Process for the preparation of benzotriazole acicular crystals

Abstract

A method for preparing benzotriazole needle crystals, the method comprising the following steps: 1) mixing benzotriazole with an organic solvent and stirring to dissolve it, obtaining a clear and homogeneous solution; 2) feeding the solution into a vacuum flash crystallization vessel, controlling the pressure inside the vessel to gradually decrease from atmospheric pressure and simultaneously adjusting the system temperature to form a stable and controllable supersaturated environment; 3) applying an alternating electric field during the crystallization stage to induce molecular orientation, promoting the preferential growth of crystals along the direction of the electric field and inhibiting disordered nucleation and impurity entrainment; and 4) removing the mother liquor after crystallization, drying the obtained crystals to obtain high-purity benzotriazole needle crystals.

Description

Technical Field

[0001] This invention relates to the field of organic fine chemical crystallization, specifically to a method for preparing benzotriazole (BTA) needle crystals based on vacuum flash evaporation and electric field induction. Background Technology

[0002] Benzotriazole (BTA, chemical formula C6H5N3) is an important nitrogen-containing heterocyclic compound widely used in metal corrosion inhibitors, polymer stabilizers, electronic chemical materials, and pharmaceutical intermediates. Its crystal morphology, purity, and particle size distribution directly affect the dispersibility, color, and thermal stability of downstream products.

[0003] Currently, the following types of crystallization processes are mainly used in industry: Aqueous solution cooling crystallization method: As described in patent CN111732550B, water is used as the solvent, and needle-like crystals are obtained by cooling-induced crystallization. However, benzotriazole has extremely low solubility in water (approximately 0.1 g / 100 g at 25 °C). - ¹), the system requires long-term cooling, has limited production capacity, high mother liquor carry-out rate, and large cooling load, resulting in high energy consumption and difficulty in scaling up.

[0004] Melt-sweating crystallization method: Patent CN115974798B reports obtaining high-purity products through melt crystallization and sweating purification of benzotriazole, a process that avoids the use of solvents. However, this method requires high temperature maintenance (>100 ℃), resulting in high energy consumption, and the obtained crystals are mostly granular or short needle-shaped, with difficult morphology control and unstable color.

[0005] Solution evaporation crystallization method: Literature and patents (such as CN104628664A, CN110016001A) propose using thermal evaporation to promote supersaturation and crystal formation. Although it can increase the crystallization rate, the system requires continuous heating and evaporation, resulting in low solvent utilization, easy formation of crystal agglomeration and non-uniform nucleation, and causing wide crystal size distribution and high entrainment.

[0006] Therefore, the following core bottlenecks still exist in the existing preparation of benzotriazole needle crystals: (a) The water system has low productivity and high energy consumption; (b) Crystal orientation and morphology are uncontrollable, and needle length distribution is wide; (c) The crystallization process lacks an effective mechanism to remove impurities and metal ions, thus limiting the purity.

[0007] To address the above issues, it is of great significance to develop a method for preparing benzotriazole (BTA) needle crystals with low energy consumption, high purity, tunable crystal morphology, and low color. Summary of the Invention

[0008] The purpose of this application is to overcome the technical problems existing in the crystallization methods of benzotriazole, such as high energy consumption, uncontrollable crystal morphology, unstable purity and color, low solvent circulation efficiency, and impurity accumulation. This application proposes a method for preparing benzotriazole needle-like crystals based on the synergistic control of vacuum flash evaporation and electric field induction. This method introduces adiabatic flash pressure-controlled crystallization and an alternating electric field-induced orientation growth mechanism into a high-solubility organic solvent system, achieving a controllable crystallization process at the molecular level of benzotriazole. This results in high-purity crystals with large needle-like growth, low color, and the ability to be produced continuously.

[0009] The first aspect of this application provides a method for preparing benzotriazole needle-like crystals, the method comprising the following steps in sequence: 1) Mix benzotriazole with an organic solvent, stir to dissolve, and obtain a clear and homogeneous solution; 2) The solution is fed into a vacuum flash crystallization reactor, and the pressure inside the reactor is gradually reduced from atmospheric pressure while the system temperature is adjusted simultaneously to create a stable and controllable supersaturated environment. 3) Applying an alternating electric field during the crystallization stage induces molecular orientation, promotes preferential crystal growth along the electric field direction, and suppresses disordered nucleation and impurity entrainment; and 4) After crystallization, remove the mother liquor and dry the obtained crystals to obtain high-purity benzotriazole needle crystals.

[0010] Another aspect of this application provides benzotriazole needle crystals prepared by the method described in this application, characterized in that: the crystal purity is ≥97.9%, and the metal ion residue is ≤8 mg·kg⁻¹. - ¹, with an average length ≥70 μm and an aspect ratio ≥6.5.

[0011] In another aspect, this application provides a system for the method described in this application, the system comprising: a dissolution unit, a vacuum flash crystallization unit, an electric field-induced orientation crystallization unit, a solid-liquid separation unit, and a vacuum drying unit.

[0012] The advantages of this application are: Compared with existing conventional technologies, it has the following significant advantages: 1) Energy consumption is significantly reduced: During the decompression process, the solvent partially vaporizes, and its latent heat is entirely supplied by the sensible heat of the solution, causing the system temperature to drop automatically. At this point, the heat flow within the system is a closed loop, requiring no external energy supply. This reduces heat loss by approximately 40% or more compared to aqueous solvothermal evaporation or melting methods.

[0013] 2) Crystal morphology is controllable: During crystallization, an alternating electric field (AC field, 0.5–2 kHz) is applied, causing benzotriazole molecules to undergo orientation polarization due to their inherent dipole moment. This orientation behavior leads to: ordered molecular arrangement: molecules form low-energy orientations along the electric field direction, promoting preferential growth along the applied electric field direction (approximately parallel to the needle axis); reduced interfacial energy: polarized orientation increases the structural order of the crystal-liquid interface layer, causing the effective interfacial energy γ_eff to decrease by approximately 12–18% compared to the absence of an electric field; and accelerated orientation growth: the decrease in interfacial energy reduces the nucleation energy barrier ΔG. As the nucleation rate decreases, the crystal elongates along a single direction, forming a uniform needle-like morphology. Under this effect, the average needle length can reach 100 μm, the aspect ratio is stabilized at 5–10, the fracture rate decreases by about 60%, and the morphology becomes repeatable and controllable.

[0014] 3) Improved purity and stability: The production process of benzotriazole often contains trace amounts of metal impurities (such as Fe³⁺). + Cu² + Ni² + These charged ions readily embed into the crystal lattice during crystal nucleation and growth, leading to increased color and decreased purity. Under the influence of an alternating electric field: the electromigration effect causes charged impurities to migrate periodically near the crystal-liquid interface, making them difficult to fix in the crystal lattice; the EHD convection effect enhances the flow of the interface layer, refreshes the boundary layer, and promotes the migration of impurities towards the mother liquor; the polarization repulsion effect causes the potential gradient on the crystal surface to form Coulomb repulsion against oppositely charged impurities. Therefore, impurities within the crystal are significantly reduced, and residual metal ions are controlled to ≤5 mg·kg⁻¹. - ¹. After 50 consecutive production batches, the purity remains ≥99.8%, and the color change is less than ±1. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the process flow for the preparation method of benzotriazole needle crystals based on vacuum flash evaporation and electric field induction according to this application.

[0016] Figure 2 These are comparative images of the needle-like crystal microstructures of the products (from left to right: crystal microstructure of Example 1 of the present invention, crystal microstructure of Comparative Example 1, crystal microstructure of Comparative Example 2, and crystal microstructure of Comparative Example 3).

[0017] Figure 3 It is a control logic diagram. Detailed Implementation

[0018] To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions used in the specification and claims are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.

[0019] The theories or mechanisms described and disclosed herein, whether right or wrong, should not in any way limit the scope of the invention, that is, the contents of the invention can be implemented without being limited by any particular theory or mechanism.

[0020] The "range" disclosed herein is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is expected that ranges of 60-110 and 80-120 are also expected. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5. In this application, unless otherwise stated, the numerical range "ab" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" have been listed in this article; "0-5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0021] Unless otherwise specified in this application, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.

[0022] Unless otherwise specified, all technical features and preferred features mentioned herein can be combined to form new technical solutions.

[0023] In this application, unless otherwise specified, all steps mentioned herein may be performed sequentially or randomly, but are preferably performed sequentially. For example, if the method includes steps (a) and (b), it means that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, if the method may also include step (c), it means that step (c) may be added to the method in any order. For example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0024] In this application, unless otherwise specified, the terms "comprising" and "including" as used herein are open-ended or closed-ended. For example, "comprising" and "including" may mean that other components not listed may also be included, or that only the listed components may be included.

[0025] In the description of this article, it should be noted that, unless otherwise stated, "above" and "below" include the number itself, and "several" in "one or more" means two or more.

[0026] In this description, unless otherwise stated, the term "or" is inclusive. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, the condition "A or B" is satisfied by any of the following conditions: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0027] Unless otherwise specified, percentages (%) or parts refer to weight percentages or parts by weight of the composition.

[0028] Unless otherwise stated herein, the sum of the contents of the components in the composition is 100%.

[0029] Unless otherwise stated herein, the sum of the parts of each component in the composition may be 100 parts by weight.

[0030] In this document, unless otherwise stated, “combination of” means a multi-component mixture of the elements, such as two, three, four, and up to the maximum possible multi-component mixture.

[0031] Unless otherwise specified, the term "a" as used in this specification means "at least one".

[0032] The first aspect of this application provides a method for preparing benzotriazole needle-like crystals, the method comprising the following steps in sequence: 1) Mix benzotriazole with an organic solvent, stir to dissolve, and obtain a clear and homogeneous solution; 2) The solution is fed into a vacuum flash crystallization reactor, and the pressure inside the reactor is gradually reduced from atmospheric pressure while the system temperature is adjusted simultaneously to create a stable and controllable supersaturated environment. 3) Applying an alternating electric field during the crystallization stage induces molecular orientation, promotes preferential crystal growth along the electric field direction, and suppresses disordered nucleation and impurity entrainment; and 4) After crystallization, remove the mother liquor and dry the obtained crystals to obtain high-purity benzotriazole needle crystals.

[0033] Step 1)

[0034] In step 1), the organic solvent is an alcohol solvent, an ether solvent, or a combination thereof; preferably, the organic solvent is selected from one or more of 2-methoxyethanol, 1-butanol, 2-methyl-2-butanol, and ethylene glycol monomethyl ether; more preferably, the organic solvent is selected from 2-methoxyethanol. The enthalpy of solubility ΔH of 1-butanol, 2-methyl-2-butanol, or ethylene glycol monomethyl ether is similar to that of 2-methoxyethanol.

[0035] In step 1), benzotriazole and an organic solvent (preferably 2-methoxyethanol) are mixed at a mass ratio of (1.8 to 2.2):1. Preferably, benzotriazole and an organic solvent are mixed at a mass ratio of (1.9 to 2.1):1. More preferably, benzotriazole and an organic solvent are mixed at a mass ratio of 2:1.

[0036] In step 1), the weight fraction of benzotriazole is 50-75 wt%, more preferably 55-70 wt%, based on the weight of the obtained solution.

[0037] In step 1), the dissolution temperature is controlled at 80–100 °C, preferably 85–95 °C or 90–100 °C, and more preferably 90 °C. Controlling the dissolution temperature within the range of 85–95 °C ensures complete dissolution while preventing the formation of chromophores. Insufficient dissolution will lead to heterogeneous nucleation, affecting crystal purity and length.

[0038] In step 1), the benzotriazole is purified by distillation.

[0039] More specifically, in step 1), benzotriazole purified by distillation is mixed with an organic solvent (preferably 2-methoxyethanol) at a mass ratio of (1.8 to 2.2):1, and stirred at 90 to 100 °C to dissolve and form a clear and transparent solution.

[0040] The BTA mass fraction in the solution is controlled at 50–70 wt% to ensure the formation of a high-concentration precursor system. The dissolution time is 15–20 min, and the stirring speed is 300–400 rpm until the system is completely clear.

[0041] Step 2)

[0042] In step 2), the solution is fed into a vacuum flash crystallization vessel by a metering pump.

[0043] In step 2), vacuum flash crystallization is an intermittent operation.

[0044] In step 2), the pressure reduction rate is controlled between 0.1 and 1.2 kPa·min. - ¹(Preferred: 0.2–1.0 kPa·min) - ¹, more preferably 0.3–0.5 kPa·min - ¹), the rate of pressure reduction dP / dt = 0.1~1.2 kPa·min - ¹, excessively rapid pressure reduction can trigger explosive nucleation and reduce orientation; excessively slow pressure reduction affects production capacity; the final pressure is 1–20 kPa (preferably 1–10 kPa, more preferably 1–5 kPa, further preferably 1–3 kPa, and most preferably 2 kPa); the final temperature is 20–60°C (preferably 25–50°C, more preferably 28–40°C, further preferably 30–35°C, and most preferably 32°C).

[0045] In step 2), the pressure reduction process is controlled by piecewise linear or S-curve to balance the nucleation rate and the crystal growth rate.

[0046] In step 2), the supersaturation of the system is maintained at S = 1.2 to 1.4, preferably 1.25 to 1.35.

[0047] More specifically, in step 2), the solution is fed into a vacuum flash crystallizer using a metering pump, and a segmented linear or S-shaped pressure reduction program is employed to achieve stable and controllable supersaturation formation. The endpoint pressure is 1–20 kPa, and the endpoint temperature is 20–60 °C.

[0048] The flash evaporation system achieves energy self-balance using the sensible heat of the solution and the latent heat of flash evaporation, eliminating the need for an external heating pump. Turbidity and temperature signals are monitored in real time to maintain the system's supersaturation S = 1.2–1.4, which is the optimal window for crystal growth.

[0049] In this application, the vacuum flash evaporation process significantly lowers the solvent boiling point by reducing system pressure, converting the sensible heat of the solution into the latent heat of vaporization, forming a closed energy loop. This maintains supersaturation growth without the need for external heating or cooling equipment; the temperature gradient is small, the supersaturation formation rate is gradual, and nucleation is uniform; the thermodynamic path of crystallization is stabilized in the low enthalpy difference region, reducing energy consumption by approximately 40% compared to traditional evaporation methods.

[0050] Step 3)

[0051] In step 3), the applied alternating electric field strength is 0.3–1.5 kV·cm. - ¹(Preferred value: 0.8–1.2 kV·cm) - ¹, more preferably 0.9–1.0 kV·cm - ¹), with a frequency of 0.5 to 2 kHz (preferably 0.8 to 1.5 kHz, more preferably 0.9 to 1.2 kHz).

[0052] In step 3), the electric field is applied in a pulsed or alternating manner.

[0053] Specifically, in step 3), after the supersaturated system is established, an alternating electric field is applied during the crystallization stage to induce the ordered arrangement of molecules. The electric field strength E = 0.3–1.5 kV·cm - ¹, frequency f = 0.5–2 kHz, electrode distance 5–8 cm. The electric field is applied in an alternating or pulsed manner with a duty cycle of 40–60% to prevent polarization heat buildup.

[0054] The electric field induces the dipole moments of benzotriazole molecules to align along the direction of the electric field, forming ordered growth precursor clusters, reducing the crystal-liquid interface energy by approximately 12–18%, and inhibiting anisotropic dendrite formation. The electric field also induces electrohydrodynamic (EHD) convection, refreshing the diffusion layer and promoting the migration of impurities and metal ions back to the mother liquor, achieving "interface purification." For systems containing trace amounts of metal impurities, the alternating polarization of the electric field significantly enhances the impurity removal rate, reducing the residual metal ion concentration to ≤5 mg·kg⁻¹. - ¹.

[0055] Step 4)

[0056] In step 4), the drying is carried out under the following conditions: vacuum degree ≤5 kPa (preferably 0.2 to 2 kPa, more preferably 0.8 to 1.5 kPa), temperature 30 to 60 °C (preferably 35 to 55 °C, more preferably 40 to 50 °C).

[0057] In step 4), the drying time is 0.5 to 5 hours (preferably 0.8 to 4 hours, more preferably 1 to 2 hours).

[0058] In step 4), after crystallization, the mother liquor is removed by centrifugation. Preferably, the liquid content of the solids after centrifugation should be controlled at 1–2 wt%, based on the total weight of the solids, to ensure the vacuum drying rate and crystal integrity.

[0059] Specifically, in step 4), after crystallization, the slurry is separated from the mother liquor by a centrifuge and then enters the vacuum drying stage. Drying conditions: vacuum degree ≤5 kPa (preferably 0.1–4 kPa, more preferably 0.2–2 kPa, even more preferably 0.8–1.5 kPa), temperature 30–60 °C (preferably 35–55 °C, even more preferably 40–50 °C), drying time 0.5–5 h (preferably 0.8–4 h, even more preferably 1–2 h).

[0060] In step 4), a pressure-temperature dual closed-loop regulation can be used to prevent needle deformation. After drying, the residual crystal solution is ≤0.10 wt%, and the needle integrity retention rate is ≥95%.

[0061] The vacuum flash crystallization reactor is equipped with pressure, temperature, and turbidity sensors. A closed-loop control system adjusts the pressure drop curve in real time. When the turbidity change rate dτ / dt is detected to be greater than the first threshold T1 0.02 min... - At time ¹, the voltage reduction rate is automatically reduced while the electric field strength is increased simultaneously, bringing |dτ / dt| back to less than or equal to the second threshold T2 for 0.005 min. - ¹, and restores the initial depressurization rate and electric field strength. This closed-loop control ensures the coexistence of "slow supersaturation + stable orientation growth," making the crystallization process thermodynamically stable and kinetically uniform. A three-coupled system of "energy-supersaturation-electric field" is formed, resulting in high crystal orientation and low batch-to-batch variation.

[0062] The turbidity change rate dτ / dt is generally positively correlated with the pressure drop rate dP / dt, but dτ / dt is also superimposed with the effects of nucleation hysteresis, crystal growth kinetics, and electric field-induced orientation. Therefore, in the vacuum flash crystallization process, the system adopts an electric field-pressure coupled logic control strategy based on turbidity feedback. The core idea is to use the pressure drop rate as the main manipulated variable and the turbidity change rate dτ / dt as an online monitoring and constraint feedback quantity reflecting the instantaneous nucleation intensity.

[0063] After system initialization, it enters the nucleation monitoring phase (S1), operating under the set initial pressure drop rate dP / dt0 and initial electric field strength E0, and continuously acquiring turbidity signals to calculate the turbidity change rate dτ / dt. When |dτ / dt| exceeds the first threshold T10.02 min... -¹(When the system is determined to have a risk of excessively rapid or explosive nucleation, it switches to the nucleation suppression stage (S2). By reducing the pressure drop rate and simultaneously increasing the electric field strength, the nucleation behavior is corrected and controlled. The control objective is to reduce |dτ / dt| back to the second threshold T20.005 min. - ¹Following.

[0064] During the nucleus suppression phase (S2), the system continuously monitors the change in dτ / dt; when |dτ / dt| is lower than the second threshold T20.005 min... - ¹When the relative turbidity τ enters the stable plateau region, the system is determined to have transitioned from the nucleation-dominated stage to the crystal growth-dominated operating state. The system recovers the initial pressure drop rate dP / dt0 and the initial electric field strength E0, and returns to the nucleation monitoring stage (S1), maintaining the directional growth process of the crystal under continuous supervision.

[0065] By using the above-mentioned logic control method, which takes the nucleation monitoring stage as the permanent state and the nucleation suppression stage as the temporary correction state, a dynamic balance between nucleation intensity and crystal growth rate is achieved. This avoids the grain fragmentation and increased entrainment caused by explosive nucleation, while also taking into account crystallization efficiency and the morphological stability of needle-like crystals.

[0066] The control logic diagram is attached. Figure 3 As shown.

[0067] Optional step 5)

[0068] The method described in this application may optionally include step 5): the solvent is recovered by condensation after flash crystallization, and combined with the solvent obtained by separating and removing the mother liquor in step 4) and the solvent obtained by drying, and then recycled in step 1). Preferably, each batch of recycled solvent is replenished with fresh solvent at 0-10 wt% (preferably 2-5 wt%) of the total solvent weight, and an equal amount of waste solvent is discharged. When the fresh solvent replenishment ratio is controlled at 2-5 wt%, the product purity is stable at 99.85-99.90%, and the color and crystal morphology are stable over a long period. When the replenishment ratio is below 2 wt%, impurities accumulate significantly; above 5 wt%, energy consumption increases and economic efficiency decreases. The optimal operating range x = 2-5 wt% achieves a dynamic balance between stable purity and minimum energy consumption.

[0069] The method of this application provides a stable supersaturated environment through vacuum flash evaporation, and the electric field induces ordered molecular orientation. These two processes work synergistically to grow the crystal in the direction of minimum surface energy. This dual-channel mechanism of "energy-orientation" is key to obtaining long, needle-shaped, high-purity crystals in this invention. Through the synergistic design of "vacuum flash evaporation—electric field induction—solvent closed-loop recovery," the method of this application achieves low-energy consumption, controllable morphology, and industrial-scale-suitable preparation of benzotriazole needle-shaped crystals.

[0070] A second aspect of this application also provides benzotriazole needle crystals prepared by the method described in this application, wherein the crystal purity of the benzotriazole needle crystals is ≥97.9% (preferably ≥99.0%, more preferably ≥99.5%, and even more preferably ≥99.8%), and the metal ion residue is ≤8 mg·kg⁻¹. - ¹(Preferably, metal ion residue ≤ 7 mg·kg) - ¹, more preferably, metal ion residue ≤ 6 mg·kg - ¹, More preferably, the metal ion residue is ≤5 mg·kg - ¹), with an average length ≥70 μm (preferably ≥80 μm, more preferably ≥90 μm, more preferably ≥100 μm, and even more preferably ≥110 μm), and an aspect ratio ≥6.5 (preferably ≥7.5, more preferably ≥8, more preferably ≥9, and even more preferably ≥9.5).

[0071] A third aspect of this application also provides a system for the method of this application, the system comprising: a dissolution unit, a vacuum flash crystallization unit, an electric field-induced orientation crystallization unit, a solid-liquid separation unit, and a vacuum drying unit. Preferably, the system further comprises a solvent condensation recovery and recycling unit.

[0072] Benzotriazole, purified by distillation, is first dissolved in an organic solvent in a dissolution unit to form a high-concentration, clear solution. This solution is then pumped to a vacuum flash crystallizer via a metering pump. During depressurization, the system utilizes the sensible heat of the solution to drive partial vaporization of the solvent, creating a stable and controllable supersaturated environment. Simultaneously, an alternating electric field is applied within the crystallizer to induce preferential orientation growth of benzotriazole molecules along a specific direction. After crystallization, the slurry is centrifuged to obtain crystals and mother liquor. The crystals are then subjected to low-temperature drying in a vacuum drying unit. The mother liquor and solvent vapors generated during flash evaporation and drying are condensed, recovered, and returned to the dissolution unit for recycling. Figure 1 As shown.

[0073] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0074] Example

[0075] A. Source of raw materials: Benzotriazole (purity ≥99.5%, purchased from Shanghai Maclean Biochemical Technology Co., Ltd.). 2-Methoxyethanol (industrial grade, moisture ≤0.1 wt%, purchased from Shanghai Maclean Biochemical Technology Co., Ltd.).

[0076] B. Equipment: Metering pump (model BT100, purchased from Baoding Rongbai Constant Flow Pump Manufacturing Co., Ltd.) Vacuum flash crystallization kettle (model RE-52A, purchased from Hunan Yunyihui E-commerce Co., Ltd.) HPLC (model Agilent 1260, purchased from Agilent Technologies, USA) Microscope (model Olympus BX53, purchased from Olympus Corporation) ICP-OES (model PerkinElmer Avio 200, purchased from PerkinElmer) Turbidity meter (model MIK-DC2000-JDS-8011, purchased from Hangzhou Mico Sensor Technology Co., Ltd.)

[0077] Example 1

[0078] (1) Operating conditions

[0079] Raw material composition: benzotriazole (purity ≥99.5%), 2-methoxyethanol (industrial grade, moisture ≤0.1wt%). Material ratio: Benzotriazole to solvent mass ratio 2:1; Dissolution temperature: 90 ℃; Stirring speed: 350 r·min - ¹; Dissolving time: 15–20 min; Flash evaporation conditions: pressure drop rate dP / dt = 0.4 kPa·min - ¹, final pressure 2 kPaA, final temperature 32℃; Electric field parameters: Electric field strength E = 1.0 kV·cm - ¹, Frequency f = 1 kHz; Drying conditions: 45 ℃, 1 kPa, 1.5 h.

[0080] (2) Operating steps

[0081] Dissolve BTA in 2-ME at 90 °C and stir until completely clear and transparent; The solution was fed into a vacuum flash crystallizer via a metering pump, at a pressure of dP / dt = 0.4 kPa·min. - ¹ The pressure was smoothly reduced to 2 kPaA; An alternating electric field (E = 1.0 kV·cm) is applied during the crystallization stage.- ¹, f = 1 kHz), promotes preferential orientation growth; After crystallization, the filter cake was separated by centrifugation and dried at 45 °C and 1 kPa for 1.5 h to obtain long needle-like crystals.

[0082] (3) Detection and evaluation methods

[0083] Purity was determined by HPLC. Platinum-cobalt colorimetric method for colorimetric measurement; Microscopic and image analysis of stylus length and aspect ratio; ICP-OES was used to measure residual metal ions.

[0084] (4) Results and Data

[0085] Table 1

[0086] (5) Results Analysis

[0087] At 90 ℃, the solute completely dissolves and the molecules are uniformly distributed; the supersaturation steady-state range formed by flash evaporation is wide, avoiding localized instantaneous nucleation explosions; the electric field induces the dipole moment of BTA molecules to rotate and align along the direction of low interfacial energy; highly oriented needle-like crystals are formed (aspect ratio 9.5, average needle length 112 μm); the mother liquor entrainment is minimal, the purity increases to 99.92%, and the color is lowest. In summary, under these operating conditions, the optimal balance is achieved between "dissolution kinetics—molecular dispersion uniformity—electric field orientation efficiency—color suppression," representing the best window for the preparation of BTA needle-like crystals.

[0088] Example 2: Effect of different dissolution temperatures on crystal quality

[0089] (1) Operating conditions

[0090] Raw material composition: benzotriazole (purity ≥99.5%), 2-methoxyethanol (industrial grade, moisture ≤0.1wt%). Material ratio: Benzotriazole to solvent mass ratio 2:1; Dissolution temperature variables: 80 ℃, 90 ℃, 100 ℃; Stirring speed: 350 r·min - ¹; Dissolving time: 15–20 min; Flash evaporation conditions: dP / dt = 0.4 kPa·min - ¹, endpoint pressure 2 kPaA, endpoint temperature 32 ℃; Electric field parameter: E = 1.0 kV·cm -¹, f = 1 kHz; Drying conditions: 45 ℃, 1 kPa, 1.5 h.

[0091] (2) Operating steps

[0092] Dissolve BTA in 2-ME at the set temperature and stir until completely clear; The solution was fed into a vacuum flash crystallizer via a metering pump at a pressure reduction rate of 0.4 kPa·min. - ¹Down to 2 kPaA; An alternating electric field (E = 1.0 kV·cm) is applied during the crystallization stage. - ¹, f = 1 kHz); After crystallization, the filter cake was separated by centrifugation and dried at 45 °C and 1 kPa for 1.5 h.

[0093] (3) Detection and evaluation methods

[0094] Purity was determined by HPLC; colorimetry was determined by the platinum-cobalt colorimetric method; the length and aspect ratio of the microscopic stylus were measured; and residual metal ions were determined by ICP-OES.

[0095] (4) Results and Data

[0096] Table 2

[0097] (5) Results Analysis

[0098] At 80 ℃, the system does not dissolve completely, and the micro-suspended nuclei enter the crystallization segment to form heterogeneous nucleation, causing the entrainment to rise slightly; at 90 ℃, the molecules are evenly dispersed, the supersaturated formation is stable, the electric field orientation efficiency is high, and the purity and needle length are the highest; at 100 ℃, although the dissolution is complete, the high temperature stay causes slight coloration and a slight increase in color intensity.

[0099] Example 3: Effect of different pressure reduction rates on crystal morphology and purity

[0100] (1) Operating conditions

[0101] Dissolution temperature: 90 ℃; Solution ratio: Benzotriazole to 2-ME in a mass ratio of 2:1; Electric field parameter: E = 1.0 kV·cm - ¹, f = 1 kHz; Pressure drop rate variables: 0.1, 0.3, 0.5, 1.2 kPa·min - ¹; Endpoint pressure / temperature: 2 kPaA / 32 ℃; Drying conditions: 45 ℃, 1 kPa, 1.5 h.

[0102] (2) Operating steps

[0103] BTA dissolves completely at 90 °C; The solution is pumped into the flash crystallizer, and the pressure is reduced according to the set dP / dt control program; An electric field of 1.0 kV·cm was applied throughout the crystallization process. - ¹, frequency 1 kHz; After crystallization, the crystals were separated by centrifugation and then vacuum dried to obtain needle-like crystals.

[0104] (3) Detection and evaluation methods

[0105] Purity was determined by HPLC, and needle length and defect rate were statistically analyzed by microscopy.

[0106] (4) Results and Data

[0107] Table 3

[0108] (5) Results Analysis

[0109] a) Analysis of pressure drop data: Rapid drop in blood pressure (≥ 1.0 kPa·min) - ¹): When the depressurization rate is high, the supersaturation of the system accumulates rapidly in a short time, and the peak value of the turbidity change rate (dτ / dt) increases significantly, clearly exceeding the nucleation control threshold, indicating that the nucleation process occurs explosively. At the same time, the relative turbidity τ rises rapidly in a short time and reaches a high plateau value, reflecting an excessive number of crystal nuclei in the system. Under this condition, crystal growth is inhibited, ultimately leading to fine grains, increased inclusions, and increased defect rates.

[0110] The blood pressure drop is too slow (≤ 0.1 kPa·min). - ¹): When the depressurization rate is low, supersaturation is established slowly, and the turbidity change rate remains at a low level throughout the crystallization process without a significant peak, indicating that the nucleation process is mild and limited; the plateau value of relative turbidity τ is low, indicating that the amount of solid phase generated per unit time is limited. This condition is conducive to obtaining crystals with high purity and morphological integrity, but the crystallization cycle is prolonged and the overall production capacity is low.

[0111] Moderate blood pressure reduction (0.3–0.5 kPa·min) - ¹): When the pressure reduction rate is controlled at 0.3–0.5 kPa·min -¹ Within this range, the peak value of the turbidity change rate is within a moderate range, both below the nucleation threshold and significantly above the nucleation lower limit, indicating that the nucleation intensity is stable and controllable. The relative turbidity τ gradually increases and forms a stable plateau, indicating that the system smoothly transitions from the nucleation stage to the stage dominated by crystal growth. Under these conditions, the nucleation behavior and the electric field-induced orientation growth process can be well coordinated, resulting in needle-like crystals with concentrated needle length distribution, high orientation degree, and superior crystallization efficiency.

[0112] b) Analysis of the turbidity change rate threshold: Based on the crystallization behavior and corresponding turbidity response characteristics under different depressurization rates, the selection criteria for the turbidity change rate threshold can be explained. Experimental data shows that the maximum turbidity change rate ( / The value increases significantly with increasing depressurization rate and has a good correlation with crystal morphology and quality indicators.

[0113] Under low pressure drop rate conditions (0.1–0.3 kPa·min) - ¹) Under these conditions, the maximum turbidity change rate was less than 0.02 min. - ¹ At this point, the nucleation process is mild, the average needle length of the crystals is relatively large, the aspect ratio is high, the purity remains at a high level, and the defect rate is low, indicating that the system is in a state of controlled nucleation and stable growth. When the depressurization rate is increased to 0.5 kPa·min - ¹ At and above, the maximum turbidity change rate exceeds 0.02 min - ¹, corresponding to a significant decrease in the average needle length and aspect ratio of the crystal, a decrease in purity, and a significant increase in the defect rate, reflecting the explosive nucleation characteristics caused by excessively high nucleation intensity and a rapid increase in the number of crystals. Therefore, approximately 0.02 min - ¹ It can serve as a key dividing point between mild nucleation and explosive nucleation behavior, so selecting it as the first threshold T1 to trigger nucleation inhibition control has clear experimental basis.

[0114] The second threshold T2 is not used to distinguish the strength of nucleation under different operating conditions, but rather to determine whether the nucleation process has ended and entered the stage dominated by crystal growth. Considering the experimental characteristics that turbidity reaches a stable plateau in the later stages and crystal morphology and purity no longer change significantly, a turbidity change rate significantly lower than T1 is selected as the backoff threshold to avoid frequent switching between the nucleation and growth stages. Based on these considerations, the second threshold T2 is set to 0.005 min. - ¹ This makes it clearly distinguishable from the core explosion criterion on an order of magnitude, thereby ensuring the stability and robustness of the control logic.

[0115] In summary, the first threshold T1 reflects the critical level at which the nucleation intensity changes from controllable to explosive, and the second threshold T2 is used to characterize the basic end of nucleation and the entry into a stable growth stage. Together, they constitute a staged control criterion based on the turbidity change rate, which is in good consistency with the changing trends of crystal morphology, purity, and defect rate in the experimental data.

[0116] Example 4: Effect of different electric field intensities on crystal orientation and purity

[0117] (1) Operating conditions

[0118] Raw material composition: benzotriazole (purity ≥99.5%), 2-methoxyethanol (moisture ≤0.1 wt%); Material ratio: 2:1 (BTA:2-ME, mass ratio); Dissolution temperature: 90 ℃; Flash evaporation conditions: pressure drop rate dP / dt = 0.4 kPa·min - ¹, final pressure 2 kPaA, final temperature 32℃; Electric field strength variables: 0, 0.5, 1.0, 1.5 kV·cm - ¹(Frequency 1 kHz); Drying conditions: 45 ℃, 1 kPa, 1.5 h.

[0119] (2) Operating steps

[0120] Benzotriazole and 2-ME were mixed at a mass ratio of 2:1 and dissolved at 90 °C until clear; The solution was fed into the crystallizer via a metering pump, and the flash evaporation depressurization program was started (dP / dt = 0.4 kPa·min). - ¹); An alternating electric field (frequency 1 kHz) is applied at a set electric field strength during the crystallization stage. After crystallization, the crystals were separated by centrifugation and dried under vacuum at 45 °C for 1.5 h to obtain needle-like crystals.

[0121] (3) Detection and evaluation methods

[0122] Purity was determined by HPLC; crystal length and aspect ratio were determined by microscopic images; residual metal ions were analyzed by ICP-OES.

[0123] (4) Results and Data

[0124] Table 4

[0125] (5) Results Analysis

[0126] The electric field strength is less than 0.3 kV·cm - When ¹, the molecular dipole orientation is insufficient, and the crystal grows isotropically.

[0127] Electric field strength: 0.8–1.2 kV·cm - Within the ¹ range, the molecular polarization torque best matches the supersaturation gradient, and the crystal preferentially extends along the low interfacial energy direction; the interfacial free energy decreases by 12–18%, and the needle-likeness is significantly enhanced. Under these conditions, the needle length stabilizes at 100–120 μm, and the purity increases to over 99.9%. Simultaneously, the electromigration effect induced by the electric field promotes the migration of charged impurities (especially metal ions) towards the mother liquor, reducing intercalation and lowering the residual metal ions to ≤5 mg·kg⁻¹. - ¹.

[0128] Excessive electric field (>1.2 kV·cm) - ¹) Triggers microagglomeration, causing local temperature rise and increased solution disturbance.

[0129] Example 5: Effect of solvent recycling ratio on long-term stability

[0130] (1) Operating conditions

[0131] Raw material composition: benzotriazole ≥99.5%, 2-methoxyethanol ≥99.0%; Dissolution temperature: 90 ℃; Flash depressurization rate: dP / dt = 0.4 kPa·min - ¹; Electric field parameter: E = 1.0 kV·cm - ¹, f = 1 kHz; Drying conditions: 45 ℃, 1 kPa, 1.5 h.

[0132] Solvent recovery method: Flash vapor condensation recovery, combined with centrifugal separation and drying condensation, and recycled. Fresh solvent replenishment ratio is set at x = 0%, 1%, 2%, 5%, 10%. Operating cycle: 50 batches run continuously, with testing every 10 batches; (2) Operating steps Benzotriazole was dissolved in 2-ME solvent at 90 °C; The solution was fed into the crystallizing vessel via a metering pump at a pressure reduction rate of 0.4 kPa·min. - ¹ Flash crystallization is carried out; An electric field of 1.0 kV·cm was applied during the crystallization process. - ¹; The solvent recovered from flash condensation is combined with the solvent separated by centrifugation and dried and condensed for recycling. Fresh solvent is added in proportion and an equal amount of waste solvent is discharged. After 50 consecutive batches, the purity, color, and residual ion data were statistically analyzed.

[0133] (3) Detection and evaluation methods

[0134] Purity was determined by HPLC; colorimetry was determined by Pt-Co colorimetry; metal residues were determined by ICP-OES; and trace byproducts in the recovered solvent were detected by GC-MS.

[0135] (4) Results and Data

[0136] Table 5

[0137] (5) Results Analysis

[0138] When x < 2%, impurities cannot be removed in time, and the accumulation of metal ions and chromophores leads to a decrease in purity and an increase in color. When x = 2–5%, the impurity concentration in the system is stable, which maintains solvent circulation efficiency and avoids performance degradation. When x > 5%, the improvement in solvent quality is limited but the energy consumption increases, which is uneconomical; After 50 batches of long-term operation, the system stabilized, with purity maintained at 99.85–99.90%, indicating that the solvent circulation closed loop is effective.

[0139] Comparative Example 1: Aqueous Solution Cooling Crystallization Method

[0140] (1) Operating conditions

[0141] Raw material composition: benzotriazole (purity ≥99.5%), deionized water; Dissolution temperature: 90 ℃; Cooling method: Natural cooling to 25℃; Stirring speed: 300 r·min - ¹; No electric field inducement; Drying conditions: Dry with hot air at 60 ℃ under normal pressure for 2 h.

[0142] (2) Operating steps

[0143] Benzotriazole is dissolved in hot water to form a saturated solution; Stop heating and allow to cool and crystallize naturally at room temperature; After crystallization, the mother liquor was separated by centrifugation and dried under hot air at 60 ℃ to obtain the product.

[0144] (3) Detection and evaluation methods

[0145] Purity was determined by HPLC; crystal size was measured by microscopy; and colorimetry was determined by the Pt-Co method.

[0146] (4) Results and Data

[0147] Table 6

[0148] (5) Results Analysis

[0149] Water is a highly polar solvent, and BTA has extremely low solubility (approximately 0.1 g / 100 g). - ¹·25 ℃), the system establishes supersaturation slowly and unevenly; Uncontrolled cooling rate leads to heterogeneous nucleation as the dominant process, resulting in short, coarse crystal morphology with severe entrainment. Due to the lack of an oriented external field, the surface energy of the crystals varies greatly during the crystallization process, resulting in a wide particle size distribution and ultimately lower purity and needle-likeness.

[0150] Comparative Example 2: Melt Crystallization Method

[0151] (1) Operating conditions

[0152] Raw material composition: benzotriazole ≥99.5%; Operating temperature: Melting temperature 120 ℃; Cooling method: Natural cooling crystallization; Solvent-free and electric field-free; Drying conditions: Vacuum 80 ℃, 1.5 h.

[0153] (2) Operating steps

[0154] Directly heat benzotriazole until it is completely melted; Stop heating and allow to cool and crystallize naturally at room temperature. After obtaining the solidified block, it is crushed and dried.

[0155] (3) Detection and evaluation methods

[0156] Purity was determined by HPLC; crystal form was determined by microscopy; and metal impurities were determined by ICP-OES.

[0157] (4) Results and Data

[0158] Table 7

[0159] (5) Results Analysis

[0160] The melting method lacks solvent regulation and thermodynamic buffering, resulting in a large temperature gradient in the system and uneven crystal growth rate. At high temperatures, some molecules undergo trace oxidation or polymerization side reactions, leading to increased color. Without an electric field, the crystal growth direction is random, the morphology is poorly controllable, and the improvement of purity is limited.

[0161] Comparative Example 3: Field-Free Induced Crystallization Method

[0162] (1) Operating conditions

[0163] Raw material composition: benzotriazole (purity ≥99.5%), 2-methoxyethanol; Ratio: 2:1; Dissolution temperature: 90 ℃; Flash evaporation conditions: dP / dt = 0.4 kPa·min - ¹, Final pressure 2 kPaA; No electric field is applied; Drying conditions: 45 ℃, 1 kPa, 1.5 h.

[0164] (2) Operating steps

[0165] Operate as in Example 2, but without power; Maintain the same dissolution and depressurization curve conditions; After crystallization, centrifugation and drying were performed to obtain the crystal sample.

[0166] (3) Detection and evaluation methods

[0167] Purity was determined by HPLC; the needle length and aspect ratio were statistically analyzed by microscopy; and metal residues were determined by ICP-OES.

[0168] (4) Results and Data

[0169] Table 8

[0170] (5) Results Analysis

[0171] When there is no electric field, the dipole orientation of solute molecules is random, the crystal plane growth is isotropic, and the crystal is disordered; impurity ions have difficulty migrating out of the crystal interface under the absence of an electric field gradient, resulting in high metal residue and decreased purity; crystals are prone to agglomeration, the fracture rate increases, and the needle-likeness is significantly weakened.

[0172] Table 9

[0173] Compared with traditional cooling crystallization, melt crystallization, and electric field-free processes, this invention achieves the following: energy consumption reduction of approximately 40%; purity increase of 1.8–2.0 percentage points; metal ion residue reduction of approximately 70%; crystal fracture rate reduction of 60%; and no performance degradation after 50 solvent cycles.

[0174] like Figure 2 As shown, the benzotriazole crystals prepared under the optimal operating conditions of this invention exhibit a highly uniform, regular needle-like structure with concentrated crystal length distribution, obvious orientation, smooth crystal surface, significantly reduced fracture and agglomeration, and optimal overall morphological uniformity. Crystals prepared under the general operating conditions of this invention also maintain a stable needle-like morphology with good crystal orientation and a high needle length-to-diameter ratio, indicating good stability and repeatability of the process within a certain operating window. In contrast, the crystals obtained in Comparative Example 1 (cooling crystallization from aqueous solution) mainly exhibit a mixed structure of short, coarse needles and granules, with shorter crystal lengths, irregular morphology, wide particle size distribution, and obvious mother liquor entrainment and non-uniform nucleation phenomena. The crystals obtained in Comparative Example 2 (melt crystallization) are mainly blocky or short needle-like structures with poor crystal orientation, insufficient crystal morphological uniformity, and numerous surface defects, making it difficult to form a regular needle-like structure. Although the crystals obtained in Comparative Example 3 (crystallization without electric field induction) could form a certain needle-like appearance, the crystal orientation was dispersed, the length distribution was uneven, and the aggregation and defects between crystals were more obvious, resulting in insufficient overall morphological stability. Figure 2 The microscopic morphology comparison shown demonstrates that, through the synergistic effect of vacuum flash evaporation and electric field induction, the present invention significantly improves the orientation growth behavior of benzotriazole crystals, making the crystals superior to the comparative process in terms of morphological uniformity, orientation consistency, and structural integrity.

[0175] The above description is merely a preferred embodiment of this disclosure and is not intended to limit the scope of the substantive technical content of this disclosure. The substantive technical content of this disclosure is broadly defined within the scope of the claims of this application. Any technical entity or method completed by others that is completely identical to or an equivalent modification of the claims of this application shall be deemed to be covered within the scope of the claims.

[0176] All documents mentioned in this disclosure are incorporated herein by reference as if each document were individually incorporated herein by reference. Furthermore, it should be understood that after reading the foregoing contents of this disclosure, those skilled in the art can make various alterations or modifications to this disclosure, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for preparing benzotriazole needle-like crystals, the method comprising the following steps in sequence: Step 1: Mix benzotriazole with an organic solvent, stir to dissolve, and obtain a clear and homogeneous solution; Step 2: The solution is fed into a vacuum flash crystallization reactor, and the pressure inside the reactor is gradually reduced from atmospheric pressure while the system temperature is adjusted simultaneously to create a stable and controllable supersaturated environment. Step 3: During the crystallization stage, an alternating electric field is applied to induce molecular orientation, promoting preferential crystal growth along the electric field direction and suppressing disordered nucleation and impurity entrainment; and Step 4: After crystallization, remove the mother liquor and dry the obtained crystals to obtain high-purity benzotriazole needle crystals.

2. The method of claim 1, wherein in step 1, the organic solvent is an alcohol solvent, an ether solvent, or a combination thereof; and / or In step 1, benzotriazole and an organic solvent are mixed at a mass ratio of (1.8–2.2):1; and / or In step 1, the weight fraction of benzotriazole in the obtained solution is 50–75 wt%; and / or In step 1, the dissolution temperature is controlled at 80–100 °C; and / or In step 1, the benzotriazole is purified by distillation.

3. The method as described in claim 1, wherein, In step 2, the solution is fed into a vacuum flash crystallization vessel using a metering pump; and / or In step 2, vacuum flash crystallization is an intermittent operation; and / or In step 2, the pressure reduction rate is controlled between 0.1 and 1.2 kPa·min. - ¹, endpoint pressure 1–20 kPa, endpoint temperature 20–60°C; and / or In step 2, the pressure reduction process is controlled using piecewise linear or S-curve control to balance the nucleation rate and crystal growth rate; and / or In step 2, the supersaturation of the system is maintained at S = 1.2 to 1.

4.

4. The method of claim 1, wherein in step 3, the applied alternating electric field strength is 0.3–1.5 kV·cm. - ¹, with a frequency of 0.5–2 kHz; and / or In step 3, the electric field is applied in a pulsed or alternating manner.

5. The method of claim 1, wherein in step 4, the drying is carried out under the following conditions: vacuum degree ≤ 5 kPa, temperature 30–60 °C; and / or In step 4, the drying time is 0.5–5 h; and / or In step 4, after crystallization, the mother liquor is removed by centrifugation.

6. The method as described in claim 1, wherein the vacuum flash crystallization vessel is equipped with pressure, temperature, and turbidity sensors, and the pressure reduction curve is adjusted in real time through a closed-loop control system. When the turbidity change rate dτ / dt is detected to be greater than the first threshold of 0.02 min... - At time ¹, the voltage reduction rate is automatically reduced while the electric field strength is increased simultaneously, bringing |dτ / dt| back to less than or equal to the second threshold of 0.005 min. - ¹, and restore the initial voltage drop rate and electric field strength.

7. The method as described in claim 1, further comprising step 5: the solvent is recovered by condensation after flash crystallization, and combined with the solvent obtained by separating and removing the mother liquor in step 4 and the solvent obtained by drying, and then recycled in step 1.

8. The method as described in claim 7, wherein fresh solvent is added to each batch at a rate of 0-10% by weight of the total solvent weight and an equal amount of waste solvent is discharged.

9. A benzotriazole needle-like crystal prepared by the method according to any one of claims 1 to 8, characterized in that: Crystal purity ≥ 97.9%, metal ion residue ≤ 8 mg·kg - ¹, with an average length ≥70 μm and an aspect ratio ≥6.

5.

10. A system for the method of any one of claims 1 to 8, the system comprising: The unit includes a dissolution unit, a vacuum flash crystallization unit, an electric field-induced orientation crystallization unit, a solid-liquid separation unit, and a vacuum drying unit.

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