CN117756655A - Method for preparing DL-serine by one-pot method - Google Patents
Method for preparing DL-serine by one-pot method Download PDFInfo
- Publication number
- CN117756655A CN117756655A CN202311813351.XA CN202311813351A CN117756655A CN 117756655 A CN117756655 A CN 117756655A CN 202311813351 A CN202311813351 A CN 202311813351A CN 117756655 A CN117756655 A CN 117756655A
- Authority
- CN
- China
- Prior art keywords
- solution
- reaction
- serine
- monochloroacetic acid
- aqueous solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- MTCFGRXMJLQNBG-UHFFFAOYSA-N serine Chemical compound OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 238000000034 method Methods 0.000 title claims abstract description 54
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 19
- 239000000243 solution Substances 0.000 claims abstract description 113
- 238000006243 chemical reaction Methods 0.000 claims abstract description 87
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 54
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 27
- 239000007864 aqueous solution Substances 0.000 claims abstract description 17
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003729 cation exchange resin Substances 0.000 claims abstract description 12
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical class [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims abstract description 10
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims abstract description 9
- 239000001099 ammonium carbonate Substances 0.000 claims abstract description 7
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims abstract description 7
- 230000035484 reaction time Effects 0.000 claims abstract description 7
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims abstract description 6
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims abstract description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 37
- 229910021529 ammonia Inorganic materials 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical group O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 claims description 12
- 238000000746 purification Methods 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 23
- 238000003786 synthesis reaction Methods 0.000 abstract description 13
- 239000002994 raw material Substances 0.000 abstract description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 8
- 238000009776 industrial production Methods 0.000 abstract description 6
- 229910052799 carbon Inorganic materials 0.000 abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 3
- 150000001721 carbon Chemical group 0.000 abstract description 2
- 229910017053 inorganic salt Inorganic materials 0.000 abstract description 2
- 230000002035 prolonged effect Effects 0.000 abstract description 2
- 239000012141 concentrate Substances 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 238000005086 pumping Methods 0.000 description 21
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000012295 chemical reaction liquid Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- KKTCWAXMXADOBB-UHFFFAOYSA-N azanium;hydrogen carbonate;hydrate Chemical class [NH4+].O.OC([O-])=O KKTCWAXMXADOBB-UHFFFAOYSA-N 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- -1 2-substituted aziridine Chemical class 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- VVYPIVJZLVJPGU-UHFFFAOYSA-L copper;2-aminoacetate Chemical compound [Cu+2].NCC([O-])=O.NCC([O-])=O VVYPIVJZLVJPGU-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- 108010064851 Plant Proteins Proteins 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- BAAYWLNVHTVAJJ-UHFFFAOYSA-L cadmium(2+);diformate Chemical compound [Cd+2].[O-]C=O.[O-]C=O BAAYWLNVHTVAJJ-UHFFFAOYSA-L 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 229910000365 copper sulfate Inorganic materials 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000021118 plant-derived protein Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 238000007059 Strecker synthesis reaction Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940116318 copper carbonate Drugs 0.000 description 1
- GEZOTWYUIKXWOA-UHFFFAOYSA-L copper;carbonate Chemical compound [Cu+2].[O-]C([O-])=O GEZOTWYUIKXWOA-UHFFFAOYSA-L 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000000490 cosmetic additive Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- MGJURKDLIJVDEO-UHFFFAOYSA-N formaldehyde;hydrate Chemical compound O.O=C MGJURKDLIJVDEO-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing DL-serine by a one-pot method, and belongs to the technical field of chemical synthesis. The invention adds monochloroacetic acid aqueous solution, sodium carbonate aqueous solution and copper (II) sulfate into saturated ammonium bicarbonate aqueous solution, controls reaction temperature, reaction time and pH of reaction solution, then separates by cation exchange resin, and concentrates to obtain DL-serine. Compared with the prior art, the invention completes chemical synthesis in the water phase, and is environment-friendly; the inorganic salt of ammonium bicarbonate is utilized to realize amino substitution on an organic carbon chain, a carbon atom is added, and the carbon chain is prolonged; the method has the advantages of wide sources of reaction raw materials, mild reaction conditions, higher product yield and better reproducibility, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a method for preparing DL-serine by a one-pot method.
Background
DL-serine is widely used in the food, feed, pharmaceutical, agricultural and cosmetic industries, and its main uses include: the plant protein additive is used as a food additive and added into animal feed, so that the absorption and utilization rate of the organism to the plant protein is improved, and the growth and development of an animal body are promoted; providing a carbon skeleton in important substances such as synthetic purine, thymine, methionine, choline and the like; because of its particular wettability, it can be used as a cosmetic additive for creams (moisturizers) that maintain the moisture of the stratum corneum. In addition, serine is also an important and irreplaceable substrate for tryptophan production by microbial enzymatic processes, directly affecting the price of tryptophan, the "second essential amino acid". Therefore, development of DL-serine production process has been attracting attention in the industry.
At present, a representative production process of DL-serine comprises the following steps:
1. improved synthesis reaction of Strecker amino acid
For example, chinese patent publication No. CN01127227, japanese patent publication No. JPH03240760a and european patent publication No. EP0376184A2 disclose a method for preparing DL-serine by using the modified Strecker reaction, respectively, and although the chemical structures of the starting materials adopted in the above patents are slightly different, cyanide is used in the reaction process, which is known to be a highly toxic compound, and the purchase and use processes are complicated, and have potential dangers, which are not favorable for industrial production.
2. Preparation with 2-substituted aziridine as intermediate
For example, japanese patent publication No. JPS61186356A, JPS61140551A, international patent publication No. WO8204044A1, european patent publications No. EP0030474A1 and EP0030475A1 disclose a process for producing DL-serine using 2-substituted aziridine as an intermediate, respectively. This route only requires hydrolysis of the 2-substituted aziridine under acidic conditions to provide serine. 2-substituted aziridines are often prepared from acrylonitrile or chloroacetaldehyde starting materials by the following routes:
the process flow shows that the synthesis route of the 2-substituted aziridine serving as the raw material is longer, sodium cyanide, chlorine and the like are used, the reaction conditions are severe, and the industrial production is also not facilitated.
3. Copper glycinate process
The method for preparing DL-serine by using the copper glycinate only needs one-step reaction, so that the loss caused by multi-step reaction is reduced. The reaction raw materials used in the copper glycinate method are glycine and formaldehyde aqueous solution, and the reaction mechanism is as follows:
the purpose of adding formaldehyde in the method is to realize the extension of carbon chains by using carbon atoms of formaldehyde.
Japanese patent publication No. JPS59163352A discloses the preparation of DL-serine by reacting copper glycinate or cuprous glycinate with aqueous formaldehyde under the catalysis of strong base. However, since the reaction is carried out under pressure, the conditions are severe and the scale-up production is difficult.
4. Preparation of monochloroacetic acid as raw material
Japanese patent publication No. JPS60218361A discloses a method for preparing serine by a "one pot" method using monochloroacetic acid and formaldehyde as raw materials. Adding monochloroacetic acid, ammonia water, ammonium carbonate, formaldehyde water solution, sodium hydroxide and catalytic amount of cadmium formate into a reactor, wherein the weight of the cadmium formate is 20kg/cm 2 The reaction was carried out at 120℃under pressure for 1 hour, and the yield of DL-serine was 23.3%. In this reaction, ammonia gas is used to replace chlorine atoms in monochloroacetic acid and carbon atoms of formaldehyde to lengthen carbon chains. The reaction is carried out at high pressure, the risk is very high, and the serine yield is very low.
In conclusion, the DL-serine preparation method has the advantages of wide sources of reaction raw materials, mild reaction conditions, higher product yield and better reproducibility, and is suitable for industrial production, and has important practical value and significance.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, in a first aspect of the present invention, there is provided a method for preparing DL-serine, which has the advantages of wide sources of raw materials, mild reaction conditions, high product yield, good reproducibility, and suitability for industrial production, based on a one-pot synthesis process, comprising the steps of:
(1) Adding an aqueous solution of monochloroacetic acid into an aqueous solution of saturated ammonium bicarbonate for reaction, exhausting air and inhibiting ammonia in the reaction process, and controlling the reaction solution to be non-alkaline to obtain a solution A;
(2) Adding sodium carbonate aqueous solution into the solution A for reaction, exhausting gas and inhibiting ammonia in the reaction process, and controlling the reaction solution to be non-alkaline to obtain solution B;
(3) Adding copper (II) sulfate into the solution B, and reacting to obtain a solution C;
(4) And separating and purifying the solution C to obtain DL-serine.
Preferably, in the step (1), the mass ratio of the ammonium bicarbonate to the monochloroacetic acid is 5-9:1.
Preferably, in the step (1), the reaction temperature is 40-80 ℃, the reaction time is 1-10 h, and the pH of the reaction solution is controlled to be 4-7.
Preferably, in the step (2), the mass ratio of the sodium carbonate to the monochloroacetic acid is 0.2-0.8:1.
Preferably, in the step (2), the reaction temperature is 40-80 ℃, the reaction time is 10-300 min, and the pH of the reaction solution is controlled to be 4-7.
Copper (ii) sulfate includes copper sulfate or copper sulfate pentahydrate, which are common in the art, and which are particularly suitable for the copper (ii) sulfate selection type of the present invention for the purpose of wider raw material sources and convenient storage.
Preferably, in the step (3), the copper (ii) sulfate is copper sulfate pentahydrate, and the mass ratio of the copper sulfate pentahydrate to the monochloroacetic acid is 0.005-0.03:1.
Preferably, in the step (3), the reaction temperature is 80-100 ℃ and the reaction time is 10-300 min.
The separation method of the DL-serine product in the field is various, and a proper purification mode can be selected according to practical application requirements. For the purposes of reducing cost and convenient operation, the common cation exchange resin in the market is a purification material particularly suitable for the process, and the purified DL-serine product can be obtained after separation and concentration.
Preferably, in the step (4), separation and purification are completed by adopting cation exchange resin, and DL-serine is obtained after concentration.
The preparation optimization difficulty of DL-serine is to simplify the synthesis flow and reduce the temperature and pressure conditions required by the reaction. Based on the technical scheme, the design concept and the special feature of the invention are that a new synthesis path is selected and the feeding step is adjusted, and the synthesis is divided into multiple feeding steps, but still a one-step reaction occurs, so that the aim of synthesizing DL-serine by a one-pot method is fulfilled, and pollution and cost increase caused by multiple separation are avoided.
The synthetic route of the present invention is as follows:
the invention utilizes the ammonium bicarbonate as an inorganic salt to realize two purposes: amino in ammonium bicarbonate replaces chlorine atom in monochloroacetic acid, and amino is introduced; the inorganic carbon in the ammonium bicarbonate is inserted into a monochloroacetic acid carbon chain, a carbon atom is added into an organic carbon chain, and the carbon chain is prolonged. In addition, sodium carbonate and copper sulfate react to form basic copper carbonate, and the catalytic reaction is carried out, so that strong alkali such as sodium hydroxide and the like is avoided. In the synthesis flow of the invention, except for monochloroacetic acid, other raw materials are inorganic salts, and the chemical synthesis is completed in a water phase, so that the production of three wastes is small and the method is environment-friendly; the production process is simple, the reaction condition is mild, the reaction can be completed by proper heating under normal pressure, and pressurization and high temperature are not needed.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the invention provides a method for preparing DL-serine by a one-pot method, which adopts a new synthesis path and optimizes the steps, has wide sources of reaction raw materials required by synthesis, mild reaction conditions, higher product yield and good reproducibility, and is suitable for industrial production.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Example 1
The one-pot method for preparing DL-serine comprises the following steps:
(1) Adding 70L of saturated ammonium bicarbonate water solution into a reaction kettle with a capacity of 100L, then dropwise adding 875mL of monochloroacetic acid water solution (2.345 kg of monochloroacetic acid is dissolved in 875mL of water), controlling the temperature of the reaction liquid to be 65 ℃, reacting for 5 hours at 65 ℃ after the dropwise adding is finished, pumping air and inhibiting ammonia in the process, reducing the pH of the reaction liquid to 5.0, and obtaining solution A after the reaction is finished;
(2) Pumping the solution A into a reaction kettle with 500L capacity, placing sodium carbonate aqueous solution (1.330 kg of sodium carbonate is dissolved in 210L of water) into a dripping tank, slowly dripping the sodium carbonate solution into the solution A, controlling the temperature of the reaction solution to 65 ℃, reacting for 40min at 65 ℃ after dripping is completed, pumping air and inhibiting ammonia, and reducing the pH of the reaction solution to 6.0 to obtain a solution B;
(3) Adding 42g of copper sulfate pentahydrate into the solution B, heating to 93 ℃ and reacting for 40min to obtain a solution C;
(4) After the solution C was cooled to room temperature, the product was isolated by cation exchange resin and concentrated to give 1.599kg of a white solid, namely DL-serine, in 61.3% yield with a melting point of 240.8 ℃.
Example 2
The one-pot method for preparing DL-serine comprises the following steps:
(1) Adding 53L of saturated ammonium bicarbonate water solution into a reaction kettle with a capacity of 100L, then dropwise adding 875mL of monochloroacetic acid water solution (2.345 kg of monochloroacetic acid is dissolved in 875mL of water), controlling the temperature of the reaction liquid to be 65 ℃, reacting for 5 hours at 65 ℃ after the dropwise adding is finished, pumping air and inhibiting ammonia in the process, reducing the pH of the reaction liquid to 5.0, and obtaining solution A after the reaction is finished;
(2) Pumping the solution A into a reaction kettle with 500L capacity, placing sodium carbonate aqueous solution (1.330 kg of sodium carbonate is dissolved in 210L of water) into a dripping tank, slowly dripping the sodium carbonate solution into the solution A, controlling the temperature of the reaction solution to 65 ℃, reacting for 40min at 65 ℃ after dripping is completed, pumping air and inhibiting ammonia, and reducing the pH of the reaction solution to 6.0 to obtain a solution B;
(3) Adding 42g of copper sulfate pentahydrate into the solution B, heating to 93 ℃ and reacting for 40min to obtain a solution C;
(4) After the solution C was cooled to room temperature, the product was separated by cation exchange resin and concentrated to give 1.398kg of a white solid, namely DL-serine, in 53.6% yield with a melting point of 241.2 ℃.
Example 3
The one-pot method for preparing DL-serine comprises the following steps:
(1) Adding 47L saturated ammonium bicarbonate water solution into a reaction kettle with a capacity of 100L, then dropwise adding 875mL of monochloroacetic acid water solution (2.345 kg of monochloroacetic acid is dissolved in 875mL of water), controlling the temperature of the reaction liquid to be 45 ℃, reacting for 2 hours at 45 ℃ after the dropwise adding is finished, pumping air and inhibiting ammonia in the process, reducing the pH of the reaction liquid to 5.0, and obtaining solution A after the reaction is finished;
(2) Pumping the solution A into a reaction kettle with 500L capacity, placing sodium carbonate aqueous solution (0.470 kg of sodium carbonate is dissolved in 210L of water) into a dripping tank, slowly dripping the sodium carbonate solution into the solution A, controlling the temperature of the reaction solution to be 45 ℃, reacting for 30min at 45 ℃ after dripping is completed, pumping air and inhibiting ammonia, and reducing the pH of the reaction solution to 6.0 to obtain a solution B;
(3) Adding 24g of copper sulfate pentahydrate into the solution B, heating to 85 ℃ and reacting for 30min to obtain a solution C;
(4) After the solution C was cooled to room temperature, the product was isolated by cation exchange resin and concentrated to give 0.837kg of a white solid, namely DL-serine, in a yield of 32.1% and a melting point of 241.1 ℃.
Example 4
The one-pot method for preparing DL-serine comprises the following steps:
(1) Adding 47L saturated ammonium bicarbonate water solution into a reaction kettle with a capacity of 100L, then dropwise adding 875mL of monochloroacetic acid water solution (2.345 kg of monochloroacetic acid is dissolved in 875mL of water), controlling the temperature of the reaction liquid to be 70 ℃, reacting for 8 hours at 70 ℃ after the dropwise adding is finished, pumping air and inhibiting ammonia in the process, reducing the pH of the reaction liquid to 5.0, and obtaining solution A after the reaction is finished;
(2) Pumping the solution A into a reaction kettle with 500L capacity, placing sodium carbonate aqueous solution (0.470 kg of sodium carbonate is dissolved in 210L of water) into a dripping tank, slowly dripping the sodium carbonate solution into the solution A, controlling the temperature of the reaction solution to be 70 ℃, reacting for 2 hours at 70 ℃ after dripping is completed, pumping air and inhibiting ammonia, and reducing the pH value of the reaction solution to 6.0 to obtain a solution B;
(3) Adding 24g of copper sulfate pentahydrate into the solution B, heating to 95 ℃ and reacting for 2 hours to obtain a solution C;
(4) After the solution C was cooled to room temperature, the product was isolated by cation exchange resin and concentrated to give 0.782kg of a white solid, namely DL-serine, at a yield of 30.0% and a melting point of 241.0 ℃.
Example 5
The one-pot method for preparing DL-serine comprises the following steps:
(1) Adding 80L of saturated ammonium bicarbonate water solution into a reaction kettle with a capacity of 100L, then dropwise adding 875mL of monochloroacetic acid water solution (2.345 kg of monochloroacetic acid is dissolved in 875mL of water), controlling the temperature of the reaction solution to be 45 ℃, reacting for 2 hours at 45 ℃ after the dropwise adding is finished, pumping air and inhibiting ammonia in the process, reducing the pH of the reaction solution to 5.0, and obtaining solution A after the reaction is finished;
(2) Pumping the solution A into a reaction kettle with 500L capacity, placing sodium carbonate aqueous solution (1.642 kg of sodium carbonate is dissolved in 210L of water) into a dripping tank, slowly dripping the sodium carbonate solution into the solution A, controlling the temperature of the reaction solution to be 45 ℃, reacting for 30min at 45 ℃ after dripping is completed, pumping air and inhibiting ammonia, and reducing the pH of the reaction solution to 6.0 to obtain a solution B;
(3) 59g of copper sulfate pentahydrate is added into the solution B, and the temperature is raised to 85 ℃ for reaction for 30min to obtain solution C;
(4) After the solution C was cooled to room temperature, the product was separated by cation exchange resin and concentrated to give 0.944kg of a white solid, namely DL-serine, in 36.2% yield with a melting point of 240.8 ℃.
Example 6
The one-pot method for preparing DL-serine comprises the following steps:
(1) Adding 80L of saturated ammonium bicarbonate water solution into a reaction kettle with a capacity of 100L, then dropwise adding 875mL of monochloroacetic acid water solution (2.345 kg of monochloroacetic acid is dissolved in 875mL of water), controlling the temperature of the reaction solution to be 70 ℃, reacting for 5 hours at 70 ℃ after the dropwise adding is finished, pumping air and inhibiting ammonia in the process, reducing the pH of the reaction solution to 5.0, and obtaining solution A after the reaction is finished;
(2) Pumping the solution A into a reaction kettle with 500L capacity, placing sodium carbonate aqueous solution (1.642 kg of sodium carbonate is dissolved in 210L of water) into a dripping tank, slowly dripping the sodium carbonate solution into the solution A, controlling the temperature of the reaction solution to be 70 ℃, reacting for 40min at 70 ℃ after dripping is completed, pumping air and inhibiting ammonia, and reducing the pH of the reaction solution to 6.0 to obtain a solution B;
(3) 59g of copper sulfate pentahydrate is added into the solution B, and the temperature is raised to 93 ℃ for reaction for 40min to obtain solution C;
(4) After the solution C was cooled to room temperature, the product was separated by cation exchange resin and concentrated to give 1.633kg of a white solid, namely DL-serine, in a yield of 62.6% and a melting point of 241.1 ℃.
Example 7
The one-pot method for preparing DL-serine comprises the following steps:
(1) Adding 80L of saturated ammonium bicarbonate water solution into a reaction kettle with a capacity of 100L, then dropwise adding 875mL of monochloroacetic acid water solution (2.345 kg of monochloroacetic acid is dissolved in 875mL of water), controlling the temperature of the reaction solution to be 70 ℃, reacting for 5 hours at 70 ℃ after the dropwise adding is finished, pumping air and inhibiting ammonia in the process, reducing the pH of the reaction solution to 4.0, and obtaining solution A after the reaction is finished;
(2) Pumping the solution A into a reaction kettle with 500L capacity, placing sodium carbonate aqueous solution (1.642 kg of sodium carbonate is dissolved in 210L of water) into a dripping tank, slowly dripping the sodium carbonate solution into the solution A, controlling the temperature of the reaction solution to be 70 ℃, reacting for 40min at 70 ℃ after dripping is completed, pumping air and inhibiting ammonia, and reducing the pH of the reaction solution to 7.0 to obtain solution B;
(3) 59g of copper sulfate pentahydrate is added into the solution B, and the temperature is raised to 93 ℃ for reaction for 40min to obtain solution C;
(4) After the solution C was cooled to room temperature, the product was isolated by cation exchange resin and concentrated to give 1.625kg of a white solid, namely DL-serine, in a yield of 62.3% and a melting point of 241.1 ℃.
In the embodiment, the DL-serine is prepared by adopting the method and the synthesis path one-pot method, all raw materials are easily available chemicals in the field, and the production process is simple. The process steps do not need pressurization, high temperature and strong alkali, and the reaction conditions are mild. The purification of the product in the embodiment can be realized by adopting cation exchange resin, the highest yield of the product can reach 62.6 percent, and the method is suitable for large-scale high-efficiency production and provides a new idea for industrially preparing DL-serine.
The foregoing describes in detail preferred embodiments of the present invention. It should be understood that numerous modifications and variations can be made in accordance with the concepts of the invention by one of ordinary skill in the art without undue burden. Therefore, all technical solutions which can be obtained by logic analysis, reasoning or limited experiments based on the prior art by the person skilled in the art according to the inventive concept shall be within the scope of protection defined by the claims.
Claims (8)
1. The method for preparing DL-serine is based on a one-pot synthesis process and is characterized by comprising the following steps:
(1) Adding an aqueous solution of monochloroacetic acid into an aqueous solution of saturated ammonium bicarbonate for reaction, exhausting air and inhibiting ammonia in the reaction process, and controlling the reaction solution to be non-alkaline to obtain a solution A;
(2) Adding sodium carbonate aqueous solution into the solution A for reaction, exhausting gas and inhibiting ammonia in the reaction process, and controlling the reaction solution to be non-alkaline to obtain solution B;
(3) Adding copper (II) sulfate into the solution B, and reacting to obtain a solution C;
(4) And separating and purifying the solution C to obtain DL-serine.
2. The method according to claim 1, characterized in that: in the step (1), the mass ratio of the ammonium bicarbonate to the monochloroacetic acid is 5-9:1.
3. The method according to claim 1, characterized in that: in the step (1), the reaction temperature is 40-80 ℃, the reaction time is 1-10 h, and the pH of the reaction solution is controlled to be 4-7.
4. The method according to claim 1, characterized in that: in the step (2), the mass ratio of the sodium carbonate to the monochloroacetic acid is 0.2-0.8:1.
5. The method according to claim 1, characterized in that: in the step (2), the reaction temperature is 40-80 ℃, the reaction time is 10-300 min, and the pH of the reaction solution is controlled to be 4-7.
6. The method according to claim 1, characterized in that: in the step (3), copper (II) sulfate is copper sulfate pentahydrate, and the mass ratio of the copper sulfate pentahydrate to monochloroacetic acid is 0.005-0.03:1.
7. The method according to claim 1, characterized in that: in the step (3), the reaction temperature is 80-100 ℃ and the reaction time is 10-300 min.
8. The method according to claim 1, characterized in that: in the step (4), separation and purification are completed by adopting cation exchange resin, and DL-serine is obtained after concentration.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311813351.XA CN117756655A (en) | 2023-12-27 | 2023-12-27 | Method for preparing DL-serine by one-pot method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311813351.XA CN117756655A (en) | 2023-12-27 | 2023-12-27 | Method for preparing DL-serine by one-pot method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117756655A true CN117756655A (en) | 2024-03-26 |
Family
ID=90319855
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311813351.XA Pending CN117756655A (en) | 2023-12-27 | 2023-12-27 | Method for preparing DL-serine by one-pot method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117756655A (en) |
-
2023
- 2023-12-27 CN CN202311813351.XA patent/CN117756655A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1834092B (en) | Preparation of pramipexole | |
| CN103664719A (en) | Method and device for using crude hydrocyanic acid to continuously produce D, L-methionine | |
| CN103641758B (en) | Cheap highly purified D, the preparation method of L-Methionine | |
| US20070207072A1 (en) | Apparatus for preparing Hydrazo-Dicarbonamide using urea as starting material | |
| CN104944398B (en) | Glyphosate mother solution recoverying and utilizing method | |
| CN109678744B (en) | Method for continuously preparing glycine | |
| CN107325015B (en) | Method for continuously preparing glycine from hydroxyacetonitrile | |
| CN113698320A (en) | Preparation method of L-Carlactonitrile | |
| CN104119243B (en) | A kind of energy-saving clean production method of iminodiethanoic acid | |
| CN114524738A (en) | Glycine preparation method for reducing iminodiacetic acid content | |
| CN104817468B (en) | A kind of preparation method of glycine | |
| WO2013159742A1 (en) | Device and method for preparing dl-methionine | |
| EP2759537A1 (en) | Device and method for preparing hydantoin | |
| CN1958559B (en) | Environmental protection clean technical method for synthesizing aminoacetic acid through fluid bed | |
| CN117756655A (en) | Method for preparing DL-serine by one-pot method | |
| CN112028931B (en) | Preparation method of L-glufosinate-ammonium powder | |
| CN112941116A (en) | Method for preparing alpha-ketoglutarate calcium by enzyme method | |
| CN107216262A (en) | A kind of method that homogeneous system intermediate ion liquid catalyst synthesizes glycine | |
| CN110143916B (en) | Synthesis process of fluazinam | |
| CN111484426A (en) | Method for synthesizing aminoacetonitrile hydrochloride from hydrocyanic acid | |
| JP3874820B2 (en) | Method for producing taurine analogs | |
| CN103896945A (en) | Simple and convenient folic acid environment-friendly production method | |
| CN106631850A (en) | Post-treatment process for synthesis of p-hydroxyphenylglycine | |
| CN114369129A (en) | Synthetic method of chlorinated nicotinamide ribose | |
| CN102808007A (en) | Method for preparing S-phenyl-L-cysteine by enzymatic conversion method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |