Creatine nitrate and methods of making the same

Abstract

This invention belongs to the field of organic synthesis technology, specifically relating to creatine nitrate and its preparation method, including the following steps: raw material pretreatment, pretreating creatine monohydrate; adding 600g of reaction solvent to a reaction vessel, stirring, adding 150g of purified creatine monohydrate from step 100, mixing evenly to obtain a reaction solution, and heating to 50-55℃; slowly adding 110g of 65% nitric acid dropwise to below the surface of the reaction solution, and after the addition is complete, maintaining the temperature at 50-55℃ for 2 hours to obtain a mixed solution; cooling the mixed solution to 0-5℃ at a cooling rate, adjusting the stirring rate, and stirring at a constant temperature for 2 hours to crystallize; filtering the above crystallization system, washing the filter cake 2-3 times with a cold solvent at 0-5℃; vacuum drying the filter cake, and sieving after drying to obtain the creatine nitrate product. This invention achieves efficient and stable preparation of creatine nitrate, significantly improving product yield and purity.

Description

Technical Field

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

[0002] Creatine nitrate is a white crystalline powder. As a highly effective fatigue recovery agent, it is widely used in food and beverage additives, health product raw materials, pharmaceutical and chemical intermediates, daily chemical raw materials, and feed and veterinary drug raw materials, and the market demand continues to grow.

[0003] Currently, the preparation of creatine nitrate mainly involves the salt formation reaction of creatine and nitric acid. However, the existing preparation process has many technical defects. For example, the reaction solvent is selected in a single way and there is no recovery design. Usually, only water is used as a solvent, resulting in insufficient dissolution of raw materials, low mass transfer efficiency, and direct discharge of organic solvents, which increases costs and pollutes the environment. At the same time, due to the rough control of its preparation process parameters, there are no clear limits on stirring rate, dropping rate, and temperature rise and fall rate, which can easily lead to problems such as excessively high local acid concentration, creatine decomposition, and uneven crystal size, resulting in low product yield and insufficient purity. Therefore, there is an urgent need for a creatine nitrate and its preparation method to solve the above problems. Summary of the Invention

[0004] To achieve the above objectives, this application employs the following technical solution: A method for preparing creatine nitrate includes the following steps: Step 100: Raw material pretreatment. Dissolve creatine monohydrate in hot water at 80-90℃, decolorize with activated carbon, and filter while hot to obtain purified creatine monohydrate filtrate for later use. Step 200, salt formation reaction: Add 600g of reaction solvent to the reaction vessel, start stirring and adjust the stirring speed, add 150g of purified creatine monohydrate from step 100, mix well to obtain a reaction solution, heat to 50~55℃; then slowly add 110g of 65% nitric acid dropwise to below the surface of the reaction solution, the dropwise addition time is 2~3h, after the dropwise addition is completed, keep the reaction at 50~55℃ for 2h to obtain a mixed solution; Step 300, low-temperature crystallization: the mixed solution in step 200 is cooled to 0~5℃ at a cooling rate of , the stirring rate is adjusted, and the mixture is stirred at a constant temperature for 2 hours to crystallize. Step 400: Filtration and washing. Filter the crystallization system from step 300. Wash the filter cake 2-3 times with a cold solvent at 0-5°C. The amount of cold solvent used is 0.5-1 times the mass of the filter cake. The cold solvent is the same as the reaction solvent in step 200. Step 500: Dry the finished product. The filter cake washed in step 400 is vacuum dried and then sieved to obtain the creatine nitrate product.

[0005] Further, in step 100, the amount of activated carbon added is 0.5 to 1% of the mass of creatine monohydrate.

[0006] Furthermore, in step 200, the stirring rate is 200~400 r / min, and the heating rate is 2~3℃ / min.

[0007] Further, in step 200, the reaction solvent is one or a mixture of two or more of purified water, methanol, and ethanol.

[0008] Furthermore, in step 300, the cooling rate is 1~2℃ / min, and the stirring rate is 100~200r / min.

[0009] Furthermore, in step 500, the vacuum drying conditions are a temperature of 40~60℃, a vacuum degree of -0.08~-0.1MPa, and a drying time of 4~6h.

[0010] Compared with the prior art, the beneficial effects of this application are: 1. The technical solution in this application abandons the vague operational requirements of traditional processes such as starting stirring, slow dripping, and cooling crystallization. It clearly quantifies and classifies the key process parameters of the entire preparation process, and constructs a complete preparation process of raw material pretreatment - salt formation reaction - low temperature crystallization - filtration and washing - vacuum drying - sieving of finished product. The links are closely connected and the operation steps are simple, which improves product yield and purity, while reducing production costs, improving process safety and industrial feasibility. 2. In this application, impurities such as creatine anhydride, urea, and inorganic salts in creatine monohydrate are removed through raw material pretreatment, which can prevent impurities from participating in the salt formation reaction and affecting the product yield and purity. At the same time, by precisely controlling the stirring rate, heating rate, nitric acid drop acceleration rate of the salt formation reaction, as well as the cooling rate and crystallization stirring rate of low-temperature crystallization, problems such as creatine decomposition and uneven crystallization particle size caused by excessively high local acid concentration are effectively avoided, ensuring sufficient reaction and complete crystallization. Attached Figure Description

[0011] Appendix Figure 1 This is a process flow diagram of the preparation method of the present invention. Detailed Implementation

[0012] The present application will be further described in conjunction with the accompanying drawings and specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the scope defined by this application.

[0013] Combined with appendix Figure 1A method for preparing creatine nitrate includes the following steps: Step 100: Raw material pretreatment. Creatine monohydrate is dissolved in hot water at 80-90℃, decolorized with activated carbon, and filtered while hot to obtain purified creatine monohydrate filtrate for later use. The amount of activated carbon added is 0.5-1% of the mass of creatine monohydrate. Step 200, salt formation reaction: Add 600g of reaction solvent to the reaction vessel, start stirring and adjust the speed to 200~400r / min to ensure that the raw materials are mixed evenly and the mass transfer efficiency is high. Add 150g of creatine monohydrate purified in step 100, mix evenly to obtain the reaction solution, and then heat it to 50~55℃ at a heating rate of 2~3℃ / min. Then slowly add 110g of 65% nitric acid dropwise to below the surface of the reaction solution. The acid concentration of the reaction system is controlled by the dropwise addition to avoid excessive local acid concentration that could cause creatine decomposition, while also reducing the loss of nitric acid due to volatilization. The addition time is 2-3 hours. After the addition is completed, keep the reaction at 50-55℃ for 2 hours to obtain a mixed solution.

[0014] The molar ratio of creatine monohydrate to 65% nitric acid is 1:1.05 to 1:1.1, which ensures complete reaction while avoiding excessive acidity and impurities caused by excessive nitric acid. The reaction solvent is one or a mixture of two or more of purified water, methanol, and ethanol. When the reaction solvent is methanol or ethanol, the solvent is recovered by vacuum distillation after the reaction. The vacuum distillation conditions are 60-70℃ and -0.09MPa.

[0015] Step 300: Low-temperature crystallization. Cool the mixed solution from step 200 to 0-5℃ at a cooling rate of 1-2℃ / min, adjust the stirring speed to 100-200r / min, and stir at a constant temperature for 2 hours to crystallize, avoiding crystal breakage and ensuring uniform crystal particle size.

[0016] Step 400: Filtration and washing. Filter the crystallization system from step 300. Wash the filter cake 2-3 times with a cold solvent at 0-5°C. The amount of cold solvent used is 0.5-1 times the mass of the filter cake. The cold solvent is the same as the reaction solvent in step 200. Step 500: Dry the finished product. Place the filter cake washed in step 400 under vacuum drying conditions of 40~60℃ and vacuum degree of -0.08~-0.1MPa for 4~6 hours to ensure the product moisture content and avoid product decomposition caused by high temperature drying. After drying, sieve through an 80~100 mesh standard sieve to obtain the creatine nitrate finished product.

[0017] Example 1 Step 100: Raw material pretreatment. Creatine monohydrate is dissolved in hot water at 80°C, decolorized with activated carbon, and filtered while hot to obtain purified creatine monohydrate filtrate for later use. The amount of activated carbon added is 0.5% of the mass of creatine monohydrate. Step 200, salt formation reaction: Add 600g of purified water to the reaction vessel, start stirring and adjust the speed to 300r / min, add 150g of creatine monohydrate from step 100, mix well to obtain the reaction solution, and then heat it to 50~55℃ at a heating rate of 2.5℃ / min. Then slowly add 110g of 65% nitric acid dropwise to below the surface of the reaction solution over a period of 2.4 hours. After the addition is complete, keep the solution at 50-55°C for 2 hours to obtain a mixed solution.

[0018] Step 300, low-temperature crystallization: the mixed solution in step 200 is cooled to 0~5℃ at a cooling rate of 1.5℃ / min, the stirring speed is adjusted to 150r / min, and the mixture is stirred at a constant temperature for 2h to crystallize.

[0019] Step 400: Filtration and washing. Filter the crystallization system from step 300. Wash the filter cake twice with a cold solvent at 0-5°C. The amount of cold solvent used is 0.8 times the mass of the filter cake.

[0020] Step 500: Dry the finished product. Place the filter cake washed in step 400 under vacuum drying conditions of 50℃ and -0.09MPa for 5 hours to ensure the product moisture content and avoid product decomposition caused by high temperature drying. After drying, sieve through a 90-mesh standard sieve to obtain 170g of creatine nitrate finished product, with a molar yield of 87% and a purity of 99.7%.

[0021] Example 2 Step 100: Raw material pretreatment. Creatine monohydrate is dissolved in hot water at 85°C, decolorized with activated carbon, and filtered while hot to obtain purified creatine monohydrate filtrate for later use. The amount of activated carbon added is 1% of the mass of creatine monohydrate. Step 200, salt formation reaction: Add 600g of methanol to the reaction vessel, start stirring and adjust the speed to 300r / min, add 150g of creatine monohydrate from step 100, mix evenly to obtain the reaction solution, and then heat it to 50~55℃ at a heating rate of 2℃ / min. Then slowly add 110g of 65% nitric acid dropwise to below the surface of the reaction solution over a period of 2.4 hours. After the addition is complete, keep the solution at 50-55°C for 2 hours to obtain a mixed solution.

[0022] Step 300, low-temperature crystallization: the mixed solution in step 200 is cooled to 0~5℃ at a cooling rate of 1℃ / min, the stirring rate is adjusted to 150r / min, and the mixture is stirred at a constant temperature for 2h to crystallize.

[0023] Step 400: Filtration and washing. Filter the crystallization system from step 300. Wash the filter cake three times with a cold solvent at 0-5°C. The amount of cold solvent used is 0.5 times the mass of the filter cake.

[0024] Step 500: Dry the finished product. Place the filter cake washed in step 400 under vacuum drying conditions of 50℃ and -0.09MPa for 5 hours to ensure the product moisture content and avoid product decomposition caused by high temperature drying. After drying, sieve through a 90-mesh standard sieve to obtain 180g of creatine nitrate finished product, with a molar yield of 93% and a purity of 99.9%.

[0025] Example 3 Step 100: Raw material pretreatment. Creatine monohydrate is dissolved in hot water at 80°C, decolorized with activated carbon, and filtered while hot to obtain purified creatine monohydrate filtrate for later use. The amount of activated carbon added is 0.75% of the mass of creatine monohydrate. Step 200, salt formation reaction: Add 600g of ethanol to the reaction vessel, start stirring and adjust the speed to 300r / min, add 150g of creatine monohydrate from step 100, mix well to obtain the reaction solution, and then heat it to 50~55℃ at a heating rate of 3℃ / min. Then slowly add 110g of 65% nitric acid dropwise to below the surface of the reaction solution over a period of 2.4 hours. After the addition is complete, keep the solution at 50-55°C for 2 hours to obtain a mixed solution.

[0026] Step 300, low-temperature crystallization: the mixed solution in step 200 is cooled to 0~5℃ at a cooling rate of 2℃ / min, the stirring rate is adjusted to 150r / min, and the mixture is stirred at a constant temperature for 2h to crystallize.

[0027] Step 400: Filtration and washing. Filter the crystallization system from step 300. Wash the filter cake twice with a cold solvent at 0-5°C. The amount of cold solvent used is 1 times the mass of the filter cake.

[0028] Step 500: Dry the finished product. Place the filter cake washed in step 400 under vacuum drying conditions of 50℃ and -0.09MPa for 5 hours to ensure the product moisture content and avoid product decomposition caused by high temperature drying. After drying, sieve through a 90-mesh standard sieve to obtain 176g of creatine nitrate finished product, with a molar yield of 90% and a purity of 99.8%.

[0029] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application.

Claims

1. A method for preparing creatine nitrate, characterized in that: Includes the following steps: Step 100: Raw material pretreatment. Dissolve creatine monohydrate in hot water at 80-90℃, decolorize with activated carbon, and filter while hot to obtain purified creatine monohydrate filtrate for later use. Step 200, salt formation reaction: Add 600g of reaction solvent to the reaction vessel, start stirring and adjust the stirring speed, add 150g of purified creatine monohydrate from step 100, mix well to obtain a reaction solution, heat to 50~55℃; then slowly add 110g of 65% nitric acid dropwise to below the surface of the reaction solution, the dropwise addition time is 2~3h, after the dropwise addition is completed, keep the reaction at 50~55℃ for 2h to obtain a mixed solution; Step 300, low-temperature crystallization: the mixed solution in step 200 is cooled to 0~5℃ at a cooling rate of , the stirring rate is adjusted, and the mixture is stirred at a constant temperature for 2 hours to crystallize. Step 400: Filtration and washing. Filter the crystallization system from step 300. Wash the filter cake 2-3 times with a cold solvent at 0-5°C. The amount of cold solvent used is 0.5-1 times the mass of the filter cake. The cold solvent is the same as the reaction solvent in step 200. Step 500: Dry the finished product. The filter cake washed in step 400 is vacuum dried and then sieved to obtain the creatine nitrate product.

2. The method for preparing creatine nitrate according to claim 1, characterized in that: In step 100, the amount of activated carbon added is 0.5 to 1% of the mass of creatine monohydrate.

3. The method for preparing creatine nitrate according to claim 1, characterized in that: In step 200, the stirring rate is 200~400 r / min and the heating rate is 2~3℃ / min.

4. The method for preparing creatine nitrate according to claim 1, characterized in that: In step 200, the reaction solvent is one or a mixture of two or more of purified water, methanol, and ethanol.

5. The method for preparing creatine nitrate according to claim 1, characterized in that: In step 300, the cooling rate is 1~2℃ / min and the stirring rate is 100~200r / min.

6. The method for preparing creatine nitrate according to claim 1, characterized in that: In step 500, the vacuum drying conditions are a temperature of 40~60℃, a vacuum degree of -0.08~-0.1MPa, and a drying time of 4~6h.

7. A creatine nitrate, characterized in that: It is prepared by the preparation method described in any one of claims 1-6.

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