Apparatus and method for glycine multistage continuous crystallization process particle size and crystal form regulation

Abstract

This invention provides an apparatus and method for controlling particle size and crystal form in a multi-stage continuous crystallization process of glycine. The apparatus includes a seed crystal generator, a primary crystallization vessel, a secondary crystallization vessel, and a final crystallization vessel connected in sequence. The material outlet of the seed crystal generator is connected to the material inlet of the primary crystallization vessel, the material outlet of the primary crystallization vessel is connected to the material inlet of the secondary crystallization vessel, the material outlet of the secondary crystallization vessel is connected to the material inlet of the final crystallization vessel, the material outlet at the top of the final crystallization vessel is connected to the material inlet of the primary crystallization vessel, and a solid-liquid separation device is connected to the material outlet at the bottom of the final crystallization vessel. This invention uses glycine mother liquor from the ammonolysis of chloroacetic acid containing impurities such as ammonium chloride and hexamethylenetetramine as raw material, achieving stable and continuous production of pure α-crystalline glycine with uniform particle size, low agglomeration, and high purity, significantly improving production efficiency and product consistency.

Description

Technical Field

[0001] This invention relates to the field of chemical technology, and in particular to an apparatus and method for controlling particle size and crystal form in a multi-stage continuous crystallization process of glycine. Background Technology

[0002] Glycine, also known as aminoacetic acid, commonly exists in α and γ crystal forms. As an important fine chemical intermediate, it is widely used in pesticides, pharmaceuticals, food, feed, and optoelectronic materials. Industrially, glycine is generally produced via ammonolysis of chloroacetic acid. This process introduces impurities such as ammonium chloride and hexamethylenetetramine into the system. These impurities significantly affect the crystallization kinetics of glycine, leading to problems such as uneven particle size distribution and mixing of α and γ crystal forms, severely impacting downstream processing efficiency and product performance.

[0003] To improve product quality, existing technologies mostly focus on optimizing batch or semi-batch crystallization processes. Chinese Patent 106748849A discloses a method for particle size control during the cooling crystallization process of glycine, which regulates particle size by controlling the degree of supersaturation during nucleation. Chinese Patent 110746314A discloses a semi-continuous dissolution crystallization method for glycine, which achieves stable production of large and uniform α-crystalline glycine at room temperature by continuously adding saturated glycine aqueous solution and ethanol aqueous solution to the crystallizer. Chinese Patent CN11606319A achieves controllable synthesis of glycine crystal form by adjusting the amount of salt additives, seed crystals, temperature, and cooling rate, significantly improving product stability and anti-caking properties. While these patents use batch crystallization to control particle size and crystal form, batch operation suffers from low production efficiency, large batch-to-batch quality fluctuations, high energy consumption, and limited automation, making it difficult to meet the urgent needs of modern chemical industry for process intensification, continuous operation, and intelligent processes.

[0004] Continuous crystallization technology has become the development direction of industrial crystallization due to its ability to produce consistent products with high efficiency. However, in the glycine system, directly switching to continuous crystallization faces severe challenges: during continuous crystallization, improper control of supersaturation can easily lead to a widening of the product particle size distribution; in the presence of industrial impurities, the difficulty of crystal form control in multi-stage continuous crystallization systems increases significantly, easily causing mixed crystals and product agglomeration, thus limiting the development of continuous crystallization technology for glycine.

[0005] Therefore, developing a stable process that can adapt to industrial impurity environments and simultaneously solve the problems of particle size and crystal form control in continuous crystallization is a technical bottleneck that urgently needs to be overcome in this field. Summary of the Invention

[0006] In view of the problems existing in the prior art, the present invention provides an apparatus and method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. By controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process, the continuous production of glycine is promoted, while solving problems such as uneven particle size distribution, mixed crystal forms, and poor industrial adaptability in the continuous crystallization process.

[0007] To achieve this objective, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides an apparatus for controlling the particle size and crystal form of a multi-stage continuous crystallization process of glycine, the apparatus comprising a seed crystal generator, a primary crystallization vessel, a secondary crystallization vessel and a final crystallization vessel connected in sequence;

[0009] The material outlet of the seed crystal generator is connected to the material inlet of the primary crystallizer, the material outlet of the primary crystallizer is connected to the material inlet of the secondary crystallizer, the material outlet of the secondary crystallizer is connected to the material inlet of the final crystallizer, the material outlet at the top of the final crystallizer is connected to the material inlet of the primary crystallizer, and a solid-liquid separation device is connected to the material outlet at the bottom of the final crystallizer.

[0010] The secondary crystallizer and the final crystallizer are each independently equipped with a solvent inlet.

[0011] This invention employs a four-stage tandem continuous mixed suspension mixed discharge (MSMPR) crystallization system with continuous seed supply. The system includes a seed generator, a primary crystallizer, a secondary crystallizer, and a final crystallizer. The mother liquor and solvent are premixed in the primary crystallizer, and the crystals crystallized in this step are used as seed crystals to be continuously transported into subsequent crystallizers. This controls the particle size and crystal form of glycine, promotes the continuous production of glycine, and solves problems such as uneven particle size distribution, mixed crystal forms, and poor industrial adaptability during continuous crystallization.

[0012] As a preferred embodiment of the present invention, the seed generator, the primary crystallizer, the secondary crystallizer, and the final crystallizer are each independently a jacketed vessel.

[0013] Preferably, the jacketed vessel is connected to the constant temperature bath.

[0014] As a preferred embodiment of the present invention, the seed crystal generator, the primary crystallization vessel, the secondary crystallization vessel, and the final crystallization vessel are each independently equipped with a stirring device.

[0015] As a preferred embodiment of the present invention, each material conveying pipeline of the device is independently equipped with a fluid conveying device.

[0016] Preferably, the fluid delivery device includes a peristaltic pump.

[0017] In a second aspect, the present invention provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process, wherein the method is carried out in the apparatus described in the first aspect, and the method includes the following steps:

[0018] (1) The first solvent and the first crystallization mother liquor are sequentially introduced into the seed crystal generator to induce primary nucleation and obtain the first crystal slurry;

[0019] (2) The first crystal slurry and the second crystallization mother liquor are simultaneously introduced into the first-stage crystallization vessel to induce crystal growth and obtain the second crystal slurry;

[0020] (3) The second crystal slurry and the second solvent are introduced into the secondary crystallization vessel to promote further crystal growth and obtain the third crystal slurry;

[0021] (4) The third crystal slurry and the third solvent are introduced into the final crystallization vessel to promote crystal growth and obtain the fourth crystal slurry;

[0022] (5) Part of the fourth crystal slurry is returned to the first-stage crystallizer through the material outlet at the top of the last-stage crystallizer, and the other part is transported to the solid-liquid separation device through the material outlet at the bottom of the last-stage crystallizer for separation to obtain glycine.

[0023] This invention utilizes a multi-stage continuous crystallization process for glycine, using glycine mother liquor from the ammonolysis of chloroacetic acid containing impurities such as ammonium chloride and hexamethylenetetramine as raw material. It employs a four-stage series continuous mixing suspension mixing discharge (MSMPR) crystallization system with continuous seed supply. This system includes a seed generator, a primary crystallizer, a secondary crystallizer, and a final crystallizer. In the seed generator, α-crystalline seeds are continuously generated in situ through high-supersaturation instantaneous premixing of the mother liquor and solvent. The primary crystallizer is a cooling vessel where a large amount of mother liquor is mixed with the crystal slurry from the seed generator, inducing stable growth of α-crystalline crystals. The secondary and final crystallizers are solvent crystallization vessels, increasing overall yield. Simultaneously, the fine-crystal-rich slurry from the upper layer of the final crystallizer is refluxed back to the primary crystallizer at a specific mass reflux ratio, allowing sufficient growth time for the fine crystals and providing more α-crystalline seeds for the continuous crystallization system. This invention achieves stable and continuous production of pure α-crystalline glycine with uniform particle size, low agglomeration, and high purity, significantly improving production efficiency and product consistency.

[0024] As a preferred embodiment of the present invention, the first solvent, the second solvent, and the third solvent each independently comprise methanol.

[0025] As a preferred technical solution of the present invention, the initial temperatures of the first crystallization mother liquor and the second crystallization mother liquor are independently 55-65℃, for example, 55℃, 56℃, 57℃, 58℃, 59℃, 60℃, 61℃, 62℃, 63℃, 64℃ or 65℃, etc., but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0026] Preferably, the temperature of the seed generator is 55-65℃, for example, it can be 55℃, 56℃, 57℃, 58℃, 59℃, 60℃, 61℃, 62℃, 63℃, 64℃ or 65℃, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0027] As a preferred technical solution of the present invention, the residence time of the material in the seed generator is 5-15 min, for example, it can be 5 min, 7 min, 9 min, 11 min, 13 min or 15 min, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0028] As a preferred technical solution of the present invention, the mass ratio of the first solvent to the first crystallization mother liquor is (0.1-0.3):1, for example, it can be 0.1:1, 0.15:1, 0.2:1, 0.25:1 or 0.3:1, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0029] This invention controls the mass ratio of solvent to crystallization mother liquor in the seed crystal generator within the above-mentioned range, which can generate pure α-crystalline microcrystals as seed crystals in situ, continuously and stably. If the mass ratio of solvent to crystallization mother liquor is too high, the supersaturation will be too large, resulting in an excessive aspect ratio of the seed crystals, making them easy to break, which in turn leads to a deterioration in crystal morphology and a wider particle size distribution. If the mass ratio of solvent to crystallization mother liquor is too low, mixed glycine crystals will be obtained, affecting the purity of the glycine product.

[0030] Preferably, the temperature of the primary crystallizer is 30-45℃, for example, it can be 30℃, 33℃, 36℃, 39℃, 42℃ or 45℃, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0031] Preferably, the residence time of the material in the primary crystallizer is 50-150 min, for example, it can be 50 min, 70 min, 90 min, 110 min, 130 min or 150 min, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0032] Preferably, the mass ratio of the second crystallization mother liquor to the first crystal slurry is (0.25-0.5):1, for example, it can be 0.25:1, 0.3:1, 0.35:1, 0.4:1, 0.45:1 or 0.5:1, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0033] Preferably, the temperature of the secondary crystallization vessel is 30-45℃, for example, it can be 30℃, 33℃, 36℃, 39℃, 42℃ or 45℃, etc., but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0034] Preferably, the residence time of the material in the secondary crystallizer is 50-150 min, for example, it can be 50 min, 70 min, 90 min, 110 min, 130 min or 150 min, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0035] Preferably, the mass ratio of the second solvent to the second crystal slurry is (0.4-0.8):1, for example, it can be 0.4:1, 0.45:1, 0.5:1, 0.55:1, 0.6:1, 0.65:1, 0.7:1, 0.75:1 or 0.8:1, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0036] Preferably, the temperature of the final crystallizer is 25-35℃, for example, it can be 25℃, 26℃, 27℃, 28℃, 29℃, 30℃, 31℃, 32℃, 33℃, 34℃ or 35℃, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0037] Preferably, the residence time of the material in the final crystallizer is 50-150 min, for example, it can be 50 min, 70 min, 90 min, 110 min, 130 min or 150 min, etc., but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0038] Preferably, the mass ratio of the third solvent to the third crystal slurry is (0.36-1):1, for example, it can be 0.36:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1 or 1:1, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0039] Preferably, the mass reflux ratio in the final crystallizer is (0.1-0.4):1, for example, it can be 0.1:1, 0.15:1, 0.2:1, 0.25:1, 0.3:1, 0.35:1 or 0.4:1, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0040] This invention controls the mass reflux ratio in the final crystallizer within the above-mentioned range, returning the upper crystal slurry rich in fine crystals to the first-stage crystallizer. This not only enhances the uniformity of particle size distribution as an internal seed crystal but also significantly improves the utilization rate of the mother liquor. If the reflux ratio is too large, excessive backmixing will lead to problems such as low overall system production efficiency (more circulation and less output), increased energy consumption, and impurity accumulation. If the reflux ratio is too small, it will result in a large number of small particles in the crystallized product, resulting in a low yield and waste of mother liquor.

[0041] The method for controlling particle size and crystal form in the multi-stage continuous crystallization process of glycine provided by this invention specifically includes:

[0042] (1) Using glycine mother liquor from chloroacetic acid ammonolysis at an initial temperature of 55-65℃ as the first crystallization mother liquor, and methanol as the first solvent, methanol and the first crystallization mother liquor are sequentially introduced into a seed crystal generator at a temperature of 55-65℃, wherein the mass ratio of methanol to the first crystallization mother liquor is (0.1-0.3):1, stirred evenly and held for 5-15 min to obtain the first crystal slurry;

[0043] (2) The first crystal slurry and the second crystallization mother liquor are simultaneously introduced into a primary crystallization vessel at a temperature of 30-45℃, wherein the mass ratio of the second crystallization mother liquor to the first crystal slurry is (0.25-0.5):1. The mixture is stirred evenly and held for 50-150 min to obtain the second crystal slurry.

[0044] (3) The second crystal slurry and methanol are simultaneously introduced into a secondary crystallization vessel at a temperature of 30-45℃, wherein the mass ratio of methanol to the second crystal slurry is (0.4-0.8):1. The mixture is stirred evenly and held for 50-150 min to obtain the third crystal slurry.

[0045] (4) The third crystal slurry and methanol are simultaneously introduced into a final crystallization vessel at a temperature of 25-35℃, wherein the mass ratio of methanol to the third crystal slurry is (0.36-1):1. The mixture is stirred evenly and held for 50-150 min to obtain the fourth crystal slurry.

[0046] (5) A portion of the fourth crystal slurry is returned to the first-stage crystallizer through the material outlet at the top of the final crystallizer, with a mass reflux ratio of (0.1-0.4):1, wherein the refluxed material is the upper layer of the fourth crystal slurry, and the other portion is transported to the filtration device through the material outlet at the bottom of the final crystallizer for filtration and separation to obtain glycine.

[0047] Compared with existing technical solutions, the present invention has at least the following beneficial effects:

[0048] (1) The device for controlling the particle size and crystal form of glycine in the multi-stage continuous crystallization process provided by the present invention decouples the complex crystallization process into multiple independent stages such as "nucleation" and "growth" through a four-stage series continuous crystallization design, allowing precise and independent control of the temperature, supersaturation and residence time of each crystallization vessel, thereby achieving graded and targeted control of glycine particle size and crystal form.

[0049] (2) The method for controlling the particle size and crystal form of glycine in the multi-stage continuous crystallization process provided by the present invention firstly uses an independent seed generator to induce the precise generation of seed crystals of the target crystal form through a solvent, thus laying the foundation for crystal form control from the source. Subsequently, the multi-stage crystallizer adopts a step-by-step solvent addition strategy, which effectively avoids the explosive nucleation caused by the surge of supersaturation in a single stage, allowing the crystals to grow stably step by step, significantly optimizing the particle size distribution and crystal habit regularity, controlling the coefficient of variation to within 0.5, and ensuring that the crystal form is a single α crystal form within the preferred range. The upper crystal slurry rich in fine crystals in the final crystallizer is returned to the first-stage crystallizer, which not only serves as an endogenous seed crystal to enhance the uniformity of particle size distribution, but also greatly improves the utilization rate of the mother liquor. Finally, it realizes the integrated and precise control from seed crystal preparation, particle size optimization to product separation, significantly improving the purity, particle size uniformity and crystal form stability of glycine products. Attached Figure Description

[0050] Figure 1 This is a schematic diagram of the process flow for particle size and crystal form control in the multi-stage continuous crystallization process of glycine provided by the present invention;

[0051] In the diagram: 1-seed crystal generator, 2-first-stage crystallizer, 3-second-stage crystallizer, 4-final-stage crystallizer. Detailed Implementation

[0052] To facilitate understanding of the present invention, the following embodiments are provided. Those skilled in the art should understand that these embodiments are merely illustrative and should not be construed as limiting the scope of the invention.

[0053] It should be clarified that any use of the process provided in the embodiments of the present invention or any substitution or change of conventional data falls within the protection and disclosure scope of the present invention.

[0054] Example 1

[0055] This embodiment provides a device for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The device includes a seed crystal generator, a primary crystallization vessel, a secondary crystallization vessel, and a final crystallization vessel connected in sequence. The seed crystal generator, the primary crystallization vessel, the secondary crystallization vessel, and the final crystallization vessel are all jacketed vessels. The jacket cavity of the outer wall of the jacketed vessel is connected to a constant temperature bath. Each of the seed crystal generator, the primary crystallization vessel, the secondary crystallization vessel, and the final crystallization vessel is independently equipped with a stirring paddle.

[0056] The material outlet of the seed crystal generator is connected to the material inlet of the primary crystallizer, the material outlet of the primary crystallizer is connected to the material inlet of the secondary crystallizer, the material outlet of the secondary crystallizer is connected to the material inlet of the final crystallizer, the material outlet at the top of the final crystallizer is connected to the material inlet of the primary crystallizer, and a solid-liquid separation device is connected to the material outlet at the bottom of the final crystallizer.

[0057] The secondary crystallizer and the final crystallizer are each independently equipped with a solvent inlet, and the material conveying pipeline of the device is independently equipped with a peristaltic pump.

[0058] Comparative Example 1

[0059] This comparative example provides an apparatus for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The only difference between the apparatus and Example 1 is that the apparatus does not include a seed crystal generator, but only includes a primary crystallization vessel, a secondary crystallization vessel, and a final crystallization vessel. All other aspects are the same as in Example 1.

[0060] Comparative Example 2

[0061] This comparative example provides an apparatus for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The only difference between the apparatus and Example 1 is that the apparatus does not include a primary crystallization vessel, but only includes a seed crystal generator, a secondary crystallization vessel, and a final crystallization vessel. All other aspects are the same as in Example 1.

[0062] Application Example 1

[0063] This application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The method is performed in the apparatus for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process provided in Example 1. The method includes:

[0064] (1) Using glycine mother liquor from chloroacetic acid ammonolysis at an initial temperature of 60℃ as crystallization mother liquor, wherein the crystallization mother liquor is prepared according to the 95% yield of chloroacetic acid ammonolysis, and the ratio of glycine:ammonium chloride:hexamethylenetetramine:water = 0.52:0.37:0.27:1, methanol is used as the solvent, and methanol and crystallization mother liquor are sequentially introduced into a seed crystal generator at a temperature of 60℃, wherein the mass ratio of methanol to crystallization mother liquor is 0.2:1, stirred evenly and held for 10 min to obtain the first crystal slurry;

[0065] (2) The first crystal slurry and the crystallization mother liquor are simultaneously added to the first crystallization reactor at a temperature of 30°C through the material inlet of the first crystallization reactor, wherein the mass ratio of the crystallization mother liquor to the first crystal slurry is 0.1:1. The mixture is stirred evenly and held for 60 min to obtain the second crystal slurry.

[0066] (3) The second crystal slurry and methanol are simultaneously added to the secondary crystallizer at a temperature of 30°C through the material inlet of the secondary crystallizer, wherein the mass ratio of methanol to the second crystal slurry is 0.6:1. The mixture is stirred evenly and held for 60 min to obtain the third crystal slurry.

[0067] (4) The third crystal slurry and methanol are simultaneously added to the final crystallizer at a temperature of 30°C through the material inlet of the final crystallizer, wherein the mass ratio of methanol to the third crystal slurry is 0.6:1. The mixture is stirred evenly and held for 60 min to obtain the fourth crystal slurry.

[0068] (5) A portion of the fourth crystal slurry is returned to the first-stage crystallizer through the material outlet at the top of the final crystallizer, with a mass reflux ratio of 0.1:1. The refluxed material is the upper layer of the fourth crystal slurry. The other portion is transported to the filtration device through the material outlet at the bottom of the final crystallizer for filtration and separation to obtain glycine.

[0069] Application Example 2

[0070] This application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The method is performed in the apparatus for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process provided in Example 1. The method includes:

[0071] (1) Using glycine mother liquor from chloroacetic acid ammonolysis at an initial temperature of 55℃ as the crystallization mother liquor, wherein the crystallization mother liquor is prepared according to the 95% yield of chloroacetic acid ammonolysis, and the ratio of glycine:ammonium chloride:hexamethylenetetramine:water = 0.52:0.37:0.27:1, and methanol as the solvent, methanol and crystallization mother liquor are sequentially introduced into a seed crystal generator at a temperature of 65℃, wherein the mass ratio of methanol to crystallization mother liquor is 0.4:1, stirred evenly and held for 5 min to obtain the first crystal slurry;

[0072] (2) The first crystal slurry and the crystallization mother liquor are simultaneously added to the first crystallization reactor at a temperature of 40°C through the material inlet of the first crystallization reactor, wherein the mass ratio of the crystallization mother liquor to the first crystal slurry is 0.5:1. The mixture is stirred evenly and left to stand for 50 min to obtain the second crystal slurry.

[0073] (3) The second crystal slurry and methanol are simultaneously added to the secondary crystallizer at a temperature of 40°C through the material inlet of the secondary crystallizer, wherein the mass ratio of methanol to the second crystal slurry is 0.4:1. The mixture is stirred evenly and held for 60 min to obtain the third crystal slurry.

[0074] (4) The third crystal slurry and methanol are simultaneously added to the final crystallizer at a temperature of 25°C through the material inlet of the final crystallizer, wherein the mass ratio of methanol to the third crystal slurry is 1:1. The mixture is stirred evenly and kept for 60 min to obtain the fourth crystal slurry.

[0075] (5) A portion of the fourth crystal slurry is returned to the first-stage crystallizer through the material outlet at the top of the final crystallizer, with a mass reflux ratio of 0.3:1. The refluxed material is the upper layer of the fourth crystal slurry. The other portion is transported to the filtration device through the material outlet at the bottom of the final crystallizer for filtration and separation to obtain glycine.

[0076] Application Example 3

[0077] This application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The method is performed in the apparatus for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process provided in Example 1. The method includes:

[0078] (1) Using glycine mother liquor from chloroacetic acid ammonolysis at an initial temperature of 65℃ as crystallization mother liquor, wherein the crystallization mother liquor is prepared according to the 95% yield of chloroacetic acid ammonolysis, and the ratio of glycine:ammonium chloride:hexamethylenetetramine:water = 0.52:0.37:0.27:1, methanol is used as the solvent, and methanol and crystallization mother liquor are sequentially introduced into a seed crystal generator at a temperature of 55℃, wherein the mass ratio of methanol to crystallization mother liquor is 0.3:1, stirred evenly and held for 15 min to obtain the first crystal slurry;

[0079] (2) The first crystal slurry and the crystallization mother liquor are simultaneously added to the first crystallization reactor at a temperature of 45°C through the material inlet of the first crystallization reactor, wherein the mass ratio of the crystallization mother liquor to the first crystal slurry is 0.25:1. The mixture is stirred evenly and held for 150 min to obtain the second crystal slurry.

[0080] (3) The second crystal slurry and methanol are simultaneously added to the secondary crystallizer at a temperature of 45°C through the material inlet of the secondary crystallizer, wherein the mass ratio of methanol to the second crystal slurry is 0.8:1. The mixture is stirred evenly and held for 150 min to obtain the third crystal slurry.

[0081] (4) The third crystal slurry and methanol are simultaneously added to the final crystallizer at a temperature of 35°C through the material inlet of the final crystallizer, wherein the mass ratio of methanol to the third crystal slurry is 0.36:1. The mixture is stirred evenly and held for 150 min to obtain the fourth crystal slurry.

[0082] (5) A portion of the fourth crystal slurry is returned to the first-stage crystallizer through the material outlet at the top of the final crystallizer, with a mass reflux ratio of 0.4:1. The refluxed material is the upper layer of the fourth crystal slurry. The other portion is transported to the filtration device through the material outlet at the bottom of the final crystallizer for filtration and separation to obtain glycine.

[0083] Application Example 4

[0084] This application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The only difference between this method and Application Example 1 is that the mass ratio of methanol to crystallization mother liquor in the seed crystal generator is changed to 0.05:1, while the rest is the same as Application Example 1.

[0085] Application Example 5

[0086] This application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The only difference between this method and Application Example 1 is that the mass ratio of methanol to crystallization mother liquor in the seed crystal generator is changed to 0.35:1, while the rest is the same as Application Example 1.

[0087] Application Example 6

[0088] This application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The only difference between this method and Application Example 1 is that the mass reflux ratio of the final crystallizer is changed to 0.05:1, while the rest is the same as Application Example 1.

[0089] Application Example 7

[0090] This application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The only difference between this method and Application Example 1 is that the mass reflux ratio of the final crystallizer is changed to 0.45:1, while the rest is the same as Application Example 1.

[0091] Comparative Application Example 1

[0092] This comparative application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The method is carried out in the apparatus provided in Comparative Example 1. The corresponding method is as follows: the crystallization mother liquor is directly and continuously added to the primary crystallization vessel, and methanol is added at the same time. The seed crystal generator is not used. All other aspects are the same as in Application Example 1.

[0093] Comparative Application Example 2

[0094] This comparative application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The method is carried out in the apparatus provided in Comparative Example 2. The corresponding method is as follows: the first crystal slurry flows directly from the seed crystal generator into the secondary crystallizer without passing through the primary crystallizer; the second crystallization mother liquor is also directly fed into the secondary crystallizer; the reflux liquid in the final crystallizer is directly fed into the secondary crystallizer; and the rest is the same as in Application Example 1.

[0095] Comparative Application Example 3

[0096] This comparative application example provides a method for controlling the particle size and crystal form of glycine in a multi-stage continuous crystallization process. The only difference between this method and Application Example 1 is that the crystal slurry in the final crystallization vessel is not refluxed, but is only transported to a filtration device for filtration and separation. All other aspects are the same as in Application Example 1.

[0097] Performance testing

[0098] The glycine prepared by the method for particle size and crystal form control in the multi-stage continuous crystallization process of glycine provided in the application examples and comparative application examples was characterized. The crystal form was tested by X-ray diffraction analysis (XRD), and the average particle size was tested by a laser particle size analyzer. The results are shown in Table 1.

[0099] The formula for calculating the coefficient of variation is:

[0100]

[0101] Table 1

[0102]

[0103] As shown in Table 1, the method provided by this invention can obtain glycine products with larger particle size, uniform distribution, and high crystal purity, significantly improving the efficiency of downstream crystal processing. Compared with existing technologies, it achieves particle size and crystal form control in a continuous crystallization process without the need for special equipment, which is beneficial to existing industrial production.

[0104] A comprehensive comparison of Application Examples 1 and 4-5 reveals that the mass ratio of methanol to mother liquor in the seed generator significantly influences primary nucleation behavior and subsequent crystal growth. When the methanol / mother liquor ratio is within the preferred range, the product obtained in Application Example 1 is α-crystalline with an average particle size of 498 μm and a coefficient of variation of only 0.24. However, when this ratio decreases to 0.05:1, mixed α and γ crystals appear. This indicates that when the methanol content is too low, the instantaneous supersaturation of the system is insufficient, making it difficult to continuously and stably induce the formation of sufficient target α-crystalline seeds in the seed generator. Conversely, when the methanol / mother liquor ratio increases to 0.35:1, Application Example 5 still mainly exhibits α-crystalline form, but the average particle size further decreases to 342 μm, and the coefficient of variation increases to 0.46. This indicates that excessively high supersaturation easily triggers explosive nucleation, increases the number of fine crystals, intensifies competitive growth in the system, and leads to a decrease in the final product particle size and a wider particle size distribution. Therefore, controlling the mass ratio of methanol to crystallization mother liquor in the seed crystal generator within the optimal range is beneficial for balancing α-crystal orientation induction and appropriate crystal nucleation, which is a necessary condition for obtaining products with larger particle size and uniform distribution.

[0105] A comprehensive comparison of Application Examples 1 and 6-7 shows that the reflux ratio of the final crystallizer has a significant impact on the reuse of fine crystals, particle size uniformity, and the stability of continuous crystallization. In Application Example 1, with a reflux ratio of 0.1:1, the average particle size of glycine obtained was 498 μm, with a coefficient of variation of 0.24. When the reflux ratio decreased to 0.05:1, the average particle size in Application Example 6 decreased to 411 μm, and the coefficient of variation increased to 0.36. This result indicates that when the reflux ratio is too low, the fine-crystal-rich slurry in the upper layer of the final crystallizer cannot be fully returned to the primary crystallizer for continued growth, resulting in insufficient overall crystal growth and a correspondingly wider particle size distribution. When the reflux ratio increased to 0.45:1, the average particle size in Application Example 7 was 438 μm. Although it still maintained the α-crystal form, the coefficient of variation increased to 0.41, indicating that an excessively high reflux ratio would exacerbate system backmixing, increase the probability of secondary nucleation, and be detrimental to the uniform growth of the crystal population, ultimately leading to a wider particle size distribution. The above results show that controlling the reflux ratio of the final crystallizer within the optimal range helps to improve the uniformity of product particle size.

[0106] A comprehensive comparison of Application Example 1 and Comparative Application Example 1 reveals that in systems containing ammonium chloride and hexamethylenetetramine impurities, without a high supersaturation-induced in-situ nucleation process of the α-crystal form, the impurities significantly interfere with nucleation kinetics, making crystal form control difficult. In Comparative Application Example 1, due to the elimination of the seed generator, the resulting product exhibits a mixture of α and γ crystals with an average particle size of only 301 μm and a coefficient of variation as high as 0.55, significantly inferior to Application Example 1. This demonstrates that the seed generator plays a crucial role in the continuous induction of the target crystal form and subsequent particle size control.

[0107] A comprehensive comparison of Application Example 1 and Comparative Application Example 2 reveals that without a primary crystallizer, the seed crystals, along with the subsequent mother liquor and solvent, directly enter the subsequent crystallizer under high crystallization driving forces. This easily leads to the crystals continuing the dissolution process before they have fully stabilized and grown, resulting in a significant reduction in the average particle size and a wider particle size distribution of the product. The average particle size of Comparative Application Example 2 is only 320 μm, with a coefficient of variation of 0.52, significantly lower than the 498 μm of Application Example 1 and significantly higher than its 0.24. This demonstrates that the primary crystallizer plays a crucial role in receiving the seed crystals generated by the seed generator and promoting their stable growth.

[0108] A comprehensive comparison of Application Example 1 and Comparative Application Example 3 shows that when the final crystallizer does not have reflux, although the product can still maintain the α-crystal form, the average particle size decreases from 498 μm to 356 μm, and the coefficient of variation increases from 0.24 to 0.44, indicating a significant deterioration in product particle size uniformity. Without reflux, the fine-crystal-rich slurry in the upper layer of the final crystallizer cannot return to the primary crystallizer for further growth; the fine crystals are directly discharged as product. This weakens the fine-crystal regrowth process and reduces the continuous replenishment of source crystals within the system, ultimately resulting in a decrease in average particle size and a wider particle size distribution. This demonstrates that the final-stage reflux structure is one of the key structural features of this invention for achieving synergistic control of particle size and crystal form.

[0109] The present invention has been illustrated with the above embodiments to illustrate its detailed structural features. However, the present invention is not limited to the above detailed structural features, that is, it does not mean that the present invention must rely on the above detailed structural features to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions for the components used in the present invention, additions of auxiliary components, and selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A device for controlling particle size and crystal form in a multi-stage continuous crystallization process of glycine, characterized in that, The device includes a seed crystal generator, a primary crystallization vessel, a secondary crystallization vessel, and a final crystallization vessel connected in sequence. The material outlet of the seed crystal generator is connected to the material inlet of the primary crystallizer, the material outlet of the primary crystallizer is connected to the material inlet of the secondary crystallizer, the material outlet of the secondary crystallizer is connected to the material inlet of the final crystallizer, the material outlet at the top of the final crystallizer is connected to the material inlet of the primary crystallizer, and a solid-liquid separation device is connected to the material outlet at the bottom of the final crystallizer. The secondary crystallizer and the final crystallizer are each independently equipped with a solvent inlet.

2. The apparatus according to claim 1, characterized in that, The seed crystal generator, primary crystallization vessel, secondary crystallization vessel, and final crystallization vessel are each independently a jacketed vessel; Preferably, the jacketed vessel is connected to the constant temperature bath.

3. The apparatus according to claim 1 or 2, characterized in that, Each of the seed crystal generator, primary crystallizer, secondary crystallizer, and final crystallizer is independently equipped with a stirring device.

4. The apparatus according to any one of claims 1 to 3, characterized in that, Each of the material conveying pipelines in the device is independently equipped with a fluid conveying device; Preferably, the fluid delivery device includes a peristaltic pump.

5. A method for controlling particle size and crystal form in a multi-stage continuous crystallization process of glycine, characterized in that, The method is performed in the apparatus described in any one of claims 1 to 4.

6. The method according to claim 5, characterized in that, The method includes the following steps: (1) The first solvent and the first crystallization mother liquor are sequentially introduced into the seed crystal generator to induce primary nucleation and obtain the first crystal slurry; (2) The first crystal slurry and the second crystallization mother liquor are simultaneously introduced into the first-stage crystallization vessel to induce crystal growth and obtain the second crystal slurry; (3) The second crystal slurry and the second solvent are introduced into the secondary crystallization vessel to promote further crystal growth and obtain the third crystal slurry; (4) The third crystal slurry and the third solvent are introduced into the final crystallization vessel to promote crystal growth and obtain the fourth crystal slurry; (5) Part of the fourth crystal slurry is returned to the first-stage crystallizer through the material outlet at the top of the last-stage crystallizer, and the other part is transported to the solid-liquid separation device through the material outlet at the bottom of the last-stage crystallizer for separation to obtain glycine.

7. The method according to claim 5 or 6, characterized in that, The first solvent, the second solvent, and the third solvent each independently comprise methanol.

8. The method according to any one of claims 5 to 7, characterized in that, The initial temperatures of the first and second crystallization mother liquors are independently 55-65℃; Preferably, the temperature of the seed crystal generator is 55-65°C; Preferably, the residence time of the material in the seed generator is 5-15 min; Preferably, the mass ratio of the first solvent to the first crystallization mother liquor is (0.1-0.3):1; Preferably, the temperature of the primary crystallizer is 30-45℃; Preferably, the residence time of the material in the primary crystallizer is 50-150 min; Preferably, the mass ratio of the second crystallization mother liquor to the first crystal slurry is (0.25-0.5):

1.

9. The method according to any one of claims 5 to 8, characterized in that, The temperature of the secondary crystallization reactor is 30-45℃; Preferably, the residence time of the material in the secondary crystallizer is 50-150 min; Preferably, the mass ratio of the second solvent to the second crystal slurry is (0.4-0.8):

1.

10. The method according to any one of claims 5 to 9, characterized in that, The temperature of the final crystallization vessel is 25-35℃; Preferably, the residence time of the material in the final stage crystallizer is 50-150 min; Preferably, the mass ratio of the third solvent to the third crystal slurry is (0.36-1):1; Preferably, the mass reflux ratio in the final crystallizer is (0.1-0.4):1.

Images