Purification method of high-content prohexadione calcium

Abstract

The invention discloses a purification method of high-content prohexadione calcium, and belongs to the technical field of fine chemical engineering. The method comprises the following steps: S1, acidolysis: mixing crude prohexadione calcium with a hydrochloric acid aqueous solution for reaction, and carrying out solid-liquid separation to obtain a prohexadione wet material; s2, purification: mixing the wet material with an organic solvent, carrying out heating reflux and hot filtration, and carrying out cooling crystallization and solid-liquid separation on the filtrate to obtain high-purity prohexadione; and S3, calcification: dissolving the high-purity prohexadione in alkali liquor, adjusting the pH value to 6.5-7.5, adding a calcium salt solution for reaction, and carrying out solid-liquid separation, washing and drying to obtain the high-purity prohexadione calcium. Inorganic and organic impurities are effectively separated through a process route of acidolysis, solvent purification and calcification, efficient purification of prohexadione calcium is successfully achieved by adopting mother liquor circulation and solvent recovery technologies, the product purity is larger than or equal to 98%, and the method is high in yield, low in cost, environmentally friendly and suitable for industrial production.

Description

Technical Field

[0001] This invention relates to a purification method for high-content calcium cyclohexane, belonging to the field of fine chemical technology. Background Technology

[0002] Prohexadione-calcium is a highly bioactive plant growth regulator, belonging to the gibberellin biosynthesis inhibitors. It can effectively control excessive crop growth, improve lodging resistance, and enhance crop stress resistance. It is widely used in economic crops such as rice, wheat, peanuts, and fruit trees.

[0003] Currently, the industrial synthesis of calcium cyclohexane typically involves chemical condensation and cyclization reactions, resulting in initial products (crude products) with generally low purity (usually between 90% and 93%), containing unreacted raw materials, synthetic intermediates, byproducts, and various impurities such as inorganic salts. The presence of these impurities not only affects the efficacy and safety of calcium cyclohexane products but also limits their application in high-end agriculture. Therefore, developing efficient purification processes to obtain high-content (e.g., ≥98%) calcium cyclohexane products is of great significance for improving product quality and market competitiveness.

[0004] Numerous purification methods for calcium cyclohexanoate have been reported in the prior art, with common purification methods including recrystallization and solvent washing. However, these conventional methods have several limitations: Purity bottleneck: Simple recrystallization often fails to effectively separate organic impurities with similar structures, resulting in limited improvement in product purity and making it difficult to consistently achieve high standards of over 98%.

[0005] Yield loss: In pursuit of higher purity, repeated crystallization is often required, which leads to a significant decrease in the final yield and an increase in production costs.

[0006] Solvent consumption and environmental pressure: The multiple crystallization and washing processes require the use of large amounts of organic solvents, which not only increases production costs but also increases the pressure of subsequent waste treatment and the risk of environmental pollution.

[0007] Complex processes: Some process routes are lengthy, involving multiple solid-liquid separations and conversions, which are not suitable for large-scale industrial production.

[0008] Therefore, there is an urgent need in this field to develop a new purification method that can overcome the shortcomings of the existing technology and achieve stable production of high-content calcium cyclohexane products in a high-yield, low-cost, and environmentally friendly manner. Summary of the Invention

[0009] The purpose of this invention is to provide a purification method for high-content calcium cyclohexane, which is simple in process, has good purification effect, high yield, low cost, and is suitable for industrial production.

[0010] The purification method for high-content calcium cyclohexane provided by this invention includes the following steps: S1, acid hydrolysis The crude calcium cyclohexane was mixed with hydrochloric acid aqueous solution for acid hydrolysis. After the reaction was completed, solid-liquid separation was performed to obtain wet cyclohexane. S2, Purification The wet cyclic acid material is mixed with an organic solvent, heated under reflux and then hot filtered. The resulting filtrate is cooled and crystallized, and high-purity cyclic acid is obtained after solid-liquid separation. S3, calcification The high-purity cyclic acid is dissolved in an alkaline solution and water system. After adjusting the pH to neutral or weakly alkaline with alkali, a calcium salt solution is added to carry out a calcification reaction. After the reaction is completed, solid-liquid separation, washing, and drying are performed to obtain high-purity calcium cyclic acid.

[0011] In the purification method of this invention, the target product is converted from its calcium salt form to a free acid form through the acidolysis step in step S1. The free acid has low solubility in water and precipitates out as a solid, thus allowing it to be separated from a large number of water-soluble impurities through filtration.

[0012] In the purification method of this invention, the acid hydrolysis step in step S1 mainly removes water-soluble inorganic impurities and soluble salts: excess calcium sources (such as CaO, Ca(OH)2), catalyst residues, or other metal ion salts that may be contained in the crude product will react with hydrochloric acid to generate soluble chlorides (such as CaCl2, MgCl2, FeCl2, etc.), which will be removed by entering the filtrate during suction filtration. Some water-soluble organic matter: some water-soluble synthetic intermediates or by-products will also be washed away during filtration and rinsing.

[0013] In the purification method of this invention, acid hydrolysis in step S1 is a "pretreatment" and "preliminary purification" step. It converts calcium salts, which are difficult to purify directly, into a free acid form that is easier to refine through recrystallization, removing most (approximately 60-70%) of inorganic impurities. If these impurities directly enter the subsequent ethanol reflux crystallization step, they will severely contaminate the solvent, affect crystal quality, reduce crystallization yield, and may even form oily substances or colloids due to excessive impurities, leading to purification failure. By converting the product into a free acid and filtering it, the product is concentrated and collected for the first time, avoiding losses during solution processing.

[0014] In the purification method of the present invention, the concentration of the hydrochloric acid aqueous solution is 15-20%, and the mass ratio of the crude calcium cyclamate to the hydrochloric acid aqueous solution is 1:2.5-3.0.

[0015] In the purification method of the present invention, in step S1, the acid hydrolysis reaction is carried out at room temperature for 0.5-1 hour. The solid-liquid separation method is vacuum filtration; After solid-liquid separation, the solid is rinsed with clean water to thoroughly wash away the mother liquor containing a large number of impurities that is wrapped on the surface and inside of the filter cake particles, greatly reducing the burden on subsequent purification steps.

[0016] In the purification method of the present invention, in step S2, the organic solvent is one or more of ethanol, methanol and isopropanol; The mass ratio of the organic solvent to the crude calcium cyclohexane is 1.5-2.0:1.

[0017] In the purification method of the present invention, the purification step in step S2 is used to remove organic impurities from the acid hydrolysate, such as synthesis intermediates, by-products, pigments, resinous polymers, etc.

[0018] In the purification method of this invention, the recrystallization in step S2 (reflecting the significant difference in solubility between the target product and impurities in a specific solvent at different temperatures) includes the following stages: Dissolution stage (heating and reflux): At high temperature, the solubility of the target product (cyclohexane) and impurities in ethanol increases, forming a homogeneous solution.

[0019] Impurity removal stage (hot filtration): Filtration is performed while the alcohol is hot to completely remove impurities that are insoluble in hot ethanol (such as some inorganic particles and polymers). This is the first step in purification.

[0020] Crystallization stage (cooling crystallization): After the filtrate cools, the solubility of the target product, cyclohexane, in ethanol decreases sharply, and it will preferentially precipitate out in the form of pure crystals. Most impurities, due to their higher solubility or lower concentration, remain in the mother liquor. Programmed cooling (ultimately to -2°C) aims to minimize product solubility, increase yield, and control crystal morphology.

[0021] Efficiency Enhancement Stage (Secondary Crystallization): After primary crystallization, a small amount of product and highly soluble impurities still remain dissolved in the mother liquor. Secondary crystallization allows for further product recovery and ensures that impurities are fully enriched in the final mother liquor, thus achieving both high yield and high purity.

[0022] In the purification method of this invention, the organic impurities that determine the final purity of the product are removed through the purification step in step S2. This process treats the wet material after acid hydrolysis, avoiding the additional energy consumption and losses associated with drying and re-dissolving the wet material. The resulting high-purity cyclohexanoic acid provides excellent raw material for the subsequent calcification reaction, ensuring a high content of the final cyclohexanoic acid calcium salt.

[0023] In the purification method of the present invention, in step S2, the cooling crystallization is a stepped cooling crystallization or a programmed temperature-controlled crystallization, and the final crystallization temperature range is -5℃ to 5℃.

[0024] In the purification method of the present invention, in step S2, after cooling and crystallization, solid-liquid separation is performed, and the resulting filtrate is cooled, crystallized, and separated again to achieve secondary purification and further improve the yield and purity.

[0025] In the purification method of this invention, the calcification step in step S2 includes a neutralization reaction and a metathesis reaction (precipitation reaction). The purpose of the neutralization reaction is to convert free cyclohexanoic acid into a soluble sodium cyclohexanoate salt, ensuring its complete dissolution in the aqueous system, thus preparing for the subsequent homogeneous precipitation reaction. The purpose of the precipitation reaction is to introduce calcium ions (Ca) into the sodium cyclohexanoate solution. 2+ This process generates calcium cyclohexane precipitate with extremely low solubility, thereby achieving efficient precipitation of the product from the solution.

[0026] In the purification method of this invention, the precise control of pH value is crucial in the calcification step of step S2. Adjusting the pH to neutral serves to: ensure complete reaction; and ensure that the system contains no excess acid (H+). + There is also no excess alkali (O). - Excess acid will react with CaCl2, consuming the calcium source; excess alkali will introduce OH-. - , possibly related to Ca 2+ It generates slightly soluble Ca(OH)2 impurities, contaminating the final product. Furthermore, calcium cyclohexanoate is most stable at a specific neutral pH, avoiding hydrolysis or other degradation side reactions at excessively high or low pH levels.

[0027] In the purification method of the present invention, in step S3, the alkaline solution is an aqueous solution of sodium hydroxide or potassium hydroxide, with a concentration of 25-35%. The calcium salt solution is an aqueous solution of calcium chloride or calcium nitrate.

[0028] In the purification method of the present invention, in step S3, the pH is adjusted to 6.5-7.5; The molar ratio of calcium ions to cyclohexane in the calcium salt solution is 1-1.1:1.

[0029] In the purification method of this invention, in step S2 and / or step S3, the mother liquor generated during separation is recycled for use in the same production step of the next batch. In the purification method of the present invention, in step S2, the organic solvent is recovered by distillation and then recycled.

[0030] Compared with the prior art, the present invention has the following beneficial technical effects: High product purity: Inorganic impurities are effectively removed through the "acid hydrolysis" step, and organic impurities are efficiently separated through the "organic solvent reflux crystallization" step. In particular, combined with the secondary crystallization process, it can stably produce high-purity calcium cyclohexane with a content of ≥98%.

[0031] High product yield: The unique process design avoids product loss caused by repeated crystallization, and the overall yield is increased to over 98% through secondary crystallization and recycling of mother liquor, which significantly reduces production costs.

[0032] The process is simple and efficient: the process is short, the operation is simple, and the reaction conditions are mild (room temperature and pressure), making it very suitable for large-scale industrial production.

[0033] Green and environmentally friendly: By recycling mother liquor and reusing solvents, waste liquid discharge and the amount of fresh solvent used are greatly reduced, thus reducing the environmental burden and production costs. Detailed Implementation

[0034] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0035] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0036] This invention provides a purification method for high-content calcium cyclohexane, which adopts a process of "acid hydrolysis-solvent purification-recalcification" and is supplemented by mother liquor recycling, thereby achieving a simultaneous and significant improvement in product purity and yield.

[0037] 1. Acid hydrolysis treatment (removal of inorganic impurities) Low-content crude calcium cyclohexane was reacted with a certain concentration of hydrochloric acid aqueous solution at room temperature.

[0038] Objective: To convert calcium cyclohexane into free cyclohexane, and to effectively remove soluble inorganic salts and other impurities carried in the raw material through filtration and rinsing with water, in order to prepare for subsequent deep purification.

[0039] 2. Solvent purification and crystallization (removal of organic impurities) The acidified cyclic acid wet material is mixed with an organic solvent (such as ethanol), dissolved by heating under reflux, and then filtered hot. The filtrate is then cooled and crystallized at low temperature.

[0040] A secondary crystallization process is adopted, in which the mother liquor after the first crystallization is not discarded, but continues to be crystallized again to extract the product to the maximum extent.

[0041] Objective: To efficiently separate organic impurities by recrystallization based on the difference in solubility between the target product and organic impurities in solvents, thereby obtaining a high-purity cyclic acid intermediate.

[0042] 3. Calcification reaction (finished product shaping and final purification) High-purity cyclohexane was dissolved in an alkaline solution and the pH was precisely adjusted to neutral. Then, a calcium salt solution was added to carry out a precipitation reaction.

[0043] Objective: To convert purified cyclohexane back into the target product—calcium cyclohexane. Subsequent filtration and thorough rinsing with clean water remove soluble salts (such as NaCl) generated during the reaction, ensuring the high purity of the final product.

[0044] 4. Resource recycling and efficiency improvement Mother liquor reuse: The mother liquor generated during the purification, crystallization and calcification steps is recycled for the next batch of production.

[0045] Results: Significantly improved raw material utilization, increasing the overall yield to over 98%, while reducing waste liquid discharge and lowering production costs.

[0046] Example 1 Acid hydrolysis: Weigh 350 g of crude calcium cyclohexane with a purity of 92% and place it in a 2000 mL reaction flask. Add 940 g of 18% hydrochloric acid aqueous solution and stir the mixture at 25 °C for 0.5 hours. After the reaction is complete, filter the mixture and rinse the filter cake three times with 200 mL of water to obtain wet cyclohexane.

[0047] Purification: Transfer the above wet material to a 2000 mL round-bottom flask, add 600 g of ethanol, and heat to 78 °C under reflux for 0.5 hours. Stop heating and filter while hot (place the flask in an ice-water bath to prevent crystallization blockage). Quickly transfer the resulting filtrate to a crystallization vessel and cool at -2 °C for 10 minutes to crystallize. Filter to obtain the first crystallized product.

[0048] The mother liquor from the first crystallization was cooled again at -2°C for 10 minutes, and then filtered again to obtain the second crystallization product. The two crystallization products were combined to obtain high-purity cyclohexane.

[0049] Calcification: Place the obtained high-purity cyclohexane in a 1000 mL reaction flask, add 220 g of 32% sodium hydroxide aqueous solution and 330 g of water, and stir until completely dissolved. The solution is alkaline, as tested with pH paper. Finely adjust the pH to 7.0 with a small amount of dilute hydrochloric acid.

[0050] While stirring, a solution prepared by dissolving 140 g of calcium chloride in 700 g of water was slowly added dropwise. After the addition was complete, stirring was continued for 0.5 hours. The mixture was then filtered, and the filter cake was rinsed three times with 150 mL of water. The molar ratio of calcium ions to cyclohexane was 1:1.

[0051] The wet filter cake was placed in a vacuum drying oven and dried at 80℃ and -0.09MPa for 4 hours to obtain a white powdery high-purity calcium cyclohexane product.

[0052] Mother liquor reuse: The second crystallization mother liquor from the purification step in this embodiment is retained and used in the next batch purification step as a partial solvent to replace fresh ethanol.

[0053] High-performance liquid chromatography (HPLC) analysis showed that the product content obtained in this example was 98.5%. Based on the mass of calcium cyclohexanoate in the initial crude product, the yield of the purified product in this example was 98.2%.

[0054] Example 2 Weigh 350 grams of crude calcium cyclohexane with a content of 90%, and perform acid hydrolysis and rinsing according to the method described in Example 1 to obtain wet material.

[0055] The wet material was mixed with 600 g of 95% industrial ethanol and refluxed and hot filtered under the conditions described in Example 1. The filtrate was crystallized using a programmed cooling method: first, the temperature was lowered from 70°C to 0°C at a rate of 10°C / hour, then rapidly lowered to -2°C and aged for 20 minutes. After filtration, the mother liquor was subjected to secondary crystallization. The crystallized products were combined.

[0056] The subsequent calcification, washing, and drying steps are exactly the same as in Example 1.

[0057] HPLC analysis showed that the final product contained 98.2% calcium cyclohexane, with a calculated yield of 97.8%.

[0058] Example 3 The production was carried out according to the method of Example 1, except that in step 2 "purification", of the 600g of ethanol added initially, 300g was ethanol recovered from the previous batch (obtained by distillation of the mother liquor) and the other 300g was fresh ethanol.

[0059] The obtained product, analyzed by HPLC, had a content of 98.3% and a yield of 98.0%. This is comparable to the results of Example 1, demonstrating that the reuse of recovered ethanol in production is entirely feasible, does not affect product quality or yield, and significantly reduces production costs.

[0060] Comparative Example 1: Changing the pH value during calcification The steps of Example 1 were repeated, but in the calcification step, the pH was no longer precisely controlled after adjustment, and the final pH of the reaction system was approximately 9.

[0061] The obtained product, analyzed by HPLC, had a purity of 95.8%. A small number of impurity peaks were found in the product, presumably byproducts that may have been generated under alkaline conditions or introduced calcium hydroxide impurities. The yield was 97.5%. This comparative example demonstrates that precisely adjusting the pH to neutral is crucial to ensuring the high purity of the final product.

[0062] Comparative Example 2: Crystallization was performed only once. Acid hydrolysis and ethanol reflux were performed under the exact same conditions as in Example 1 of this invention, but after cooling and crystallization, only one filtration was performed, the mother liquor was discarded, and no secondary crystallization was performed.

[0063] result: This yields a product with high purity (approximately 97%), but the yield is significantly reduced to only 70%.

[0064] Furthermore, a large amount of product remains in the mother liquor, resulting in waste.

[0065] This comparative example demonstrates that secondary crystallization plays a decisive role in achieving high yields (≥98%), resolving the traditional contradiction in purification processes where "purity" and "yield" are difficult to achieve simultaneously.

[0066] Comparative Example 3: Purification using different solvents Use methanol or acetone, replacing ethanol, for the reflux purification step under the same conditions.

[0067] result: Methanol: It is more toxic, and due to differences in solubility, its crystal morphology or purity is not as good as that of the ethanol system.

[0068] Acetone: has a low boiling point and large volatilization losses, resulting in inconvenient operation, poor safety, increased costs, and potentially low crystallization yield.

[0069] This comparative example demonstrates that ethanol, as a solvent, achieves the best balance in terms of solubility, safety, cost, ease of recovery, and crystallization effect.

Claims

1. A purification method of high-content calcium probenecid, comprising the following steps: S1, acidolysis mixing crude calcium probenecid with hydrochloric acid aqueous solution for acidolysis reaction, after the reaction is completed, solid-liquid separation is performed to obtain probenic acid wet material; S2, purification mixing the probenic acid wet material with organic solvent, heating and refluxing, then hot filtration, cooling crystallization is performed on the obtained filtrate, after solid-liquid separation, high-purity probenic acid is obtained; S3, calcification dissolving high-purity probenic acid in alkali solution and water system, adjusting pH to neutral or weak alkaline with alkali, then adding calcium salt solution for calcification reaction, after the reaction is completed, solid-liquid separation, washing and drying are performed to obtain high-purity calcium probenecid.

2. The purification method according to claim 1, characterized in that: The concentration of the hydrochloric acid aqueous solution is 15-20%, and the mass ratio of the crude calcium probenecid to the hydrochloric acid aqueous solution is 1:2.5-3.

0.

3. The purification method according to claim 1 or 2, characterized in that: In step S1, the acidolysis reaction is performed at room temperature, and the reaction time is 0.5-1 hour; The solid-liquid separation is performed by suction filtration; After the solid-liquid separation, the solid is rinsed with clean water.

4. The purification method according to any one of claims 1 to 3, characterized in that: In step S2, the organic solvent is one or more of ethanol, methanol and isopropanol; The mass ratio of the organic solvent to the crude calcium probenecid is 1.5-2.0:

1.

5. The purification method according to any one of claims 1 to 4, characterized in that: In step S2, the cooling crystallization is stepwise cooling crystallization or program-controlled temperature crystallization, and the final crystallization temperature range is-5℃-5℃.

6. The purification method according to any one of claims 1 to 5, characterized in that: In step S2, after the cooling crystallization, solid-liquid separation is performed on the obtained filtrate, and the filtrate is subjected to cooling crystallization and solid-liquid separation again to realize secondary purification.

7. The purification method according to any one of claims 1 to 6, characterized in that: In step S3, the alkali solution is sodium hydroxide aqueous solution or potassium hydroxide aqueous solution, and the concentration is 25-35%; The calcium salt solution is calcium chloride aqueous solution or calcium nitrate aqueous solution.

8. The purification method according to any one of claims 1 to 7, characterized in that: In step S3, the pH is adjusted to 6.5-7.5; The molar ratio of calcium ions in the calcium salt solution to probenic acid is 1-1.1:

1.

9. The purification method according to any one of claims 1 to 8, characterized in that, In step S2 and / or step S3, the mother liquor produced in the separation is recycled for the same production step of the next batch.

10. The purification method according to claim 1, characterized by, In step S2, the organic solvent is recycled after distillation recovery.