CN115010623A - Preparation method of 2-cyanoethyl diethyl malonate - Google Patents
Preparation method of 2-cyanoethyl diethyl malonate Download PDFInfo
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- diethyl malonate
- cyanoethyl
- diethyl
- cyanoethylmalonate
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- -1 2-cyanoethyl diethyl malonate Chemical compound 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims abstract description 36
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 23
- 239000007788 liquid Substances 0.000 claims abstract description 18
- 238000004821 distillation Methods 0.000 claims abstract description 17
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 11
- 238000005292 vacuum distillation Methods 0.000 claims abstract description 8
- YJJLOESDBPRZIP-UHFFFAOYSA-N diethyl 2-(2-cyanoethyl)propanedioate Chemical compound CCOC(=O)C(CCC#N)C(=O)OCC YJJLOESDBPRZIP-UHFFFAOYSA-N 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 239000011259 mixed solution Substances 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- 230000003472 neutralizing effect Effects 0.000 claims description 5
- 230000006798 recombination Effects 0.000 claims description 5
- 238000005215 recombination Methods 0.000 claims description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 230000014759 maintenance of location Effects 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 238000006386 neutralization reaction Methods 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000007278 cyanoethylation reaction Methods 0.000 abstract description 7
- 238000005265 energy consumption Methods 0.000 abstract description 6
- 230000018044 dehydration Effects 0.000 abstract description 4
- 238000006297 dehydration reaction Methods 0.000 abstract description 4
- 238000000605 extraction Methods 0.000 abstract description 4
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 238000000926 separation method Methods 0.000 abstract description 4
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 238000004817 gas chromatography Methods 0.000 description 14
- 238000000034 method Methods 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KAESGTBHXNCAHO-UHFFFAOYSA-N diethyl 2,2-bis(2-cyanoethyl)propanedioate Chemical compound CCOC(=O)C(CCC#N)(CCC#N)C(=O)OCC KAESGTBHXNCAHO-UHFFFAOYSA-N 0.000 description 5
- 239000012535 impurity Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 230000007547 defect Effects 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 2
- 229960003987 melatonin Drugs 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
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- 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
-
- 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
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2-cyanoethyl diethyl malonate, wherein mixed liquid of diethyl malonate and an alkaline catalyst is introduced into a continuous reactor, and acrylonitrile is introduced to carry out cyanoethylation reaction to obtain 2-cyanoethyl diethyl malonate reaction liquid; the 2-cyanoethyl diethyl malonate is obtained through continuous separation of a rectifying tower and distillation treatment of a high vacuum distillation system. The invention improves the selectivity of the 2-cyanoethyl diethyl malonate, avoids the use of organic solvents, extraction, dehydration and other operations while improving the yield of the 2-cyanoethyl diethyl malonate, thereby reducing the problems of high risk, high energy consumption and high three wastes brought by the operations, providing a preparation process with low safety risk, high utilization rate of raw materials, low production energy consumption and low cost, and being better suitable for industrial large-scale production.
Description
Technical Field
The invention relates to the technical field of chemical intermediate synthesis, in particular to a synthesis method of 2-cyanoethyl diethyl malonate.
Background
Diethyl 2-cyanoethylmalonate is one of important intermediates for synthesizing melatonin which is a raw material of health care products. The synthesis methods adopted in the prior art mainly comprise the following two methods:
firstly, diethyl malonate and acrylonitrile are subjected to cyanoethylation reaction in a solvent of ethyl acetate under the action of potassium carbonate as an alkaline catalyst to obtain 2-cyanoethyl diethyl malonate. The method has the disadvantages that ethyl acetate is easy to hydrolyze under alkaline conditions, the decomposed acetic acid consumes alkaline catalysts, the amount of the alkaline catalysts in the reaction process is insufficient, operations such as extraction, dehydration and the like are required, and the process is complex.
Secondly, by using a solvent-free method, diethyl malonate directly reacts with acrylonitrile in a cyanoethylation reaction under the action of metal sodium as an alkaline catalyst, and then is distilled and purified, so that the final yield is 63.7%. The method has the disadvantages that the metal sodium is used as an alkaline catalyst, the alkalinity of the metal sodium is too strong, more diethyl malonate is over cyanoethylated in the heat preservation process, more diethyl bis-cyanoethylmalonate impurities are generated, the yield is reduced, and the metal sodium is not easy to operate in the production process and is accompanied with larger safety risk.
In the existing process, more diethyl malonate is subjected to over cyanoethylation in the reaction process, so that the yield is easily reduced, unreacted diethyl malonate exists in reaction liquid, the diethyl malonate raw material utilization rate is low, the cost is high, the diethyl malonate is purified by using operations such as washing, dehydration and the like, the operation is relatively complex, impurities generated in the reaction process are not removed as much as possible in the washing process, and residual impurities have a poisoning effect on a catalyst used in the subsequent hydrogenation process, so that the preparation of 2-cyanoethyl diethyl malonate and the purification of 2-cyanoethyl diethyl malonate are extremely critical to the production of melatonin.
The synthesis process of diethyl 2-cyanoethylmalonate reported in the prior art uses batch type reaction kettles, and has the defects of complicated operation, low mass and heat transfer efficiency, long reaction time, low utilization rate of diethyl malonate raw material, high safety risk and the like.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a preparation method of 2-cyanoethyl diethyl malonate, which avoids the use of organic solvents, extraction, dehydration and other operations while improving the yield of the 2-cyanoethyl diethyl malonate, thereby reducing the problems of high risk, high energy consumption and high three wastes caused by the operations, and providing a preparation process which has low safety risk, high utilization rate of raw materials, low production energy consumption and low cost and is better suitable for industrial large-scale production.
The purpose of the invention is realized by the following technical scheme:
the invention provides a preparation method of 2-cyanoethyl diethyl malonate, which comprises the following steps:
(1) mixing diethyl malonate and an alkaline catalyst according to a molar ratio of 1: 0.01-0.1, preferably 1: 0.03-0.07 to obtain a diethyl malonate mixed solution;
(2) according to the molar ratio of 1: 0.8-1.5 of diethyl malonate mixed liquid to 1: 1-1.5 of acrylonitrile, preferably 1: 1-1.1, simultaneously introducing the diethyl malonate mixed liquid and the acrylonitrile into a continuous reactor with the reaction temperature of 30-70 ℃, preferably 50-60 ℃, and allowing the diethyl malonate mixed liquid and the acrylonitrile to stay for 10-30 min, preferably 15-25 min to obtain 2-cyanoethyl diethyl malonate reaction liquid;
(3) neutralizing the reaction liquid of the 2-cyanoethyl diethyl malonate with acid until the pH value is 6-7, and then continuously separating the reaction liquid in a rectifying tower, wherein the light component at the top of the tower is unreacted diethyl malonate and can be directly recycled; the tower bottom recombination is a mixed solution of 2-cyanoethyl diethyl malonate and bis-cyanoethyl diethyl malonate, the mixed solution is distilled in a high vacuum distillation system with the vacuum degree of more than-0.098 Mpa to obtain condensate of 2-cyanoethyl diethyl malonate, and distillation residues are incinerated.
Further, the distillation temperature of the high vacuum distillation system in the step (3) is 100-150 ℃.
In the scheme, the alkaline catalyst is potassium hydroxide, sodium methoxide, sodium ethoxide, sodium/potassium tert-butoxide, triethylamine or aniline. The acid used for acid neutralization in the step (3) is hydrochloric acid, sulfuric acid, formic acid, acetic acid or carbonic acid. The continuous reactor comprises a microchannel reactor or a pipeline reactor.
The invention has the following beneficial effects:
(1) the cyanoethylation process uses a continuous reactor, and converts the traditional batch reaction into a continuous reaction, so that the cyanoethylation control is completed in a short time, the heat transfer and mass transfer are enhanced while the reaction volume is reduced, the phenomenon that the diethyl 2-cyanoethylmalonate is excessively cyanoethylated to form diethyl bis-cyanoethylmalonate impurities under the condition of long time and high temperature is avoided, the utilization rate of raw materials is improved, and the molar yield of the diethyl 2-cyanoethylmalonate is increased to over 80%.
(2) The cyanoethylation process does not use an organic solvent, does not need operations such as extraction and separation, avoids the influence of the problems of the organic solvent and the three wastes on the production environment, and has the advantages of low safety risk and small environmental protection influence.
(3) 2-cyanoethyl diethyl malonate reaction liquid is rectified by a continuous rectifying tower, high-purity unreacted diethyl malonate is continuously produced at the tower top, the purity can reach over 99 percent, and the raw material can be directly recycled; the mixed liquid of the 2-cyanoethyl diethyl malonate and the bis-cyanoethyl diethyl malonate is continuously extracted from the tower bottom, and the continuous rectification can reduce the distillation energy consumption, improve the distillation efficiency and have the characteristics of high separation degree of raw material liquid.
(4) The mixed liquid of the 2-cyanoethyl diethyl malonate and the bis-cyanoethyl diethyl malonate is obtained after the 2-cyanoethyl diethyl malonate reaction liquid passes through the rectifying tower, the boiling point difference between the two is large, so that the 2-cyanoethyl diethyl malonate with the purity of over 96 percent can be obtained during secondary distillation of the mixed liquid, the poisoning to a catalyst in the subsequent hydrogenation process can be reduced, and the cost of the catalyst is reduced.
(5) The invention improves the selectivity of the 2-cyanoethyl diethyl malonate, thereby effectively solving the defects of low selectivity of the 2-cyanoethyl diethyl malonate and insufficient subsequent separation degree of products in the existing preparation method; the continuous production is beneficial to the regulation and control of the reaction, continuous and stable products can be easily obtained for industrial production, the reaction time is reduced, the energy consumption is reduced, and the method has great advantages in industrial production.
Drawings
The invention will now be described in further detail with reference to the following examples and the accompanying drawings:
FIG. 1 shows the results of Gas Chromatography (GC) detection of diethyl 2-cyanoethylmalonate in the first embodiment of the invention.
Detailed Description
The first embodiment is as follows:
the preparation method of diethyl 2-cyanoethylmalonate comprises the following steps:
(1) mixing 150g (0.9375mol) of diethyl malonate with 3.2g (0.047mol) of sodium ethoxide to obtain diethyl malonate mixed liquid;
(2) under the condition that the reaction temperature is 55 ℃, a feed pump is used for pumping the diethyl malonate mixed liquid into a microchannel reactor at the flow rate of 30ml/min, and simultaneously, 49.75g (0.9375mol) of acrylonitrile is pumped into the microchannel reactor at the flow rate of 12ml/min, the residence time in the microchannel reactor is 20min, and the 2-cyanoethyl diethyl malonate reaction liquid is obtained;
(3) neutralizing the reaction liquid of the 2-cyanoethyl diethyl malonate by using hydrochloric acid until the pH value is 7, detecting that the GC content of the reaction liquid is 82.3%, continuously separating the reaction liquid in a rectifying tower, wherein the light component at the top of the tower is unreacted diethyl malonate with the weight of 26.4g, and the GC content is detected to be 99.1%, so that the reaction liquid can be directly recycled; the tower bottom recombination is mixed liquid of 2-cyanoethyl diethyl malonate and bis-cyanoethyl diethyl malonate, the mixed liquid enters a high vacuum distillation system for distillation, the vacuum degree is controlled to be more than-0.098 Mpa, condensate begins to be produced at the temperature of 108 ℃, the final temperature is 125 ℃, the condensate, namely 164.1g of 2-cyanoethyl diethyl malonate is obtained, the GC content is detected to be 98.1 percent (shown in figure 1), and the molar yield is 82.1 percent; 19.2g of distillation residue, wherein 2.4% of diethyl 2-cyanoethylmalonate and 96.1% of diethyl bis-cyanoethylmalonate were subjected to GC content measurement, and the distillation residue was subjected to incineration treatment.
Example two:
the preparation method of diethyl 2-cyanoethylmalonate comprises the following steps:
(1) mixing 150g (0.9375mol) of diethyl malonate with 1.8g (0.0562mol) of sodium methoxide to obtain diethyl malonate mixed solution;
(2) under the condition that the reaction temperature is 60 ℃, a feed pump is used for pumping the diethyl malonate mixed liquid into a microchannel reactor at the flow rate of 20ml/min, and simultaneously, 52.24g (0.9844mol) of acrylonitrile is pumped into the microchannel reactor at the flow rate of 8.4ml/min, the retention time in the microchannel reactor is 15min, and the 2-cyanoethyl diethyl malonate reaction liquid is obtained;
(3) neutralizing the reaction liquid of the 2-cyanoethyl diethyl malonate with acetic acid until the pH value is 7, detecting that the GC content of the reaction liquid is 84.7%, continuously separating the reaction liquid in a rectifying tower, wherein the light component at the top of the tower is unreacted diethyl malonate with the weight of 24.2g, and the GC content is detected to be 99.2%, so that the reaction liquid can be directly recycled; the tower bottom recombination is a mixed solution of 2-cyanoethyl diethyl malonate and bis-cyanoethyl diethyl malonate, the mixed solution enters a high vacuum distillation system for distillation, the vacuum degree is controlled to be greater than-0.098 Mpa, the condensate begins to be discharged at the temperature of 106 ℃, the final temperature is 128 ℃, 170.7g of the condensate, namely 2-cyanoethyl diethyl malonate is obtained, the GC content is detected to be 97.4%, and the molar yield is 85.4%; 8.6g of distillation residue, wherein 1.9% of diethyl 2-cyanoethylmalonate and 96.4% of diethyl bis-cyanoethylmalonate were measured for GC content, and the distillation residue was subjected to incineration treatment.
Example three:
the preparation method of diethyl 2-cyanoethylmalonate comprises the following steps:
(1) mixing 150g (0.9375mol) of diethyl malonate with 3.6g (0.0375mol) of sodium tert-butoxide to obtain diethyl malonate mixed solution;
(2) under the condition that the reaction temperature is 50 ℃, a feed pump is used for pumping the diethyl malonate mixed liquid into a microchannel reactor at the flow rate of 15ml/min, simultaneously, 54.73g (1.0313mol) of acrylonitrile is pumped into the microchannel reactor at the flow rate of 6.6ml/min, and the retention time in the microchannel reactor is 25min, so as to obtain a 2-cyanoethyl diethyl malonate reaction liquid;
(3) neutralizing the reaction liquid of the 2-cyanoethyl diethyl malonate by using sulfuric acid until the pH value is 7, detecting that the GC content of the reaction liquid is 79.7%, continuously separating the reaction liquid in a rectifying tower, wherein the light component at the top of the tower is unreacted diethyl malonate, the weight of the unreacted diethyl malonate is 31.7g, the detected GC content is 99.2%, and directly recycling the unreacted diethyl malonate; the tower bottom recombination is mixed liquid of 2-cyanoethyl diethyl malonate and bis-cyanoethyl diethyl malonate, the mixed liquid enters a high vacuum distillation system for distillation, the vacuum degree is controlled to be more than-0.098 Mpa, condensate begins to be produced at the temperature of 111 ℃, the final temperature is 124 ℃, 160.5g of condensate, namely the 2-cyanoethyl diethyl malonate is obtained, the GC content is 96.8% through detection, and the molar yield is 80.3%; 24.9g of distillation residue, wherein 2.7% of diethyl 2-cyanoethylmalonate and 97.6% of diethyl bis-cyanoethylmalonate were measured for GC content, and the distillation residue was subjected to incineration treatment.
Claims (7)
1. A preparation method of 2-cyanoethyl diethyl malonate is characterized by comprising the following steps:
(1) mixing diethyl malonate and an alkaline catalyst according to a molar ratio of 1: 0.01-0.1 to obtain diethyl malonate mixed liquid;
(2) according to the mol ratio of 1: 0.8-1.5, simultaneously introducing the diethyl malonate mixed solution and acrylonitrile into a continuous reactor with the reaction temperature of 30-70 ℃, and keeping for 10-30 min to obtain a 2-cyanoethyl diethyl malonate reaction solution;
(3) neutralizing the reaction liquid of the 2-cyanoethyl diethyl malonate with acid until the pH value is 6-7, and then continuously separating the reaction liquid in a rectifying tower, wherein the light component at the top of the tower is unreacted diethyl malonate and can be directly recycled; the tower bottom recombination is a mixed solution of 2-cyanoethyl diethyl malonate and bis-cyanoethyl diethyl malonate, the mixed solution is distilled in a high vacuum distillation system with the vacuum degree of more than-0.098 Mpa to obtain condensate of 2-cyanoethyl diethyl malonate, and distillation residues are incinerated.
2. The method for producing diethyl 2-cyanoethylmalonate according to claim 1, characterized in that: in the step (1), diethyl malonate and an alkaline catalyst are mixed according to a molar ratio of 1: 0.03-0.07.
3. The method for producing diethyl 2-cyanoethylmalonate according to claim 1, characterized in that: in the step (2), diethyl malonate mixed liquid and acrylonitrile are mixed according to a molar ratio of 1: 1-1.1; the reaction temperature is 50-60 ℃, and the retention time is 15-25 min.
4. The method for producing diethyl 2-cyanoethylmalonate according to claim 1, characterized in that: and (3) the distillation temperature of the high vacuum distillation system in the step (3) is 100-150 ℃.
5. The method for producing diethyl 2-cyanoethylmalonate according to claim 1, characterized in that: the alkaline catalyst is potassium hydroxide, sodium methoxide, sodium ethoxide, sodium/potassium tert-butoxide, triethylamine or aniline.
6. The method for producing diethyl 2-cyanoethylmalonate according to claim 1, characterized in that: the acid used for acid neutralization in the step (3) is hydrochloric acid, sulfuric acid, formic acid, acetic acid or carbonic acid.
7. The method for producing diethyl 2-cyanoethylmalonate according to claim 1, characterized in that: the continuous reactor comprises a microchannel reactor or a pipeline reactor.
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| CN104496882A (en) * | 2014-11-29 | 2015-04-08 | 湖北金赛药业有限公司 | Synthesis method of melatonin |
| CN108484484A (en) * | 2018-05-22 | 2018-09-04 | 上海泾维化工科技有限公司 | The preparation method of 2- oxygen-ethyl nipecotate |
| CN109053535A (en) * | 2018-09-29 | 2018-12-21 | 罗田县新普生药业有限公司 | A kind of preparation method of n-acetyl-5-methoxytryptamine |
| CN112920104A (en) * | 2021-01-25 | 2021-06-08 | 福建科宏生物工程股份有限公司 | Preparation method for green synthesis of N-acetyl-5-methoxytryptamine |
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| Publication number | Priority date | Publication date | Assignee | Title |
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