Synthesis method of allantoin

Abstract

The invention relates to the technical field of allantoin preparation, in particular to a synthesis method of allantoin. The synthesis method comprises the following steps: (1) mixing and stirring glyoxal and nitric acid to react; (2) adding calcium hydroxide powder while stirring at room temperature, separating out white precipitate, and standing; (3) after filtering, washing filter residues with water, adding calcium chloride into the filtered mother liquor, stirring and dissolving, dropwise adding a sodium hydroxide aqueous solution, stopping adding alkali when the pH value reaches 3.0-3.5, and standing to obtain a fine-particle calcium glyoxylate white solid; (4) dissolving the prepared calcium glyoxylate with hydrochloric acid, adding urea, stirring and reacting, and generating white precipitate along with the reaction; and filtering, washing and drying the obtained precipitate to obtain the product allantoin. The invention aims to provide a synthesis method of allantoin, and aims to reduce the production cost and improve the product yield and purity.

Description

Technical Field

[0001] The invention relates to the technical field of allantoin preparation, and in particular to a method for synthesizing allantoin. Background Art

[0002] Allantoin (C4H6N4O3) is an important organic compound with a wide range of applications, such as medicine, cosmetics and pesticides. The heterocyclic structure in its molecular structure gives it unique chemical and biological activities, making it an important ingredient in a variety of products. Traditional methods of extracting allantoin mainly come from organisms, such as cystic fluid, fetal urine and some plants, but these methods are costly and difficult to meet the needs of large-scale industrial production.

[0003] There are many methods for synthesizing allantoin, and the development and evolution of these methods have gone through a long process. Early research mainly focused on preparing allantoin through chemical synthesis methods, such as urea and permanganate oxidation method, glyoxylic acid calcium hydrochloride dissolution method, glyoxylic acid urea condensation cyclization method, etc. Although these methods can achieve the synthesis of allantoin to a certain extent, there are problems such as complex process, high cost, and low yield, which limits its industrial application.

[0004] With the advancement of science and technology and the continuous development of chemical technology, new allantoin synthesis methods continue to emerge. Among them, the glyoxal oxidation-urea condensation cyclization method is currently a method commonly used in the domestic and foreign industrial circles. This method uses an acidic medium to react urea with glyoxylic acid under specific temperature and stirring conditions to generate a white precipitate of allantoin. This process has the advantages of a wide source of raw materials, low production cost, simple process flow, few by-products, simple three waste treatment, and low energy consumption, showing good development potential.

[0005] In addition to the glyoxal oxidation-urea condensation cyclization method, there are other innovative allantoin synthesis methods. For example, the synthesis method using glyoxylic acid and urea as raw materials and using a mixture of hydrogen sulfate and sulfuric acid, a mixture of hydrogen phosphate and phosphoric acid, hydrogen sulfate or hydrogen phosphate as a catalyst can significantly improve the yield of allantoin and reduce the acidity of the synthetic mother liquor, so that the mother liquor can be used as a fertilizer after treatment, achieving green energy conservation and environmental protection and good ecological effects.

[0006] In addition, there is a synthesis method using acidic ionic liquid as a catalyst, which also uses glyoxylic acid and urea as raw materials and achieves a high-yield synthesis of allantoin through a simple process flow. This process not only has easy raw materials and is easy to promote industrialization, but is also pollution-free, green, energy-saving and environmentally friendly, and has good social and economic benefits.

[0007] The synthesis method of allantoin has experienced a continuous development and optimization process from complexity to simplicity, from high cost to low cost, and from low yield to high yield. At present, the glyoxal oxidation-urea condensation cyclization method and its improved method have become the mainstream technology for industrial production of allantoin. However, with the progress of science and technology and the changes in market demand, it is still necessary to continuously explore and innovate the synthesis method of allantoin to meet the demand for allantoin in different fields. Based on this, the present invention proposes a synthesis method of allantoin. Summary of the invention

[0008] The invention aims to provide a method for synthesizing allantoin, aiming to reduce production cost and improve product yield and purity.

[0009] The present invention provides a method for synthesizing allantoin, comprising the steps of: (1) mixing glyoxal and nitric acid to react; (2) Add calcium hydroxide powder while stirring at room temperature, and let stand after a white precipitate is precipitated; (3) After filtering, wash the filter residue with water, add calcium chloride to the filtered mother liquor, stir to dissolve, then add sodium hydroxide aqueous solution dropwise, stop adding alkali when the pH reaches 3.0-3.5, and let stand to obtain fine granular calcium glyoxylate white solid; (4) Dissolve the prepared calcium glyoxylate with hydrochloric acid, add urea and stir to react. As the reaction proceeds, a white precipitate is generated. Filter, wash and dry the obtained precipitate to obtain the product allantoin.

[0010] Furthermore, in step (1), the reaction temperature is 40-45° C. and the reaction time is 3-4 h.

[0011] Furthermore, in step (2), the pH is controlled to be 0.7-0.8.

[0012] Furthermore, the standing time in step (2) is 30-40 minutes.

[0013] Furthermore, the volume fraction of the sodium hydroxide solution in step (3) is 20-24%.

[0014] Furthermore, the concentration of hydrochloric acid in step (4) is 0.5-1 mol / L.

[0015] Furthermore, the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride and sodium hydroxide is 1:(1-1.5):(1-2):(2-3):(1-2).

[0016] Furthermore, the molar ratio of calcium glyoxylate, hydrochloric acid and urea is 1:(1-2):(4-6).

[0017] Furthermore, the reaction temperature of step (4) is 72-75° C., and the reaction time is 2-3 h.

[0018] Furthermore, in step (4), the drying temperature is 50-60° C. and the drying time is 3-4 hours.

[0019] The beneficial effects of the present invention are: The main raw materials used in the method provided by the present invention, such as glyoxal, nitric acid, calcium hydroxide, calcium chloride, sodium hydroxide and urea, are all common chemical raw materials, which are easy to purchase and have relatively low costs, and are conducive to reducing production costs; In the preparation process of the present invention, by adjusting conditions such as pH value and temperature, the generation of by-products can be effectively controlled, thereby reducing pollution to the environment. Meanwhile, the three waste substances such as waste water, waste gas and waste residue generated are relatively small and easy to handle. The steps are simple to operate, and the by-products generated during the synthesis process are small, so that a high-purity allantoin product can be obtained, and industrial production can be easily realized. DETAILED DESCRIPTION

[0020] The technical solution of the present invention is described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0021] Example 1 This embodiment provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 42°C and the reaction time is 3.5 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.75, and let stand for 35 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 22% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.25, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.25:1.5:2.5:1.5; (4) The prepared calcium glyoxylate was dissolved in a 0.75 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 73°C and the reaction time was 2.5 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 55°C and the drying time was 3.5 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1.5:5.

[0022] The final allantoin yield was 84% ​​and the purity was 92.8%.

[0023] Example 2 This embodiment provides a method for synthesizing allantoin, the steps comprising: (1) Mixing glyoxal and nitric acid and stirring them for reaction; the reaction temperature is 40°C and the reaction time is 3 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.7, and let stand for 30 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 20% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.0, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1:1:2:1; (4) The prepared calcium glyoxylate was dissolved in a 0.5 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 72°C and the reaction time was 2 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 50°C and the drying time was 3 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1:4.

[0024] The final allantoin yield was 82% and the purity was 92.2%.

[0025] Example 3 This embodiment provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 45°C and the reaction time is 4 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.8, and let stand for 40 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 24% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.5, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.5:2:3:2; (4) The prepared calcium glyoxylate was dissolved in a 1 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 75°C and the reaction time was 3 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 60°C and the drying time was 4 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:2:6.

[0026] The final allantoin yield was 80% and the purity was 92.4%.

[0027] Example 4 This embodiment provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 40°C and the reaction time is 4 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.7, and let stand for 40 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 20% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.5, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1:2:2:2; (4) The prepared calcium glyoxylate was dissolved in a 0.5 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 75°C and the reaction time was 2 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 60°C and the drying time was 3 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:2:4.

[0028] The final allantoin yield was 81% and the purity was 92.0%.

[0029] Comparative Example 1 This comparative example provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 30°C and the reaction time is 3.5 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.75, and let stand for 35 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 22% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.25, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.25:1.5:2.5:1.5; (4) The prepared calcium glyoxylate was dissolved in a 0.75 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 73°C and the reaction time was 2.5 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 55°C and the drying time was 3.5 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1.5:5.

[0030] The final allantoin yield was 78% and the purity was 90.3%.

[0031] Comparative Example 2 This comparative example provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 50°C and the reaction time is 3.5 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.75, and let stand for 35 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 22% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.25, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.25:1.5:2.5:1.5; (4) The prepared calcium glyoxylate was dissolved in a 0.75 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 73°C and the reaction time was 2.5 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 55°C and the drying time was 3.5 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1.5:5.

[0032] The final allantoin yield was 75% and the purity was 91.4%.

[0033] Comparative Example 3 This comparative example provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 42°C and the reaction time is 3.5 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.75, and let stand for 35 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 22% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.25, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.25:1.5:2.5:1.5; (4) The prepared calcium glyoxylate was dissolved in a 0.75 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 60°C and the reaction time was 2.5 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 55°C and the drying time was 3.5 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1.5:5.

[0034] The final allantoin yield was 79% and the purity was 89.4%.

[0035] Comparative Example 4 This comparative example provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 42°C and the reaction time is 3.5 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.75, and let stand for 35 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 22% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.25, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.25:1.5:2.5:1.5; (4) The prepared calcium glyoxylate was dissolved in a 0.75 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 80°C and the reaction time was 2.5 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 55°C and the drying time was 3.5 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1.5:5.

[0036] The final allantoin yield was 74% and the purity was 88.1%.

[0037] Comparative Example 5 This comparative example provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 42°C and the reaction time is 3.5 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.75, and let stand for 35 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 22% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.25, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.25:1.5:2.5:1.5; (4) The prepared calcium glyoxylate was dissolved in a 0.75 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 73°C and the reaction time was 2 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 55°C and the drying time was 3.5 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1.5:5.

[0038] The final allantoin yield was 76% and the purity was 85.7%.

[0039] Comparative Example 6 This comparative example provides a method for synthesizing allantoin, the steps comprising: (1) Mix glyoxal and nitric acid and stir them for reaction; the reaction temperature is 42°C and the reaction time is 3.5 hours; (2) Add calcium hydroxide powder while stirring at room temperature, control the pH to 0.75, and let stand for 35 minutes after a white precipitate is precipitated; (3) After filtering, the filter residue is washed with water, calcium chloride is added to the filtered mother liquor, and after stirring to dissolve, a 22% by volume sodium hydroxide aqueous solution is added dropwise, and when the pH reaches 3.25, the addition of alkali is stopped, and fine granular calcium glyoxylate white solid is obtained after standing; the molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride, and sodium hydroxide is 1:1.25:1.5:2.5:1.5; (4) The prepared calcium glyoxylate was dissolved in a 0.75 mol / L aqueous hydrochloric acid solution, and urea was added and stirred for reaction. The reaction temperature was 73°C and the reaction time was 3 h. As the reaction proceeded, a white precipitate was generated. The obtained precipitate was filtered, washed and dried to obtain the product allantoin. The drying temperature was 55°C and the drying time was 3.5 h. The molar ratio of calcium glyoxylate, hydrochloric acid and urea was 1:1.5:5.

[0040] The final allantoin yield was 78% and the purity was 86.1%.

[0041] Finally, it should be noted that: the inventor declares that the present invention illustrates the product and detailed preparation method of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned product and detailed preparation method, that is, it does not mean that the present invention must rely on the above-mentioned product and detailed preparation method to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention and addition of auxiliary materials, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0042] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited to the specific details in the above embodiments, and the technical solution of the present invention can be subjected to a variety of simple modifications within the technical concept of the present invention. These simple modifications all belong to the protection scope of the present invention.

[0043] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0044] In addition, various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A method for synthesizing allantoin, characterized in that the steps include: (1) mixing glyoxal and nitric acid to react; (2) Add calcium hydroxide powder while stirring at room temperature, and let stand after a white precipitate is precipitated; (3) After filtering, wash the filter residue with water, add calcium chloride to the filtered mother liquor, stir to dissolve, then add sodium hydroxide aqueous solution dropwise, stop adding alkali when the pH reaches 3.0-3.5, and let stand to obtain fine granular calcium glyoxylate white solid; (4) Dissolve the prepared calcium glyoxylate with hydrochloric acid, add urea and stir to react. As the reaction proceeds, a white precipitate is generated. Filter, wash and dry the obtained precipitate to obtain the product allantoin.

2. The method for synthesizing allantoin according to claim 1, characterized in that: In the step (1), the reaction temperature is 40-45° C. and the reaction time is 3-4 h.

3. The method for synthesizing allantoin according to claim 1, characterized in that: In the step (2), the pH is controlled to be 0.7-0.

8.

4. The method for synthesizing allantoin according to claim 1, characterized in that: The standing time in step (2) is 30-40 minutes.

5. The method for synthesizing allantoin according to claim 1, characterized in that: The volume fraction of the sodium hydroxide solution in step (3) is 20-24%.

6. The method for synthesizing allantoin according to claim 5, characterized in that: The concentration of hydrochloric acid in step (4) is 0.5-1 mol / L.

7. The method for synthesizing allantoin according to claim 6, characterized in that: The molar ratio of glyoxal, nitric acid, calcium hydroxide, calcium chloride and sodium hydroxide is 1:(1-1.5):(1-2):(2-3):(1-2).

8. The method for synthesizing allantoin according to claim 7, characterized in that: The molar ratio of calcium glyoxylate, hydrochloric acid and urea is 1:(1-2):(4-6).

9. The method for synthesizing allantoin according to claim 1, characterized in that: The reaction temperature of step (4) is 72-75°C and the reaction time is 2-3h.

10. The method for synthesizing allantoin according to claim 1, characterized in that: In step (4), the drying temperature is 50-60° C. and the drying time is 3-4 hours.