Method for synthesizing high-purity guanidinoacetic acid through alkali-free catalysis

Abstract

The invention belongs to the technical field of chemical production, and particularly relates to a method for synthesizing high-purity guanidinoacetic acid through alkali-free catalysis. Glycine and cyanamide are used as reactants, hydrophobic SBA-15 is used for constructing a hydrophobic reaction environment, and high-purity guanidinoacetic acid is obtained through nucleophilic addition-elimination reaction and refining. According to the invention, by regulating and controlling the feeding amount of glycine and utilizing the glycine to construct a proper weakly acidic reaction microenvironment, side reactions such as hydrolysis and self-polymerization of cyanamide under an alkaline condition are effectively inhibited. Meanwhile, a hydrophobically modified SBA-15 material is introduced, an ordered mesoporous structure is beneficial to adsorption and enrichment of reactants, and a hydrophobic pore channel not only can remarkably improve the concentration of glycine and cyanamide and accelerate the reaction rate, but also can timely remove water molecules generated by condensation reaction and promote forward movement of reaction balance, so that the reaction efficiency is improved. Meanwhile, the local microenvironment with less water is also beneficial to inhibiting the hydrolysis of cyanamide, so that the high-purity guanidinoacetic acid is efficiently synthesized.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of chemical production, and more particularly relates to a method for synthesizing high-purity guanidino acetic acid without alkali. BACKGROUND

[0002] Guanidino acetic acid is a key precursor for the synthesis of creatine and plays an indispensable role in cell energy metabolism. Guanidino acetic acid can significantly increase the storage of phosphocreatine in muscle tissue, thereby promoting animal growth, improving feed conversion rate and enhancing meat quality. Due to its significant effect and high safety, guanidino acetic acid has become a green and efficient additive for reducing the use of phosphorus sources, and its market demand is increasing, which promotes the continuous development and optimization of its synthesis technology.

[0003] At present, the synthesis of guanidino acetic acid has made certain progress. In some prior art, calcium cyanamide and water are mixed and then carbon dioxide gas is introduced, after the reaction is completed, solid-liquid separation is performed to obtain a cyanamide aqueous solution, the cyanamide aqueous solution and a glycine aqueous solution are mixed, and the pH is adjusted to 7-8 to obtain guanidino acetic acid. In some prior art, guanidino ethanol is first obtained by reacting ethanolamine with cyanamide, and then guanidino acetic acid is obtained by catalyzing the obtained guanidino ethanol with tetramethylpiperidine oxide. In some prior art, glycine and a solvent are stirred until completely dissolved, liquid ammonia is added to adjust the pH of the solution to 10-11, 50% cyanamide aqueous solution is slowly added to the reaction container, stirring reaction is performed, and guanidino acetic acid is obtained by vacuum filtration.

[0004] However, the synthesis of guanidino acetic acid in the prior art is all under alkaline conditions, and sodium hydroxide or other alkalis are used to adjust to alkalinity. However, the alkaline environment easily intensifies the hydrolysis and self-polymerization of cyanamide and other side reactions, the side reactions in the product are difficult to control, cyanamide is easy to polymerize to form dicyanamide, and a large amount of salt is also formed, resulting in obvious deficiency in raw material utilization rate and purity. Therefore, it is of great significance to develop a method for synthesizing high-purity guanidino acetic acid without alkali to improve product competitiveness. SUMMARY

[0005] The purpose of the present application is to provide a method for synthesizing high-purity guanidino acetic acid without alkali, so as to solve the problems existing in the prior art and realize the synthesis of high-purity guanidino acetic acid without alkali.

[0006] To achieve the above-mentioned purpose, the present application provides the following solutions.

[0007] One of the technical solutions of the present application provides an application of hydrophobic SBA-15 in the synthesis of high-purity guanidino acetic acid without alkali.

[0008] Further, the hydrophobic SBA-15 is obtained by modifying SBA-15 with a hydrophobic silane coupling agent.

[0009] Optionally, the step of modifying SBA-15 using a hydrophobic silane coupling agent comprises:

[0010] SBA-15 is dispersed in an organic solvent, a hydrophobic silane coupling agent is added, and ultrasonic treatment is performed for 1-3 h, followed by washing to obtain hydrophobic SBA-15.

[0011] Preferably, the mass ratio of SBA-15 to the hydrophobic silane coupling agent is 1:0.5-3.

[0012] Preferably, the organic solvent comprises one of ethanol, methanol, toluene, and n-hexane.

[0013] Preferably, the hydrophobic silane coupling agent is one of trimethylsilane, methyltrimethoxysilane, and tridecafluorooctyltriethoxysilane.

[0014] Preferably, the washing is performed using at least one of water, methanol, and ethanol.

[0015] Solution two of the present application: a method for synthesizing guanidino acetic acid without alkali catalyst is provided, and the steps comprise:

[0016] Glycine and monocyanamide are used as reactants, a hydrophobic reaction environment is constructed by using hydrophobic SBA-15, nucleophilic addition-elimination reaction and purification are performed to obtain guanidino acetic acid.

[0017] In the present application, a hydrophobic environment is constructed by using hydrophobic SBA-15, which significantly inhibits the occurrence of side reactions such as hydrolysis (urea is generated) and polymerization (dicyandiamide is generated) of monocyanamide, the obtained product has less by-products, subsequent purification is simpler, high-purity products are easily obtained, and the hydrophobic SBA-15 is easy to recycle after reaction, which meets the principle of green chemistry and ingeniously solves the core pain points in the traditional process.

[0018] Further, the molar ratio of glycine to monocyanamide is 1:0.2-1.0.

[0019] Further, the mass ratio of glycine to hydrophobic SBA-15 is 1:0.5-3.

[0020] Further, the reaction temperature of the nucleophilic addition-elimination reaction is 50-120 ℃, and the reaction time is 2-8 h.

[0021] Further, the purification comprises the procedures of reduced-pressure rotary evaporation concentration, drying, and impurity removal.

[0022] Optionally, the temperature of the reduced-pressure rotary evaporation concentration is 50-150 ℃, and the time is 1-3 h.

[0023] Optionally, the temperature of the drying is 40-60 ℃, and the time is 6-24 h.

[0024] Optionally, the step of removing impurities comprises: adding the dried product into an organic solvent, stirring at 30-70℃ for 1-3h, solid-liquid separation, and then drying at 60-80℃ for 4-10h.

[0025] Preferably, the organic solvent comprises at least one of ethanol, methanol, N,N-dimethylformamide and diethyl ether.

[0026] Preferably, the solid-liquid separation is filtration separation or centrifugal separation.

[0027] Further, the hydrophobic SBA-15 is obtained by modifying SBA-15 using a hydrophobic silane coupling agent.

[0028] Optionally, the step of modifying SBA-15 using a hydrophobic silane coupling agent comprises:

[0029] dispersing SBA-15 in an organic solvent, adding a hydrophobic silane coupling agent, ultrasonic treatment for 1-3h, and washing to obtain the hydrophobic SBA-15.

[0030] Preferably, the mass ratio of SBA-15 to the hydrophobic silane coupling agent is 1:0.5-3.

[0031] Preferably, the organic solvent comprises one of ethanol, methanol, toluene and n-hexane.

[0032] Preferably, the hydrophobic silane coupling agent is one of trimethylsilane, methyltrimethoxysilane and tridecafluorooctyltriethoxysilane.

[0033] Preferably, the washing is washing using at least one of water, methanol and ethanol.

[0034] The present application discloses the following technical effects:

[0035] The present application effectively inhibits the hydrolysis and self-polymerization of monocyamine under alkaline conditions by regulating the feeding amount of glycine, using its own structure to construct a suitable weakly acidic reaction microenvironment. Specifically, the present application drops monocyamine solution in the glycine solution. Since glycine is in excess during the dropping process, the reaction environment is weakly acidic, and the hydrolysis and self-polymerization of monocyamine occur under alkaline conditions. The weakly acidic environment does not support the occurrence of the side reactions. In addition, the hydrophobic SBA-15 has a capillary effect, which can adsorb the reactants and make them react on the SBA-15. The reaction interface has less water content due to the hydrophobic effect, thereby inhibiting the occurrence of the hydrolysis reaction. The combination of the above two purposes achieves the purpose of inhibiting the occurrence of side reactions. At the same time, the introduction of the hydrophobic modified SBA-15 material has an ordered mesoporous structure, which is beneficial to the adsorption and enrichment of the reactants. The hydrophobic pore can not only significantly increase the concentration of glycine and monocyamine and accelerate the reaction rate, but also can remove the water molecules generated by the condensation reaction in time, promote the forward movement of the reaction equilibrium, and at the same time, the local microenvironment with less water also helps to inhibit the hydrolysis of monocyamine, thereby efficiently synthesizing guanidino acetic acid with high purity. BRIEF DESCRIPTION OF DRAWINGS

[0036] The accompanying drawings, which form a part of the present application, are used to provide further understanding of the application and are incorporated in and constitute a part of the specification. The illustrative embodiments of the present application and their description serve to explain the present application. In the drawings:

[0037] Figure 1 TEM image of the hydrophobic SBA-15 prepared for Example 1. DETAILED DESCRIPTION

[0038] The various illustrative embodiments of the present application will now be described in detail below. The detailed description is not intended to limit the present application, but rather to explain certain aspects, features, and embodiments of the present application.

[0039] It should be understood that the terms used in the present application merely describe particular embodiments and are not intended to limit the present application. In addition, for the numerical ranges in the present application, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Each smaller range between any stated value or stated range, and any other stated value or intermediate value in the stated range is also included in the present application. The upper limit and the lower limit of these smaller ranges can be independently included or excluded from the range.

[0040] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0041] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0042] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0043] Unless otherwise specified, all raw materials and reagents involved in the specific embodiments of this invention are commercially available products.

[0044] Unless otherwise specified, room temperature and normal temperature in the specific embodiments of this invention refer to 20-30℃.

[0045] It should be noted that any aspects not described in detail in this invention are conventional practices in the field and are not the focus of this invention.

[0046] Guanidinoacetic acid is commonly synthesized by the condensation of glycine and cyanamide under alkaline conditions. This method requires an external alkaline catalyst, which not only introduces a large amount of inorganic salt byproducts into the reaction system, affecting product purity, but also generates high-salt wastewater. Furthermore, the alkaline environment easily triggers side reactions such as hydrolysis (generating urea) and self-polymerization (generating dicyandiamide) of cyanamide, resulting in low raw material utilization. To address these problems, this invention provides, in some specific embodiments, a method for the alkaline-free catalytic synthesis of high-purity guanidinoacetic acid, comprising the following steps:

[0047] S1. Mix glycine and water at a molar ratio of 1:1.2-3.5 and stir at 30-80 °C until completely dissolved to obtain an aqueous solution of glycine.

[0048] S2. Mix cyanamide and water to prepare an aqueous solution of cyanamide with a concentration of 30-60 wt%.

[0049] S3. Add P123 template agent and HCl to deionized water at a mass ratio of 1:1.5-4 and stir until completely dissolved. Then add tetraethyl orthosilicate at a mass ratio of 1:0.5-3 to P123 template agent and stir for 1-3 h. Then transfer to a polytetrafluoroethylene liner for crystallization (90-150 ℃, 12-96 h), drying (80-100 ℃, 6-12 h), and calcination (400-650 ℃, 3-10 h) to obtain SBA-15.

[0050] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (one of ethanol, methanol, toluene and n-hexane), add a hydrophobic silane coupling agent (one of trimethylsilane, methyltrimethoxysilane and tridecafluorooctyltriethoxysilane), sonicate for 1-3 hours, and wash (using at least one of water, methanol and ethanol) to obtain hydrophobic SBA-15.

[0051] The mass ratio of SBA-15 to the hydrophobic silane coupling agent is 1:0.5-3.

[0052] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 50-120 °C for 2-8 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 50-150 °C for 1-3 h, and then dry it at 40-60 °C for 6-24 h to obtain the crude product.

[0053] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:0.5-3; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.2-1.0.

[0054] S6. Disperse the crude product in an organic solvent (at least one of ethanol, methanol, N,N-dimethylformamide and diethyl ether), stir at 30-70 °C for 1-3 h, cool to crystallize, separate the solid and liquid (by filtration or centrifugation), and then dry at 60-80 °C for 4-10 h to obtain high-purity guanidinoacetic acid.

[0055] The above method effectively suppresses side reactions such as hydrolysis and self-polymerization of cyanamide under alkaline conditions by controlling the amount of glycine fed and utilizing its own ability to construct a suitable weakly acidic reaction microenvironment. Simultaneously, the introduction of hydrophobically modified SBA-15 material, with its ordered mesoporous structure, facilitates the adsorption and enrichment of reactants. The hydrophobic channels not only significantly increase the concentrations of glycine and cyanamide, accelerating the reaction rate, but also promptly remove water molecules generated in the condensation reaction, promoting a forward shift in the reaction equilibrium. Furthermore, the locally water-deficient microenvironment helps inhibit the hydrolysis of cyanamide, thereby efficiently synthesizing high-purity guanidinoacetic acid.

[0056] Example 1

[0057] The steps for the base-free catalytic synthesis of high-purity guanidinoacetic acid include:

[0058] S1. Glycine and water are mixed at a molar ratio of 1:1.5 and stirred at 50 °C until completely dissolved to obtain an aqueous solution of glycine.

[0059] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 50 wt%.

[0060] S3. P123 template agent and HCl were added to deionized water at a mass ratio of 1:1.5 and stirred until completely dissolved. Then, tetraethyl orthosilicate was added at a mass ratio of 1:1.5 to P123 template agent and stirred for 2 h. Subsequently, it was transferred to a polytetrafluoroethylene liner for crystallization (100 ℃, 24 h), drying (80 ℃, 10 h), and calcination (550 ℃, 5 h) to obtain SBA-15.

[0061] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (ethanol), add a hydrophobic silane coupling agent (trimethylsilane), sonicate for 1 hour, and wash (with water) to obtain hydrophobic SBA-15.

[0062] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0063] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 90 °C for 3 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 90 °C for 1 h, and then dry it at 60 °C for 12 h to obtain the crude product.

[0064] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:1.5; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.8.

[0065] S6. Disperse the crude product in an organic solvent (ethanol), stir at 40 °C for 1 h, cool to crystallize, separate the solid and liquid (filter separation), and then dry at 70 °C for 5 h to obtain high-purity guanidinoacetic acid.

[0066] Example 2

[0067] The steps for the base-free catalytic synthesis of high-purity guanidinoacetic acid include:

[0068] S1. Glycine and water are mixed at a molar ratio of 1:3.5 and stirred at 80 °C until completely dissolved to obtain an aqueous solution of glycine.

[0069] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 60 wt%.

[0070] S3. P123 template agent and HCl were added to deionized water at a mass ratio of 1:4 and stirred until completely dissolved. Then, tetraethyl orthosilicate was added at a mass ratio of 1:3 to P123 template agent and stirred for 3 h. Subsequently, it was transferred to a polytetrafluoroethylene liner for crystallization (150 ℃, 12 h), drying (100 ℃, 6 h), and calcination (650 ℃, 3 h) to obtain SBA-15.

[0071] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (methanol), add a hydrophobic silane coupling agent (methyltrimethoxysilane), sonicate for 3 hours, and wash (ethanol) to obtain hydrophobic SBA-15.

[0072] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0073] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 120 °C for 2 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 150 °C for 1 h, and then dry it at 60 °C for 24 h to obtain the crude product.

[0074] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:3; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:1.

[0075] S6. Disperse the crude product in an organic solvent (methanol), stir at 70 °C for 1 h, cool to crystallize, separate the solid and liquid (filter separation), and then dry at 80 °C for 4 h to obtain high-purity guanidinoacetic acid.

[0076] Example 3

[0077] The steps for the base-free catalytic synthesis of high-purity guanidinoacetic acid include:

[0078] S1. Glycine and water are mixed at a molar ratio of 1:1.2 and stirred at 30 °C until completely dissolved to obtain an aqueous solution of glycine.

[0079] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 30 wt%.

[0080] S3. P123 template agent and HCl were added to deionized water at a mass ratio of 1:1.5 and stirred until completely dissolved. Then, tetraethyl orthosilicate was added at a mass ratio of 1:0.5 to P123 template agent and stirred for 1 h. Subsequently, it was transferred to a polytetrafluoroethylene liner for crystallization (90 ℃, 96 h), drying (80 ℃, 12 h), and calcination (400 ℃, 10 h) to obtain SBA-15.

[0081] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (one of methanol, toluene and n-hexane), add a hydrophobic silane coupling agent (one of trimethylsilane, methyltrimethoxysilane and tridecafluorooctyltriethoxysilane), sonicate for 2 h, and wash (with ethanol) to obtain hydrophobic SBA-15.

[0082] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0083] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 50 °C for 2 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 50 °C for 3 h, and then dry it at 40 °C for 24 h to obtain the crude product.

[0084] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:0.5; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.2.

[0085] S6. Disperse the crude product in an organic solvent (N,N-dimethylformamide), stir at 30 °C for 3 h, cool to crystallize, separate the solid and liquid (centrifuge), and then dry at 60 °C for 10 h to obtain high-purity guanidinoacetic acid.

[0086] Example 4

[0087] The steps for the base-free catalytic synthesis of high-purity guanidinoacetic acid include:

[0088] S1. Glycine and water are mixed at a molar ratio of 1:1.5 and stirred at 50 °C until completely dissolved to obtain an aqueous solution of glycine.

[0089] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 50 wt%.

[0090] S3. P123 template agent and HCl were added to deionized water at a mass ratio of 1:1.8 and stirred until completely dissolved. Then, tetraethyl orthosilicate was added at a mass ratio of 1:2.5 to P123 template agent and stirred for 2 h. Subsequently, it was transferred to a polytetrafluoroethylene liner for crystallization (100 ℃, 48 h), drying (90 ℃, 10 h), and calcination (500 ℃, 8 h) to obtain SBA-15.

[0091] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (toluene), add a hydrophobic silane coupling agent (trimethylsilane), sonicate for 1 hour, and wash (methanol) to obtain hydrophobic SBA-15.

[0092] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0093] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 90 °C for 5 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 90 °C for 2 h, and then dry it at 50 °C for 12 h to obtain the crude product.

[0094] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:0.8; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.6.

[0095] S6. Disperse the crude product in an organic solvent (diethyl ether), stir at 60 °C for 2 h, cool to crystallize, separate the solid and liquid (centrifuge), and then dry at 70 °C for 8 h to obtain high-purity guanidinoacetic acid.

[0096] Example 5

[0097] The steps for the base-free catalytic synthesis of high-purity guanidinoacetic acid include:

[0098] S1. Glycine and water are mixed in a molar ratio of 1:2 and stirred at 50 °C until completely dissolved to obtain an aqueous solution of glycine.

[0099] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 50 wt%.

[0100] S3. P123 template agent and HCl were added to deionized water at a mass ratio of 1:3 and stirred until completely dissolved. Then, tetraethyl orthosilicate was added at a mass ratio of 1:2.5 to P123 template agent and stirred for 2 h. Subsequently, it was transferred to a polytetrafluoroethylene liner for crystallization (100 ℃, 24 h), drying (80 ℃, 12 h), and calcination (550 ℃, 6 h) to obtain SBA-15.

[0101] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (toluene), then add a hydrophobic silane coupling agent (tridecylfluorooctyltriethoxysilane) and sonicate for 2 hours, then wash (with methanol) to obtain hydrophobic SBA-15.

[0102] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0103] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 90 °C for 8 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 100 °C for 1 h, and then dry it at 60 °C for 6 h to obtain the crude product.

[0104] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:1.5; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.7.

[0105] S6. Disperse the crude product in an organic solvent (diethyl ether), stir at 70 °C for 1 h, cool to crystallize, separate the solid and liquid (centrifuge), and then dry at 60 °C for 8 h to obtain high-purity guanidinoacetic acid.

[0106] Example 6

[0107] The steps for the base-free catalytic synthesis of high-purity guanidinoacetic acid include:

[0108] S1. Glycine and water are mixed in a molar ratio of 1:3 and stirred at 80 °C until completely dissolved to obtain an aqueous solution of glycine.

[0109] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 60 wt%.

[0110] S3. Add P123 template agent and HCl to deionized water at a mass ratio of 1:3.5 and stir until completely dissolved. Then add tetraethyl orthosilicate at a mass ratio of 1:3 to P123 template agent and stir for 3 h. Then transfer to a polytetrafluoroethylene liner for crystallization (120 ℃, 12 h), drying (80 ℃, 6 h), and calcination (550 ℃, 10 h) to obtain SBA-15.

[0111] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (n-hexane), add a hydrophobic silane coupling agent (trimethylsilane), sonicate for 2 h, and wash (with water) to obtain hydrophobic SBA-15.

[0112] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0113] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 100 °C for 8 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 60 °C for 2 h, and then dry it at 60 °C for 10 h to obtain the crude product.

[0114] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:2; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:1.

[0115] S6. Disperse the crude product in an organic solvent (at least one of ethanol, methanol, N,N-dimethylformamide and diethyl ether), stir at 50 °C for 2 h, cool to crystallize, separate the solid and liquid (by filtration or centrifugation), and then dry at 80 °C for 4 h to obtain high-purity guanidinoacetic acid.

[0116] Example 7

[0117] The steps for the base-free catalytic synthesis of high-purity guanidinoacetic acid include:

[0118] S1. Glycine and water are mixed in a molar ratio of 1:2 and stirred at 70 °C until completely dissolved to obtain an aqueous solution of glycine.

[0119] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 50 wt%.

[0120] S3. Add P123 template agent and HCl to deionized water at a mass ratio of 1:3 and stir until completely dissolved. Then add tetraethyl orthosilicate at a mass ratio of 1:2 to P123 template agent and stir for 2 h. Then transfer to a polytetrafluoroethylene liner for crystallization (100 ℃, 24 h), drying (80 ℃, 10 h), and calcination (500 ℃, 10 h) to obtain SBA-15.

[0121] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (toluene), add a hydrophobic silane coupling agent (trimethylsilane), sonicate for 2 h, and wash (with water) to obtain hydrophobic SBA-15.

[0122] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0123] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 90 °C for 5 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 70 °C for 3 h, and then dry it at 50 °C for 6 h to obtain the crude product.

[0124] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:2.5; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.8.

[0125] S6. Disperse the crude product in an organic solvent (ethanol), stir at 60 °C for 3 h, cool to crystallize, separate the solid and liquid (filter separation), and then dry at 70 °C for 5 h to obtain high-purity guanidinoacetic acid.

[0126] Comparative Example 1

[0127] The steps for synthesizing guanidinoacetic acid include:

[0128] S1. Glycine and water are mixed at a molar ratio of 1:1.5 and stirred at 50 °C until completely dissolved to obtain an aqueous solution of glycine.

[0129] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 50 wt%.

[0130] S3. P123 template agent and HCl were added to deionized water at a mass ratio of 1:1.5 and stirred until completely dissolved. Then, tetraethyl orthosilicate was added at a mass ratio of 1:1.5 to P123 template agent and stirred for 2 h. Subsequently, it was transferred to a polytetrafluoroethylene liner for crystallization (100 ℃, 24 h), drying (80 ℃, 10 h), and calcination (550 ℃, 5 h) to obtain SBA-15.

[0131] S4. Disperse the SBA-15 obtained in step S3 in an organic solvent (ethanol), add a hydrophobic silane coupling agent (trimethylsilane), sonicate for 1 hour, and wash (with water) to obtain hydrophobic SBA-15.

[0132] The mass ratio of SBA-15 to hydrophobic silane coupling agent is 1:3.

[0133] S5. Add the hydrophobic SBA-15 obtained in step S4 to the glycine aqueous solution obtained in step S1, adjust the pH to between 10 and 11 using sodium hydroxide, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 90 °C for 3 h. After the reaction is complete, separate the solid and liquid components. Concentrate the liquid component by rotary evaporation under reduced pressure at 90 °C for 1 h, and then dry it at 60 °C for 12 h to obtain the crude product.

[0134] The mass ratio of glycine to hydrophobic SBA-15 in the glycine aqueous solution is 1:1.5; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.8.

[0135] S6. Disperse the crude product in an organic solvent (ethanol), stir at 40 °C for 1 h, cool to crystallize, separate the solid and liquid (by filtration), and then dry at 70 °C for 5 h to obtain guanidinoacetic acid.

[0136] Comparative Example 2

[0137] The steps for synthesizing guanidinoacetic acid include:

[0138] S1. Glycine and water are mixed at a molar ratio of 1:1.5 and stirred at 50 °C until completely dissolved to obtain an aqueous solution of glycine.

[0139] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 50 wt%.

[0140] S3. Add the aqueous solution of cyanamide prepared in step S2 dropwise to the aqueous solution of glycine obtained in step S1, and carry out a nucleophilic addition-elimination reaction at 90 °C for 3 h. After the reaction is completed, concentrate the product by rotary evaporation under reduced pressure at 90 °C for 1 h, and then dry it at 60 °C for 12 h to obtain the crude product.

[0141] The molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.8.

[0142] S4. Disperse the crude product in an organic solvent (ethanol), stir at 40 °C for 1 h, cool to crystallize, separate the solid and liquid (by filtration), and then dry at 70 °C for 5 h to obtain guanidinoacetic acid.

[0143] Comparative Example 3

[0144] The steps for synthesizing guanidinoacetic acid include:

[0145] S1. Glycine and water are mixed at a molar ratio of 1:1.5 and stirred at 50 °C until completely dissolved to obtain an aqueous solution of glycine.

[0146] S2. Mix cyanamide and water to prepare a cyanamide aqueous solution with a concentration of 50 wt%.

[0147] S3. P123 template agent and HCl were added to deionized water at a mass ratio of 1:1.5 and stirred until completely dissolved. Then, tetraethyl orthosilicate was added at a mass ratio of 1:1.5 to P123 template agent and stirred for 2 h. Subsequently, it was transferred to a polytetrafluoroethylene liner for crystallization (100 ℃, 24 h), drying (80 ℃, 10 h), and calcination (550 ℃, 5 h) to obtain SBA-15.

[0148] S4. Add the SBA-15 obtained in step S3 to the glycine aqueous solution obtained in step S1, and then add the cyanamide aqueous solution obtained in step S2 dropwise. Perform a nucleophilic addition-elimination reaction at 90 °C for 3 h. After the reaction is completed, separate the solid and liquid. Concentrate the liquid part by rotary evaporation under reduced pressure at 90 °C for 1 h, and then dry it at 60 °C for 12 h to obtain the crude product.

[0149] The mass ratio of glycine to SBA-15 in the glycine aqueous solution is 1:1.5; the molar ratio of glycine in the glycine aqueous solution to cyanamide in the cyanamide aqueous solution is 1:0.8.

[0150] S5. Disperse the crude product in an organic solvent (ethanol), stir at 40 °C for 1 h, cool to crystallize, separate the solid and liquid (filter separation), and then dry at 70 °C for 5 h to obtain guanidinoacetic acid.

[0151] Test case

[0152] Using acetone as an internal standard, the purity and yield of the products obtained in the examples and comparative examples were analyzed using a combination of external and internal standards. The results of Examples 1-7 are shown in Table 1, and the results of Comparative Examples 1-3 are shown in Table 2. The specific steps are as follows:

[0153] The purity of creatine monohydrate was determined by high-performance liquid chromatography (HPLC). The HPLC test conditions were as follows:

[0154] The mobile phase was a mixture of methanol and water, with a methanol:water ratio of 5:95 (volume ratio), and the flow rate was 1.0 mL / min. -1 The detection wavelength was 210 nm, the column temperature was 25 ℃, and acetone was used as an internal standard.

[0155] The prepared guanidinoacetic acid and internal standard solutions were added to headspace vials and placed on an automated high-performance liquid chromatography (HPLC) autosampler. The program was then set for automatic injection. First, each standard solution was injected individually to determine the peak position of each impurity in creatine. The injection volume was controlled by the autosampler to adjust the concentration of the injected standard solutions, establishing a method for detecting trace impurities in creatine monohydrate. Then, the obtained guanidinoacetic acid and acetone were injected to determine the purity of the guanidinoacetic acid.

[0156] Table 1

[0157] Examples Yield (%) (based on monomethylamine) Purity (%) 1 68.5 86.5 2 92.3 88.7 3 64.3 90.2 4 87.5 94.7 5 75.0 96.8 6 61.4 98.4 7 110.8 99.2

[0158] Table 2

[0159] Comparative Example Yield (%) (based on monomethylamine) Purity (%) 1 81.4 94.5 2 65.1 88.6 3 73.2 89.3

[0160] As can be seen from the data in Tables 1 and 2, by adjusting the amount of glycine to create a weakly acidic environment in the reaction system and constructing a hydrophobic environment using SBA-15, the hydrolysis and self-polymerization of cyanamide can be effectively inhibited, thereby increasing the yield of guanidinoacetic acid.

[0161] Figure 1 The image shows a TEM image of the hydrophobic SBA-15 prepared in Example 1.

[0162] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0163] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. The application of a hydrophobic SBA-15 in the base-free catalytic synthesis of high-purity guanidinoacetic acid, characterized in that, The hydrophobic SBA-15 was obtained by modifying SBA-15 with a hydrophobic silane coupling agent.

2. A method for the base-free catalytic synthesis of guanidinoacetic acid, characterized in that the step... include: Using glycine and cyanamide as reactants, a hydrophobic reaction environment was constructed through hydrophobic SBA-15, followed by nucleophilic addition-elimination reaction and purification to obtain guanidinoacetic acid.

3. The method as described in claim 2, characterized in that, The molar ratio of glycine to cyanamide is 1:0.2-1.0; And / or, the mass ratio of the glycine to the hydrophobic SBA-15 is 1:0.5-3.

4. The method as described in claim 2, characterized in that, The nucleophilic addition-elimination reaction is carried out at a temperature of 50-120 °C for 2-8 h.

5. The method as described in claim 2, characterized in that, The refining process includes vacuum rotary evaporation for concentration, drying, and impurity removal.

6. The method as described in claim 5, characterized in that, The vacuum rotary evaporation concentration is carried out at a temperature of 50-150 ℃ for 1-3 h. And / or, the drying temperature is 40-60 °C, and the time is 6-24 h; And / or, the impurity removal step includes: adding the dried product to an organic solvent, stirring at 30-70 °C for 1-3 h, separating the solid and liquid, and then drying at 60-80 °C for 4-10 h.

7. The method as described in claim 6, characterized in that, The organic solvent includes at least one selected from ethanol, methanol, N,N-dimethylformamide, and diethyl ether; And / or, the solid-liquid separation is filtration separation or centrifugal separation.

8. The method as described in claim 2, characterized in that, The hydrophobic SBA-15 was obtained by modifying SBA-15 with a hydrophobic silane coupling agent.

9. The method as described in claim 8, characterized in that, The step of modifying SBA-15 using a hydrophobic silane coupling agent includes: SBA-15 was dispersed in an organic solvent, and then a hydrophobic silane coupling agent was added. The mixture was ultrasonically treated for 1-3 hours and then washed to obtain hydrophobic SBA-15.

10. The method as described in claim 9, characterized in that, The mass ratio of SBA-15 to the hydrophobic silane coupling agent is 1:0.5-3; And / or, the organic solvent includes one of ethanol, methanol, toluene, and n-hexane; And / or, the hydrophobic silane coupling agent is one of trimethylsilane, methyltrimethoxysilane and tridecafluorooctyltriethoxysilane; And / or, the washing is performed using at least one of water, methanol, and ethanol.

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