CN111875520A - Novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile - Google Patents
Novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile Download PDFInfo
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- CN111875520A CN111875520A CN202010766733.1A CN202010766733A CN111875520A CN 111875520 A CN111875520 A CN 111875520A CN 202010766733 A CN202010766733 A CN 202010766733A CN 111875520 A CN111875520 A CN 111875520A
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- hydroxybutyronitrile
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- epichlorohydrin
- hydrogen cyanide
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- LHBPNZDUNCZWFL-BYPYZUCNSA-N (3s)-4-chloro-3-hydroxybutanenitrile Chemical compound ClC[C@@H](O)CC#N LHBPNZDUNCZWFL-BYPYZUCNSA-N 0.000 title claims abstract description 32
- 238000001308 synthesis method Methods 0.000 title claims abstract description 17
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims abstract description 52
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims abstract description 24
- 150000001412 amines Chemical class 0.000 claims abstract description 22
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 21
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000007788 liquid Substances 0.000 claims abstract description 12
- 230000018044 dehydration Effects 0.000 claims abstract description 11
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 9
- 238000004821 distillation Methods 0.000 claims abstract description 9
- 238000012544 monitoring process Methods 0.000 claims abstract description 9
- 238000004321 preservation Methods 0.000 claims abstract description 9
- 238000005070 sampling Methods 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 9
- 238000009423 ventilation Methods 0.000 claims abstract description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 10
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 6
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
- 238000011534 incubation Methods 0.000 claims 1
- 239000002699 waste material Substances 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- 230000001276 controlling effect Effects 0.000 description 14
- 239000012153 distilled water Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 5
- 239000002351 wastewater Substances 0.000 description 3
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 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
- 230000006837 decompression Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/16—Preparation of carboxylic acid nitriles by reaction of cyanides with lactones or compounds containing hydroxy groups or etherified or esterified hydroxy 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
-
- 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
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile, which comprises the following steps: (1) reaction: putting ammonia water or organic amine aqueous solution, epichlorohydrin and water into a reaction flask, starting stirring, controlling the temperature at 10-50 ℃, introducing hydrogen cyanide, and monitoring the pH value to be 7-9 on line in the ventilation process; after the hydrogen cyanide is introduced, controlling the temperature at 10-50 ℃, preserving the heat for 3-12h, after the heat preservation is finished, carrying out center control sampling, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction; (2) and (3) post-treatment: and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the removed liquid can be applied to the next batch of reaction, and the residual liquid is distilled to obtain the (S) -4-chloro-3-hydroxybutyronitrile finished product. The novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile has the advantages of mild reaction, high yield, high purity, wider system pH control range, no waste salt generation and low environmental protection cost.
Description
Technical Field
The invention relates to the technical field of drug synthesis, in particular to a novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile.
Background
(S) -4-chloro-3-hydroxybutyronitrile is a key intermediate of atorvastatin, which is an HMG-CoA reductase selective inhibitor and is mainly used for reducing plasma cholesterol and lipoprotein levels, increasing the level of low-density lipoprotein (LDL) on the surface of liver cells and being a common medicine for regulating blood fat in the lower cardiovascular system.
The current process synthetic route is as follows:
however, the existing synthesis process has the following disadvantages:
(1) the synthetic route has the advantages of large sodium cyanide consumption, low utilization rate, 1.6-1.7 times of the molar ratio of epoxy chloropropane, generation of a large amount of cyanide-containing wastewater and high treatment cost;
(2) the synthesis route requires a pH value of 8-8.3 for reaction control, the escape of hydrocyanic acid is easily caused due to too low pH value control, the reaction rate is influenced due to too high pH value, the reaction control requirement is high, and the operation cost is high;
(3) the synthetic route reacts to generate a large amount of sodium sulfate, and the cyanide-containing wastewater is treated to generate a large amount of waste sodium sulfate and wastewater, so that the environmental-friendly treatment cost is high.
Disclosure of Invention
The invention aims to provide a novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile, which has the advantages of mild reaction, high yield, high purity, wider system pH control, no waste salt generation and low environmental protection cost.
In order to achieve the purpose, the invention is realized by the following technical scheme:
a new synthesis method of (S) -4-chloro-3-hydroxybutyronitrile comprises the following steps:
(1) reaction:
putting ammonia water or organic amine aqueous solution, epichlorohydrin and water into a reaction flask, starting stirring, controlling the temperature at 10-50 ℃, introducing hydrogen cyanide, and monitoring the pH value to be 7-9 on line in the ventilation process; after the hydrogen cyanide is introduced, controlling the temperature at 10-50 ℃, preserving the heat for 3-12h, after the heat preservation is finished, carrying out center control sampling, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction;
(2) and (3) post-treatment:
and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the removed liquid can be applied to the next batch of reaction, and the residual liquid is distilled to obtain the (S) -4-chloro-3-hydroxybutyronitrile finished product.
The new synthesis process route is as follows:
preferably, in the step (1), the organic amine is one or a combination of several of methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine and triethylamine.
Preferably, the mole ratio of the epichlorohydrin to the alkali to the hydrogen cyanide is 1: 0.25-0.35: 1.3-1.8. Further preferably, the molar ratio of the epichlorohydrin to the alkali to the hydrogen cyanide is 1: 0.3: 1.5.
preferably, the molar volume ratio of the epichlorohydrin to the water is 1: 0.3-0.4 mol/L.
Preferably, in step (1), the temperature is controlled to be 20-30 ℃.
Preferably, in the step (1), the holding time is 8 h.
The invention has the beneficial effects that:
(1) the synthetic route uses epoxy chloropropane and hydrocyanic acid as reaction raw materials, and uses ammonia water or aqueous solution of organic amine (methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine and other organic amines) as a reaction system buffering agent. The ammonia water or the aqueous solution of organic amine is used for dissolving the hydrogen cyanide, so that the hydrogen cyanide is slowly released in the reaction process, the reaction is mild, the yield is improved, the pH value of the system is more widely controlled, and the pH value is controlled to be 7-9.
(2) After the reaction is finished, the ammonia water or organic amine and the like in the reaction system are directly brought out by water after decompression and dehydration, the distilled water contains the ammonia water or the organic amine and the like, and can be directly applied to the production of the next batch.
(3) After the dehydration is finished, the generated (S) -4-chloro-3-hydroxybutyronitrile is directly evaporated out under reduced pressure to obtain a finished product, thereby avoiding the operation link of extracting by using an organic solvent in the prior art and saving the manpower and the consumption of related solvents.
(4) Compared with the prior art, the new synthesis process route of the (S) -4-chloro-3-hydroxybutyronitrile reduces the cost of three-waste treatment, equipment investment, manual investment and other links, and increases the technical advancement of the product.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1:
a new synthesis method of (S) -4-chloro-3-hydroxybutyronitrile comprises the following steps:
(1) reaction: adding 9.25g (0.1mol) of epichlorohydrin, 2g (containing 0.5g (0.03mol)) of ammonia water and 35ml of water into a reaction bottle, starting stirring, controlling the temperature to be 20-30 ℃, introducing 4.05g (0.15mol) of hydrogen cyanide, and monitoring the pH value to be 7-9 in an on-line manner in the ventilation process; after the hydrogen cyanide is introduced, controlling the temperature at 20-30 ℃, preserving the heat for 8h, carrying out central control sampling after the heat preservation is finished, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction.
(2) And (3) post-treatment: and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the distilled water contains ammonia water or organic amine and the like, the ammonia water or the organic amine can be recycled for reaction, and the residual liquid is distilled to obtain 10.6g (the purity is more than or equal to 98.5%) of the finished (S) -4-chloro-3-hydroxybutyronitrile product with the yield of 88.7%.
Example 2:
a new synthesis method of (S) -4-chloro-3-hydroxybutyronitrile comprises the following steps:
(1) reaction: adding 9.25g (0.1mol) of epichlorohydrin, 3.38g (containing 1.35g (0.03mol)) of dimethylamine aqueous solution and 35ml of water into a reaction bottle, starting stirring, controlling the temperature at 20-30 ℃, introducing 4.05g (0.15mol) of hydrogen cyanide, and monitoring the pH value at 7-9 in an on-line ventilation process; after the hydrogen cyanide is introduced, controlling the temperature at 20-30 ℃, preserving the heat for 8h, carrying out central control sampling after the heat preservation is finished, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction.
(2) And (3) post-treatment: and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the distilled water contains ammonia water or organic amine and the like, the ammonia water or the organic amine can be recycled for reaction, and the residual liquid is distilled to obtain 10.8g (the purity is more than or equal to 98.5%) of the finished (S) -4-chloro-3-hydroxybutyronitrile product with the yield of 90.4%.
Example 3:
a new synthesis method of (S) -4-chloro-3-hydroxybutyronitrile comprises the following steps:
(1) reaction: adding 9.25g (0.1mol) of epichlorohydrin, 3.40g (containing 1.35g (0.03mol)) of ethylamine aqueous solution and 35ml of water into a reaction bottle, starting stirring, controlling the temperature at 25-35 ℃, introducing 4.86g (0.18mol) of hydrogen cyanide, and monitoring the pH value at 7-9 in an on-line manner in the ventilation process; and after the hydrogen cyanide is introduced, controlling the temperature at 25-35 ℃, preserving the heat for 10 hours, carrying out central control sampling after the heat preservation is finished, wherein the content of the epichlorohydrin is less than or equal to 0.5%, and finishing the reaction.
(2) And (3) post-treatment: and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the distilled water contains ammonia water or organic amine and the like, the ammonia water or the organic amine can be recycled for reaction, and the residual liquid is distilled to obtain 10.6g (the purity is more than or equal to 98.5%) of the finished (S) -4-chloro-3-hydroxybutyronitrile product with the yield of 88.7%.
Example 4:
a new synthesis method of (S) -4-chloro-3-hydroxybutyronitrile comprises the following steps:
(1) reaction: adding 9.25g (0.1mol) of epichlorohydrin, 2.38g (containing 0.595g (0.035mol)) of ammonia water and 40ml of water into a reaction bottle, starting stirring, controlling the temperature at 30-40 ℃, introducing 4.05g (0.15mol) of hydrogen cyanide, and monitoring the pH value at 7-9 in an on-line manner in the ventilation process; and after the hydrogen cyanide is introduced, controlling the temperature at 30-40 ℃, preserving the heat for 6h, carrying out central control sampling after the heat preservation is finished, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction.
(2) And (3) post-treatment: and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the distilled water contains ammonia water or organic amine and the like, the ammonia water or the organic amine can be recycled for reaction, and the residual liquid is distilled to obtain 10.5g (the purity is more than or equal to 98.5%) of the finished (S) -4-chloro-3-hydroxybutyronitrile product with the yield of 87.9%.
Example 5:
a new synthesis method of (S) -4-chloro-3-hydroxybutyronitrile comprises the following steps:
(1) reaction: adding 9.25g (0.1mol) of epichlorohydrin, 6.33g (containing 2.53g (0.025mol)) of triethylamine aqueous solution and 35ml of water into a reaction bottle, starting stirring, controlling the temperature at 10-20 ℃, introducing 4.05g (0.15mol) of hydrogen cyanide, and monitoring the pH value at 7-9 in an on-line manner in the ventilation process; after the hydrogen cyanide is introduced, controlling the temperature at 20-30 ℃, preserving the heat for 12h, carrying out central control sampling after the heat preservation is finished, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction.
(2) And (3) post-treatment: and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the distilled water contains ammonia water or organic amine and the like, the ammonia water or the organic amine can be recycled for reaction, and the residual liquid is distilled to obtain 10.4g (the purity is more than or equal to 98.5%) of the finished (S) -4-chloro-3-hydroxybutyronitrile product with the yield of 87%.
Example 6:
a new synthesis method of (S) -4-chloro-3-hydroxybutyronitrile comprises the following steps:
(1) reaction: adding 9.25g (0.1mol) of epichlorohydrin, 3.38g (containing 1.35g (0.03mol)) of dimethylamine aqueous solution and 30ml of water into a reaction bottle, starting stirring, controlling the temperature at 40-50 ℃, introducing 3.51g (0.13mol) of hydrogen cyanide, and monitoring the pH value at 7-9 in an on-line ventilation process; after the hydrogen cyanide is introduced, controlling the temperature at 20-30 ℃, preserving the heat for 5 hours, carrying out central control sampling after the heat preservation is finished, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction.
(2) And (3) post-treatment: and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the distilled water contains ammonia water or organic amine and the like, the ammonia water or the organic amine can be recycled for reaction, and the residual liquid is distilled to obtain 10.4g (the purity is more than or equal to 98.5%) of the finished (S) -4-chloro-3-hydroxybutyronitrile product with the yield of 87%.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (7)
1. A novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile is characterized by comprising the following steps:
(1) reaction:
putting ammonia water or organic amine aqueous solution, epichlorohydrin and water into a reaction flask, starting stirring, controlling the temperature at 10-50 ℃, introducing hydrogen cyanide, and monitoring the pH value to be 7-9 on line in the ventilation process; after the hydrogen cyanide is introduced, controlling the temperature at 10-50 ℃, preserving the heat for 3-12h, after the heat preservation is finished, carrying out center control sampling, wherein the content of epichlorohydrin is less than or equal to 0.5%, and finishing the reaction;
(2) and (3) post-treatment:
and (2) carrying out reduced pressure distillation and dehydration on the reaction liquid obtained in the step (1), wherein the removed liquid can be applied to the next batch of reaction, and the residual liquid is distilled to obtain the (S) -4-chloro-3-hydroxybutyronitrile finished product.
2. The novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile according to claim 1, wherein in step (1), the organic amine is one or a combination of methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine and triethylamine.
3. The new synthesis process of (S) -4-chloro-3-hydroxybutyronitrile according to claim 1, wherein the molar ratio of epichlorohydrin, base and hydrogen cyanide is 1: 0.25-0.35: 1.3-1.8.
4. The new synthesis process of (S) -4-chloro-3-hydroxybutyronitrile according to claim 3, wherein the molar ratio of epichlorohydrin, base and hydrogen cyanide is 1: 0.3: 1.5.
5. the new synthesis process of (S) -4-chloro-3-hydroxybutyronitrile according to claim 1, wherein the molar volume ratio of epichlorohydrin to water is 1: 0.3-0.4 mol/L.
6. The novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile according to claim 1, wherein the temperature in step (1) is controlled to be 20-30 ℃.
7. The novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile according to claim 1, wherein in step (1), the incubation time is 8 h.
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Cited By (2)
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CN113831261A (en) * | 2021-10-29 | 2021-12-24 | 营口德瑞化工有限公司 | Method for synthesizing high-content (S) -4-chloro-3-hydroxybutyronitrile |
CN115894292A (en) * | 2022-12-16 | 2023-04-04 | 山东阳谷华泰化工股份有限公司 | Preparation method of L-Carlactonitrile |
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