CN116444399A - Method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction - Google Patents
Method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction Download PDFInfo
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- CN116444399A CN116444399A CN202310458584.6A CN202310458584A CN116444399A CN 116444399 A CN116444399 A CN 116444399A CN 202310458584 A CN202310458584 A CN 202310458584A CN 116444399 A CN116444399 A CN 116444399A
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- ethyl ester
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 25
- CNEFRTDDIMNTHC-GORDUTHDSA-N (2e)-2-cyano-2-hydroxyiminoacetic acid Chemical compound O\N=C(/C#N)C(O)=O CNEFRTDDIMNTHC-GORDUTHDSA-N 0.000 title claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 10
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims abstract description 40
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 claims abstract description 25
- MGWGWNFMUOTEHG-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-1,3-thiazol-2-amine Chemical compound CC1=CC(C)=CC(C=2N=C(N)SC=2)=C1 MGWGWNFMUOTEHG-UHFFFAOYSA-N 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 20
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 7
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910010271 silicon carbide Inorganic materials 0.000 claims abstract description 7
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 6
- 238000002425 crystallisation Methods 0.000 claims abstract description 6
- 230000008025 crystallization Effects 0.000 claims abstract description 6
- 239000007789 gas Substances 0.000 claims description 25
- 238000001308 synthesis method Methods 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000006146 oximation reaction Methods 0.000 abstract description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 abstract description 6
- 239000002351 wastewater Substances 0.000 abstract description 5
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 235000010288 sodium nitrite Nutrition 0.000 abstract description 3
- 230000002860 competitive effect Effects 0.000 abstract description 2
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 abstract 1
- 239000002699 waste material Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- LCFXLZAXGXOXAP-QPJJXVBHSA-N ethyl (2e)-2-cyano-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(=N\O)\C#N LCFXLZAXGXOXAP-QPJJXVBHSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000008240 homogeneous mixture Substances 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 2
- KPFBUSLHFFWMAI-HYRPPVSQSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-6-formyl-3-methoxy-10,13-dimethyl-1,2,7,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1C[C@@H]2[C@](CCC(OC)=C3)(C)C3=C(C=O)C[C@H]2[C@@H]2CC[C@](OC(C)=O)(C(C)=O)[C@]21C KPFBUSLHFFWMAI-HYRPPVSQSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- IJJJSNBMFDDFBC-UHFFFAOYSA-N 2-cyanoethyl acetate Chemical compound CC(=O)OCCC#N IJJJSNBMFDDFBC-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
- GPDHNZNLPKYHCN-DZOOLQPHSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-morpholin-4-ylmethylidene]-dimethylazanium;hexafluorophosphate Chemical compound F[P-](F)(F)(F)(F)F.CCOC(=O)C(\C#N)=N/OC(=[N+](C)C)N1CCOCC1 GPDHNZNLPKYHCN-DZOOLQPHSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000002440 industrial waste Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00819—Materials of construction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
-
- 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
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction, which comprises the steps of introducing a mixture of cyano-acetic acid ethyl ester and water into a micro-channel reactor made of silicon carbide at room temperature, then introducing nitric oxide and nitrogen dioxide into the reactor at the same time, transferring the obtained reaction liquid into a dynamic tubular reactor after the reaction is finished, adjusting the pH value by hydrochloric acid, preserving heat for crystallization, and filtering to obtain (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester. The method for synthesizing the (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction does not need to add sodium nitrite, protonic acid and the like as oximation reagents, does not generate acidic high-salt wastewater, realizes the reutilization of the atmospheric pollution waste nitric oxide and nitrogen dioxide, has mild reaction conditions and low energy consumption, can effectively improve the competitive advantage of products, and is a novel environment-friendly preparation method suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemical technology, and particularly relates to a method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction.
Background
(2E) Ethyl 2-cyano-2-hydroxyiminoacetate (Oxyma), commonly used as an additive in combination with carbodiimide condensing agents, is used to build specific amide linkages, thereby effectively inhibiting racemization of the target product. The water-soluble organic compound has stable property, high water solubility, easy post-treatment and low toxicity, thereby showing very good activity in the synthesis reaction of various compounds containing amide bonds. In addition, the oxime hydroxyl of the modified compound is further modified based on the Oxyma structure, so that the preparation of fourth generation amine acid condensing agents such as TOTU and COMU can be realized, and the preparation of more innovative medicaments and basic medicaments containing amide bonds is facilitated.
The current synthesis method of (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester mainly uses cyanoacetic acid ethyl ester and sodium nitrite as raw materials, and comprises the steps of heating reaction, adjusting pH of reaction liquid, and crystallizing at low temperature to obtain 2-oxime cyanoacetic acid ethyl ester. For example CN 112778333A, CN 112724157A, CN 112851692A and Archiv der Pharmazie (Weinheim, germany), 2021,354 (9): 2000470, crystal Growth & Design,19 (2), 678-693; in the work of 2019, CN 107311961A and the like, ethyl cyanoacetate is taken as a raw material, sodium nitrite is taken as an oximation reagent, the oximation reaction of alpha methylene of the ethyl cyanoacetate is realized by controlling the addition of concentrated phosphoric acid, sulfuric acid or hydrochloric acid and other protonic acid under the low-temperature condition, and finally the pH value of the reaction solution is regulated, and the target product is obtained through low-temperature crystallization. However, the process needs to strictly control the dropping speed of phosphoric acid in the oximation reaction process, and the dropping speed of phosphoric acid is too fast, so that the system is severely exothermic and cannot be effectively transferred, the generated nitrous acid is decomposed less than the nitrous acid which participates in the oximation reaction, so that the cyanoethyl acetate cannot be completely converted to reduce the product yield and the reaction efficiency, and meanwhile, the configuration of the (2E) -2-cyano-2-hydroxy iminoethyl acetate generated in the system is reversed to generate cis-isomer, so that the reaction product is oily and is difficult to separate. In addition, the above methods can generate a large amount of acidic high-salt wastewater, especially sulfuric acid is used as oximation reagent, and a large amount of sodium sulfate generated by the reaction is mixed with the product and is difficult to separate. In addition, the oximation reaction of ethyl cyanoacetate needs to be carried out at low temperature, and the reaction conditions are harsh, which is not beneficial to industrial production. Therefore, the development of a green, novel and efficient synthetic method of the (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester is significant.
Compared with the conventional reaction kettle, the micro-channel reactor has large specific surface area and high heat and mass transfer efficiency, greatly shortens the time of chemical reaction, and can regulate and control the reaction conditions such as temperature, pressure and the like more accurately. Therefore, aiming at the problems of harsh reaction conditions, low efficiency and difficult treatment of high-salt wastewater in the existing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester synthesis process, the patent provides a method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction, nitric oxide and nitrogen dioxide are respectively introduced into a micro-channel reactor to complete oximation reaction with a mixture of cyanoacetic acid ethyl ester and water in situ, and controllable reaction system can be realized at room temperature, so that the generation of acidic high-salt wastewater is avoided, and the safe, efficient and environment-friendly synthesis of high-quality (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester is realized, and the technical defects and difficulties existing in the existing synthesis method are effectively overcome.
Disclosure of Invention
The invention aims to develop a method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction, and compared with the conventional reaction kettle method, the micro-reaction synthesis method provided by the invention has the advantages of easiness in operation and control, mild conditions and high-efficiency synthesis, and realizes the high-efficiency utilization of nitric oxide and nitrogen dioxide in pollution industrial waste gas.
The invention discloses a method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction, which is characterized by comprising the following steps:
at room temperature, introducing a mixture of ethyl cyanoacetate and water into a microchannel reactor made of silicon carbide, simultaneously introducing nitric oxide gas and nitrogen dioxide gas into the reactor, transferring the obtained reaction liquid into a dynamic tubular reactor after a certain time of system reaction, regulating the pH value of the system by hydrochloric acid, preserving heat, and filtering to obtain the (2E) -2-cyano-2-hydroxy iminoethyl acetate after the product is fully crystallized.
Further, the concentration of ethyl cyanoacetate in the mixture of ethyl cyanoacetate and water was 2mol/L.
Further, the pressure of the nitric oxide gas and the nitrogen dioxide gas is 0.1-1MPa.
Further, the molar flow ratio of the nitric oxide gas to the nitrogen dioxide gas is 1:1.
further, the molar flow ratio of the nitric oxide gas to the mixture of ethyl cyanoacetate and water is (1-1.5): 1, the molar flow ratio of nitrogen dioxide gas to the mixture of ethyl cyanoacetate and water is (1-1.5): 1.
further, the reaction time is 0.5 to 3 minutes.
Further, the concentration of the hydrochloric acid is 4-12mol/L.
Further, the pH value of the reaction liquid system is adjusted to be 1-4.
Further, the crystallization temperature is-10-10 ℃.
Further, the crystallization time is 0.5 to 3 hours.
The method for synthesizing the (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction does not generate acidic high-salt wastewater, realizes the reutilization of atmospheric pollutants, has mild reaction conditions, further reduces the energy consumption in the synthesis process, can effectively reduce the production cost of products, improves the market competitive advantage of the products, and is an environment-friendly novel preparation method. The purity of the obtained product (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester is more than 99 percent, and the yield is more than 95 percent.
Detailed Description
The following technical solutions in the embodiments of the present invention will be fully described so that those skilled in the art may better understand the advantages and features of the present invention, and thus the protection scope of the present invention is more clearly defined. The described embodiments of the present invention are only a few embodiments of the present invention, and all other embodiments that can be obtained by a person of ordinary skill in the art without making any inventive effort are intended to fall within the scope of the present invention.
Example 1:
a homogeneous mixture (500 mL, ethyl cyanoacetate concentration 2 mol/L) of ethyl cyanoacetate (113 g) and water (394 mL) was introduced into a silicon carbide microchannel reactor at a flow rate of 1mol/h, then nitric oxide (pressure 0.1 MPa) gas and nitrogen dioxide (pressure 0.1 MPa) gas were simultaneously introduced into the reactor, the flow rates of nitric oxide and nitrogen dioxide were both controlled to be 1mol/h, the reaction was carried out for 0.5 min, the reaction mixture was transferred to a dynamic tube reactor, the pH of the system was adjusted to 4 with 4mol/L hydrochloric acid, the reaction mixture was kept at 0℃for 30 min, and after the product was sufficiently crystallized, 135.6g of ethyl (2E) -2-cyano-2-hydroxyiminoacetate (yield 95.4% and purity 99.55%) was obtained by filtration.
Example 2:
a homogeneous mixture (500 mL, ethyl cyanoacetate concentration 2 mol/L) of ethyl cyanoacetate (113 g) and water (394 mL) at room temperature was introduced into a microchannel reactor made of silicon carbide at a flow rate of 1mol/h, then nitric oxide (pressure: 1 MPa) gas and nitrogen dioxide (pressure: 1 MPa) gas were simultaneously introduced into the reactor, the flow rates of nitric oxide and nitrogen dioxide were both controlled to be 1.5mol/h, the reaction was carried out for 3 minutes, the obtained reaction solution was transferred into a dynamic tube reactor, the pH of the system was adjusted to 1 with 12mol/L hydrochloric acid, the temperature was kept at-10℃for 3 hours, and after the product was sufficiently crystallized, 141.9g of (2E) -2-cyano-2-hydroxyiminoacetic acid ethyl ester (yield: 97.1%, purity: 99.81%) was obtained by filtration.
Example 3:
a homogeneous mixture (500 mL, ethyl cyanoacetate concentration 2 mol/L) of ethyl cyanoacetate (113 g) and water (394 mL) at room temperature was introduced into a silicon carbide microchannel reactor at a flow rate of 1mol/h, then nitric oxide (pressure 0.4 MPa) gas and nitrogen dioxide (pressure 0.4 MPa) gas were simultaneously introduced into the reactor, the flow rates of nitric oxide and nitrogen dioxide were both controlled to be 1.2mol/h, the reaction was carried out for 1 minute, the obtained reaction solution was transferred into a dynamic tube reactor, the pH of the system was adjusted to 3 with 8mol/L hydrochloric acid, the temperature was kept at 10℃for 1.5 hours, and after the product was sufficiently crystallized, 140.3g of (2E) -2-cyano-2-hydroxyiminoacetic acid ethyl ester (yield 96%, purity 99.67%) was obtained by filtration.
Example 4:
a homogeneous mixture (500 mL, ethyl cyanoacetate concentration 2 mol/L) of ethyl cyanoacetate (113 g) and water (394 mL) at room temperature was introduced into a silicon carbide microchannel reactor at a flow rate of 1mol/h, then nitric oxide (pressure 0.7 MPa) gas and nitrogen dioxide (pressure 0.7 MPa) gas were simultaneously introduced into the reactor, the flow rates of both nitric oxide and nitrogen dioxide were controlled to be 1.4mol/h, the reaction was carried out for 2 minutes, the obtained reaction solution was transferred into a dynamic tube reactor, the pH of the system was adjusted to 1.5 with 10mol/L hydrochloric acid, the reaction solution was kept at-5℃for 2 hours, and after the product was sufficiently crystallized, 141g of (2E) -2-cyano-2-hydroxyiminoacetic acid ethyl ester (yield 96.5%, purity 99.78%) was obtained by filtration.
Claims (10)
1. A method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction, which is characterized in that the synthesis method comprises the following steps:
at room temperature, introducing a mixture of ethyl cyanoacetate and water into a microchannel reactor made of silicon carbide, simultaneously introducing nitric oxide gas and nitrogen dioxide gas into the reactor, transferring the obtained reaction liquid into a dynamic tubular reactor after a certain time of system reaction, regulating the pH value of the system by hydrochloric acid, preserving heat, and filtering to obtain the (2E) -2-cyano-2-hydroxy iminoethyl acetate after the product is fully crystallized.
2. The method according to claim 1, wherein the concentration of ethyl cyanoacetate in the mixture of ethyl cyanoacetate and water is 2mol/L.
3. The method according to claim 1, wherein the nitric oxide gas and the nitrogen dioxide gas have a pressure of 0.1-1MPa.
4. The method according to claim 1, wherein the molar flow ratio of nitric oxide gas and nitrogen dioxide gas is 1:1.
5. the method according to claim 1, wherein the molar flow ratio of nitric oxide gas to the mixture of ethyl cyanoacetate and water is (1-1.5): 1, the molar flow ratio of nitrogen dioxide gas to the mixture of ethyl cyanoacetate and water is (1-1.5): 1.
6. the method of claim 1, wherein the reaction time is 0.5 to 3 minutes.
7. The method according to claim 1, wherein the concentration of the hydrochloric acid is 4-12mol/L.
8. The method according to claim 1, wherein the pH of the reaction liquid system is adjusted to a range of 1 to 4.
9. The method of claim 1, wherein the crystallization temperature is-10-10 ℃.
10. The method of claim 1, wherein the crystallization time is 0.5 to 3 hours.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310458584.6A CN116444399A (en) | 2023-04-26 | 2023-04-26 | Method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction |
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| CN202310458584.6A CN116444399A (en) | 2023-04-26 | 2023-04-26 | Method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction |
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| CN202310458584.6A Pending CN116444399A (en) | 2023-04-26 | 2023-04-26 | Method for synthesizing (2E) -2-cyano-2-hydroxy iminoacetic acid ethyl ester by micro-reaction |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5003099A (en) * | 1988-05-17 | 1991-03-26 | Lonza Ltd. | Method for the production of aminocyanoacetamide |
| CN107793316A (en) * | 2017-12-05 | 2018-03-13 | 中国科学院大连化学物理研究所 | A kind of method of microreactor synthesis methyl nitrite |
| CN110981751A (en) * | 2019-11-28 | 2020-04-10 | 湖州柏特生物科技有限公司 | Production method of diacetyl monoxime |
| CN113003552A (en) * | 2021-03-09 | 2021-06-22 | 扬州大学 | Preparation method of nitrous acid |
-
2023
- 2023-04-26 CN CN202310458584.6A patent/CN116444399A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5003099A (en) * | 1988-05-17 | 1991-03-26 | Lonza Ltd. | Method for the production of aminocyanoacetamide |
| CN107793316A (en) * | 2017-12-05 | 2018-03-13 | 中国科学院大连化学物理研究所 | A kind of method of microreactor synthesis methyl nitrite |
| CN110981751A (en) * | 2019-11-28 | 2020-04-10 | 湖州柏特生物科技有限公司 | Production method of diacetyl monoxime |
| CN113003552A (en) * | 2021-03-09 | 2021-06-22 | 扬州大学 | Preparation method of nitrous acid |
Non-Patent Citations (2)
| Title |
|---|
| 上海市经济团体联合会: "《节能减排理论基础与装备技术》", vol. 978, 31 May 2010, 华东理工大学出版社 , pages: 272 - 273 * |
| 陈小明: "《化学反应器基础及操作》", vol. 978, 1 December 2021, 中国轻工业出版社, pages: 157 - 159 * |
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