened by 20-30% compared with traditional thin film evaporators, thus shortening the production time.
[0016] 3) Strong operational stability: The scraper is made of corrosion-resistant material, which can effectively prevent material from sticking to the wall and extend the service life of the equipment; the nitrogen protection device and the design of the heat-insulated conveying pipeline prevent product oxidation and discoloration and condensation and crystallization from clogging the pipeline, further ensuring the continuity of the production process and the stability of product quality.
[0017] 4) Energy saving and environmental protection: Through the efficient condensation and recovery system, the low boiling point solvent recovery rate is ≥90%, which improves the solvent recovery rate and utilization rate and reduces raw material waste; the vacuum environment reduces the distillation temperature and reduces distillation energy consumption, which is in line with the concept of green chemical production. Attached Figure Description
[0018] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0019] Figure 1 A schematic diagram of the distillation and purification apparatus for phenyl thiochloroformate provided in one embodiment of this utility model; Figure 2 A schematic diagram of the distillation and purification apparatus for phenyl thiochloroformate provided in another embodiment of the present invention. Figure 3 This is a schematic diagram of the structure of a scraper still provided in one embodiment of the present invention.
[0020] Explanation of reference numerals in the attached figures: 1. Scraped still, 2. Vacuum pump, 3. Fore-fraction collection tank, 4. Finished product collection tank, 5. High-boiling-point residue collection tank, 11. Inner cylinder, 12. Heat exchange jacket, 13. Motor, 14. Shaft, 15. Scraper, 16. Liquid distributor, 17. Finished product outlet, 31. First condenser, 32. Second condenser, 41. Third condenser, 61. Jacket heating device, 62. Crude product tank, 63. Crude product discharge pump, 64. Feed pump, 65. Insulated conveying pipeline, 66. Electric heat tracing device. Detailed Implementation
[0021] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions in the embodiments of this utility model are described clearly and completely below. Obviously, the described embodiments are only some embodiments of this utility model, not all embodiments. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are also within the protection scope of this utility model.
[0022] like Figure 1 This utility model discloses a distillation and purification apparatus for phenyl thiochloroformate, comprising: a scraped plate still 1; the feed inlet at the top of the scraped plate still 1 is connected to the outlet of a pretreatment unit; the pretreatment unit is used to preheat the crude PTCF material and feed it into the scraped plate still 1; a gas phase outlet is provided at the top of the scraped plate still 1, and the gas phase outlet is connected to a condensation unit, which is used to recover low-boiling-point solvents and impurities to the pre-fraction collection tank 3; a finished product outlet 17 is provided in the middle of the scraped plate still 1, and the finished product outlet 17 is connected to the finished product collection tank 4 through a third condenser 41; a residue outlet is provided at the bottom of the scraped plate still 1, and the residue outlet is connected to a high-boiling-point residue collection tank 5; a vacuum pump 2 is connected to the top of the pre-fraction collection tank 3 and the finished product collection tank 4, respectively, and the vacuum pump 2 is used to maintain the vacuum environment of the entire apparatus.
[0023] The pretreatment unit feeds crude PTCF into the scraped plate still 1, preheating it to accelerate distillation and improve separation and purification. The crude PTCF is distilled in the scraped plate still 1. Low-boiling-point substances are discharged through the vapor outlet and liquefied by the condenser unit, then recovered to the pre-fraction collection tank 3. PTCF is collected through the finished product outlet 17, cooled by the third condenser 41, and recovered to the finished product collection tank 4. High-boiling-point impurities collect at the bottom of the scraped plate still 1 and are sent to the high-boiling-point residue collection tank 5 through the residue outlet. Vacuum pump 2 provides vacuum to scraped still 1, ensuring rapid evaporation of low-boiling-point substances. Vacuum is also applied to the entire process of distillation, condensation, and collection to ensure consistent vacuum levels (100~500Pa) in each unit. This avoids localized gas accumulation that could affect separation and condensation efficiency, prevents pressure differences in the collection tanks that could lead to poor material discharge, and prevents air from entering the system and causing PTCF oxidation and discoloration.
[0024] The above-mentioned complete distillation and purification device is designed for the characteristics of the crude PTCF material system. Through the efficient film formation and precise separation capabilities of the scraped plate still 1, it achieves simultaneous separation of solvent, product and impurities. The separation efficiency is high and the purification effect is excellent. It effectively solves the problems of easy discoloration and insufficient purity stability of the product after purification by existing thin film evaporators, and ensures that the PTCF product has a stable and uniform light yellow appearance, which meets the quality requirements of high-end pharmaceutical intermediates.
[0025] like Figure 2 In some embodiments, the pretreatment unit includes a jacketed heating device 61, the inlet of which is connected to the crude product tank 62 via a crude product discharge pump 63, the outlet of which is connected to a feed pump 64, and the inlet of the scraped plate still 1 is connected to the outlet of the feed pump 64 via an insulated conveying pipe 65.
[0026] In some implementations, the outer wall of the insulated conveying pipeline 65 is equipped with an electric heat tracing device 66; the jacketed heating device 61 is a jacketed heat exchanger that uses steam heating; a first temperature sensor is installed at the outlet of the jacketed heating device 61. The pretreatment unit uses the jacketed heating device 61 to preheat the crude PTCF material to 60~80℃ to prevent the material from cooling and crystallizing due to excessively low temperature during transportation. The electric heat tracing device 66 on the outer wall of the insulated conveying pipeline 65 further ensures the temperature stability of the material during transportation and avoids pipeline blockage due to cooling and crystallization. The electric heat tracing device 66 is a commonly used electric heat tracing tape in the prior art.
[0027] In some embodiments, the condensation unit includes a first condenser 31 and a second condenser 32 connected in series. The gas phase outlet of the scraped still 1 is connected to the input end of the first condenser 31, the gas phase outlet of the first condenser 31 is connected to the input end of the second condenser 32, and the liquid phase outlet of the first condenser 31 and the output end of the second condenser 32 are respectively connected to the pre-fraction collection tank 3.
[0028] In some implementations, the first condenser 31 is a shell-and-tube condenser, with a condensing medium of chilled brine at -10 to 0°C; the second condenser 32 is a plate condenser, with a condensing medium of low-temperature ethylene glycol solution at -30 to -20°C. The crude PTCF material comes from the reaction product system of the reaction section, containing solvents and impurities below the boiling point of PTCF. After two-stage condensation using the chilled brine in the first condenser 31 and the low-temperature ethylene glycol solution in the second condenser 32, the solvent can be fully recovered and reused, ensuring a solvent recovery rate ≥90%, improving solvent recovery and utilization, and reducing resource waste.
[0029] like Figure 3 In some embodiments, the scraped still 1 includes an inner cylinder 11 and a heat exchange jacket 12 surrounding the inner cylinder 11. The inner cylinder 11 is provided with a scraping film mechanism. The scraping film mechanism includes a motor 13, which is fixedly connected to the top of the scraped still 1. The output shaft of the motor 13 is fixedly connected to a rotating shaft 14 that extends into the inner cylinder 11. Multiple scrapers 15 are evenly distributed on the rotating shaft 14. The gap between the scrapers 15 and the inner wall of the inner cylinder 11 is 0.5~2mm. A liquid distributor 16 is provided above the scrapers 15.
[0030] Motor 13 drives shaft 14 to rotate, thereby rotating scraper 15. When crude PTCF material enters inner cylinder 11 through top feed port, it is distributed to inner wall of inner cylinder 11 by liquid distributor 16. During descent, it is scraped into a thin film by continuously rotating scraper 15. The material passes through inner cylinder 11 and exchanges heat with heat medium in heat exchange jacket 12. After absorbing heat, low boiling point substances are continuously evaporated, and substances with different boiling points will be gradually separated, thereby achieving the purpose of distillation and purification separation.
[0031] The gap between the scraper 15 and the inner wall of the inner cylinder 11 is controlled at 0.5~2mm, which can scrape the material into a uniform film. The appropriate film thickness helps to improve the heat transfer efficiency, evaporation efficiency and separation effect of the equipment, shorten the production time, and can also scrape off and collect the solid residue adhering to the inner cylinder 11 wall, preventing material from sticking to the wall and clogging. The scraper 15 can be detachably connected to the rotating shaft 14, which facilitates disassembly and maintenance and reduces the difficulty of maintenance. The liquid distributor 16 and other mechanisms and components in the scraper still 1 are the same as in the prior art, so they are not described in detail here.
[0032] In some implementations, the heat exchange jacket 12 of the scraped still 1 is steam-heated; the scraper 15 is made of polytetrafluoroethylene (PTFE) or Hastelloy, and its shape is triangular or trapezoidal. The scraped still 1, heated by steam, controls the operating temperature to 110~130℃. Combined with a vacuum environment, this allows for the rapid removal of low-boiling-point solvents and impurities while preventing the decomposition or oxidation of PTCF due to high temperatures. The scraper 15 is made of PTFE or Hastelloy, which offers good wear resistance, corrosion resistance, and high-temperature resistance, effectively extending its service life.
[0033] In some embodiments, the finished product outlet 17 of the scraped still 1 is located at 1 / 3 to 1 / 2 of the height of the inner cylinder 11, and a second temperature sensor and a solenoid valve are provided at the finished product outlet 17, with the second temperature sensor and the solenoid valve interlocked.
[0034] The finished product outlet 17 of the scraped plate still 1 mainly corresponds to the PTCF distillation area, which is the area where "the gas phase has been separated after the material has formed a film and evaporated, and the high-boiling-point residue has not settled." It is used to collect the fraction at 81~83℃, i.e., the PTCF product. The discharge temperature is monitored in real time by a second temperature sensor to ensure that only qualified PTCF product is discharged, avoiding the mixing of high-boiling-point residue or unseparated gas phase. The second temperature sensor and the solenoid valve are interlocked with a control system commonly used in existing technology. The discharge rate can be adjusted in time according to the monitored temperature and the distillation rhythm. Specifically, a temperature threshold (81~83℃) is set. If the discharge temperature exceeds the set temperature ±5℃, the solenoid valve is triggered to automatically switch its on / off state, ensuring that the purity of the collected PTCF product can reach above 99.0%.
[0035] In some implementations, both the finished product collection tank 4 and the pre-fraction collection tank 3 are equipped with nitrogen protection devices. These devices prevent direct contact between the materials in the finished product collection tank 4 and the pre-fraction collection tank 3 and air, thus preventing material volatilization or oxidation and discoloration, further ensuring the appearance quality of the PTCF product. The nitrogen protection devices are commonly used nitrogen sealing devices in the prior art and will not be described in detail here.
[0036] It should be noted that arrows without reference numerals indicate the flow direction of gas-liquid mixtures, gas phases, or liquid phases.
[0037] In the distillation and purification apparatus for phenyl thiochloroformate described above, during operation, the crude product discharge pump 63 sends the crude PTCF material from the crude product tank 62 to the jacketed heating device 61. After preheating to 60~80℃, the material is then conveyed to the scraped plate still 1 through the insulated conveying pipeline 65 via the feed pump 64. The electric heating device 66 of the insulated conveying pipeline 65 maintains the temperature at around 70℃ to prevent material crystallization. Vacuum pump 2 provides a vacuum to scraped plate still 1, maintaining the vacuum level at 100~500Pa. Steam is introduced into the heat exchange jacket 12 of scraped plate still 1, and motor 13 is started to drive the rotating shaft 14 to rotate, thereby rotating the scraper 15. When the crude PTCF material enters the inner cylinder 11 through the top feed port, it is distributed to the inner wall of the inner cylinder 11 by the liquid distributor 16. During the descent, it is scraped into a thin film by the continuously rotating scraper 15. The material exchanges heat with the heat medium in the heat exchange jacket 12 through the cylinder wall of the inner cylinder 11, controlling the working temperature at 110~130℃. After absorbing heat, substances with different boiling points will gradually separate. Low-boiling-point substances are continuously evaporated and discharged from the gas phase outlet. The discharged gas phase is liquefied after two-stage condensation in the first condenser 31 (cryogenic brine) and the second condenser 32 (low-temperature ethylene glycol solution), and is recovered to the pre-fraction collection tank 3. PTCF is extracted through the finished product outlet 17, cooled by the third condenser 41, and then recycled to the finished product collection tank 4 equipped with a nitrogen protection device. High-boiling-point impurities are collected at the bottom of the scraped plate still 1 and sent to the high-boiling-point residue collection tank 5 through the residue discharge outlet. The residue is cleaned periodically.
[0038] Testing revealed that the purified PTCF product had a purity of 99.2%, a uniform light yellow appearance, and a low-boiling-point solvent recovery rate of 90%, fully meeting the requirements of downstream pharmaceutical companies. Furthermore, the production process was continuous and stable, with no issues of material buildup on equipment or product discoloration.
[0039] It should be noted that the detailed structure of some devices in this utility model is not described in detail, but belongs to the prior art known to those skilled in the art, and therefore will not be described again here. In addition, the parts of this device not described are the same as or can be implemented using existing technology.
[0040] It should be noted that those skilled in the art, under the guidance of this utility model, can also make some modifications to the design of the above system. For example, the equipment in the system is also equipped with level gauges, overflow / nitrogen pipelines, etc.; pumps, pressure sensors, flow meters or temperature sensors are installed on the conveying pipelines inside the system in different units or devices, and different valves, such as pressure relief valves, pressure regulating valves, safety valves, pneumatic valves, etc., are also installed to regulate and stabilize the pressure of the entire system, and the opening degree of the valves can also be adjusted to regulate the flow rate of materials in the pipeline, etc.
[0041] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this utility model, and not to limit it; although the utility model has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this utility model.
Claims
1. A distillation and purification apparatus for phenyl thiochloroformate, characterized in that, include: A scraped plate still is included; the feed inlet at the top of the scraped plate still is connected to the outlet of a pretreatment unit; the pretreatment unit is used to preheat the crude PTCF material and feed it into the scraped plate still; a gas phase outlet is provided at the top of the scraped plate still, which is connected to a condensation unit, used to recover low-boiling-point solvents and impurities to a pre-fraction collection tank; a finished product outlet is provided in the middle of the scraped plate still, which is connected to a finished product collection tank via a third condenser; a residue outlet is provided at the bottom of the scraped plate still, which is connected to a high-boiling-point residue collection tank; vacuum pumps are connected to the tops of the pre-fraction collection tank and the finished product collection tank, respectively, and the vacuum pumps are used to maintain a vacuum environment for the entire unit.
2. The distillation and purification apparatus for phenyl thiochloroformate according to claim 1, characterized in that, The pretreatment unit includes a jacketed heating device. The inlet of the jacketed heating device is connected to the crude product tank via a crude product discharge pump. The outlet of the jacketed heating device is connected to a feed pump. The inlet of the scraped plate still is connected to the outlet of the feed pump via an insulated conveying pipe.
3. The distillation and purification apparatus for phenyl thiochloroformate according to claim 2, characterized in that, The outer wall of the insulated conveying pipeline is equipped with an electric heat tracing device; the jacketed heating device is a jacketed heat exchanger that uses steam heating; a first temperature sensor is installed at the outlet of the jacketed heating device.
4. The distillation and purification apparatus for phenyl thiochloroformate according to claim 1, characterized in that, The condensation unit includes a first condenser and a second condenser connected in series. The gas phase outlet of the scraped still is connected to the input end of the first condenser, the gas phase outlet of the first condenser is connected to the input end of the second condenser, and the liquid phase outlet of the first condenser and the output end of the second condenser are respectively connected to the pre-fraction collection tank.
5. The distillation and purification apparatus for phenyl thiochloroformate according to claim 4, characterized in that, The first condenser is a shell-and-tube condenser, and the condensing medium is a chilled brine solution at -10 to 0°C; the second condenser is a plate condenser, and the condensing medium is a low-temperature ethylene glycol solution at -30 to -20°C.
6. The distillation and purification apparatus for phenyl thiochloroformate according to claim 1, characterized in that, The scraped plate still includes an inner cylinder and a heat exchange jacket surrounding the outer side of the inner cylinder. A scraping film mechanism is provided in the inner cylinder. The scraping film mechanism includes a motor, which is fixedly connected to the top of the scraped plate still. The output shaft of the motor is fixedly connected to a rotating shaft extending into the inner cylinder. Multiple scrapers are evenly distributed on the rotating shaft. The gap between the scrapers and the inner wall of the inner cylinder is 0.5~2mm. A liquid distributor is provided above the scrapers.
7. The distillation and purification apparatus for phenyl thiochloroformate according to claim 6, characterized in that, The heat exchange jacket of the scraped still is heated by steam; the scraper is made of polytetrafluoroethylene or Hastelloy, and the shape of the scraper is triangular or trapezoidal.
8. The distillation and purification apparatus for phenyl thiochloroformate according to claim 6, characterized in that, The finished product outlet of the scraped plate still is located at 1 / 3 to 1 / 2 of the height of the inner cylinder. A second temperature sensor and a solenoid valve are provided at the finished product outlet, and the second temperature sensor and the solenoid valve are interlocked.
9. The distillation and purification apparatus for phenyl thiochloroformate according to any one of claims 1-8, characterized in that, Both the finished product collection tank and the fore-distillate collection tank are equipped with nitrogen protection devices.