CN104892521A - Synthesis and purification method for alpha-amino acid compound - Google Patents

Synthesis and purification method for alpha-amino acid compound Download PDF

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CN104892521A
CN104892521A CN201510113479.4A CN201510113479A CN104892521A CN 104892521 A CN104892521 A CN 104892521A CN 201510113479 A CN201510113479 A CN 201510113479A CN 104892521 A CN104892521 A CN 104892521A
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amino acid
alpha
acid compound
purifying
synthesizing
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CN104892521B (en
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贾成国
王双珠
史秀肖
马彩霞
范立攀
张银霄
杨达
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HEBEI VEYONG BIO-CHEMICAL Co Ltd
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HEBEI VEYONG BIO-CHEMICAL Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl

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Abstract

The invention relates to a synthesis and purification method for an alpha-amino acid compound. The synthesis and purification method is characterized by comprising the following steps: (1) adding substituted alpha-amino nitrile or a substituted hydantoin-based compound into alkali M(OH)x or metal oxide MxO, adding water or an alcohol and water mixed solvent, and heating for reaction to obtain alpha-amino acid salt; (2) adding ammonium carbonate or ammonium bicarbonate or introducing carbon dioxide into the solution in the step (1), separating to obtain filter liquor and precipitates MxHyCO3, performing reduced pressure concentration on the filter liquor, and recrystallizing in an alcohol solvent to obtain the alpha-amino acid compound (I). The synthesis and purification method for the alpha-amino acid compound is simple, the yield and purity of the obtained alpha-amino acid compound are high; furthermore, recycling utilization and cleaning production of materials can be realized; the synthesis and purification method is especially suitable for synthesis of the alpha-amino acid compound with high water solubility.

Description

Synthesis and purification method of alpha-amino acid compound
Technical Field
The invention relates to a method for synthesizing and purifying an alpha-amino acid compound.
Background
Amino acids are the basic constituent units of biologically functional macromolecular proteins and are the basic substances that constitute proteins required for animal nutrition. The carboxylic acid with the amino group attached to the alpha-carbon is an alpha-amino acid. The alpha-amino acid compound is widely applied to the industries of food, medicine, pesticide, daily chemicals and the like. At present, the main synthetic methods of amino acid mainly comprise a microbial fermentation method, a chemical synthesis method and an enzyme method. The chemical synthesis method mainly comprises the following steps:
a) method for introducing amino and carboxyl
(1) Strecker method
Introducing ammonia or adding ammonium salt into aldehyde, carrying out cyanidation reaction, adding acid or alkali into the generated intermediate for hydrolysis, and synthesizing the alpha-amino acid. When in use, ammonia and hydrocyanic acid can be replaced by ammonium chloride and potassium cyanide, and the intermediate separation is not carried out in most cases during synthesis.
(2) Buchere process
This method is an improvement of the Strecker method. The amino acid is prepared by reacting alkali cyanide and ammonium carbonate with aldehyde, and hydrolyzing intermediate hydantoin. Hydantoin is typically hydrolyzed in an acidic or basic environment to yield an alpha-amino acid.
(3) By carbonylation
The method for synthesizing N-acetylamino acid by reacting aldehyde, amide and carbon monoxide at high pressure and high temperature by using cobaltous octacarbonyl as a catalyst. N-acetylamino acids are generally synthesized by hydrolysis using ethyl acetate and dioxane as solvents.
b) Method for introducing amino group into carboxylic acid
(1) Amination of alpha-halocarboxylic acids
A process for synthesizing an alpha-amino acid by reacting an alpha-halocarboxylic acid with an excess of ammonia in water or an alcohol. This method is almost entirely suitable for the synthesis of aliphatic amino acids. The yield is increased if ammonium carbonate is added.
(2) By introducing amino groups by reduction
This is a method for synthesizing an α -form of an amino acid by reducing an α -keto acid with platinum, nickel or the like in the presence of ammonia by contact reduction, or by reducing an α -keto acid with sodium and an alcohol. The method can synthesize various amino acids.
(3) Method for introducing amino groups into double bonds
A process for synthesizing DL-diaspartic acid by reacting maleic acid ester or fumaric acid vinegar with ammonia under pressure to bond the ammonia to the double bond to form a diketopiperazine derivative, and hydrolyzing the diketopiperazine derivative under alkaline conditions.
c) A method of introducing a carboxyl group into an amino compound (a method of oxidizing an amino alcohol)
The amino of beta-amino alcohol is protected properly, hydroxymethyl is oxidized into carboxyl, and then hydrolysis is carried out to synthesize alpha-amino acid. The oxidant used is potassium permanganate, potassium dichromate, etc. Examples of the amino group-protecting agent to be used include acyl groups such as benzoyl and phthaloyl. Salts such as sulfates can also be used as protecting groups.
d) Acetamide malonate method
The activated methine group of the acetamide malonate is readily condensed with a halogenated primary alkyl, and the alpha-amino acid can be synthesized by hydrolysis of the condensate. The condensation is usually carried out in the presence of an equivalent molar amount of sodium ethoxide, using an alcohol as the solvent. In the presence of sodium hydroxide, the reaction may be carried out in an inactive solvent such as toluene. The hydrolysis of the condensate is performed by refluxing with an acid or a base, but acid hydrolysis is generally preferred.
According to the traditional method for synthesizing the alpha-amino acid, hydrolysis is carried out under a strong alkaline condition, the dosage of alkali is generally 3-5 eq, and a large amount of acid is added for adjusting the isoelectric point of the amino acid to separate to obtain a product by utilizing the principle that the solubility of the amino acid at the isoelectric point is the worst. In the process, a large amount of acid and alkali are used, a large amount of waste salt is formed after neutralization, the process is not applicable to all amino acids, such as amino acids with high water solubility, and the high-purity product is difficult to separate through post-treatment.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for synthesizing and purifying alpha-amino acid compounds, particularly for synthesizing amino acid with good water solubility, high-quality amino acid products can be separated at high yield, and the recycling and clean production of materials are realized.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for synthesizing and purifying alpha-amino acid compounds specifically comprises the following steps:
(1) adding a substituted alpha-aminonitrile (II) or a substituted hydantoin compound (III) to a base M (OH)xOr metal oxides MxO, adding the mixture into water or an alcohol-water mixed solvent, and heating for reaction to obtain alpha-amino acid salt;
(2) adding ammonium carbonate or ammonium bicarbonate or introducing carbon dioxide into the solution obtained in the step (1), separating to obtain filtrate and precipitateStarch MxHyCO3Concentrating the filtrate under reduced pressure, and recrystallizing in alcohol solvent to obtain alpha-amino acid compound (I) with a reaction formula shown in formula (1);
(1)
wherein R is selected from the following substituents:
wherein,
R1，R2each independently selected from linear alkyl or branched alkyl groups of H, C1-C6.
n = 1, 2, 3, 4 or 5;
x = 1 or 2;
y = 0 or 1;
m is selected from sodium, calcium or magnesium, when M is selected from calcium or magnesium, the alkali M (OH) is added in the step (1)xOr metal oxides MxAnd adding organic amine, ammonia gas or ammonia water at the same time, before or after the step of O.
As a further improvement of the invention, the organic amine is selected from methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine or propylamine, the concentration of the ammonia water is 3-30% or ammonia gas, and the amount of the ammonia or the amine is 0.5-6 equivalents of the substrate substituted alpha-aminonitrile (II) or the substituted hydantoin compound (III).
As a further improvement of the invention, in the step (1), when M is selected from calcium or magnesium, a catalyst is also added in the step (1), the catalyst is a quaternary ammonium salt catalyst and a quaternary phosphonium salt catalyst or polyethylene glycol with the molecular weight of 400-8000, and the quaternary ammonium salt catalyst and the quaternary phosphonium salt catalyst are selected from tetraalkylammonium sulfate, tetraalkylammonium hydrogen sulfate, tetraalkylammonium phosphate, and tetraalkyl ammonium sulfateAmmonium dihydrogen phosphate, ammonium triethylbenzylsulfate, tetraalkylammonium chloride, triethylbenzylammonium chloride, and tetraalkyl phosphine sulfate, tetraalkyl phosphine phosphate, triethylbenzylphosphine sulfate, triethylbenzylphosphine chloride, said alkyl group being selected from C1~C16The amount of the catalyst is 0.5-10% of the weight of the substrate.
As a further improvement of the invention, the base M (OH)xOr metal oxides MxThe molar weight of the added O is 1 to 4 times of that of the substituted alpha-aminonitrile (II) or the substituted hydantoin compound (III).
As a further improvement of the invention, the alcohol in the alcohol-water mixed solvent is selected from C1~C4The alcohol of (2) is preferably methanol, ethanol, ethylene glycol, propanol, isopropanol, butanol, isobutanol and tert-butanol, and the ratio of the alcohol to water is 1:10 to 1:5 (w/w).
As a further improvement of the invention, the reaction temperature of the step (1) is controlled to be 80-200 ℃.
As a further improvement of the method, the reaction pressure in the step (1) is 0.1 MPa-10 MPa.
As a further improvement of the invention, the amount of the ammonium carbonate or ammonium bicarbonate or the introduced carbon dioxide in the step (2) is 0.5-3 equivalents of the substrate substituted alpha-aminonitrile (II) or the substituted hydantoin compound (III).
As a further improvement of the invention, the alpha-amino acid compound obtained in the step (2) is purified by a method of recrystallization by using an alcohol solvent, wherein the alcohol solvent is one or more than two selected from methanol, ethanol and propanol.
As a further improvement of the invention, the method comprises the step (3) of precipitating the obtained precipitate MxHyCO3The waste heat can be recycled to the step (1) by burning, and the specific method is as follows:
when M isxHyCO3In the case of calcium carbonate, CO is recovered by firing2And a calcium oxide,CO2recycling the calcium oxide for neutralization reaction in the step (2), and recycling the calcium oxide for hydrolysis reaction process in the step (1);
when M isxHyCO3In the case of magnesium carbonate, CO is recovered by burning2And magnesium oxide, CO2Recycling the magnesium oxide for the neutralization reaction in the step (2), and recycling the magnesium oxide for the hydrolysis reaction in the step (1);
when M isxHyCO3In the case of sodium bicarbonate, it is used as a weak base to neutralize the acid.
Compared with the prior art, the invention has the following beneficial effects:
the general substituted alpha-aminonitrile or substituted hydantoin is hydrolyzed under strong alkaline condition, and then the principle that the solubility of amino acid at isoelectric point is worst is utilized, and a large amount of acid is added in the post-treatment to adjust the isoelectric point of the amino acid, so as to obtain the product. In the process, a large amount of acid and alkali are used, a large amount of waste salt is formed after neutralization, the process is not applicable to all amino acids, such as amino acids with high water solubility, and the high-purity product is difficult to separate through post-treatment.
The invention uses sodium hydroxide, magnesium hydroxide, calcium hydroxide, and corresponding oxides to hydrolyze substituted alpha-aminonitrile or substituted hydantoin compound to obtain alpha-amino acid salt. Using MxHyCO3The principle of poor water solubility is to separate and remove inorganic salts. The high-purity product is obtained by separation by a method of recrystallization by using a solvent.
The alpha-amino nitrile or hydantoin compound is hydrolyzed by sodium hydroxide to obtain alpha-sodium amino acid, and then carbon dioxide is introduced to generate sodium bicarbonate, which has low solubility, especially in the presence of alcohol, and can be removed by filtration. The sodium bicarbonate produced can be widely used to neutralize acids.
Hydrolyzing alpha-amino nitrile or hydantoin compound with calcium hydroxide or magnesium hydroxide to obtain alpha-amino acid calcium salt or magnesium salt, introducing carbon dioxide or adding carbonWhen the acid salt is formed, the generated calcium carbonate or magnesium carbonate is precipitated and separated by filtration. The generated calcium carbonate or magnesium carbonate is burned to obtain CO2And calcium oxide or magnesium oxide, CO2Realizes recycling, and the calcium oxide or the magnesium oxide can be recycled for hydrolysis reaction. The whole process realizes the recycling of the main raw materials and achieves clean production.
The reaction can be carried out under the condition of catalyst or no catalyst, the catalyst is quaternary ammonium salt and quaternary phosphonium salt catalyst or polyethylene glycol with molecular weight of 400-8000, and the addition of the catalyst improves the reaction speed and yield, so that the reaction can be carried out smoothly and more ideal yield is obtained.
The method is simple, the obtained alpha-amino acid compound has high yield and high purity, and the method can realize the recycling of materials and clean production.
Detailed Description
The present invention will be described in further detail with reference to specific examples.
Example 1: synthesis of 2-amino-4-methylthiobutyric acid
130g (1 mol) of 2-amino-4-methylthiobutyronitrile is added into a 1L autoclave, 68g of 25 percent ammonia water and 56g (1 mol) of calcium oxide are added, 2g of tetrabutylammonium hydrogen sulfate and 500g of water are added, and the mixture is heated to 180-oAnd C, reacting for 5 hours under the pressure of 2 DEG, 5-3.0 MPa, cooling to room temperature, introducing carbon dioxide to the reaction solution until the pH is =8 while stirring, filtering, concentrating the mother solution under reduced pressure, adding 150g of methanol into the residue, refluxing for 2 hours, cooling, and separating out crystals. Filtration, vacuum 120oC, drying for 4 hours to obtain 118.3g of 2-amino-4-methylthiobutyric acid with the purity of 96 percent and the yield of 79.4 percent.
Example 2: synthesis of 2-amino-3- (4-imidazolyl) propionic acid
5- [ (4-Imidazoyl) methyl group was charged into a 1L autoclave]180g (1 mol) of hydantoin, 68g of 25 percent ammonia water and 110g (1.5 mol) of calcium hydroxide and 500g of water are added and heated to 160-oAnd C, reacting for 8 hours under the pressure of 1.5-2.0 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8 under stirring, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2 hours, cooling, and separating out crystals. Filtration, vacuum 120oDrying the mixture for 4 hours to obtain 124.2g of 2-amino-3- (4-imidazolyl) propionic acid, wherein the purity is 96 percent, and the yield is 80.1 percent.
Example 3: synthesis of 2-amino-3- (4-imidazolyl) propionic acid
5- [ (4-Imidazoyl) methyl group was charged into a 1L autoclave]Hydantoin 180g (1 mol), 25% ammonia water 68g and calcium hydroxide 110g (1.5 mol), triethylbenzylammonium sulfate 3g, water 500g, heating to 160-oAnd C, reacting for 3 hours under the pressure of 1.5-2.0 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2 hours, cooling, and separating out crystals. Filtration, vacuum 120oDrying the mixture for 4 hours to obtain 134.5g of 2-amino-3- (4-imidazolyl) propionic acid, wherein the purity is 96 percent, and the yield is 86.8 percent.
Example 4: synthesis of 2-amino-3- (4-imidazolyl) propionic acid
5- [ (4-Imidazoyl) methyl group was charged into a 1L autoclave]180g (1 mol) of hydantoin, 34g of 25% ammonia water and 110g (1.5 mol) of calcium hydroxide and 500g of water are added and heated to 160-oAnd C, reacting for 8 hours under the pressure of 1.5-2.0 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2 hours, cooling, and separating out crystals. Filtration, vacuum 120oDrying the mixture for 4 hours to obtain 121.3g of 2-amino-3- (4-imidazolyl) propionic acid, wherein the purity is 96 percent, and the yield is 78.3 percent.
Example 5: synthesis of 2-amino-3-hydroxybutyric acid
144g (1 mol) of 5- (1-hydroxyethyl) hydantoin, 68g of 25% ammonia water and 110g (1.5 mol) of calcium hydroxide, 500g of water and 50mL of n-butanol are added into a 1L autoclave and heated to 160-170-oAnd C, reacting for 4 hours under the pressure of 1.5-2.0 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2 hours, cooling, and separating out crystals. Filtration, cake vacuum 120oDrying the mixture for 4 hours to obtain 106.4g of 2-amino-3-hydroxybutyric acid, wherein the purity is 96 percent and the yield is 89.4 percent.
Example 6: synthesis of 2-amino-3-hydroxypropionic acid
86g (1 mol) of 2-amino-3-hydroxypropionitrile, 136g of 25% ammonia water and 110g (1.5 mol) of calcium hydroxide, 3g of triethylbenzylammonium sulfate and 500g of water were placed in a 1L autoclave and heated to 190 ℃ CoC, reacting for 4 hours under the pressure of 2.5-3.0 MPa, and reducing the temperature to 40-50 DEGoAnd C, adding 118g (1.5 mol) of ammonium bicarbonate, stirring for 1h, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2h, cooling, and separating out crystals. Filtration, vacuum 120oC, drying for 4h to obtain 92.3g of 2-amino-3-hydroxypropionic acid, the purity is 96 percent, and the yield is 87.9 percent.
Example 7: synthesis of 2-amino-3-hydroxypropionic acid
86g (1 mol) of 2-amino-3-hydroxypropionitrile, 136g of 25% ammonia water and 87g (1.5 mol) of magnesium hydroxide, 4g of triethylbenzylammonium sulfate and 500g of water were placed in a 1L autoclave and heated to a temperature of 170 ℃ and 180 DEGoC, reacting for 3 hours under the pressure of 2.0-2.5 MPa, and reducing the temperature to 40-50 DEGoAnd C, adding 144g (1.5 mol) of ammonium carbonate, stirring for 1h, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2h, cooling, and separating out crystals. Filtration, cake vacuum 120oDrying the mixture for 4 hours to obtain 91.1g of 2-amino-3-hydroxypropionic acid, wherein the purity is 96 percent and the yield is 86.8 percent.
Example 8: synthesis of ammonium 2-amino-4- [ hydroxy (methyl) phosphono ] butanoate
2-amino-4- [ ethoxy (methyl) phosphono group was added to a 1L autoclave]190g (1 mol) of butyronitrile, 204g of 25% ammonia solution, 67g (1.2 mol) of calcium oxide, 4g of tetrabutylammonium sulfate and 500g of water are added and heated to 190-oC, reacting for 5 hours under the pressure of 2.5-3.0 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8, filtering, evaporating the mother liquor under reduced pressure, adding 150g of methanol, refluxing for 2 hours, cooling, separating out crystals, filtering, and carrying out vacuum 120oDrying for 4h to obtain 2-amino-4- [ hydroxy (methyl) phosphono group]169.8g of ammonium butyrate, 96% of purity and 85.8% of yield.
Example 9: synthesis of ammonium 2-amino-4- [ hydroxy (methyl) phosphono ] butanoate
2-amino-4- [ ethoxy (methyl) phosphono group was added to a 1L autoclave]190g (1 mol) of butyronitrile, 533.3g (4 mol) of 30% sodium hydroxide and 30mL of ethanol, and the temperature is raised to 160-oC, reacting for 5 hours under the pressure of 0.7-0.9 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol and 15g of water, introducing 34g of ammonia gas, stirring for 6 hours, filtering, concentrating the filtrate under reduced pressure, heating 150g of methanol to reflux for 2 hours, cooling, separating out crystals, filtering, and performing vacuum 120oDrying for 4h to obtain 2-amino-4- [ hydroxy (methyl) phosphono group]159.7g of ammonium butyrate, 95.7% of purity and 80.7% of yield.
Example 10: synthesis of 2-amino-4-methylthiobutyric acid
130g (1 mol) of 2-amino-4-methylthiobutyronitrile is added into a 1L autoclave, 62g of monomethylamine and 56g (1 mol) of calcium oxide are introduced, 1g of polyethylene glycol 400 and 550g of water are added, and the mixture is heated to 180-oC, reacting for 5 hours under the pressure of 2.5-3.0 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8 under stirring, filtering, concentrating the mother liquor under reduced pressure, adding 150g of A into the residueAlcohol is refluxed for 2 hours, and the temperature is reduced, so that crystals are separated out. Filtration, vacuum 120oDrying the mixture for 4 hours to obtain 105.8g of 2-amino-4-methylthiobutyric acid with the purity of 96 percent.
Example 11: recovery and utilization of calcium carbonate
In embodiments 2, 3, 4 and 5, the filtered calcium carbonate is burned in a gas-making furnace to recover carbon dioxide, which can be recycled to embodiment 6 or used in reactions requiring carbon dioxide. The calcium oxide residue after firing, which was used for the hydrolysis reaction, was used in example 1.
Comparative example 1: synthesis of 2-amino-3-hydroxybutyric acid
144g (1 mol) of 5- (1-hydroxyethyl) hydantoin and 136g of 25% ammonia water, 3g of triethylbenzylammonium sulfate and 500g of water are added into a 1L autoclave, and the temperature is raised to 160-oAnd C, reacting for 5 hours under the pressure of 1.5-2.0 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2 hours, cooling, and separating out crystals. Filtration, vacuum 120oDrying the mixture for 4 hours to obtain 53.8g of 2-amino-3-hydroxybutyric acid, wherein the purity is 96 percent and the yield is 45 percent.
Comparative example 2: synthesis of 2-amino-3-hydroxybutyric acid
144g (1 mol) of 5- (1-hydroxyethyl) hydantoin, 112g (2 mol) of calcium oxide, 3g of triethylbenzylammonium sulfate and 500g of water are added into a 1L autoclave and heated to 160-oAnd C, reacting for 4 hours under the pressure of 0.7-0.9 MPa, cooling to room temperature, introducing carbon dioxide to the pH =8, filtering, concentrating the mother liquor under reduced pressure, adding 150g of methanol into the residue, refluxing for 2 hours, cooling, and separating out crystals. Filtration, cake vacuum 120oC, drying for 4 hours to obtain 65.7g of 2-amino-3-hydroxybutyric acid, the purity is 96 percent, and the yield is 55.2 percent.
Comparative example 3: synthesis of 2-amino-3- (4-imidazolyl) propionic acid
Adding into 1L four-mouth bottle5- [ (4-Imidazoyl) methyl group]Hydantoin 180g (1 mol), 25% ammonia water 68g, calcium hydroxide 110g (1.5 mol) and water 500g are added, stirring and heating are carried out for refluxing for 46h, the temperature is reduced to room temperature, carbon dioxide is introduced until Ph =8, filtering is carried out, mother liquor is concentrated under reduced pressure, residues are added with methanol 150g and refluxed for 2h, the temperature is reduced, and crystals are separated out. Filtration, vacuum 120oDrying the mixture for 4 hours to obtain 49.6g of 2-amino-3- (4-imidazolyl) propionic acid, wherein the purity is 96 percent, and the yield is 32.0 percent.
The embodiments described above are only preferred embodiments of the invention and are not exhaustive of the possible implementations of the invention. Any obvious modifications to the above would be obvious to those of ordinary skill in the art, but would not bring the invention so modified beyond the spirit and scope of the present invention.

Claims (10)

1. A method for synthesizing and purifying alpha-amino acid compounds is characterized by comprising the following steps:
(1) adding a substituted alpha-aminonitrile (II) or a substituted hydantoin compound (III) to a base M (OH)xOr metal oxides MxO, adding the mixture into water or an alcohol-water mixed solvent, and heating for reaction to obtain alpha-amino acid salt;
(2) adding ammonium carbonate or ammonium bicarbonate or introducing carbon dioxide into the solution obtained in the step (1), and separating to obtain filtrate and precipitate MxHyCO3The filtrate is decompressedConcentrating, and recrystallizing in alcohol solvent to obtain alpha-amino acid compound (I) with a reaction formula shown in formula (1);
(1)
wherein R is selected from the following substituents:
wherein,
R1，R2each independently selected from linear alkyl or branched alkyl groups of H, C1-C6;
n = 1, 2, 3, 4 or 5;
x = 1 or 2;
y = 0 or 1;
m is selected from sodium, calcium or magnesium, when M is selected from calcium or magnesium, the alkali M (OH) is added in the step (1)xOr metal oxides MxAnd adding organic amine, ammonia gas or ammonia water at the same time, before or after the step of O.
2. The method for synthesizing and purifying an alpha-amino acid compound according to claim 1, wherein: the organic amine is selected from methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine or propylamine, the concentration of the ammonia water is 3-30% or ammonia gas, and the dosage of the ammonia or the amine is 0.5-6 equivalent of the substrate substituted alpha-aminonitrile (II) or the substituted hydantoin compound (III).
3. The method for synthesizing and purifying an alpha-amino acid compound according to claim 1, wherein: when M is selected from calcium or magnesium, a catalyst is also added in the step (1), the catalyst is quaternary ammonium salt and quaternary phosphonium salt catalyst or polyethylene glycol with molecular weight of 400-8000, and the quaternary ammonium salt and quaternary phosphonium salt catalyst is selected from tetraalkylammonium sulfate, tetraalkylammonium hydrogen sulfate, tetraalkylammonium phosphate, tetraalkylammonium dihydrogen phosphate, triethylbenzylammonium sulfate, tetraalkylammonium chloride, and mixtures thereof,Triethylbenzylammonium chloride, and tetraalkyl phosphonium sulfate, tetraalkyl phosphonium phosphate, triethylbenzylphosphonium sulfate, triethylbenzylphosphonium chloride, said alkyl being selected from the group consisting of C1~C16The amount of the catalyst is 0.5-10% of the weight of the substrate.
4. A method for synthesizing and purifying an α -amino acid compound according to any one of claims 1 to 3, wherein: the base M (OH)xOr metal oxides MxThe molar weight of the added O is 1 to 4 times of that of the substituted alpha-aminonitrile (II) or the substituted hydantoin compound (III).
5. A method for synthesizing and purifying an α -amino acid compound according to any one of claims 1 to 3, wherein: the alcohol in the alcohol-water mixed solvent is selected from C1~C4The alcohol (b) is preferably methanol, ethanol, ethylene glycol, propanol, isopropanol, butanol, isobutanol or tert-butanol, and the ratio of the alcohol to the water is 1:20 to 1:5 (w/w).
6. A method for synthesizing and purifying an α -amino acid compound according to any one of claims 1 to 3, wherein: the reaction temperature in the step (1) is controlled to be 80-200 ℃.
7. A method for synthesizing and purifying an α -amino acid compound according to any one of claims 1 to 3, wherein: the reaction pressure in the step (1) is 0.1 MPa-10 MPa.
8. A method for synthesizing and purifying an α -amino acid compound according to any one of claims 1 to 3, wherein: the amount of the ammonium carbonate or the ammonium bicarbonate or the introduced carbon dioxide in the step (2) is 0.5-3 equivalent of that of the substrate substituted alpha-aminonitrile (II) or the substituted hydantoin compound (III).
9. A method for synthesizing and purifying an α -amino acid compound according to any one of claims 1 to 3, wherein: and (3) purifying the alpha-amino acid compound obtained in the step (2) by using an alcohol solvent for recrystallization, wherein the alcohol solvent is one or two or more selected from methanol, ethanol and propanol.
10. A method for synthesizing and purifying an α -amino acid compound according to any one of claims 1 to 3, wherein: comprises the step (3) of precipitating the obtained precipitate MxHyCO3The waste heat can be recycled to the step (1) by burning, and the specific method is as follows:
when M isxHyCO3In the case of calcium carbonate, CO is recovered by firing2And calcium oxide, CO2Recycling the calcium oxide for neutralization reaction in the step (2), and recycling the calcium oxide for hydrolysis reaction process in the step (1);
when M isxHyCO3In the case of magnesium carbonate, CO is recovered by burning2And magnesium oxide, CO2Recycling the magnesium oxide for the neutralization reaction in the step (2), and recycling the magnesium oxide for the hydrolysis reaction in the step (1);
when M isxHyCO3In the case of sodium bicarbonate, it is used as a weak base to neutralize the acid.
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