Synthetic method of water creatine
By using supercritical carbon dioxide as solvent and supported zirconium sulfate catalyst in the synthesis of water creatine, the problems of low esterification reaction efficiency and catalyst pollution are solved, and efficient and environmentally friendly synthesis of water creatine is achieved, which improves the yield and purity of the product.
Patent Information
- Application Number
- CN202411878218.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-19
- Publication Date
- 2025-03-25
AI Technical Summary
In the existing hydrocreatine synthesis methods, the esterification reaction efficiency is low and the solvent is difficult to recover, which increases the synthesis cost; at the same time, the use of catalysts such as sulfuric acid has problems such as environmental pollution and low catalytic efficiency.
Supercritical carbon dioxide is used as the solvent for the esterification reaction, and a supported zirconium sulfate catalyst is used to prepare high-purity hydrocreatine through steps such as esterification reaction, hydrolysis reaction, crystallization reaction and centrifugal drying.
It improves the yield and purity of water creatine, meets the needs of green production, reduces environmental pollution and synthesis costs, and ensures the synthesis quality of water creatine through multiple purification steps.
Smart Images
Figure CN119684162A_ABST
Abstract
Description
Technical field:
[0001] The invention relates to the technical field of creatine hydrate synthesis, in particular to a method for synthesizing creatine hydrate. Background technology:
[0002] Creatine hydrate is creatine monohydrate, and its particles are smaller, so it has higher solubility and absorption rate in water. Creatine hydrate is very popular in sports nutrition supplements, mainly because of its role in enhancing muscle strength, promoting muscle growth and improving sports performance. Creatine can increase the water content in muscle cells, making muscles look fuller and stronger. At the same time, creatine can stimulate the synthesis of muscle protein, promote muscle growth and repair, and reduce the decomposition of muscle protein, protecting muscles from damage caused by overtraining.
[0003] The existing creatine hydrate synthesis method can basically meet the daily use needs, but the esterification method for synthesizing creatine hydrate requires the use of corrosive catalysts such as sulfuric acid or p-toluenesulfonic acid, which is difficult to meet the processing needs of green production and is easy to pollute the environment; at the same time, the esterification reaction is firstly related to the characteristics of the solvent itself, resulting in low efficiency of the esterification reaction, and the consumed solvent is difficult to recover and reuse, which increases the synthesis cost of creatine hydrate; and the crystallization and purification process after the preparation of creatine hydrate is simple, and the doping rate after preparation is high, which affects the synthesis quality of creatine hydrate; therefore, it is necessary to design a creatine hydrate synthesis method. Summary of the invention:
[0004] In order to solve the above problems and overcome the shortcomings of the prior art, the present invention provides a method for synthesizing creatine hydrate.
[0005] The first technical problem to be solved is that the esterification reaction is firstly related to the characteristics of the solvent itself, which leads to low efficiency of the esterification reaction. At the same time, the consumed solvent is difficult to be recycled and reused, which increases the synthesis cost of creatine hydrate.
[0006] The second technical problem to be solved is the low catalytic efficiency and difficulty in post-processing of corrosive catalysts such as sulfuric acid.
[0007] The specific technical solution of the present invention to solve the above technical problems is: a method for synthesizing creatine hydrate, comprising the following steps:
[0008] (1) slowly adding the prepared supercritical carbon dioxide as a solvent into glycine and cyanoacetic acid, and adding the prepared supported zirconium sulfate catalyst, and performing an esterification reaction in a reactor,
[0009] (2) cooling the obtained mixture to room temperature after the esterification reaction, adding it to deionized water, and then adding an alkaline catalyst to carry out a hydrolysis reaction, and cooling the obtained blend to room temperature after the hydrolysis reaction;
[0010] (3) placing the obtained blend in cold water for crystallization reaction, filtering and drying to obtain a crude product of creatine hydrate;
[0011] (4) Adding the crude creatine hydrate into methanol, heating to dissolve, cooling the filtrate after filtering, and centrifuging. After centrifugation, vacuum drying the solid matter to obtain creatine hydrate.
[0012] Furthermore, during the esterification reaction, the temperature in the reactor is 80-100° C., and the reaction time is 180-360 min; during the esterification reaction, the pressure in the reactor is 72.9-75.5 atm, and the stirring speed of the stirring frame in the reactor is 45-55 r / min.
[0013] Furthermore, the preparation of the supported zirconium sulfate catalyst is as follows: the prepared zirconium oxide carrier powder is immersed in a zirconium sulfate solution with a concentration of 10% to 15% to uniformly load sulfate ions on the surface of the zirconium oxide; the impregnated zirconium oxide powder is then dried at a temperature of 100 to 120° C. for 1200 to 1300 minutes to remove moisture, and finally the dried powder is activated in a muffle furnace at 500 to 800° C. for 180 to 540 minutes to firmly bind sulfate ions to the surface of the zirconium oxide to form a supported zirconium sulfate catalyst.
[0014] Furthermore, the preparation method of the zirconium oxide carrier powder includes: dissolving zirconium sulfate in deionized water to form a transparent solution, then stirring at a stirring rate of 30 to 60 r / min, slowly adding ammonia water during stirring to adjust the pH value of the solution to 7 to 8, so that the zirconium sulfate is hydrolyzed to form a zirconium hydroxide gel; then aging the zirconium hydroxide gel at room temperature for 1440 to 1500 minutes to increase the uniformity and stability of its structure, and then drying the aged gel at a temperature of 100 to 120° C. for 1200 to 1300 minutes to remove moisture, and then calcining the dried gel at 500 to 800° C. in a muffle furnace for 180 to 540 minutes to obtain the zirconium oxide carrier powder.
[0015] Furthermore, the supercritical carbon dioxide preparation method: first, use a high-pressure pump to compress the pressure of liquid carbon dioxide to 72.9-75.5atm; and the compressed carbon dioxide is heated to 35-40°C by a heating device, and then the heated supercritical carbon dioxide is introduced into a high-pressure reactor, and a pressure sensor and a temperature sensor are used to monitor the pressure and temperature in the reactor in real time to ensure that it is maintained in a supercritical state.
[0016] Furthermore, the alkaline catalyst used is sodium hydroxide.
[0017] Furthermore, the amount of deionized water used is 1200% to 1500% by mass of the mixture.
[0018] Furthermore, the hydrolysis reaction process is as follows: raising the temperature of the deionized water to 60-80° C. and maintaining the temperature constant, continuously stirring at a stirring speed of 30-35 r / min, and the hydrolysis reaction time is 120-150 min.
[0019] Furthermore, the crystallization reaction process is as follows: the water temperature is 8-15° C., the drying temperature in the drying oven is 38-40° C., and the drying time is 120-150 min.
[0020] Furthermore, the heating and dissolving process is as follows: raising the temperature of methanol to 45-48°C, placing it in a centrifuge for cooling and lowering the temperature of the filtrate to 8-15°C, the centrifugal speed during the centrifugal treatment is 300-480r / min, and the centrifugal treatment time is 3-5min, the vacuum drying temperature is 38-40°C, and the drying time is 120-150min.
[0021] The beneficial effects of the present invention are:
[0022] The present invention uses zirconium sulfate as a precursor and zirconium oxide as a carrier, and prepares the zirconium oxide carrier by a sol-gel method to prepare a supported zirconium sulfate catalyst that can replace sulfuric acid. This not only meets the processing requirements of green production and reduces the pollution caused by the synthesis process to the environment, but also greatly improves the product yield and purity under the same reaction conditions.
[0023] Liquid carbon dioxide is used as a raw material to prepare supercritical carbon dioxide as a reaction solvent for the subsequent esterification reaction, which improves the efficiency of the esterification reaction and facilitates recycling after the reaction, thereby reducing the synthesis cost of creatine hydrate; after the separation process, methanol is used as a solvent to dissolve the initial creatine hydrate material, and then the creatine hydrate is purified again after cooling, centrifugation and drying, which reduces the doping rate after preparation and ensures the synthesis quality of creatine hydrate. Description of the drawings:
[0024] Attached Figure 1 This is the liquid phase detection spectrum of creatine water in Example 1 of the present invention;
[0025] Attached Figure 2 This is the liquid phase detection spectrum of creatine water in comparative example 2 of the present invention;
[0026] Attached Figure 3 This is the liquid phase detection spectrum of creatine water in comparative example 4 of the present invention;
[0027] Attached Figure 4 This is the liquid phase detection spectrum of creatine water in comparative example 5 of the present invention; Specific implementation method:
[0028] In the description of the present invention, specific details are only for a full understanding of the embodiments of the present invention, but those skilled in the art should know that the implementation of the present invention is not limited to these details. In addition, well-known structures and functions are not described or shown in detail to avoid blurring the key points of the embodiments of the present invention. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.
[0029] Specific implementation of the present invention:
[0030] In order to better understand the present invention, a specific embodiment is used for illustration. It is worth emphasizing that the effect of this embodiment is not substantially different from the various embodiments within the protection scope of the present invention, including the respective reagents and the content ratio of the reagents, and all of them can achieve the effects described in the present invention and solve the above-mentioned problems. Other combinations are not described here.
[0031] Embodiment 1:
[0032] (1) The prepared supercritical carbon dioxide is used as a solvent and slowly added to the reaction moles of glycine and cyanoacetic acid at a material-liquid ratio of 1:10, and the prepared supported zirconium sulfate catalyst is added at 3% of the amount of glycine added, and an esterification reaction is carried out in a reactor.
[0033] The supercritical carbon dioxide preparation method comprises the following steps: first, using a high-pressure pump to compress the pressure of liquid carbon dioxide to 72.9 atm; and heating the compressed carbon dioxide to 35° C. by a heating device; and then introducing the heated supercritical carbon dioxide into a high-pressure reactor; and using a pressure sensor and a temperature sensor to monitor the pressure and temperature in the reactor in real time to ensure that it is maintained in a supercritical state.
[0034] The preparation of the supported zirconium sulfate catalyst is as follows: the prepared zirconium oxide carrier powder is immersed in a zirconium sulfate solution with a concentration of 10% to uniformly load sulfate ions on the surface of the zirconium oxide; the impregnated zirconium oxide powder is then dried at a temperature of 100°C for 1200 minutes to remove moisture, and finally the dried powder is activated in a muffle furnace at 500°C for 180 minutes to firmly bind sulfate ions to the surface of the zirconium oxide to form a supported zirconium sulfate catalyst.
[0035] Furthermore, the preparation method of the zirconium oxide carrier powder includes: dissolving zirconium sulfate in deionized water to form a transparent solution, then stirring at a stirring rate of 30 r / min, slowly adding ammonia water during stirring to adjust the pH value of the solution to 7, so that the zirconium sulfate is hydrolyzed to form a zirconium hydroxide gel; then aging the zirconium hydroxide gel at room temperature for 1440 minutes to increase the uniformity and stability of its structure, and then drying the aged gel at a temperature of 100°C for 1200 minutes to remove moisture, and then calcining the dried gel at 500°C in a muffle furnace for 180 minutes to obtain the zirconium oxide carrier powder.
[0036] (2) After the esterification reaction, the obtained mixture is cooled to room temperature and added to deionized water, and then an alkaline catalyst-sodium hydroxide is added to carry out a hydrolysis reaction. After the hydrolysis reaction, the obtained blend is cooled to room temperature; the amount of deionized water used is 1200% by mass of the mixture.
[0037] The hydrolysis reaction process is as follows: raising the temperature of deionized water to 60-80° C. and maintaining the temperature unchanged, stirring continuously at a stirring speed of 30-35 r / min, and the hydrolysis reaction time is 120-150 min.
[0038] During the esterification reaction, the temperature in the reactor was 80° C., and the reaction time was 180 min. During the esterification reaction, the pressure in the reactor was 72.9 atm, and the stirring speed of the stirring frame in the reactor was 45 r / min.
[0039] (3) placing the obtained blend in cold water for crystallization reaction, filtering and drying to obtain crude creatine hydrate; the crystallization reaction process is as follows: the water temperature is 8° C., the drying temperature in the drying oven is 38° C., and the drying time is 120 min.
[0040] (4) adding the crude creatine hydrate into methanol, heating and dissolving, filtering, cooling the filtrate, centrifuging, and vacuum drying the solid matter after centrifugation to obtain creatine hydrate;
[0041] The heating and dissolving process is as follows: raising the temperature of methanol to 45°C, placing it in a centrifuge for cooling and lowering the temperature of the filtrate to 8°C, the centrifugal speed during the centrifugal treatment is 300r / min, and the centrifugal treatment time is 3min, the vacuum drying temperature is 38°C, and the drying time is 120min.
[0042] Embodiment 2:
[0043] (1) the prepared supercritical carbon dioxide is slowly added as a solvent to the reaction moles of glycine and cyanoacetic acid at a material-liquid ratio of 1:20, and the prepared supported zirconium sulfate catalyst is added at 8% of the amount of glycine added, and an esterification reaction is carried out in a reactor,
[0044] The supercritical carbon dioxide preparation method comprises the following steps: firstly, using a high-pressure pump to compress the pressure of liquid carbon dioxide to 75.5 atm; and heating the compressed carbon dioxide to 40° C. by a heating device, and then introducing the heated supercritical carbon dioxide into a high-pressure reactor, and using a pressure sensor and a temperature sensor to monitor the pressure and temperature in the reactor in real time to ensure that it is maintained in a supercritical state.
[0045] The preparation of the supported zirconium sulfate catalyst is as follows: the prepared zirconium oxide carrier powder is immersed in a zirconium sulfate solution with a concentration of 15% to uniformly load sulfate ions on the surface of the zirconium oxide; the impregnated zirconium oxide powder is then dried at a temperature of 120°C for 1300 minutes to remove moisture, and finally the dried powder is activated in a muffle furnace at 800°C for 540 minutes to firmly bind sulfate ions to the surface of the zirconium oxide to form a supported zirconium sulfate catalyst.
[0046] Furthermore, the preparation method of the zirconium oxide carrier powder includes: dissolving zirconium sulfate in deionized water to form a transparent solution, then stirring at a stirring rate of 60r / min, slowly adding ammonia water during stirring to adjust the pH value of the solution to 8, so that the zirconium sulfate is hydrolyzed to form a zirconium hydroxide gel; then aging the zirconium hydroxide gel at room temperature for 1500min to increase the uniformity and stability of its structure, and then drying the aged gel at a temperature of 120°C for 1300min to remove moisture, and then calcining the dried gel at 800°C in a muffle furnace for 540min to obtain the zirconium oxide carrier powder.
[0047] (2) After the esterification reaction, the obtained mixture is cooled to room temperature and added to deionized water, and then an alkaline catalyst-sodium hydroxide is added to carry out a hydrolysis reaction. After the hydrolysis reaction, the obtained blend is cooled to room temperature; the amount of deionized water used is 1500% by mass of the mixture.
[0048] The hydrolysis reaction process is as follows: raising the temperature of deionized water to 80° C. and maintaining the temperature unchanged, stirring continuously at a stirring speed of 30 to 35 r / min, and the hydrolysis reaction time is 150 min.
[0049] During the esterification reaction, the temperature in the reactor is 100° C., and the reaction time is 360 min. During the esterification reaction, the pressure in the reactor is 75.5 atm, and the stirring speed of the stirring frame in the reactor is 45-55 r / min.
[0050] (3) placing the obtained blend in cold water for crystallization reaction, filtering and drying to obtain crude creatine hydrate; the crystallization reaction process is as follows: the water temperature is 15° C., the drying temperature in the drying oven is 40° C., and the drying time is 150 min.
[0051] (4) adding the crude creatine hydrate into methanol, heating and dissolving, filtering, cooling the filtrate, centrifuging, and vacuum drying the solid matter after centrifugation to obtain creatine hydrate;
[0052] The heating and dissolving process is as follows: raising the temperature of methanol to 48°C, placing it in a centrifuge for cooling and lowering the temperature of the filtrate to 15°C, the centrifugal speed during the centrifugal treatment is 480r / min, and the centrifugal treatment time is 5min, the vacuum drying temperature is 40°C, and the drying time is 150min.
[0053] Embodiment 3:
[0054] (1) the prepared supercritical carbon dioxide is slowly added as a solvent to the reaction moles of glycine and cyanoacetic acid at a material-liquid ratio of 1:15, and the prepared supported zirconium sulfate catalyst is added at 6% of the amount of glycine added, and an esterification reaction is carried out in a reactor,
[0055] The supercritical carbon dioxide preparation method comprises the following steps: firstly, using a high-pressure pump to compress the pressure of liquid carbon dioxide to 74 atm; and heating the compressed carbon dioxide to 38° C. by a heating device; and then introducing the heated supercritical carbon dioxide into a high-pressure reactor; and using a pressure sensor and a temperature sensor to monitor the pressure and temperature in the reactor in real time to ensure that the reactor is maintained in a supercritical state.
[0056] The preparation of the supported zirconium sulfate catalyst is as follows: the prepared zirconium oxide carrier powder is immersed in a zirconium sulfate solution with a concentration of 13% to uniformly load sulfate ions on the surface of the zirconium oxide; the impregnated zirconium oxide powder is then dried at a temperature of 110° C. for 1250 minutes to remove moisture, and finally the dried powder is activated in a muffle furnace at 600° C. for 420 minutes to firmly bind sulfate ions to the surface of the zirconium oxide to form a supported zirconium sulfate catalyst.
[0057] Furthermore, the preparation method of the zirconium oxide carrier powder includes: dissolving zirconium sulfate in deionized water to form a transparent solution, then stirring at a stirring rate of 50 r / min, slowly adding ammonia water during stirring to adjust the pH value of the solution to 7.5, so that the zirconium sulfate is hydrolyzed to form a zirconium hydroxide gel; then aging the zirconium hydroxide gel at room temperature for 1460 minutes to increase the uniformity and stability of its structure, and then drying the aged gel at a temperature of 110°C for 1250 minutes to remove moisture, and then calcining the dried gel at 600°C in a muffle furnace for 350 minutes to obtain the zirconium oxide carrier powder.
[0058] (2) After the esterification reaction, the obtained mixture is cooled to room temperature and added to deionized water, and then an alkaline catalyst-sodium hydroxide is added to carry out a hydrolysis reaction. After the hydrolysis reaction, the obtained blend is cooled to room temperature; the amount of deionized water used is 1400% by mass of the mixture.
[0059] The hydrolysis reaction process is as follows: the temperature of the deionized water is raised to 70° C., and the temperature is maintained constant, stirring is continued at a stirring speed of 32 r / min, and the hydrolysis reaction time is 130 min.
[0060] During the esterification reaction, the temperature in the reactor is 90° C., and the reaction time is 180 to 360 min. During the esterification reaction, the pressure in the reactor is 74.9 atm, and the stirring speed of the stirring frame in the reactor is 50 r / min.
[0061] (3) placing the obtained blend in cold water for crystallization reaction, filtering and drying to obtain crude creatine hydrate; the crystallization reaction process is as follows: the water temperature is 10° C., the drying temperature in the drying oven is 39° C., and the drying time is 130 min.
[0062] (4) adding the crude creatine hydrate into methanol, heating and dissolving, filtering, cooling the filtrate, centrifuging, and vacuum drying the solid matter after centrifugation to obtain creatine hydrate;
[0063] The heating and dissolving process is as follows: raising the temperature of methanol to 45-48°C, placing it in a centrifuge for cooling and lowering the temperature of the filtrate to 8-15°C, the centrifugal speed during the centrifugal treatment is 380r / min, and the centrifugal treatment time is 4min, the vacuum drying temperature is 38-40°C, and the drying time is 130min.
[0064] In order to more intuitively demonstrate the process advantages of the present invention, the present invention uses a method for synthesizing creatine with water and a method using equivalent replacement in the same process for comparison.
[0065] Comparative Example 1:
[0066] The preparation method is the same as that of Example 1, except that: in the preparation process of this comparative example, no supported zirconium sulfate catalyst is added;
[0067] Comparative Example 2:
[0068] The preparation method is the same as that of Example 1, except that: in the preparation process of this comparative example, the added supported zirconium sulfate catalyst is replaced with zirconium sulfate;
[0069] Comparative Example 3:
[0070] The preparation method is the same as that of Example 1, except that: in the preparation process of this comparative example, the added supported zirconium sulfate catalyst is replaced with zirconium oxide;
[0071] Comparative Example 4:
[0072] The preparation method is the same as that of Example 1, except that in the preparation process of this comparative example, the added supported zirconium sulfate catalyst is replaced with sulfuric acid;
[0073] Comparative Example 5:
[0074] The preparation method is the same as that of Example 1, except that in the preparation process of this comparative example, supercritical carbon dioxide is added instead of n-butanol;
[0075] The content of creatine in water was detected by liquid chromatography, and the detection conditions of the chromatography were:
[0076] UV detector: Detection wavelength: 210nm Flow rate: 1.0ml / min Injection volume: 20ul
[0077] Chromatographic column: C18 4.6×250mm 5um Column temperature: 30℃
[0078] Mobile phase: Use a pipette to take 0.12 ml of phosphoric acid, dissolve it in 60 ml of water, add 40 ml of acetonitrile, then add 900 ml of water, shake well, and put it on the ultrasonic for 15 minutes. The results are as follows:
[0079] Table 1: Comparison of yield and purity of creatine hydrate prepared in different embodiments and comparative examples
[0080]
[0081] (1) Embodiment 1-3:
[0082] Since the supported zirconium sulfate catalyst is immiscible with the solvent, it is very easy to separate. At the same time, by using zirconium sulfate as a precursor and zirconium oxide as a carrier, the zirconium oxide carrier is prepared by a sol-gel method, and then sulfate ions are introduced to prepare the supported zirconium sulfate catalyst, which has a high catalytic effect as a catalyst for preparing aqueous creatine, even higher than the catalytic effect of sulfuric acid, and can completely replace sulfuric acid.
[0083] Therefore, the present invention uses zirconium sulfate as a precursor and zirconium oxide as a carrier, prepares the zirconium oxide carrier by a sol-gel method, and then introduces sulfate ions to prepare a supported zirconium sulfate catalyst that can replace sulfuric acid, which not only meets the processing requirements of green production and reduces the pollution to the environment caused by the synthesis process, but also greatly improves the product yield and purity under the same reaction conditions; after the separation and treatment process, methanol is used as a solvent to dissolve the initial creatine water material, and then the creatine water is purified again through cooling, centrifugation and drying, which reduces the doping rate after preparation and ensures the synthesis quality of creatine water.
[0084] (2) Comparative Example 1: The difference is that no catalyst is added;
[0085] Since there is no catalyst in the reaction, the reaction cannot proceed and has no research significance.
[0086] (3) Comparative Example 2: The difference is that the supported zirconium sulfate catalyst is replaced with zirconium sulfate;
[0087] Although zirconium sulfate has a certain catalytic effect, its catalytic efficiency is extremely low and cannot meet the needs of the process;
[0088] (4) Comparative Example 3: The difference is that the supported zirconium sulfate catalyst is replaced with zirconium oxide;
[0089] Zirconium oxide has almost no catalytic effect in the reaction, which makes the reaction unable to proceed and has no research significance. Combining Comparative Example 3 and the embodiment, the supported zirconium sulfate catalyst has significant differences as a catalyst for preparing creatine hydrate compared with zirconium sulfate or zirconium oxide.
[0090] (5) Comparative Example 4: The difference is that the supported zirconium sulfate catalyst is added instead of sulfuric acid;
[0091] It can be seen from the experimental data that sulfuric acid as a catalyst can achieve the purity and conversion rate of the present invention, but since sulfuric acid is a corrosive catalyst, it is difficult to meet the processing requirements of green production and is likely to cause environmental pollution; in particular, the characteristics of the solvent itself in the esterification reaction lead to low efficiency of the esterification reaction, and the consumed solvent is difficult to recycle and reuse, which affects the overall yield of creatine hydrate.
[0092] (5) Comparative Example 5: The difference is that supercritical carbon dioxide is replaced with n-butanol,
[0093] It can be seen that n-butanol as a solvent also has a small effect on the purity of creatine hydrate. This may be due to the fact that n-butanol dissolves some impurities, or the effect of n-butanol itself on liquid chromatography detection. Overall, the impact is not significant.
[0094] However, in terms of yield, the yield of n-butanol as a solvent is only 70.3%, which is far lower than 99.15% of the present invention. This reflects the advantage of supercritical carbon dioxide as a solvent. Supercritical carbon dioxide can achieve zero solvent residue as it evaporates, and will not cause yield loss due to the production of solvent distillation process.
[0095] In summary: the present invention uses zirconium sulfate as a precursor and zirconium oxide as a carrier, prepares the zirconium oxide carrier by a sol-gel method, and prepares a supported zirconium sulfate catalyst that can replace sulfuric acid, which not only meets the processing requirements of green production and reduces the pollution caused by the synthesis process to the environment, but also greatly improves the product yield and purity under the same reaction conditions;
[0096] Liquid carbon dioxide is used as a raw material to prepare supercritical carbon dioxide as a reaction solvent for the subsequent esterification reaction, which improves the efficiency of the esterification reaction and facilitates recycling after the reaction, thereby reducing the synthesis cost of creatine hydrate; after the separation and treatment process, methanol is used as a solvent to dissolve the initial creatine hydrate material, and then the creatine hydrate is purified again through cooling, centrifugation and drying, which reduces the doping rate after preparation and ensures the synthesis quality of creatine hydrate.
Claims
1. A method for synthesizing creatine hydrate, characterized in that The following steps are involved: (1) slowly adding the prepared supercritical carbon dioxide as a solvent into glycine and cyanoacetic acid, and adding the prepared supported zirconium sulfate catalyst, and performing an esterification reaction in a reactor, (2) cooling the obtained mixture to room temperature after the esterification reaction, adding it to deionized water, adding an alkaline catalyst to carry out a hydrolysis reaction, and cooling the obtained blend to room temperature after the hydrolysis reaction; (3) placing the blend in cold water for crystallization reaction, filtering and drying to obtain a crude product of creatine hydrate; (4) Adding the crude creatine hydrate into methanol, heating to dissolve, cooling the filtrate after filtering, and centrifuging. After centrifugation, vacuum drying the solid matter to obtain creatine hydrate.
2. The method for synthesizing creatine hydrate according to claim 1, characterized in that During the esterification reaction, the temperature in the reactor is 80-100° C., and the reaction time is 180-360 min. During the esterification reaction, the pressure in the reactor is 72.9-75.5 atm, and the stirring speed of the stirring frame in the reactor is 45-55 r / min.
3. The method for synthesizing creatine hydrate according to claim 1, characterized in that The preparation of the supported zirconium sulfate catalyst comprises the following steps: immersing the prepared zirconium oxide carrier powder into a zirconium sulfate solution with a concentration of 10% to 15% to uniformly load sulfate ions on the surface of the zirconium oxide; subsequently drying the impregnated zirconium oxide powder at a temperature of 100 to 120° C. for 1200 to 1300 minutes to remove moisture; and finally activating the dried powder in a muffle furnace at 500 to 800° C. for 180 to 540 minutes to firmly bind sulfate ions on the surface of the zirconium oxide to form a supported zirconium sulfate catalyst.
4. The method for synthesizing creatine hydrate according to claim 3, characterized in that The preparation method of the zirconium oxide carrier powder comprises: dissolving zirconium sulfate in deionized water to form a transparent solution, then stirring at a stirring rate of 30 to 60 r / min, slowly adding ammonia water during stirring to adjust the pH value of the solution to 7 to 8, so that the zirconium sulfate is hydrolyzed to form a zirconium hydroxide gel; then aging the zirconium hydroxide gel at room temperature for 1440 to 1500 minutes to increase the uniformity and stability of its structure, then drying the aged gel at a temperature of 100 to 120° C. for 1200 to 1300 minutes to remove moisture, and then calcining the dried gel at 500 to 800° C. in a muffle furnace for 180 to 540 minutes to obtain the zirconium oxide carrier powder.
5. The method for synthesizing creatine hydrate according to claim 1, characterized in that The supercritical carbon dioxide preparation method comprises the following steps: firstly, using a high-pressure pump to compress the pressure of liquid carbon dioxide to 72.9-75.5 atm; and heating the compressed carbon dioxide to 35-40° C. by a heating device; and then introducing the heated supercritical carbon dioxide into a high-pressure reactor; and using a pressure sensor and a temperature sensor to monitor the pressure and temperature in the reactor in real time to ensure that the reactor is maintained in a supercritical state.
6. The method for synthesizing creatine hydrate according to claim 1, characterized in that The alkaline catalyst used is sodium hydroxide.
7. The method for synthesizing creatine hydrate according to claim 1, characterized in that The usage amount of the deionized water is 1200% to 1500% of the mass fraction of the mixture.
8. The method for synthesizing creatine hydrate according to claim 1, characterized in that The hydrolysis reaction process is as follows: raising the temperature of deionized water to 60-80° C. and maintaining the temperature unchanged, stirring continuously at a stirring speed of 30-35 r / min, and the hydrolysis reaction time is 120-150 min.
9. The method for synthesizing creatine hydrate according to claim 1, characterized in that The crystallization reaction process is as follows: the water temperature is 8-15° C., the drying temperature in the drying oven is 38-40° C., and the drying time is 120-150 min.
10. The method for synthesizing creatine hydrate according to claim 1, characterized in that The heating and dissolving process is as follows: raising the temperature of methanol to 45-48°C, placing it in a centrifuge for cooling and lowering the temperature of the filtrate to 8-15°C, the centrifugal speed during the centrifugal treatment is 300-480r / min, and the centrifugal treatment time is 3-5min, the vacuum drying temperature is 38-40°C, and the drying time is 120-150min.