A creatine salt and its preparation method

Abstract

This invention proposes a creatine salt, belonging to the field of organic synthesis technology. Through steps such as feeding and mixing, dropwise reaction, cooling and crystallization, and post-treatment, it uses low-carbon alcohols such as methanol and ethanol as reaction solvents, and a low-carbon alcohol solution of hydrogen chloride instead of traditional concentrated hydrochloric acid as the hydrogen chloride source. This completely avoids the introduction of large amounts of water, effectively suppresses side reactions such as hydrolysis, significantly reduces the impurity content in the product, and achieves a product purity of up to 99.9%. Secondary recrystallization is unnecessary, simplifying the process. The reaction solvent can be recovered and reused through distillation, significantly reducing the generation of waste and environmental treatment costs, conforming to the production concept of green chemistry, and suitable for large-scale industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a creatine salt and its preparation method. Background Technology

[0002] Creatine hydrochloride, CAS number 17050-09-8, molecular formula C4H 10 ClN3O2, with a molecular weight of 167.594, is a white crystalline powder at room temperature. Creatine salts, as a highly efficient fatigue recovery agent, possess excellent water solubility, high absorption rate, and superior bioavailability. They are widely used in various fields, including food and beverage additives, health products, pharmaceutical raw materials, pharmaceutical and chemical intermediates, daily chemical raw materials, feed, and veterinary drug raw materials, and have broad market application prospects.

[0003] Currently, most existing technologies for preparing creatine salts involve the direct reaction of creatine monohydrate with concentrated hydrochloric acid. This type of process has several drawbacks: First, the large-scale use of concentrated hydrochloric acid generates a large amount of highly acidic wastewater, resulting in high environmental treatment costs and significant environmental pressure, which does not meet the production requirements of green chemistry. Second, the high water content in the reaction system easily leads to side reactions, resulting in high impurity content in the product and difficulty in achieving the high purity requirements of food and pharmaceutical grades. Multiple recrystallization purifications are required, significantly reducing product yield and increasing production costs. Third, some processes involve high reaction temperatures and harsh reaction conditions, resulting in poor operational controllability, insufficient product quality stability, and difficulty in achieving large-scale continuous industrial production.

[0004] Therefore, developing a method for preparing creatine salts that features mild reaction conditions, simple and controllable operation, high product yield, high purity, good environmental performance, and easy industrial scale-up has become an urgent technical problem to be solved in this field. Summary of the Invention

[0005] This invention addresses the problems of the prior art by providing a creatine salt and its preparation method.

[0006] To achieve the above objectives, the technical solution adopted in this application is as follows: In a first aspect, a creatine salt salt, said creatine salt salt being a white crystalline powder with a product purity ≥99.6% and a preparation molar yield ≥91%.

[0007] Preferably, the chemical formula of the creatine salt is as follows: .

[0008] Secondly, a method for preparing creatine salt, the specific steps of which are as follows: Preferably, in step one, the low-carbon alcohol solvent is any one of methanol and ethanol, or a mixture of both.

[0009] Preferably, in step one, the mass ratio of the low-carbon alcohol solvent to creatine monohydrate is 3~5:1, preferably 4:1.

[0010] Preferably, in step one, the preset reaction temperature is -10~70℃, more preferably 40℃~50℃, and even more preferably 40℃~45℃.

[0011] Preferably, in step two, the hydrogen chloride-lower alcohol solution is a 35% hydrochloric acid-ethanol solution or a 35% hydrochloric acid-methanol solution.

[0012] Preferably, in step two, the mass ratio of the hydrogen chloride-lower alcohol solution to creatine monohydrate is 0.7~0.9:1, preferably 0.77:1; the reaction time after the addition is completed is 1~4 hours, preferably 2 hours; and the addition time is controlled to be 2~3 hours.

[0013] Preferably, in step three, the preset crystallization temperature is -5℃ to 10℃, more preferably 0℃ to 5℃; the time for heat preservation and stirring crystallization is 1 to 4 hours, more preferably 2 hours.

[0014] Preferably, in step four, the drying is performed by atmospheric pressure forced air drying or vacuum drying, at a temperature of 40~60℃, until the product moisture content is ≤0.5%.

[0015] Compared with the prior art, the advantages and positive effects of the present invention are as follows: This application discloses a creatine salt and its preparation method. Through steps such as feeding and mixing, dropwise reaction, cooling and crystallization, and post-treatment, it uses low-carbon alcohols such as methanol and ethanol as reaction solvents. Simultaneously, it uses a low-carbon alcohol solution of hydrogen chloride instead of traditional concentrated hydrochloric acid as the hydrogen chloride source, completely avoiding the introduction of large amounts of water, effectively suppressing side reactions such as hydrolysis, and significantly reducing the impurity content in the product. The product purity can reach up to 99.9%, eliminating the need for secondary recrystallization and simplifying the process. The reaction solvent can be recovered and reused through distillation, significantly reducing the generation of waste and environmental treatment costs, conforming to the production concept of green chemistry, and suitable for large-scale industrial production. Furthermore, the method for preparing creatine salt salt of this application features mild reaction conditions, with the reaction temperature controlled at 40~45℃, avoiding problems such as hydrogen chloride volatilization, product discoloration, and increased side reactions caused by high-temperature reactions. The reaction process is simple and controllable, and the product quality is highly stable with minimal batch-to-batch variation. By optimizing the dropping process, reaction parameters, and crystallization conditions, this application achieves a stable molar yield of over 91%, reaching up to 93%, significantly improving raw material utilization and reducing production costs, thus possessing extremely high economic and application value. The obtained creatine salt salt is a white crystalline powder with stable crystal form, uniform particle size, and good water solubility, making it widely applicable to various fields such as food and beverage, health products, pharmaceutical raw materials, and feed additives. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 This is a flowchart of a method for preparing creatine salt according to this application. Detailed Implementation

[0018] To better understand the above-mentioned objectives, features, and advantages of the present invention, the present invention will be further described below in conjunction with the accompanying drawings and embodiments. It should be noted that, unless otherwise specified, the embodiments and features described in these embodiments can be combined with each other.

[0019] Numerous specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways than those described herein, and therefore the invention is not limited to the specific embodiments disclosed in the following specification.

[0020] Example 1, such as Figure 1 As shown, the specific preparation method of a creatine salt of this application is as follows: Add 600g of ethanol to a 1000ml reaction flask, start stirring, add 150g of creatine monohydrate, heat to 40-45℃, and slowly add 116g of a 35% hydrochloric acid-ethanol solution over 2-3 hours. After the addition is complete, maintain the temperature at 40-45℃ and continue the reaction for 2 hours. After the reaction is complete, cool the system to 0-5℃ and stir for 2 hours to induce crystallization. After crystallization, filter the solution, and dry the filter cake in a forced-air drying oven at 50℃ to constant weight to obtain 152g of white crystalline powder creatine salt. The molar yield of the product was 91%, and the purity was 99.6% as determined by high-performance liquid chromatography (HPLC).

[0021] Example 2 describes the preparation method of a creatine salt. Add 600g of methanol to a 1000ml reaction flask, start stirring, add 150g of creatine monohydrate, heat to 40-45℃, and slowly add 116g of a 35% (w / w) hydrochloric acid-methanol solution over 2-3 hours. After the addition is complete, maintain the temperature at 40-45℃ and continue the reaction for 2 hours. After the reaction is complete, cool the system to 0-5℃ and stir for 2 hours to induce crystallization. After crystallization, filter the solution, and dry the filter cake in a vacuum drying oven at 45℃ to constant weight to obtain 156g of white crystalline powdered creatine salt. The molar yield of the product was 93%, and the purity was 99.9% as determined by high-performance liquid chromatography (HPLC).

[0022] Example 3: A creatine salt, prepared by the following method: Add 400 kg of anhydrous ethanol to a 1000 L reactor, start stirring, add 100 kg of creatine monohydrate, heat to 40-45 °C, and slowly add 77 kg of a 35% hydrochloric acid-ethanol solution dropwise over 2-3 hours. After the addition is complete, maintain the temperature at 40-45 °C and continue the reaction for 2 hours. After the reaction is complete, cool the system to 0-5 °C and stir for 2 hours to induce crystallization. After crystallization, centrifuge and filter the solution. Place the filter cake in a double-cone rotary vacuum dryer and dry it at 50 °C to constant weight to obtain 101.5 kg of white crystalline powdered creatine salt. The molar yield of the product was 90.7%, and the purity was 99.7% as determined by high performance liquid chromatography (HPLC).

[0023] Comparative Example 1 prepared creatine salt using a traditional concentrated hydrochloric acid process. The specific steps are as follows: Add 600 g of concentrated hydrochloric acid to a 1000 ml reaction flask, start stirring, add 150 g of creatine monohydrate, and heat to 60 °C for 4 hours. After the reaction is complete, remove most of the water and excess hydrogen chloride by vacuum distillation, cool to room temperature, add 600 g of ethanol, stir to precipitate crystals for 2 hours, filter, and dry the filter cake to obtain 128 g of creatine salt, with a molar yield of 76.6% and a purity of 98.2% as determined by HPLC. Secondary recrystallization is required to achieve a purity of over 99.5%, but the yield after recrystallization is only 62%.

[0024] The comparison between the examples and comparative examples shows that the preparation method of the present invention increases the product yield by more than 15% compared with the traditional concentrated hydrochloric acid process, and the product purity can reach more than 99.6% without recrystallization. At the same time, the process steps are simpler, and no large amount of high-salt wastewater is generated, which has significant advantages in terms of environmental protection and economy.

[0025] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments that can be applied to other fields. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A creatine salt, characterized in that, The creatine salt is a white crystalline powder with a purity ≥99.6% and a molar yield ≥91%.

2. The creatine salt according to claim 1, characterized in that, The chemical formula of the creatine salt is shown below: 。 3. The method for preparing creatine salt according to claim 2, characterized in that, The specific steps are as follows: Step 1: Feeding and mixing: Add low-carbon alcohol solvent to the reaction vessel, start stirring, add creatine monohydrate, and heat to the preset reaction temperature; Step 2: Droplet addition reaction: Slowly add hydrogen chloride-lower alcohol solution dropwise to the mixture obtained in Step 1. After the addition is complete, keep the temperature constant to carry out the synthesis reaction. Step 3: Cooling and Crystallization: Cool the system from Step 2 to the crystallization temperature and stir at a constant temperature to complete crystallization; Step 4: Post-processing: Filter the system after crystallization in step 3, and dry the filter cake to obtain the creatine salt product.

4. The method for preparing creatine salt according to claim 3, characterized in that, In step one, the low-carbon alcohol solvent is any one of methanol and ethanol, or a mixture of the two.

5. The method for preparing creatine salt according to claim 4, characterized in that, In step one, the mass ratio of the low-carbon alcohol solvent to creatine monohydrate is 3~5:

1.

6. The method for preparing creatine salt according to claim 3, characterized in that, In step one, the preset reaction temperature is -10~70℃.

7. The method for preparing creatine salt according to claim 3, characterized in that, In step two, the hydrogen chloride-lower alcohol solution is a 35% hydrochloric acid ethanol solution or a 35% hydrochloric acid methanol solution.

8. The method for preparing creatine salt according to claim 1, characterized in that, In step two, the mass ratio of the hydrogen chloride-lower alcohol solution to creatine monohydrate is 0.7~0.9:1, and the reaction time after the addition is completed is 1~4 hours; the addition time is controlled to be 2~3 hours.

9. The method for preparing creatine salt according to claim 3, characterized in that, In step three, the preset crystallization temperature is -5℃ to 10℃; the time for heat preservation and stirring crystallization is 1 to 4 hours.

10. The method for preparing creatine salt according to claim 3, characterized in that, In step four, the drying is performed by atmospheric pressure forced air drying or vacuum drying at a temperature of 40~60℃ until the product moisture content is ≤0.5%.

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