Use method of 2, 4-dihydroxybenzoic acid dissolving and recrystallizing equipment

Abstract

The invention discloses a use method of 2, 4-dihydroxybenzoic acid dissolving and recrystallizing equipment, the 2, 4-dihydroxybenzoic acid dissolving and recrystallizing equipment comprises a closed dissolving kettle, a crystallization kettle and a mother liquor storage tank, the closed dissolving kettle, a first separator, a first filtrate storage tank and the crystallization kettle are connected in sequence, and the mother liquor storage tank is connected with a second separator. A discharge port of the crystallization kettle is connected with a feed port of a second separator, a filtrate discharge port of the second separator is connected with a liquid inlet of a second filtrate storage tank, and a liquid outlet of the second filtrate storage tank is communicated with a liquid inlet of the mother liquid storage tank through a third pipeline; the second pipeline between the first separation column and the second pump body is communicated with a liquid outlet of the mother liquid storage tank through a fourth pipeline; the second pipeline between the second pump body and the fourth pipeline is communicated with one end of a backflow pipeline, and the other end of the backflow pipeline is communicated with the first pipeline. The 2, 4-dihydroxy benzoic acid dissolving and recrystallizing equipment disclosed by the invention can be used for preparing 2, 4-dihydroxy benzoic acid with the purity of 99.68%, and the content of metal ions is reduced to 0.15 ppm.

Description

Technical Field

[0001] This invention belongs to the field of recrystallization and refining technology of heat-sensitive substances, specifically relating to a method for using a 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus. Background Technology

[0002] 2,4-Dihydroxybenzoic acid (2,4-DHBA), also known as β-resorcinol, is a key raw material for aerospace composite materials monomers, electronic etching solution ligands, and intermediates in anticancer drugs. Its purity directly determines the performance of the final product. The pharmaceutical and aerospace fields have particularly high purity requirements (>99%), but currently, no products on the market meet these requirements. Synthetic methods for 2,4-dihydroxybenzoic acid include recrystallization, solvent extraction, and boric acid affinity synthesis. However, due to the similar physicochemical properties among dihydroxybenzoic acid isomers, such as the poor solubility of 2,4-DHBA and 2,6-DHBA, a single technique cannot simultaneously achieve selectivity and economy, and industrial scale-up is difficult. Traditional recrystallization methods have poor selectivity for isomers, with a purity limit of only 98%; the single boric acid affinity method can only remove the 1,2-dihydroxy isomer, and the synthesis purity is also limited; the combination of solvent extraction with recrystallization or high-performance liquid chromatography can effectively improve product purity, but it consumes a lot of organic solvents and is difficult to realize in industrial production.

[0003] The industrial production of 2,4-dihydroxybenzoic acid currently faces three major technical challenges:

[0004] (1) Low efficiency of isomer separation: The physical properties of isomers such as 2,4-dihydroxybenzoic acid and 2,6-dihydroxybenzoic acid are very similar, and the solubility difference is <5%. Industrial chromatography separation method requires 200L of solvent per kilogram of product, and the cost is $420 / kg.

[0005] (2) Insufficient trace metal removal technology: Traditional chelating resins are ineffective against Fe 3+ The adsorption capacity is ≤15mg / g, and the stainless steel material of the equipment leaches ions >5ppm;

[0006] (3) Lack of precision control in thermosensitive crystallization: The temperature of existing crystallization equipment fluctuates greatly, and the temperature difference at the edge of the industrial reactor is large, which can easily cause impurities to be encapsulated. Summary of the Invention

[0007] For special compounds such as 2,4-dihydroxybenzoic acid, which are difficult to separate isomers, sensitive to trace metals, and have strict requirements for lattice stability, the purpose of this invention is to provide a 2,4-dihydroxybenzoic acid dissolution and recrystallization device.

[0008] Another object of the present invention is to provide a method of using the above-described 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus.

[0009] The objective of this invention is achieved through the following technical solutions.

[0010] A 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus includes: a closed dissolution vessel, a crystallization vessel, and a mother liquor storage tank; the closed dissolution vessel is equipped with a feeding port; the crystallization vessel is made of glass.

[0011] The sealed dissolving vessel is connected to one end of the first pipeline, which is used to introduce solvent into the sealed dissolving vessel.

[0012] A closed dissolving vessel is used to hold the solvent, crude 2,4-dihydroxybenzoic acid, and phenylboronic acid derivatives. This allows the phenylboronic acid derivatives and 1,2-dihydroxybenzoic acid in the crude 2,4-dihydroxybenzoic acid to form a borate ester precipitate and a first filtrate. The outlet of the closed dissolving vessel is connected to the inlet of a first separator via a pipeline. The outlet of the first separator is connected to the inlet of a first filtrate storage tank. The outlet of the first filtrate storage tank is connected to the inlet of a crystallization vessel via a second pipeline. A second pump and a first separation column are installed on the second pipeline. The first separation column uses mercaptosilicone or carboxylated silica gel (if the impurities are mainly Fe). 3+ / Cu 2+ When ordinary metal ions are present, carboxylated silica gel is used as filler; the outlet of the crystallization vessel is connected to the inlet of the second separator, the filtrate outlet of the second separator is connected to the inlet of a second filtrate storage tank, the outlet of the second filtrate storage tank is connected to the inlet of the mother liquor storage tank through a third pipeline, and a third pump body is installed on the third pipeline; the second pipeline between the first separation column and the second pump body is connected to the outlet of the mother liquor storage tank through a fourth pipeline, and a fourth pump body is installed on the fourth pipeline;

[0013] The second pipeline between the second pump body and the fourth pipeline is connected to one end of a return pipeline, and the other end of the return pipeline is connected to the first pipeline.

[0014] The first filtrate storage tank is equipped with a turbidity meter, which is used to detect the turbidity of the first filtrate storage tank.

[0015] The crystallization vessel is equipped with an online infrared spectrometer, which is used to detect supersaturation within the crystallization vessel.

[0016] A first condenser is connected to a closed dissolving vessel. The first condenser is used to collect solvent and return it to the closed dissolving vessel. A second condenser is connected to a crystallizing vessel. The outlet of the second condenser is connected to the inlet of a solvent recovery tank. The second condenser is used to recover solvent to the solvent recovery tank.

[0017] The above technical solution also includes: a solvent storage tank, which is used to hold solvent, and the outlet of the solvent storage tank is connected to the other end of the first pipeline, and a first pump body is installed on the first pipeline.

[0018] The method of using the above-mentioned 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment includes the following steps:

[0019] Step 1: 2,4-Dihydroxybenzoic acid crude product and phenylboronic acid derivative are added into a closed dissolving vessel through the feeding port. Solvent is pumped into the closed dissolving vessel to maintain the temperature of the vessel at 45-85℃. The vessel is stirred at 50-150 rpm for 0.5-2 hours. During the reaction, 1,2-dihydroxybenzoic acid in the crude 2,4-dihydroxybenzoic acid reacts with the phenylboronic acid derivative to form a borate ester precipitate. Immediately after the reaction, the precipitate is filtered through a first separator to obtain the borate ester precipitate and the first filtrate. The first filtrate is stored in a first filtrate storage tank.

[0020] The turbidity of the filtrate in the first filtrate storage tank is detected by a turbidity meter. If the turbidity is >10 NTU, it is returned to the closed dissolving vessel through the reflux pipeline to start the second filtration. If the turbidity is ≤10 NTU, it is pumped into the first separation column.

[0021] Step 2, crystallization: After the first filtrate is separated by the first separation column to remove metal ions, it enters the crystallization kettle for vacuum evaporation crystallization. Vacuum evaporation crystallization includes the following steps in sequence: solvent evaporation stage, cooling crystallization stage, and reheating crystal growth stage.

[0022] Solvent evaporation stage: The solvent is evaporated in the crystallization vessel at -0.09MPa and 35~55℃, with a stirring speed of 80~200rpm. The solvent evaporated in the solvent evaporation stage is condensed by the second condenser and recovered to the solvent recovery tank. During the solvent evaporation stage, the supersaturation of the solution in the crystallization vessel is monitored by an online infrared spectrometer until the supersaturation of the solution reaches 1.3.

[0023] Cooling crystallization stage: When the supersaturation of the solution in the crystallization vessel reaches 1.3, 2,4-dihydroxybenzoic acid crystal seeds are injected into the crystallization vessel through a microfluidic seed injector. At the same time, the stirring speed of the crystallization vessel is adjusted to 120~150 rpm, and the crystallization vessel is cooled to 30℃ at a rate of 0.2-2.0℃ / min. When the temperature drops to 30℃, the vacuum degree of the crystallization vessel is adjusted to -0.09~-0.08MPa, and the crystallization vessel is further cooled to 19-25℃. When the temperature inside the crystallization vessel reaches 19-25℃, the vacuum degree of the crystallization vessel is gradually restored to atmospheric pressure. The crystallization vessel is kept stirred throughout the cooling crystallization stage.

[0024] Warming and crystal growth stage: Adjust the rotation speed inside the crystallization vessel to 30-80 rpm, and heat the crystallization vessel to 35℃ at a rate of 0.3-1.0℃ / min until no more crystals are continuously generated, then stop crystallization;

[0025] Step 3: The solution containing crystals is fed into the second separator F102 through the outlet of the crystallization kettle for filtration to obtain the second filtrate and the second precipitate. The second precipitate is then vacuum dried to obtain the product.

[0026] In the above technical solution, the 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment also includes: a vacuum drying oven, which is used to dry the second precipitate.

[0027] In the above technical solution, the 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment further includes: a third condenser, a first filtrate storage tank, a second filtrate storage tank, a second condenser, and a vacuum drying oven, all of which are connected to the gas inlet of the third condenser. The liquid outlet of the third condenser is connected to a buffer tank. The third condenser is used to recover the solvent, and the solvent is condensed and recovered to the buffer tank by the third condenser.

[0028] In the above technical solution, the outlet of the solvent recovery tank and the outlet of the buffer tank are both connected to one end of a fifth pipeline, and the other end of the fifth pipeline is connected to the return pipeline. A fifth pump body P105 is installed on the fifth pipeline. A four-way valve is installed on the second pipeline. The four-way valve has four connected ports, of which two ports are connected in series in the second pipeline, and the other two ports are connected to the fifth pipeline and the return pipeline, respectively.

[0029] In the above technical solution, the 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment further includes: a refrigerant generator and a heat-refrigerant integrated unit. The refrigerant generator provides cooling medium for the first condenser, the second condenser, and the third condenser. The closed dissolution vessel and the crystallization vessel are respectively equipped with jackets. The heat-refrigerant integrated unit delivers heat exchange medium to the jackets of the closed dissolution vessel and the crystallization vessel, respectively, to control the temperature of the closed dissolution vessel and the crystallization vessel.

[0030] In the above technical solution, the buffer tank is connected to a vacuum pump, which can create a negative pressure environment in the buffer tank.

[0031] In the above technical solution, the crystallization vessel includes: a vessel body, a cover, a motor, a distribution plate, and a stirring paddle. A jacket is installed outside the vessel body, the cover is installed on the vessel body, the stirring paddle is located inside the vessel body, the motor is located above the vessel body, and the motor output shaft passes through the cover and is connected to the stirring paddle shaft. The stirring paddle shaft is hollow, and an optical fiber temperature sensor is installed inside the shaft to measure the temperature at the center position inside the vessel body.

[0032] The liquid inlet of the crystallization vessel is located on the cover, and the distribution plate is located below the cover and is horizontally fixed in the vessel body. The upper surface of the distribution plate forms a cross-shaped flow divider and four guide grooves. The cross-shaped flow divider is opposite to the liquid inlet of the cover. The cross-shaped flow divider is formed by two rigid plates perpendicularly intersecting to form a cross and dividing it into four areas. The four areas are recessed relative to the upper surface of the distribution plate. The rigid plates are perpendicular to the horizontal direction. Each area is connected to one end of a guide groove. The four areas are connected to four guide grooves. Each guide groove has a through hole. The four guide grooves are curved.

[0033] A spiral distributed fiber optic temperature sensor is installed on the inner wall of the vessel. The spiral distributed fiber optic temperature sensor is electrically connected to the PLC controller. The radial temperature difference is obtained through the temperature difference between the spiral distributed fiber optic temperature sensor and the fiber optic temperature sensor.

[0034] The vessel is equipped with a multi-point platinum resistance sensor, which is used to obtain the axial temperature difference inside the vessel. The multi-point platinum resistance sensor is electrically connected to the PLC controller.

[0035] In the above technical solution, during the solvent evaporation stage, when the radial temperature difference increases by 2°C or the axial temperature difference increases by 1.5°C, the speed of the stirring paddle is increased by 15%. The initial value of the stirring paddle is set to 80 rpm, and the maximum speed of the stirring paddle is 200 rpm.

[0036] During the cooling crystallization stage, when the radial temperature difference increases by 1.5℃ or the axial temperature difference increases by 1℃, the speed of the stirring paddle increases by 5%, and the flow rate of the medium in the jacket of the crystallizer increases by 10%. The initial value of the stirring paddle is set to 120 rpm, and the maximum speed of the stirring paddle is 150 rpm.

[0037] During the warming and crystal growth stage, when the radial temperature difference increases by 3°C or the axial temperature difference increases by 2.5°C, a reverse stirring pulse is activated for 5 seconds until crystal formation stops.

[0038] In the above technical solution, the solvent is methanol, ethanol or ethyl acetate.

[0039] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0040] 1. Using the 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment of the present invention, 2,4-dihydroxybenzoic acid with a purity of 99.68% can be prepared, and the metal ion content is reduced to 0.15 ppm.

[0041] 2. The 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment of the present invention can recover and reuse the solvent, and the solvent consumption rate is only 4% of the initial amount added.

[0042] 3. The 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment of the present invention can be operated through the automatic control system of the equipment, which is simple and quick to operate, frees up manpower, and speeds up the production rate. Attached Figure Description

[0043] Figure 1 This is a schematic diagram of the 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus of the present invention;

[0044] Figure 2 This is a cross-sectional view of the crystallization vessel of the 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus of the present invention;

[0045] Figure 3 This is a top view of the distribution plate of the crystallization vessel in the 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus of the present invention.

[0046] 1: Kettle body, 2: Cover body, 3: Motor, 4: Distribution plate, 4-1: Cross-shaped flow divider, 4-2: Flow guide groove, 5: Stirring paddle, 6: Spiral distributed fiber optic temperature sensor, 7: Fiber optic temperature sensor, 8: Multi-point platinum resistance sensor, 9: Microfluidic seed injector, 10: Four-way valve. Detailed Implementation

[0047] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings.

[0048] The purity and source of the reagents used in the following examples are as follows:

[0049] Crude 2,4-dihydroxybenzoic acid (98.5%) was purchased from Jining Qicai Chemical Co., Ltd.

[0050] 2,4-Dihydroxybenzoic acid crystals (average particle size = 74 μm) were purchased from Fisher Chemical Reagents and sieved using a 200-mesh sieve.

[0051] 3-Aminophenylboronic acid (98%) and mercaptosilica gel (38~74 microns) were purchased from Shanghai Maclean Bioreactor Co., Ltd.

[0052] Example 1

[0053] like Figure 1 As shown, a 2,4-dihydroxybenzoic acid dissolution and recrystallization device includes: a closed dissolution vessel R101, a crystallization vessel R102 (the crystallization vessel R102 has a vacuum degree of -0.1 MPa) and a mother liquor storage tank V104. The closed dissolution vessel R101 is equipped with a feeding port; the crystallization vessel R102 is made of glass (to prevent metal ions from seeping out during the crystallization process).

[0054] The sealed dissolving vessel R101 is connected to one end of the first pipeline, which is used to introduce solvent into the sealed dissolving vessel R101.

[0055] A closed dissolving vessel R101 is used to hold solvent, crude 2,4-dihydroxybenzoic acid, and a phenylboronic acid derivative (directing agent) to cause the 1,2-dihydroxybenzoic acid (an isomer of 2,4-dihydroxybenzoic acid) in the phenylboronic acid derivative and crude 2,4-dihydroxybenzoic acid to form a borate ester precipitate and a first filtrate. The outlet of the closed dissolving vessel R101 is connected to the inlet of the first separator F101 via a pipeline. The outlet of the first separator F101 is connected to the inlet of the first filtrate storage tank V102. The outlet of the first filtrate storage tank V102 is connected to the inlet of the crystallizing vessel R102 via a second pipeline. A second pump body P102 and a first separation column S101 are installed on the second pipeline. The first separation column S101 is filled with mercaptosilicone and is used to adsorb metal ions Pb through chemical action. 2+ Hg 2+ The outlet of the crystallization vessel R102 is connected to the inlet of the second separator F102. The filtrate outlet of the second separator F102 is connected to the inlet of a second filtrate storage tank V103. The outlet of the second filtrate storage tank V103 is connected to the inlet of the mother liquor storage tank V104 through a third pipeline. A third pump body P103 is installed on the third pipeline. The second pipeline between the first separation column S101 and the second pump body P102 is connected to the outlet of the mother liquor storage tank V104 through a fourth pipeline. A fourth pump body P104 is installed on the fourth pipeline.

[0056] The second pipeline between the second pump body P102 and the fourth pipeline is connected to one end of a return pipeline, and the other end of the return pipeline is connected to the first pipeline.

[0057] The first filtrate storage tank V102 is equipped with a turbidity meter, which is used to detect the turbidity of the first filtrate storage tank V102; the crystallization vessel R102 is equipped with an online infrared spectrometer, which is used to detect the supersaturation in the crystallization vessel R102.

[0058] A first condenser E101 is connected to a closed dissolving vessel R101. The first condenser E101 is used to collect solvent and return it to the closed dissolving vessel R101. A second condenser E102 is connected to a crystallizing vessel R102. The condensate outlet of the second condenser E102 is connected to the inlet of a solvent recovery tank V105. The second condenser E102 is used to recover solvent to the solvent recovery tank V105.

[0059] It also includes: a solvent storage tank V101, which holds solvent; the outlet of the solvent storage tank V101 is connected to the other end of the first pipeline; and a first pump P101 is installed on the first pipeline between the solvent storage tank V101 and the return pipeline. The solvent storage tank V101 not only allows solvent to be introduced into the closed dissolving vessel R101, but also, through the first pump P101 connected to the solvent storage tank V101, it enables the washing of each container, effectively removing small amounts of solid residue from the surface of the vessel.

[0060] The method of using the above-mentioned 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment includes the following steps:

[0061] Step 1: 25 kg of crude 2,4-dihydroxybenzoic acid and 0.15 kg of phenylboronic acid derivative (3-aminophenylboronic acid) are added to the closed dissolving vessel R101 through the feed port. (The first pump body P101 is turned on) 60 L of solvent (from solvent storage tank V101) is pumped into the closed dissolving vessel R101 to maintain the temperature of the closed dissolving vessel R101 at 80 °C. The closed dissolving vessel R101 is stirred and reacted for 1 hour at a speed of 80 rpm. During the reaction, 1,2-dihydroxybenzoic acid in the crude 2,4-dihydroxybenzoic acid reacts with the phenylboronic acid derivative to form a borate ester precipitate. Immediately after the reaction, the precipitate is filtered through the first separator F101 to obtain the borate ester precipitate and the first filtrate. The first filtrate is stored in the first filtrate storage tank V102. The solvent is ethanol.

[0062] The turbidity of the filtrate in the first filtrate storage tank V102 is measured using a turbidity meter. If the turbidity is >10 NTU, it is returned to the closed dissolving vessel R101 via the reflux pipeline to start the second filtration. If the turbidity is ≤10 NTU, it is pumped into the first separation column S101, where trace metals are adsorbed and removed by the mercaptosilicone in the first separation column S101 (Fe). 3+ The content decreased from 85 ppm to 0.5 ppm.

[0063] Step 2, crystallization: After the first filtrate is deionized by the first separation column S101, it enters the crystallization vessel R102 (the liquid level in the crystallization vessel R102 is not lower than 20% of its volume) for vacuum evaporation crystallization. Vacuum evaporation crystallization includes the following steps in sequence: solvent evaporation stage, cooling crystallization stage, and reheating crystal growth stage.

[0064] Solvent evaporation stage: The solvent is evaporated in crystallization vessel R102 at -0.09MPa and 35℃ (stirring speed is 80~200rpm). The solvent evaporated in the solvent evaporation stage is condensed in the second condenser E102 and recovered to the solvent recovery tank V105. During the solvent evaporation stage, the supersaturation of the solution in crystallization vessel R102 is monitored by an online infrared spectrometer until the supersaturation of the solution reaches 1.3.

[0065] Cooling crystallization stage: When the supersaturation of the solution in crystallization vessel R102 reaches 1.3, 37.5g of seed crystals (2,4-dihydroxybenzoic acid crystals with an average particle size of 74μm) are injected into crystallization vessel R102 through microfluidic seed injector 9. At the same time, the stirring speed of crystallization vessel R102 is adjusted to 120~150rpm, and crystallization vessel R102 is cooled to 30℃ at a rate of 0.5℃ / min. When the temperature drops to 30℃, the vacuum degree of crystallization vessel R102 is adjusted to -0.08MPa, and then crystallization vessel R102 is cooled to 25℃. When the temperature inside crystallization vessel R102 reaches 25℃, the vacuum degree of crystallization vessel R102 is gradually restored to atmospheric pressure. During the cooling crystallization stage, crystallization vessel R102 is always stirred.

[0066] Warm-up crystal growth stage: Adjust the rotation speed inside crystallizer R102 to 60 rpm, and heat crystallizer R102 to 35℃ at a rate of 0.5℃ / min until no more crystals are continuously generated, then stop crystallization;

[0067] Step 3: The solution containing crystals is filtered through the outlet of crystallizer R102 into the second separator F102 to obtain a second filtrate and a second precipitate. The second precipitate is then vacuum dried at 60℃ for 6 hours (-0.08MPa) to obtain 24.375 kg of product, with a calculated yield of 97.5%. HPLC analysis showed that the purity of 2,4-dihydroxybenzoic acid in the product was 99.68%, and the metal ion content was 0.15 ppm.

[0068] The second filtrate is temporarily stored in the second filtrate storage tank V103, and can be further collected to the mother liquor storage tank V104 through the third pipeline. The second filtrate in the mother liquor storage tank V104 can be pumped into the second pipeline by the fourth pump body P104 through the fourth pipeline, filtered by the first separation column S101, and then entered the crystallization kettle R102 for recycling.

[0069] Example 2

[0070] A 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus, based on Example 1, further includes a vacuum drying oven GX101, which is used to dry a second precipitate. The second precipitate is placed in the vacuum drying oven GX101 and vacuum dried at 60°C for 6 hours to obtain the product.

[0071] The 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment also includes: a third condenser E103; a first filtrate storage tank V102; a second filtrate storage tank V103; a second condenser E102; and a vacuum drying oven GX101, all connected to the gas inlet of the third condenser E103. The liquid outlet of the third condenser E103 is connected to a buffer tank V106. The third condenser E103 is used to recover the solvent, which is then condensed and recovered to the buffer tank V106. During the above reaction process, 57.5 L of solvent was recovered in the solvent recovery tank V105 and the buffer tank V106, representing a solvent recovery rate of approximately 96%.

[0072] The outlet of the solvent recovery tank V105 and the outlet of the buffer tank V106 are both connected to one end of a fifth pipeline, and the other end of the fifth pipeline is connected to the return pipeline. A fifth pump body P105 is installed on the fifth pipeline. A four-way valve 10 is installed on the second pipeline. The four-way valve has four connected ports, two of which are connected in series in the second pipeline, and the other two ports are connected to the fifth pipeline and the return pipeline, respectively.

[0073] The 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment also includes: a refrigerant compressor and a combined heat and refrigerant compressor (not shown in the figure). Both the refrigerant compressor and the combined heat and refrigerant compressor use water as the medium. The refrigerant compressor provides cooling medium for the first condenser E101, the second condenser E102, and the third condenser E103. The closed dissolution vessel R101 and the crystallization vessel R102 are respectively equipped with jackets. The combined heat and refrigerant compressor supplies heat exchange medium to the jackets of the closed dissolution vessel R101 and the crystallization vessel R102, respectively, to control the temperature of the closed dissolution vessel R101 and the crystallization vessel R102.

[0074] A vacuum pump P106 is connected to the buffer tank V106, which can create a negative pressure environment in the buffer tank V106.

[0075] Example 3

[0076] A 2,4-dihydroxybenzoic acid dissolution and recrystallization device, based on Example 2, is provided with liquid level sensors in solvent storage tank V101, mother liquor storage tank V104, solvent recovery tank V105 and buffer tank V106.

[0077] Electric valves are installed at the feed inlets of both the first separator F101 and the second separator F102. Fiber optic level switches are installed inside both the first separator F101 and the second separator F102. The fiber optic level switches are used to detect the material level inside the corresponding first separator F101 or second separator F102 and output a material level detection electrical signal to control the opening and closing of the corresponding electric valve. When the fiber optic level switch detects that the material level is higher than the set value, it automatically controls the closing of its corresponding electric valve and stops the feeding at the feed inlet.

[0078] An online ion spectrometer is connected to the outlet of the first separation column S101 to detect the concentration of metal ions in the solution entering the crystallization vessel R102. The opening of the electric regulating valve at the inlet of the first separation column S101 is controlled according to the concentration of metal ions detected by the online ion spectrometer to adjust the removal efficiency of metal ions.

[0079] Pressure sensors are installed on the outlet side of the first pump body P101, the second pump body P102, the third pump body P103, the fourth pump body P104, and the fifth pump body P105 to detect the pressure after the pump.

[0080] To prevent the risk of deflagration due to steam overflow during filtration, the first separator F101 is fitted with a polytetrafluoroethylene (PTFE) explosion-proof thermal filter funnel sleeve. The PTFE material of the explosion-proof thermal filter funnel sleeve is 0.5~1mm thick, has a temperature resistance range of -200℃~260℃, and a surface tension of ≤18dyn / cm. This makes the first separator F101 suitable for thermal filtration of flammable solvents with a boiling point ≤80℃, and can reduce steam overflow by more than 90%.

[0081] Example 4

[0082] A 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus, based on Example 3, such as... Figures 2-3 As shown, the crystallization vessel R102 includes: vessel body 1, cover body 2, motor 3, distribution plate 4 and stirring paddle 5. A jacket is installed outside the vessel body 1, the cover body is installed on the vessel body, the stirring paddle is located inside the vessel body, the motor is located above the vessel body, and the motor output shaft passes through the cover body and is connected to the stirring paddle shaft. The stirring paddle shaft is hollow, and an optical fiber temperature sensor 7 is installed inside the shaft to measure the temperature at the center position inside the vessel body.

[0083] The crystallization vessel R102 is made of borosilicate glass with an inner wall roughness of ≤0.1μm. It has high chemical corrosion resistance, high strength, high smoothness and good optical clarity, which makes it easy to monitor the crystallization process. At the same time, it is resistant to acid corrosion during production and is not easy to form scale on the wall.

[0084] The liquid inlet of the crystallizing vessel R102 is located on the cover. The distribution plate is located below the cover and is horizontally fixed inside the vessel. The upper surface of the distribution plate has a cross-shaped flow divider 4-1 and four guide grooves 4-2. The cross-shaped flow divider is opposite to the liquid inlet of the cover. The cross-shaped flow divider is formed by two rigid plates perpendicularly intersecting to form a cross and dividing it into four areas. The four areas are recessed relative to the upper surface of the distribution plate. The rigid plates are perpendicular to the horizontal direction. Each area is connected to one end of a guide groove. The four areas are connected to the four guide grooves. Each guide groove has a through hole. The four guide grooves are curved.

[0085] A spiral distributed fiber optic temperature sensor 6 is installed on the inner wall of the vessel. The spiral distributed fiber optic temperature sensor is electrically connected to the PLC controller. The radial temperature difference is obtained through the temperature difference between the spiral distributed fiber optic temperature sensor and the fiber optic temperature sensor. The PLC controller can adjust the speed of the stirring paddle and the temperature of the crystallizing vessel R102 according to the radial temperature difference and the axial temperature difference.

[0086] A multi-point platinum resistance sensor 8 is installed inside the vessel. The multi-point platinum resistance sensor is used to obtain the axial temperature difference (axial temperature gradient) inside the vessel. The multi-point platinum resistance sensor is electrically connected to the PLC controller.

[0087] Preferably, the lid and the vessel body are connected by a flange and sealed with vacuum grease.

[0088] Preferably, the agitator is a double-layer agitator, with the upper layer having four-bladed propeller blades and the lower layer having four-bladed turbine blades, in order to generate strong axial flow, eliminate bottom crystal deposition, and promote uniform temperature distribution of the fluid inside the vessel.

[0089] It also includes: a PLC controller, the motor is electrically connected to the PLC controller, and the cycle and speed of the stirring paddle's forward and reverse rotation can be set through the PLC controller.

[0090] Example 5

[0091] The method of using the 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment is based on Example 1:

[0092] During the solvent evaporation stage, when the radial temperature difference increases by 2°C or the axial temperature difference increases by 1.5°C, the speed of the agitator is increased by 15%, with the initial value set at 80 rpm and the maximum speed at 200 rpm.

[0093] During the cooling crystallization stage, for every 1.5℃ increase in radial temperature difference or 1℃ increase in axial temperature difference, the speed of the stirring paddle increases by 5%, and the flow rate of the medium in the jacket of crystallizer R102 increases by 10%, with the initial value set at 120 rpm and the maximum speed of the stirring paddle at 150 rpm.

[0094] During the warming and crystal growth stage, when the radial temperature difference increases by 3°C or the axial temperature difference increases by 2.5°C, a reverse stirring pulse is activated for 5 seconds to prevent crystal aggregation. Crystallization is stopped when no more crystals are continuously generated.

[0095] The present invention has been described above by way of example. It should be noted that any simple modifications, alterations or other equivalent substitutions that can be made by those skilled in the art without creative effort without departing from the core of the present invention fall within the protection scope of the present invention.

Claims

1. A method for using a 2,4-dihydroxybenzoic acid dissolution and recrystallization apparatus, characterized in that, The 2,4-dihydroxybenzoic acid dissolution and recrystallization equipment includes: a closed dissolution vessel, a crystallization vessel, and a mother liquor storage tank. The closed dissolution vessel is equipped with a feeding port; the crystallization vessel is made of glass. The sealed dissolving vessel is connected to one end of the first pipeline, which is used to introduce solvent into the sealed dissolving vessel. A sealed dissolving vessel is used to hold solvent, crude 2,4-dihydroxybenzoic acid, and phenylboronic acid derivatives, so that the phenylboronic acid derivatives and 1,2-dihydroxybenzoic acid in the crude 2,4-dihydroxybenzoic acid form a borate ester precipitate and a first filtrate. The outlet of the sealed dissolving vessel is connected to the inlet of the first separator via a pipeline. The outlet of the first separator is connected to the inlet of the first filtrate storage tank. The outlet of the first filtrate storage tank is connected to the inlet of the crystallization vessel via a second pipeline. A first... Two pump bodies and a first separation column, the first separation column being filled with mercaptosilicone or carboxylated silica gel; the outlet of the crystallization vessel is connected to the inlet of the second separator, the filtrate outlet of the second separator is connected to the inlet of a second filtrate storage tank, the outlet of the second filtrate storage tank is connected to the inlet of the mother liquor storage tank via a third pipeline, on which a third pump body is installed; a second pipeline between the first separation column and the second pump body is connected to the outlet of the mother liquor storage tank via a fourth pipeline, on which a fourth pump body is installed; The second pipeline between the second pump body and the fourth pipeline is connected to one end of a return pipeline, and the other end of the return pipeline is connected to the first pipeline. The first filtrate storage tank is equipped with a turbidity meter, which is used to detect the turbidity of the first filtrate storage tank. The crystallization vessel is equipped with an online infrared spectrometer, which is used to detect supersaturation within the crystallization vessel. A first condenser is connected to a closed dissolving vessel. The first condenser is used to collect the solvent and return it to the closed dissolving vessel. A second condenser is connected to a crystallizing vessel. The outlet of the second condenser is connected to the inlet of a solvent recovery tank. The second condenser is used to recover the solvent to the solvent recovery tank. The usage method includes the following steps: Step 1: 2,4-Dihydroxybenzoic acid crude product and phenylboronic acid derivative are added into a closed dissolving vessel through the feeding port. Solvent is pumped into the closed dissolving vessel to maintain the temperature of the vessel at 45-85℃. The vessel is stirred at 50-150 rpm for 0.5-2 hours. During the reaction, 1,2-dihydroxybenzoic acid in the crude 2,4-dihydroxybenzoic acid reacts with the phenylboronic acid derivative to form a borate ester precipitate. Immediately after the reaction, the precipitate is filtered through a first separator to obtain the borate ester precipitate and the first filtrate. The first filtrate is stored in a first filtrate storage tank. The turbidity of the filtrate in the first filtrate storage tank is detected by a turbidity meter. If the turbidity is >10 NTU, it is returned to the closed dissolving vessel through the reflux pipeline to start the second filtration. If the turbidity is ≤10 NTU, it is pumped into the first separation column. Step 2, crystallization: After the first filtrate is separated by the first separation column to remove metal ions, it enters the crystallization kettle for vacuum evaporation crystallization. Vacuum evaporation crystallization includes the following steps in sequence: solvent evaporation stage, cooling crystallization stage, and reheating crystal growth stage. Solvent evaporation stage: The solvent is evaporated in the crystallization vessel at -0.09MPa and 35~55℃, with a stirring speed of 80~200rpm. The solvent evaporated in the solvent evaporation stage is condensed by the second condenser and recovered to the solvent recovery tank. During the solvent evaporation stage, the supersaturation of the solution in the crystallization vessel is monitored by an online infrared spectrometer until the supersaturation of the solution reaches 1.

3. Cooling crystallization stage: When the supersaturation of the solution in the crystallization vessel reaches 1.3, 2,4-dihydroxybenzoic acid crystal seeds are injected into the crystallization vessel through a microfluidic seed injector. At the same time, the stirring speed of the crystallization vessel is adjusted to 120~150 rpm, and the crystallization vessel is cooled to 30℃ at a rate of 0.2-2.0℃ / min. When the temperature drops to 30℃, the vacuum degree of the crystallization vessel is adjusted to -0.09~-0.08MPa, and the crystallization vessel is further cooled to 19-25℃. When the temperature inside the crystallization vessel reaches 19-25℃, the vacuum degree of the crystallization vessel is gradually restored to atmospheric pressure. The crystallization vessel is kept stirred throughout the cooling crystallization stage. Warming and crystal growth stage: Adjust the rotation speed inside the crystallization vessel to 30-80 rpm, and heat the crystallization vessel to 35℃ at a rate of 0.3-1.0℃ / min until no more crystals are continuously generated, then stop crystallization; Step 3: The solution containing crystals is fed into the second separator through the outlet of the crystallization vessel for filtration to obtain the second filtrate and the second precipitate. The second precipitate is then vacuum dried to obtain the product.

2. The method of use according to claim 1, characterized in that, Also includes: A solvent storage tank, the outlet of which is connected to the other end of a first pipeline, on which a first pump body is installed.

3. The method of use according to claim 1, characterized in that, Also includes: Vacuum drying oven is used to dry the second precipitate.

4. The method of use according to claim 3, characterized in that, Also includes: The third condenser, the first filtrate storage tank, the second filtrate storage tank, the second condenser, and the vacuum drying oven are all connected to the gas inlet of the third condenser, and the liquid outlet of the third condenser is connected to a buffer tank.

5. The method of use according to claim 4, characterized in that, The outlet of the solvent recovery tank and the outlet of the buffer tank are both connected to one end of a fifth pipeline, and the other end of the fifth pipeline is connected to the return pipeline. A fifth pump body is installed on the fifth pipeline. A four-way valve is installed on the second pipeline. The four-way valve has four connected ports, two of which are connected in series in the second pipeline, and the other two ports are connected to the fifth pipeline and the return pipeline, respectively.

6. The method of use according to claim 5, characterized in that, Also includes: A refrigerant compressor and a heat exchanger compressor are provided. The refrigerant compressor provides cooling medium to the first condenser, the second condenser, and the third condenser. The closed melting vessel and the crystallizing vessel are each equipped with a jacket. The heat exchanger compressor delivers heat exchange medium to the jackets of the closed melting vessel and the crystallizing vessel, respectively, to control the temperature of the closed melting vessel and the crystallizing vessel.

7. The method of use according to claim 6, characterized in that, The buffer tank is connected to a vacuum pump, which creates a negative pressure environment in the buffer tank.

8. The method of use according to claim 1, characterized in that, The crystallization vessel includes: The vessel consists of a vessel body, a lid, a motor, a distribution plate, and a stirring paddle. A jacket is installed outside the vessel body, the lid is installed on the vessel body, the stirring paddle is located inside the vessel body, and the motor is located above the vessel body. The motor output shaft passes through the lid and is connected to the stirring paddle shaft. The stirring paddle shaft is hollow, and a fiber optic temperature sensor is installed inside the shaft to measure the temperature at the center of the vessel body. The liquid inlet of the crystallization vessel is located on the cover, and the distribution plate is located below the cover and is horizontally fixed inside the vessel. The upper surface of the distribution plate has a cross-shaped flow divider and four guide grooves. The cross-shaped flow divider is opposite to the liquid inlet of the cover. The cross-shaped flow divider is formed by two rigid plates perpendicularly intersecting to form a cross and dividing it into four areas. The four areas are recessed relative to the upper surface of the distribution plate. The rigid plates are perpendicular to the horizontal direction. Each area is connected to one end of a guide groove. The four areas are connected to four guide grooves. Each guide groove has a through hole. The four guide grooves are curved. A spiral distributed fiber optic temperature sensor is installed on the inner wall of the vessel. The spiral distributed fiber optic temperature sensor is electrically connected to the PLC controller. The radial temperature difference is obtained through the temperature difference between the spiral distributed fiber optic temperature sensor and the fiber optic temperature sensor. The vessel is equipped with a multi-point platinum resistance sensor, which is used to obtain the axial temperature difference inside the vessel. The multi-point platinum resistance sensor is electrically connected to the PLC controller.

9. The method of use according to claim 8, characterized in that, During the solvent evaporation stage, when the radial temperature difference increases by 2°C or the axial temperature difference increases by 1.5°C, the speed of the agitator is increased by 15%. The initial speed of the agitator is set to 80 rpm, and the maximum speed of the agitator is 200 rpm. During the cooling crystallization stage, when the radial temperature difference increases by 1.5℃ or the axial temperature difference increases by 1℃, the speed of the stirring paddle increases by 5%, and the flow rate of the medium in the jacket of the crystallizer increases by 10%. The initial value of the stirring paddle is set to 120 rpm, and the maximum speed of the stirring paddle is 150 rpm. During the warming and crystal growth stage, when the radial temperature difference increases by 3°C or the axial temperature difference increases by 2.5°C, a reverse stirring pulse is activated for 5 seconds until crystal formation stops.

10. The method of use according to claim 1, characterized in that, The solvent is methanol, ethanol or ethyl acetate.

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