CN114702410A - Preparation method of glycocyamine - Google Patents
Preparation method of glycocyamine Download PDFInfo
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- CN114702410A CN114702410A CN202210290079.0A CN202210290079A CN114702410A CN 114702410 A CN114702410 A CN 114702410A CN 202210290079 A CN202210290079 A CN 202210290079A CN 114702410 A CN114702410 A CN 114702410A
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- BPMFZUMJYQTVII-UHFFFAOYSA-N guanidinoacetic acid Chemical compound NC(=N)NCC(O)=O BPMFZUMJYQTVII-UHFFFAOYSA-N 0.000 title claims abstract description 134
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 76
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 58
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims abstract description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 42
- 229910001868 water Inorganic materials 0.000 claims abstract description 34
- 239000004471 Glycine Substances 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 27
- 238000003756 stirring Methods 0.000 claims abstract description 20
- MVXMNHYVCLMLDD-UHFFFAOYSA-N 4-methoxynaphthalene-1-carbaldehyde Chemical compound C1=CC=C2C(OC)=CC=C(C=O)C2=C1 MVXMNHYVCLMLDD-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000012043 crude product Substances 0.000 claims abstract description 17
- 239000007864 aqueous solution Substances 0.000 claims description 46
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 25
- 238000002156 mixing Methods 0.000 claims description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 15
- 238000000926 separation method Methods 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- 239000001569 carbon dioxide Substances 0.000 claims description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 239000011259 mixed solution Substances 0.000 claims description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 8
- 239000012265 solid product Substances 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 4
- 239000000047 product Substances 0.000 abstract description 18
- 239000002994 raw material Substances 0.000 abstract description 10
- 238000009776 industrial production Methods 0.000 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000008367 deionised water Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229910000019 calcium carbonate Inorganic materials 0.000 description 6
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- SWXXKWPYNMZFTE-UHFFFAOYSA-N (c-ethylsulfanylcarbonimidoyl)azanium;bromide Chemical compound Br.CCSC(N)=N SWXXKWPYNMZFTE-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- FCEQRBOTYXIORK-UHFFFAOYSA-N 2-(diaminomethylideneamino)benzoic acid Chemical compound NC(=N)NC1=CC=CC=C1C(O)=O FCEQRBOTYXIORK-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- -1 after mixing Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000008642 heat stress Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01C—AMMONIA; CYANOGEN; COMPOUNDS THEREOF
- C01C3/00—Cyanogen; Compounds thereof
- C01C3/16—Cyanamide; Salts thereof
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/141—Feedstock
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of preparation of medical intermediates, and provides a preparation method of glycocyamine. The method adopts calcium cyanamide as a raw material to prepare cyanamide, then obtains a crude product of the guanidinoacetic acid through the reaction of the cyanamide and the glycine, and then adds water and stirs to purify the crude product of the guanidinoacetic acid to obtain the high-purity guanidinoacetic acid. The preparation method provided by the invention has the advantages of high product yield, high purity, simple process steps, simple and easily-obtained raw materials, low preparation cost, easiness in industrial production and obvious medicine market competitiveness. The results of the examples show that the method for preparing glycocyamine has the product yield of more than 88 percent and the purity of more than 99.3 percent.
Description
Technical Field
The invention relates to the technical field of preparation of medical intermediates, in particular to a preparation method of glycocyamine.
Background
The glycocyamine is white or yellowish crystalline powder, can be dissolved in water, and is very slightly soluble in ethanol and diethyl ether. The glycocyamine is mainly used for pharmaceutical organic synthesis intermediates, can also be used as a food and feed additive, has important effects on the aspects of improving production performance, improving meat quality, promoting energy metabolism and the like, and can also prevent bacterial infection, enhance the immune function of animals, reduce the influence of heat stress on the animals, thereby correspondingly reducing the death rate of the animals in a high-temperature environment.
The main production process of guanidinoacetic acid is reported in relevant documents as follows: thiourea reacts with bromoethane to generate S-ethylthiourea hydrobromide, and then reacts with glycine to prepare guanidinoacetic acid. The method comprises the following specific steps: mixing thiourea, bromoethane and absolute ethyl alcohol, and heating in a water bath for 3 hours to completely dissolve the thiourea; then decompressing and distilling out ethanol and excessive ethyl bromide to crystallize the residue, and drying to obtain the S-ethylthiourea hydrobromide. Then adding sodium hydroxide solution into the obtained S-ethylthiourea hydrobromide, and rapidly adding glycine and water to prepare hot solution under cooling. After crystallization, diethyl ether was added, left overnight and the mixture was cooled in an ice bath for 2h, the diethyl ether layer was separated. And (4) sucking and filtering an ether layer, washing the obtained solid product with ice water, cold ethanol and low-temperature ether in sequence, and air-drying to obtain a finished product. The method has the advantages of complex process, low yield and poor product quality, and is obviously not suitable for large-scale industrial production.
Chinese patent CN102329250A reports a chemical synthesis method of guanidinoacetic acid, which adopts isopropanol, glycine and 10% sodium hydroxide aqueous solution, after mixing, drops cyanamide into alkaline mixed liquor, and finally adds guanidinobenzoic acid and water into the crude product, thereby obtaining guanidinoacetic acid product. Chinese patent CN105503659A reports a method for synthesizing glycocyamine with high purity and high yield, wherein liquid ammonia, glycine and cyanamide are used as main raw materials to produce glycocyamine, the method has simple process and short reaction time, but the ammonia water formed by liquid ammonia in water reacts with the carboxyl in glycine and the carboxyl in glycine reacts with the amino in cyanamide, thus the kind of by-products in glycocyamine production process is obviously increased, and the cost is relatively high in the purification and separation of later-stage products, therefore the production technology is difficult to be applied industrially. In addition, chinese patent CN111393331A also reports a preparation method of glycocyamine, wherein ethanolamine and cyanamide are selected as raw materials for preparing glycocyamine, the method has low process cost and high utilization rate of raw materials, but a relatively expensive catalyst needs to be used in the preparation process, the catalyst is difficult to recover and reuse, no clear treatment scheme is given for the catalyst residue in the product, such process is relatively complex, the cost for producing glycocyamine is increased, and industrial production is difficult to realize.
In summary, the existing preparation method of glycocyamine is difficult to consider both production cost and product quality, and is difficult to carry out industrial production, and the demand is urgent at present to provide a preparation method of glycocyamine, which has simple steps, high product yield and purity, and is easy to carry out industrial production.
Disclosure of Invention
In view of the above, the invention provides a preparation method of glycocyamine. The preparation method provided by the invention has the advantages of simple steps, less side reactions, high product yield and purity, and is more suitable for industrial production.
In order to achieve the above object, the present invention provides the following technical solutions:
a preparation method of glycocyamine comprises the following steps:
(1) mixing calcium cyanamide with water, carrying out a first reaction, continuously introducing carbon dioxide gas in the first reaction process, and carrying out solid-liquid separation after the reaction is finished to obtain a cyanamide aqueous solution; the pH value of the first reaction is 5-6;
(2) mixing the cyanamide aqueous solution and the glycine aqueous solution for a second reaction to obtain a guanidinoacetic acid crude product; the pH value of the second reaction is 7-8, and the temperature is 65-75 ℃;
(3) and mixing the crude guanidinoacetic acid with water, then sequentially stirring and carrying out solid-liquid separation, and drying the obtained solid product to obtain the guanidinoacetic acid.
Preferably, the mass ratio of the calcium cyanamide to the water is 1 (2-2.5).
Preferably, the temperature of the first reaction is room temperature.
Preferably, the first reaction process specifically comprises: mixing calcium cyanamide with water, then adjusting the pH value of the obtained mixed solution to 5-6, and then continuously introducing carbon dioxide to carry out a first reaction; and the reagent for adjusting the pH value of the mixed solution is a sulfuric acid solution or a phosphoric acid solution.
Preferably, the molar ratio of the cyanamide in the cyanamide aqueous solution to the glycine in the glycine aqueous solution is 1 (0.99-1).
Preferably, the process of the second reaction is specifically as follows: dropwise adding the cyanamide aqueous solution into a glycine aqueous solution at the temperature of 20-30 ℃, adjusting the pH value of the obtained mixed solution to 7-8 after the dropwise addition is finished, and then heating to 65-75 ℃ for a second reaction; and the reagent for adjusting the pH value of the mixed solution is sodium bicarbonate aqueous solution.
Preferably, the dripping time is 20-45 min.
Preferably, the time of the second reaction is 2-5 h.
Preferably, the mass ratio of the guanidinoacetic acid crude product to water is 1: 2-5; the stirring temperature is 85-90 ℃, and the stirring time is 1-2 h.
The invention provides a preparation method of glycocyamine, which comprises the following steps: (1) mixing calcium cyanamide with water, carrying out a first reaction, continuously introducing carbon dioxide gas in the first reaction process, and carrying out solid-liquid separation after the reaction is finished to obtain a cyanamide aqueous solution; the pH value of the first reaction is 5-6; (2) mixing the cyanamide aqueous solution and the glycine aqueous solution, and then carrying out a second reaction to obtain a guanidinoacetic acid crude product; the pH value of the second reaction is 7-8, and the temperature is 65-75 ℃; (3) and mixing the crude guanidinoacetic acid with water, then sequentially stirring and carrying out solid-liquid separation, and drying the obtained solid product to obtain the guanidinoacetic acid. The method adopts calcium cyanamide as a raw material to prepare the cyanamide, and then obtains the guanidinoacetic acid through the reaction of the cyanamide and the glycine. In addition, the cyanamide is easy to polymerize to generate dicyandiamide under the alkaline condition and is extremely unfavorable for producing the guanidinoacetic acid. In addition, carbon dioxide is introduced in the process of preparing the cyanamide, and calcium carbonate as a byproduct is generated in a precipitation form in the reaction process, so that the purification process of the product can be further simplified.
The method takes water as a reaction solvent, has no pollution to the environment, can be recycled in the reaction process, avoids the waste of raw materials, improves the economical efficiency of atoms, reduces the production cost of glycocyamine, and has good social and economic benefits.
The invention also controls the pH value and the temperature of the reaction of the cyanamide and the glycine, avoids volatilization and polymerization of the cyanamide caused by overhigh temperature, and can inhibit the generation of the dicyandiamide under the condition of alkalescence, thereby improving the purity and the yield of the product.
In conclusion, the preparation method provided by the invention has the advantages of high product yield, high purity, simple process steps, simple and easily-obtained raw materials, low preparation cost, easiness in industrial production and obvious medicine market competitiveness. The results of the examples show that the method for preparing glycocyamine has the product yield of more than 88 percent and the purity of more than 99.3 percent.
Detailed Description
The invention provides a preparation method of glycocyamine, which comprises the following steps:
(1) mixing calcium cyanamide with water, carrying out a first reaction, continuously introducing carbon dioxide gas in the first reaction process, and carrying out solid-liquid separation after the reaction is finished to obtain a cyanamide aqueous solution; the pH value of the first reaction is 5-6;
(2) mixing the cyanamide aqueous solution and the glycine aqueous solution, and then carrying out a second reaction to obtain a guanidinoacetic acid crude product; the pH value of the second reaction is 7-8, and the temperature is 65-75 ℃;
(3) and mixing the crude guanidinoacetic acid with water, then sequentially stirring and carrying out solid-liquid separation, and drying the obtained solid product to obtain the guanidinoacetic acid.
The invention makes calcium cyanamide (Ca (HCN)2)2) And mixing the cyanamide with water to carry out a first reaction, continuously introducing carbon dioxide gas in the first reaction process, and carrying out solid-liquid separation after the reaction is finished to obtain a cyanamide aqueous solution. In the present invention, the purity of the calcium cyanamide is preferably 56%; the mass ratio of the calcium cyanamide to the water is preferably 1: 2-2.5, and more preferably 1: 2-2.2; the pH value of the first reaction is 5-6, preferably 5-5.5, and in the invention, if the pH value is too low, the pH value is easy to be too lowThe method controls the pH value of the first reaction to be 5-6, can ensure the stable hydrolysis of calcium cyanamide, and avoids the generation of dicyandiamide. In the present invention, the temperature of the first reaction is preferably room temperature, and in the specific embodiment of the present invention, the reaction is performed directly at room temperature without additional heating or cooling; the time of the first reaction is preferably 1-1.2 h. In the invention, the introduction rate of the carbon dioxide is preferably 5-10 mL/min.
In the specific embodiment of the invention, preferably, calcium cyanamide is mixed with water, then the pH value of the obtained mixed solution is adjusted to 5-6, and then carbon dioxide is continuously introduced for a first reaction; the reagent for adjusting the pH value of the mixed solution is preferably a sulfuric acid solution or a phosphoric acid solution, the mass fraction of the sulfuric acid solution is preferably 5%, and the mass fraction of the phosphoric acid solution is preferably 10%; in the first reaction process, it is preferable to monitor the pH of the reaction solution, and if the pH of the reaction solution is out of the above range, a sulfuric acid solution or a phosphoric acid solution is added for regulation.
In the first reaction process, calcium cyanamide is decalcified under the weak acidic condition to generate active cyanamide and Ca (OH)2The reaction is rapid, the required time is short, Ca (OH)2The calcium carbonate precipitate is produced by bubbling with water and carbon dioxide, so that more active cyanamide can be released, the generation of a single product guanidinoacetic acid in the subsequent reaction with glycine is facilitated, and the generation of a byproduct is avoided. In the present invention, the first reaction involves the following chemical equation:
Ca(OH)2+H2O+CO2→CaCO3+H2O
Ca(HCN2)2+H2O+CO2→2H2NCN+CaCO3
after the first reaction is finished, carrying out solid-liquid separation on the obtained reaction liquid to obtain a cyanamide aqueous solution. In the invention, white calcium carbonate precipitate is continuously generated in the first reaction process, and the first reaction is considered to be finished after the white precipitate is not generated any more, and in the specific embodiment of the invention, the reaction time is controlled to be 1-1.2 h, so that the reaction can be completely carried out; the solid-liquid separation mode is preferably filtration, white calcium carbonate is precipitated and removed through filtration, and the remaining clear aqueous solution is the cyanamide aqueous solution.
After the cyanamide aqueous solution is obtained, the cyanamide aqueous solution and the glycine aqueous solution are mixed and then undergo a second reaction to obtain a crude product of the guanidinoacetic acid. In the invention, the pH value of the second reaction is 7-8, preferably 7.3-7.5, and the temperature of the second reaction is 65-75 ℃, preferably 68-72 ℃; the second reaction time is preferably 2-5 h, and more preferably 2-3 h; the temperature and the pH value of the second reaction are controlled within the ranges, so that the generation of dicyandiamide can be inhibited, and the volatilization of cyanamide is avoided, thereby improving the yield and the purity of the product.
In the invention, the molar ratio of the cyanamide in the cyanamide aqueous solution to the glycine in the glycine aqueous solution is preferably 1 (0.99-1), and more preferably 1: 1; the glycine aqueous solution preferably accounts for 50-55% by mass, and preferably accounts for 52-53% by mass.
In the specific embodiment of the invention, the cyanamide aqueous solution is preferably dropwise added into a glycine aqueous solution at the temperature of 20-30 ℃, after dropwise addition, the pH value of the obtained mixed solution is adjusted to 7-8, and then the temperature is increased to 65-75 ℃ for a second reaction; in the invention, the dripping time is preferably 20-45 min, more preferably 25-30 min, and the reagent for adjusting the pH value of the mixed solution is preferably sodium bicarbonate aqueous solution. The method adds the cyanamide aqueous solution at low temperature, and can further avoid the polymerization and volatilization of the cyanamide.
In the present invention, the second reaction involves the following chemical equation:
after the second reaction is finished, preferably filtering the obtained reaction liquid, and then washing the obtained solid product by using a phosphoric acid solution to obtain a glycocyamine crude product; the mass fraction of the phosphoric acid solution is preferably 35-45%.
After the guanidinoacetic acid crude product is obtained, the guanidinoacetic acid crude product and water are mixed, stirring and solid-liquid separation are sequentially carried out, and the obtained solid product is dried to obtain the guanidinoacetic acid. In the invention, the mass ratio of the guanidinoacetic acid crude product to water is preferably 1: 2-5, and more preferably 1: 2-3; the stirring temperature is preferably 85-90 ℃, more preferably 86-88 ℃, and the stirring time is preferably 1-2 hours; in the specific embodiment of the invention, the glycocyamine crude product and water are preferably mixed, and then the temperature is increased to 85-90 ℃ for stirring. The invention removes a small amount of dicyandiamide impurities existing in guanidinoacetic acid by adding water and stirring. In the invention, the solid-liquid separation mode is preferably filtration, and the drying is preferably drying. In the present invention, the mother liquor produced after the solid-liquid separation is preferably recycled, and may be used in step (1) in place of part of the water to react with calcium cyanamide.
In the present invention, the water used in the above steps is preferably deionized water.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention.
Example 1
(1) Adding 50g of calcium cyanamide (with the content of 56%) and 100g of deionized water into a reactor, adjusting the pH value to 5-6 by using a 5% sulfuric acid solution, stirring and reacting at room temperature, continuously introducing carbon dioxide gas to obtain a white precipitate and a clear aqueous solution, reacting for 1.2h, and filtering the obtained reaction solution to obtain a cyanamide aqueous solution.
(2) Adding 26.5g of glycine and 50g of deionized water into another reactor, slowly adding the cyanamide aqueous solution generated in the step (1) into the glycine aqueous solution within 30min at 25 ℃, adjusting the pH of the reaction solution to 7-8 by using an aqueous sodium bicarbonate solution after dropwise addition, raising the reaction temperature to 70 ℃, and stirring for reaction for 2h to obtain a crude product of guanidinoacetic acid.
(3) And (3) adding the glycocyamine crude product obtained in the step (2) and 100g of deionized water into a reaction kettle, heating to 85 ℃, stirring for 2 hours, and then carrying out suction filtration, washing and drying to obtain glycocyamine.
The yield of glycocyamine in this example was 90% (36.7 g of top-quality product) with a content of 99.5%.
Example 2
(1) Adding 25Kg of calcium cyanamide (the content is 56%) and 50Kg of deionized water into a reactor, adjusting the pH to 5.05.5 by using 10% phosphoric acid aqueous solution, stirring at room temperature, continuously introducing carbon dioxide gas to obtain white precipitate and clear aqueous solution, reacting for 1h, and filtering the obtained reaction solution to obtain the cyanamide aqueous solution.
(2) And (2) adding 13.5Kg of glycine and 25Kg of deionized water into another reactor, slowly adding the cyanamide aqueous solution generated in the step (1) into the glycine aqueous solution within 45min at the temperature of 20 ℃, adjusting the pH of the reaction solution to 7.5 by using an aqueous sodium bicarbonate solution after dropwise addition, raising the reaction temperature to 75 ℃, and stirring for 2 hours to obtain a crude product of guanidinoacetic acid.
(3) And (3) putting the crude guanidinoacetic acid obtained in the step (2) and 70Kg of deionized water into a reaction kettle, heating to 90 ℃, stirring for 1h, and then carrying out suction filtration, washing and drying to obtain the guanidinoacetic acid.
In this example, guanidinoacetic acid was obtained in 88% yield (18.1 Kg of top-quality product) and in a content of 99.3%.
The method has the advantages that through screening of raw materials for synthesizing the glycocyamine and limitation of the steps for synthesizing the glycocyamine, the generation of a byproduct dicyandiamide in the process of synthesizing the glycocyamine is reduced, the utilization rate of the raw materials is improved, the production cost of the glycocyamine is reduced, the high-yield and high-purity production of the glycocyamine is realized, the steps of the method are simple, and the industrial production is easy to carry out.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (9)
1. A preparation method of glycocyamine is characterized by comprising the following steps:
(1) mixing calcium cyanamide with water, carrying out a first reaction, continuously introducing carbon dioxide gas in the first reaction process, and carrying out solid-liquid separation after the reaction is finished to obtain a cyanamide aqueous solution; the pH value of the first reaction is 5-6;
(2) mixing the cyanamide aqueous solution and the glycine aqueous solution for a second reaction to obtain a guanidinoacetic acid crude product; the pH value of the second reaction is 7-8, and the temperature is 65-75 ℃;
(3) and mixing the crude guanidinoacetic acid with water, then sequentially stirring and carrying out solid-liquid separation, and drying the obtained solid product to obtain the guanidinoacetic acid.
2. The preparation method according to claim 1, wherein the mass ratio of the calcium cyanamide to the water is 1 (2-2.5).
3. The method according to claim 1, wherein the temperature of the first reaction is room temperature.
4. The preparation method according to claim 1, 2 or 3, characterized in that the first reaction is carried out in particular by: mixing calcium cyanamide with water, then adjusting the pH value of the obtained mixed solution to 5-6, and then continuously introducing carbon dioxide to carry out a first reaction; and the reagent for adjusting the pH value of the mixed solution is a sulfuric acid solution or a phosphoric acid solution.
5. The method according to claim 1, wherein the molar ratio of the cyanamide in the aqueous solution of the cyanamide to the glycine in the aqueous solution of the glycine is 1 (0.99-1).
6. The preparation method according to claim 1 or 5, wherein the second reaction is carried out by: dropwise adding the cyanamide aqueous solution into a glycine aqueous solution at the temperature of 20-30 ℃, adjusting the pH value of the obtained mixed solution to 7-8 after the dropwise addition is finished, and then heating to 65-75 ℃ for a second reaction; the reagent for adjusting the pH value of the mixed solution is sodium bicarbonate aqueous solution.
7. The preparation method according to claim 6, wherein the dropping time is 20 to 45 min.
8. The method according to claim 1, wherein the second reaction time is 2 to 5 hours.
9. The preparation method according to claim 1, characterized in that the mass ratio of the crude guanidinoacetic acid to water is 1: 2-5; the stirring temperature is 85-90 ℃, and the stirring time is 1-2 h.
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| US5017355A (en) * | 1988-05-18 | 1991-05-21 | Nippon Carbide Kogyo Kabushiki Kaisha | Process for producing cyanamide |
| CN101016151A (en) * | 2006-08-08 | 2007-08-15 | 芮海平 | Method of preparing cyanamide aqueous solution and dicyandiamide and coproducing carbon and calcium carbonate by calcium cyanamide |
| CN101462983A (en) * | 2007-12-21 | 2009-06-24 | 上海浩洲化工有限公司 | Preparation of glycocyamine |
| CN102329250A (en) * | 2011-07-22 | 2012-01-25 | 周彬 | Chemical synthesis method of glycocyamine |
| CN103193681A (en) * | 2013-04-17 | 2013-07-10 | 北京君德同创农牧科技股份有限公司 | Clean preparation method of guanidinoacetic acid |
| CN111393331A (en) * | 2020-05-14 | 2020-07-10 | 内蒙古天翊生物科技有限公司 | Preparation method of glycocyamine |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5017355A (en) * | 1988-05-18 | 1991-05-21 | Nippon Carbide Kogyo Kabushiki Kaisha | Process for producing cyanamide |
| CN101016151A (en) * | 2006-08-08 | 2007-08-15 | 芮海平 | Method of preparing cyanamide aqueous solution and dicyandiamide and coproducing carbon and calcium carbonate by calcium cyanamide |
| CN101462983A (en) * | 2007-12-21 | 2009-06-24 | 上海浩洲化工有限公司 | Preparation of glycocyamine |
| CN102329250A (en) * | 2011-07-22 | 2012-01-25 | 周彬 | Chemical synthesis method of glycocyamine |
| CN103193681A (en) * | 2013-04-17 | 2013-07-10 | 北京君德同创农牧科技股份有限公司 | Clean preparation method of guanidinoacetic acid |
| CN111393331A (en) * | 2020-05-14 | 2020-07-10 | 内蒙古天翊生物科技有限公司 | Preparation method of glycocyamine |
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