A method for synthesizing creatine monohydrate from glycine

Abstract

The present application discloses a method for synthesizing creatine monohydrate from glycine, which includes mixing formaldehyde with an acid solution to obtain an acidic solution, and adjusting the pH of the acidic solution to 3 to 5; reacting the glycine solution with the acidic solution to obtain a reaction solution; reacting the reaction solution with a cyanamide solution to obtain a creatine reaction solution; and performing post-treatment on the creatine reaction solution to obtain creatine monohydrate. In the present application, high-purity creatine monohydrate is obtained under the environment of a low-concentration reaction solution. Compared with the prior art, the steps are simple, thus simplifying the process of synthesizing creatine monohydrate from glycine. Moreover, in this method, the yield of creatine monohydrate is greater than 70%, and the highest yield can reach 83%, improving the yield of creatine monohydrate.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical production, and in particular to a method for synthesizing creatine monohydrate from glycine. Background Art

[0002] Creatine Monohydrate is a widely used dietary supplement. It is mainly used by athletes and fitness enthusiasts in the fitness and sports fields to improve sports performance and promote muscle growth. It naturally exists in meat and fish, but the supplemented form of creatine monohydrate is often obtained through chemical synthesis.

[0003] In the prior art, the Chinese invention patent with the authorization announcement number CN115772100A specifically discloses a method for continuously producing creatine monohydrate through a microchannel reaction device, including the following steps: simultaneously pumping aqueous methylamine solution and aqueous chloroacetic acid solution into microchannel reactor I for reaction to generate aqueous sarcosine solution; simultaneously pumping aqueous sarcosine solution and sodium hydroxide solution into microchannel reactor II for reaction, and performing vacuum distillation after the reaction to obtain concentrated aqueous sarcosine solution; simultaneously pumping concentrated aqueous sarcosine solution and aqueous monocyanamide solution into tubular reactor III for reaction to obtain a creatine reaction solution; and performing post-treatment on the creatine reaction solution to obtain creatine monohydrate.

[0004] In the above technology, the steps for preparing creatine monohydrate are complex. High-temperature distillation is required to obtain concentrated aqueous sarcosine solution. At the same time, the product yield obtained is only 68%, with high energy consumption, complex process, and low yield. Summary of the Invention

[0005] Based on this, the present invention provides a method for synthesizing creatine monohydrate from glycine, which solves the technical problems in the prior art that synthesizing creatine monohydrate requires high-temperature distillation to obtain concentrated aqueous sarcosine solution, has complex steps, and the obtained product has a low yield.

[0006] A method for synthesizing creatine monohydrate from glycine includes the following steps:

[0007] S1. Mix formaldehyde with an acid solution to obtain an acidic solution, and adjust the pH of the acidic solution to 3 to 5;

[0008] S2. React the glycine solution with the acidic solution to obtain a reaction solution;

[0009] S3. React the reaction solution with a monocyanamide solution to obtain a creatine reaction solution;

[0010] S4. Perform post-treatment on the creatine reaction solution to obtain creatine monohydrate.

[0011] Preferably, in step S1, the acid solution is any one of formic acid, acetic acid, and propionic acid.

[0012] Preferably, in step S2, the molar ratio of glycine to the formaldehyde is 1:(1.1 to 1.3).

[0013] Preferably, in step S2, the concentration of the glycine solution is 30 wt% to 50 wt%.

[0014] Preferably, in step S2, the concentration of sarcosine in the reaction solution is 30 wt% to 50 wt%.

[0015] Preferably, in step S2, the glycine solution and the acidic solution are introduced into a first microchannel reactor for reaction to obtain a reaction solution, wherein the reaction temperature is 70°C to 130°C and the residence time is 2 min to 10 min.

[0016] Preferably, in step S2, the reaction solution obtained from the reaction in the first microchannel reactor is cooled to 50°C to 60°C.

[0017] Preferably, in step S3, the concentration of the cyanamide solution is 20 wt% to 30 wt%.

[0018] Preferably, in step S3, the molar ratio of cyanamide to sarcosine in the reaction solution is 1:(1 to 2).

[0019] Preferably, in step S3, the reaction solution and the cyanamide solution are introduced into a second microchannel reactor for reaction to obtain a creatine reaction solution, wherein the reaction temperature is 60°C to 90°C; the reaction time is 5 min to 15 min.

[0020] The technical solution adopted in this application can achieve the following beneficial effects:

[0021] This application discloses a method for synthesizing creatine monohydrate from glycine, including mixing formaldehyde with an acid solution to obtain an acidic solution, adjusting the pH of the acid solution to 3 to 5; reacting the glycine solution with the acidic solution; reacting the reaction solution with a cyanamide solution to obtain a creatine reaction solution; and performing post-treatment on the creatine reaction solution to obtain creatine monohydrate. In this application, high-purity creatine monohydrate is obtained in an environment of a low-concentration reaction solution, which is simpler than the prior art steps, thus simplifying the process of synthesizing creatine monohydrate from glycine. Moreover, in this method, the yield of creatine monohydrate is greater than 70%, and the highest yield can reach 83%, improving the yield of creatine monohydrate. Description of the Drawings

[0022] Figure 1 It is a process flow chart for obtaining creatine monohydrate.

[0023] Among them, there are a first microchannel reactor 100 and a second microchannel reactor 200. Detailed Embodiments

[0024] For ease of understanding this application, the following will provide a more comprehensive description of this application with reference to relevant experimental examples. Preferred embodiments of this application are given in the experimental examples. However, this application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of this application more thorough and comprehensive.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" as used herein includes any and all combinations of one or more of the related listed items.

[0026] Please refer to Figure 1 , in a specific embodiment of the present invention, a method for synthesizing creatine monohydrate from glycine includes the following steps:

[0027] S1. Mix formaldehyde with an acid solution to obtain an acidic solution, and adjust the pH of the acidic solution to 3 to 5; wherein, the chemical formula of formaldehyde is CH2O, and the molecular weight is 30.03. In this application, an excessive formaldehyde solution with a concentration of 20wt% to 40wt% is used, and it is mixed with the acid solution by stirring to obtain the acidic solution. The stirring speed should be controlled at 50r / min to 100r / min. The acid solution is any one of formic acid, acetic acid, and propionic acid. Acetic acid is a colorless organic acid.

[0028] S2. React the glycine solution with the acidic solution to obtain a reaction solution; wherein, the chemical formula of glycine is C2H5NO2, and the molecular weight is 75.067. Under certain conditions, glycine behaves as a zwitterion, that is, it has both acidic and basic groups at the same time. Therefore, the pH of the glycine solution can be adjusted by adding acid or base. In this application, the concentration of the glycine solution is preferably 30wt% to 50wt%, and the molar ratio of glycine to the formaldehyde is 1:(1.1 to 1.3). The glycine solution reacts with the acidic solution to obtain a reaction solution. Among them, formaldehyde and glycine react under acidic conditions to obtain a sarcosine solution with a concentration of 30wt% to 50wt%. The chemical formula of sarcosine is C3H7NO2, and the molecular weight is 89.09320.

[0029] S3. React the reaction solution with a cyanamide solution to obtain a creatine reaction solution; among them, cyanamide, whose scientific name is amino cyanide, is an organic compound with a molecular formula of NH2CN and a molecular weight of 42.046. It has a wide range of applications in the chemical industry. In this application, the concentration of the cyanamide solution is preferably 20 wt% to 30 wt%. Reacting the reaction solution with the cyanamide solution to obtain a creatine reaction solution is mainly the reaction between sarcosine in the reaction solution and cyanamide. The molar ratio of cyanamide to sarcosine in the reaction solution is 1:(1 to 2).

[0030] S4. Perform post-treatment on the creatine reaction solution to obtain creatine monohydrate; among them, the post-treatment of the creatine reaction solution includes transferring the creatine reaction solution to a crystallization kettle and cooling it by 10°C to 15°C. After crystallization, it is put into a centrifugal tank for centrifugation and dried at a temperature of 30°C to 40°C to obtain creatine monohydrate with a molecular formula of C4H 11 N3O3 and a molecular weight of 149.15.

[0031] Further, to enable the glycine solution to fully react with the acidic solution, in step S2, the glycine solution and the acidic solution are introduced into the first microchannel reactor 100 for reaction to obtain a reaction solution. Among them, the reaction temperature is 70°C to 130°C, and the residence time is 2 min to 10 min. Among them, the microchannel reactor is a highly advanced chemical reaction device that uses microfluidic technology to optimize the chemical reaction process. It contains micron-scale channels inside, and these channels can greatly increase the specific surface area of the reaction medium, thereby improving the mass transfer and heat transfer efficiency. The glycine solution and the acidic solution enter the first microchannel reactor 100 together. The temperature of the first microchannel reactor 100 is 70°C to 130°C, and the solution residence time is 2 min to 10 min. The glycine solution reacts in the first microchannel reactor 100 under an acidic environment to obtain a reaction solution.

[0032] Further, in step S2, cool the reaction solution obtained from the reaction in the first microchannel reactor 100 to 50°C to 60°C. Among them, methods such as natural cooling, air cooling, and liquid cooling can be used.

[0033] Further, in step S3, introduce the reaction solution and the cyanamide solution into the second microchannel reactor 200 for reaction to obtain a creatine reaction solution. Among them, the reaction temperature is 60°C to 90°C; the reaction time is 5 min to 15 min. Among them, due to its high heat transfer and mass transfer capabilities, the microchannel reactor can provide fast and uniform reaction conditions. The temperature of the second microchannel reactor 200 is 60°C to 90°C; the solution residence time is 5 min to 15 min to obtain a creatine reaction solution.

[0034] For example, the method for synthesizing creatine monohydrate from glycine includes the following steps:

[0035] Mix excessive formaldehyde with an acid solution to obtain an acidic solution, and then introduce the acidic solution and the glycine solution into the first microchannel reactor 100 at a ratio of glycine to the formaldehyde of 1:(1.1 to 1.3). The reaction temperature of the first microchannel reactor 100 is 70°C to 130°C, and the liquid residence time is 2 min to 10 min to obtain a reaction solution; cool the reaction solution to 50°C to 60°C, and then introduce the reaction solution and a cyanamide solution with a concentration of 20 wt% to 30 wt% into the second microchannel reactor 200 at a ratio of the cyanamide to sarcosine in the reaction solution of 1:(1 to 2). The reaction temperature of the second microchannel reactor 200 is 60°C to 90°C, and the liquid residence time is 5 min to 15 min to obtain a creatine reaction solution. Finally, transfer the creatine reaction solution to a crystallization kettle for cooling. After crystallization, centrifuge and dry to obtain creatine monohydrate.

[0036] Among them, the detection of the purity of creatine monohydrate includes, but is not limited to, high performance liquid chromatography (HPLC), ultraviolet-visible spectroscopy, nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS), and gravimetry, etc. This application preferably uses high performance liquid chromatography because high performance liquid chromatography can provide accurate quantitative analysis and has good reproducibility and sensitivity; the yield of creatine monohydrate is calculated using the following formula:

[0037]

[0038] It should be noted that in the above embodiments, the process temperature and process time involved are all a temperature or time adopted during the experiment. Those skilled in the art can make reasonable adjustments within the error range based on the process temperature and process time provided by the present invention, and all should be included within the protection scope of the present invention.

[0039] The following further illustrates the technical solutions and technical effects of the present invention through specific experimental examples.

[0040] Experimental Example 1

[0041] Take 900 g of formaldehyde solution (concentration 30 wt%), add acetic acid solution (concentration 30 wt%) to the formaldehyde solution and stir and mix until the pH of the mixed solution is 3, and the stirring speed is 60 r / min to obtain an acidic solution; introduce the acidic solution and 1406.5 g of glycine solution (concentration 40 wt%) into the first microchannel reactor 100 simultaneously. The reaction temperature is 120°C, the residence time is 8 min, and cool the derived reaction solution to 50°C ± 2°C to obtain a reaction solution for standby. Measure that the sarcosine concentration in the reaction solution is 40.7 wt%.

[0042] Take 320 g of the reaction solution and 168 g of the cyanamide solution (concentration 25 wt%), and simultaneously introduce them into the second microchannel reactor 200. The reaction temperature is 80 °C and the residence time is 10 min; a creatine reaction solution is prepared. Transfer the creatine reaction solution to a crystallization kettle for cooling. After crystallization, centrifuge and dry to obtain creatine monohydrate. The purity of the creatine monohydrate is detected to be 99.9%, and the yield is calculated to be 72.28% through calculation.

[0043] Experimental Example Two

[0044] Under the condition that other conditions of Experimental Example One remain unchanged, take 320 g of the reaction solution and dilute it until the sarcosine concentration in the reaction solution is diluted to 30 wt%, and then react with the cyanamide solution.

[0045] Experimental Example Three

[0046] Under the condition that other conditions of Experimental Example One remain unchanged, take 320 g of the reaction solution and concentrate it until the sarcosine concentration in the reaction solution is concentrated to 50 wt%, and then react with the cyanamide solution.

[0047] Experimental Example Four

[0048] Under the condition that other conditions of Experimental Example One remain unchanged, adjust the pH of the mixed solution from 3 to 4, and measure that the sarcosine concentration in the reaction solution is 41.6 wt%.

[0049] Experimental Example Five

[0050] Under the condition that other conditions of Experimental Example One remain unchanged, adjust the pH of the mixed solution from 3 to 5, and measure that the sarcosine concentration in the reaction solution is 40.8 wt%.

[0051] Experimental Example Six

[0052] Under the condition that other conditions of Experimental Example Four remain unchanged, take 219 g of the reaction solution in Experimental Example Four, and then react with the cyanamide solution.

[0053] Experimental Example Seven

[0054] Under the condition that other conditions of Experimental Example Four remain unchanged, take 437 g of the reaction solution in Experimental Example Four, and then react with the cyanamide solution.

[0055] Experimental Example Eight

[0056] Under the condition that other conditions of Experimental Example Four remain unchanged, replace the acetic acid solution with a formic acid solution (concentration 30 wt%).

[0057] Experimental Example Nine

[0058] While keeping other conditions in Experimental Example 4 unchanged, the acetic acid solution was replaced with a propionic acid solution (concentration: 30 wt%).

[0059] Table 1 Raw material dosage at different pH values

[0060]

[0061] Table 2 Mass table of sarcosine in the reaction solution

[0062]

[0063] Table 3 Purity and yield table of creatine monohydrate

[0064]

[0065] Referring to Tables 1 to 3, in this application, glycine and excessive formaldehyde were simultaneously introduced into the first microchannel reactor 100 for reaction under acidic conditions with a pH of 3. After the obtained reaction solution was cooled, it was then simultaneously introduced into the second microchannel reactor 200 for reaction with a monocyanamide solution. The yield of creatine monohydrate obtained was 72.28%. When the sarcosine concentration in the reaction solution was adjusted to 30 wt% and 50 wt% in Experimental Example 2 and Experimental Example 3, the fluctuation of the yield of creatine monohydrate was very small, indicating that adjusting the sarcosine concentration had little effect on the yield of creatine monohydrate. When the pH of the mixed solution was adjusted to 4 in Experimental Example 4, the yield of creatine monohydrate obtained was 83.15%, and the yield was significantly increased. When the pH was further adjusted to 5 in Experimental Example 5, the yield of creatine monohydrate obtained was 71.48%, and the yield decreased. This shows that the yield of creatine monohydrate is relatively high under acidic conditions with a pH of 4 for glycine. This phenomenon may be due to the catalytic effect of excessive formaldehyde in the second microchannel reactor 200. At the same time, it is proved that high-purity creatine monohydrate can also be prepared by reacting a low-concentration reaction solution in an acidic environment through a microchannel reactor, and the yield exceeds 70%. This application uses a low-concentration reaction solution, reducing raw material consumption.

[0066] In Experimental Example 6, when the molar ratio of monocyanamide to sarcosine in the reaction solution was 1:1, the yield of creatine monohydrate decreased. In Experimental Example 7, when the molar ratio of monocyanamide to sarcosine in the reaction solution was 1:2, the yield of creatine monohydrate was 82.89%, but it was lower than that in Experimental Example 4. This shows that excessive sarcosine is more conducive to preparing creatine monohydrate, but it should not be excessive. When the molar ratio of monocyanamide to sarcosine is 1:1.5, the effect is better, and the yield of the prepared creatine monohydrate is higher. In Experimental Example 8 and Experimental Example 9, formic acid and propionic acid were used respectively, and the yields of creatine monohydrate were both about 80%.

[0067] From the above experiments, it can be seen that in the experiments of this application, high-purity creatine monohydrate was obtained in an environment of a low-concentration reaction solution, and the yield was greater than 70%. The highest yield of creatine monohydrate could reach 83%. Using a low-concentration reaction solution reduced the consumption of raw materials.

[0068] The above embodiments only express the way of arranging the devices of this application. The description is relatively specific and detailed, but it cannot be understood as a limitation on the scope of the patent application. It should be noted that for those of ordinary skill in the art, without departing from the concept of this application, several adjustments and improvements can still be made, and these all belong to the protection scope of this application. Therefore, the protection scope of the patent of this application should be subject to the appended claims.

Claims

1. A method for synthesizing creatine monohydrate from glycine, characterized in that, It includes the following steps: S1. Mix formaldehyde with an acid solution to obtain an acidic solution, and adjust the pH of the acidic solution to 3 to 5; the acid solution is any one of formic acid, acetic acid, and propionic acid; S2. React a glycine solution with the acidic solution to obtain a reaction solution, and the concentration of sarcosine in the reaction solution is 30 wt% to 50 wt%; the molar ratio of glycine to formaldehyde is 1:(1.1 to 1.3); S3. Feed the reaction solution and a cyanamide solution into a second microchannel reactor to react under acidic conditions to obtain a creatine reaction solution, wherein the reaction temperature is 60 °C to 90 °C; the reaction time is 5 min to 15 min; S4. Perform post-treatment on the creatine reaction solution to obtain creatine monohydrate.

2. The method for synthesizing creatine monohydrate from glycine according to claim 1, wherein In step S2, the concentration of the glycine solution is 30 wt% to 50 wt%.

3. The method for synthesizing creatine monohydrate from glycine according to claim 1, wherein, In step S2, feed the glycine solution and the acidic solution into a first microchannel reactor to react to obtain a reaction solution, wherein the reaction temperature is 70 °C to 130 °C, and the residence time is 2 min to 10 min.

4. The method for synthesizing creatine monohydrate from glycine according to claim 3, wherein, In step S2, cool the reaction solution obtained from the reaction in the first microchannel reactor to 50 °C to 60 °C.

5. The method for synthesizing creatine monohydrate from glycine according to claim 1, characterized in that, In step S3, the concentration of the cyanamide solution is 20 wt% to 30 wt%.

6. The method for synthesizing creatine monohydrate from glycine according to claim 1, wherein In step S3, the molar ratio of cyanamide to sarcosine in the reaction solution is 1:(1 to 2).

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