CN111018728A - Method and device for preparing 3-chloro-alanine hydrochloride by using water as auxiliary agent - Google Patents
Method and device for preparing 3-chloro-alanine hydrochloride by using water as auxiliary agent Download PDFInfo
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 29
- IENJPSDBNBGIEL-UHFFFAOYSA-N 2-amino-3-chloropropanoic acid;hydron;chloride Chemical compound Cl.ClCC(N)C(O)=O IENJPSDBNBGIEL-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 239000012752 auxiliary agent Substances 0.000 title claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 65
- 238000006243 chemical reaction Methods 0.000 claims abstract description 60
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000000926 separation method Methods 0.000 claims abstract description 36
- 239000002994 raw material Substances 0.000 claims abstract description 31
- 239000007788 liquid Substances 0.000 claims abstract description 30
- 239000002904 solvent Substances 0.000 claims abstract description 29
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims abstract description 24
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000002156 mixing Methods 0.000 claims abstract description 10
- 239000011344 liquid material Substances 0.000 claims abstract description 3
- 239000000463 material Substances 0.000 claims description 18
- 239000000706 filtrate Substances 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 16
- 239000002912 waste gas Substances 0.000 claims description 10
- 238000003860 storage Methods 0.000 claims description 9
- 238000003828 vacuum filtration Methods 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 7
- 238000007599 discharging Methods 0.000 claims description 6
- 238000011084 recovery Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 2
- 239000011343 solid material Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 4
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- 238000005660 chlorination reaction Methods 0.000 abstract description 2
- 150000007530 organic bases Chemical class 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000007789 gas Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- ASBJGPTTYPEMLP-UHFFFAOYSA-N 3-chloroalanine Chemical compound ClCC(N)C(O)=O ASBJGPTTYPEMLP-UHFFFAOYSA-N 0.000 description 5
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical class [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- XDSSPSLGNGIIHP-VKHMYHEASA-N Se-methyl-L-selenocysteine Chemical compound C[Se]C[C@H]([NH3+])C([O-])=O XDSSPSLGNGIIHP-VKHMYHEASA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- -1 chloro-serine hydrochloride Chemical compound 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- KHUDJGGFFNDILT-VKHMYHEASA-N methyl (2r)-2-amino-3-chloropropanoate Chemical compound COC(=O)[C@@H](N)CCl KHUDJGGFFNDILT-VKHMYHEASA-N 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- SMPAPEKFGLKOIC-UHFFFAOYSA-N oxolane;hydrochloride Chemical compound Cl.C1CCOC1 SMPAPEKFGLKOIC-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 229940091258 selenium supplement Drugs 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
Abstract
The invention discloses a method and a device for preparing 3-chloro-alanine hydrochloride by using water as an auxiliary agent, which are characterized by comprising the following steps: mixing dioxane, thionyl chloride, water, an organic small molecular catalyst and serine, and stirring; after the reaction is finished, carrying out solid-liquid separation on the obtained liquid material to obtain filter residue, namely 3-chloro-alanine hydrochloride. The invention promotes the dissolution of the raw material serine in a system by adding a proper amount of water into a dioxane solvent, generates excellent catalytic action on chlorination reaction taking thionyl chloride as a raw material by using organic bases such as pyridine, dimethylformamide or triethylamine and the like, accelerates the reaction process, and obtains a satisfactory conversion rate at a lower temperature, wherein the highest conversion rate can reach 97%.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a method and a device for preparing 3-chloro-alanine hydrochloride by using water as an auxiliary agent.
Background
The chloro-serine hydrochloride is an important chemical synthesis intermediate, and is an important raw material for synthesizing compounds such as selenocysteine, methyl selenocysteine and the like. With the rapid promotion of the selenium supplement product industry, 3-chloro-alanine hydrochloride as one of the raw materials has great market potential.
Currently, the following methods are mainly used for preparing 3-chloro-alanine or hydrochloride thereof: 1) the alanine is used as a raw material to react with sulfuric acid and chlorine gas, the yield of the obtained target product is 78%, and the method has more by-products and difficult separation. 2) The 3-chloro-alanine methyl ester is used as a raw material to obtain a target product through hydrolysis reaction, the yield of the method is high and can reach 95%, but the reaction raw material is not easy to obtain. 3) Propionitrile is used as a raw material, and a product is obtained after multi-step reaction, but the reaction conditions are harsh, and the product is an enantiomer. 4) The method comprises the steps of taking hydrogen chloride-dioxane or hydrogen chloride-tetrahydrofuran as a solvent, taking serine as a raw material and thionyl chloride as a chlorinating agent, reacting at 45 ℃, concentrating at low temperature, adding water for dissolving, and finally precipitating with acetone to obtain the product. Compared with other methods, the method has the following obvious advantages: the raw materials are easy to obtain, the yield is high, and the method is the most common synthesis method at present. But there are also significant disadvantages: 1) a large amount of hydrogen chloride needs to be added into a solvent, the reaction process is volatile, a large amount of alkali is needed for neutralizing the hydrogen chloride in the post-treatment process, the environment is damaged, and the treatment is very troublesome. In addition, the hydrogen chloride-dioxane is a poison-preparing reagent specified in the clear text of the ministry of public security, and brings risks to production management. 2) The reaction requires heating, increasing equipment investment and production operating costs. 3) The post-treatment process is long, acetone is required to be added, and the reagent is also a virus-preparation-facilitating reagent specified in the clear text of the ministry of public security.
Disclosure of Invention
In order to solve the defects and shortcomings of the prior art, the invention aims at providing a method for preparing 3-chloro-alanine hydrochloride by taking water as an auxiliary agent, in the preparation method, serine is taken as a raw material, a proper amount of water, pyridine, dimethylformamide or triethylamine and the like are added into a reaction system, the reaction is carried out for a period of time at normal temperature, the 3-chloro-alanine hydrochloride is obtained through solid-liquid separation, and then the solvent is recovered for recycling. The method is simple and easy to implement, low in cost, high in yield and very obvious in economic benefit.
The invention also aims to provide a reaction device for preparing the 3-chloro-alanine hydrochloride by using water as an auxiliary agent.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for preparing 3-chloro-alanine hydrochloride by taking water as an auxiliary agent comprises the following steps:
mixing dioxane, thionyl chloride, water, an organic small molecular catalyst and serine, and stirring; after the reaction is finished, carrying out solid-liquid separation on the obtained liquid material to obtain filter residue, namely 3-chloro-alanine hydrochloride.
Preferably, the mass ratio of the dioxane, the water and the thionyl chloride is 30: (0.1-10): (1-30).
Preferably, the organic small molecule catalyst is at least one of pyridine, dimethylformamide and triethylamine; the mass ratio of the organic micromolecule catalyst to water is (0.01-10): 1.
preferably, the mass ratio of serine to dioxane is 1: (2-50).
Preferably, the temperature during the stirring reaction is 0-45 ℃, and preferably 25-35 ℃. The stirring reaction time is 10-40 hours, preferably 20-30 hours.
Preferably, after the reaction is finished, the reaction material is vacuumized, and the extracted waste gas is absorbed by alkali liquor. More preferably, the temperature of the vacuum pumping is room temperature, and the time of the vacuum pumping is 30-60 minutes.
Preferably, the filtrate collected after the solid-liquid separation can be recycled; the solid-liquid separation is vacuum filtration or centrifugal separation.
The room temperature is 20-35 ℃.
A reaction device for preparing 3-chloro-alanine hydrochloride by taking serine as a raw material comprises a reaction system and a separation system; the reaction system comprises a reactor, a dioxane tank, a water tank, a thionyl chloride tank and a raw material tank; the separation system comprises a solid-liquid separation device, a solvent recovery tank, a buffer tank, an alkali liquor tank, a vacuum pump and a chemical pump;
the top of the reactor is provided with a solid material feeding hole and a solvent feeding pipe, the inside of the reactor is provided with a stirring paddle, and the bottom of the reactor is provided with a discharging hole; a discharge pipe at the bottom of the reactor is connected with a feed pipe orifice of the solid-liquid separation device; the solid-liquid separation device, the buffer tank, the lye tank and the vacuum pump are sequentially connected; the waste gas in the solid-liquid separation device flows through the buffer tank and enters the lye tank to be absorbed under the negative pressure effect generated by the vacuum pump; the feeding pipe orifice of the solvent recovery tank is connected with the liquid discharging pipe orifice of the solid-liquid separation device, the feeding pipe orifice of the chemical pump is connected with the discharging pipe orifice of the solvent recovery storage tank, the discharge port of the chemical pump is connected with the reactor, the recovered solvent can enter the reaction system again through the chemical pump, and the solvent is recycled.
Aiming at a series of problems that at present, 3-chloro-alanine or hydrochloride thereof needs to use reagents which are easy to produce toxicity, such as hydrogen chloride-dioxane, acetone and the like, the reaction needs to be heated, and a solvent cannot be recycled, and the like, small molecular substances such as water, pyridine, dimethylformamide or triethylamine and the like are added into a system, so that the dissolution of raw materials in the system is promoted, the catalytic effect is exerted, and the high-efficiency conversion of serine to 3-chloro-alanine is realized.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1) the invention promotes the dissolution of the raw material serine in a system by adding a proper amount of water into a dioxane solvent, generates excellent catalytic action on chlorination reaction taking thionyl chloride as a raw material by using organic bases such as pyridine, dimethylformamide or triethylamine and the like, accelerates the reaction process, and obtains a satisfactory conversion rate at a lower temperature, wherein the highest conversion rate can reach 97%. In comparison with the addition of hydrogen chloride (the concentration is generally 4mol/L) in the literature, the high concentration of hydrogen chloride promotes the dissolution of the raw material serine, but at the same time may inhibit the decomposition of thionyl chloride (the decomposition product of thionyl chloride includes hydrogen chloride, and the excessive hydrogen chloride existing in the system inhibits the decomposition reaction). The invention only needs a small amount of water and small organic molecules, has less dosage, more easily obtained reagents and more convenient use and treatment.
2) Cost advantage. The invention adopts water, pyridine, dimethylformamide or triethylamine and other small molecular substances, and the cost of the reagent is obviously lower than that of a system in which hydrogen chloride is added into a solvent. The reaction in the invention is carried out at room temperature, a heating system of a reaction device can be saved, and the purchase and operation cost of the reactor is reduced, thereby achieving two purposes.
3) The safety is good. The method reported in the literature needs to use hydrogen chloride-dioxane, acetone and the like as easy-to-detoxify reagents specified in the clear text of the ministry of public security, and the invention uses conventional reagents which can avoid some potential safety risks.
4) The process is more green and environment-friendly. Water is more environmentally friendly than hydrogen chloride. The post-treatment after the reaction is simple, and the product can be obtained after simple solid-liquid separation. The solvent containing the small molecular substances can be recycled.
Drawings
FIG. 1 is a process flow diagram of the present invention.
1-dioxane solvent tank; 2-a water tank; 3-thionyl chloride tank; 4-a catalyst tank; 5-raw material feeding pipe; 6-raw material feeding pipe; 7-raw material feeding pipe; 8-raw material feeding pipe; 9-a reactor; 10-a pipeline; 11-chemical pump; 12-a recovered solvent storage tank; 13-product discharge pipe; 14-a pipeline; 15-an exhaust gas conduit; 16-a buffer tank; 17-an exhaust gas conduit; 18-lye tanks; 19-a solid-liquid separation device; 20-product storage tank; 21-a pipeline; 22-a vacuum pump; 23-an exhaust gas conduit; 24-feedstock feed pipe; 25-a raw material tank;
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto.
As shown in figure 1, a reaction device for preparing 3-chloro-alanine by taking serine as a raw material comprises a reaction system I and a solid-liquid separation system II; the reaction system I comprises a reactor 9 with a stirring paddle, a dioxane solvent tank 1, a water tank 2, a raw material tank 25, a thionyl chloride tank 3, a catalyst tank 4 (containing alkaline substances such as pyridine, dimethylformamide or triethylamine) and a chemical pump 11. The top of the reactor 9 is provided with a raw material feeding pipe 5, 6, 24, 7, 8 which are respectively connected with a dioxane solvent tank 1, a water tank 2, a raw material tank 25, a thionyl chloride tank 3 and a catalyst tank 4. The solid-liquid separation system II comprises a solid-liquid separation device 19, a buffer tank 16, an alkali liquor tank 18, a vacuum pump 22, a recovered solvent storage tank 12 and a product storage tank 20; wherein the solid-liquid separation device 19, the buffer tank 16, the lye tank 18 and the vacuum pump 22 are connected with each other through waste gas pipelines 15, 17 and 23 in turn. The solid-liquid separation device 19 is provided with a product outlet which is connected with a product storage tank 20 through a pipeline 21 and is provided with a solvent outlet which is connected with a recovered solvent storage tank 12 through a pipeline 14. The solvent in the recovered solvent storage tank 12 is injected into the reactor 9 in the reaction system I through a pipeline 10 under the action of a chemical pump 11. A product discharge pipe 13 is arranged at the bottom of the reactor 9 and is connected with the solid-liquid separation system II.
The invention relates to a method for preparing 3-chloro-alanine hydrochloride by taking serine as a raw material, which comprises the steps of respectively adding dioxane, water and thionyl chloride into a reactor 9 through feeding pipes 5, 6 and 7, stirring properly to mix the dioxane, the water and the thionyl chloride fully and uniformly, then slowly dripping a catalyst through a raw material feeding pipe 8, stirring for 2 hours slowly to release the mixing heat completely, returning to the normal temperature, then adding serine powder into the reactor 9 from a raw material tank 25 through a raw material feeding pipe 24, starting stirring for full mixing, and continuously stirring for 20-30 hours. After the reaction is completed sufficiently, the vacuum pump is started, the reaction liquid is transferred from the reactor 9 to the solid-liquid separation device 19 under the action of negative pressure, and simultaneously, part of the reaction waste gas enters the alkali liquor tank 18 to be absorbed (the waste gas is acidic gas) after passing through the waste gas pipelines 15, 17 and 23 and the buffer tank 16. After the vacuum pumping is carried out for a certain time, the solid-liquid separation device 19 is started, and filter residue (namely the product 3-chloro-alanine hydrochloride) and filtrate are collected at the same time. The filtrate can be recycled and re-enters the reactor 9 through the chemical pump 11 and the pipeline 10 to start the reaction of the next period.
Example 1:
step one, adding 2.6mL of water into 120mL of dioxane solution, shaking up, adding into a reactor, then dropwise adding 18mL of thionyl chloride, stirring uniformly (stirring speed 600r/min), dropwise adding 0.4mL of triethylamine, continuing stirring for 120 minutes (stirring speed 600r/min), finally adding 12 g of serine sample, and continuously stirring vigorously for 24 hours (stirring speed 600r/min) at normal temperature (30-35 ℃).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 60 minutes at room temperature, and absorbing the exhausted gas by saturated hydrated lime solution. And then adding the materials into a vacuum filtration device, and collecting filtrate and filter residues. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 16.6 g, with a yield of 91%. The structure of the product is determined by mass spectrum and nuclear magnetism. Mass spectrum [ M +]Peak 126;1HNMR(300MHz D2O)δ4.80(2H),δ4.18(1H),δ4.08(1H),δ4.04(1H)；13CNMR(75MHzD2o) δ 173.9(s), δ 58.3(s), δ 46.2(s), indicating that the compound is 3-chloro-alanine, data consistent with literature reports.
Example 2:
step one, adding 1.0mL of water into 40mL of dioxane solution, shaking up, adding into a reactor, then dropwise adding 4mL of thionyl chloride, stirring uniformly, dropwise adding 0.3mL of triethylamine, continuing stirring for 60 minutes, finally adding 3 g of serine sample, and continuously stirring for 21 hours at normal temperature (30-35 ℃).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 30 minutes at room temperature, and absorbing the exhausted gas by saturated hydrated lime solution. And then adding the materials into a centrifugal separation device, and collecting filtrate and filter residues. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 3.9 g, with a yield of 85%.
Example 3:
step one, adding 2.9mL of water into 200mL of dioxane solution, shaking up, adding into a reactor, then dropwise adding 20mL of thionyl chloride, stirring uniformly (stirring speed 1000r/min), dropwise adding 0.3mL of dimethylformamide, continuing stirring and mixing (stirring speed 1000r/min), finally adding 12 g of serine sample, and continuously stirring vigorously for 28 hours (stirring speed 1000r/min) at normal temperature (30-35 ℃).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 30 minutes at room temperature, and absorbing the exhausted gas by saturated hydrated lime solution. And then adding the materials into a vacuum filtration device, and collecting filtrate and filter residues. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 17.4 g, with a yield of 95%.
Example 4:
step one, adding 1.8mL of water into 120mL of dioxane solution, shaking up, adding into a reactor, then dropwise adding 17mL of thionyl chloride, stirring and mixing uniformly, dropwise adding 0.1mL of dimethylformamide and 0.1mL of pyridine, continuing stirring for 60 minutes (stirring speed of 1000r/min), finally adding 12 g of serine sample, and continuously stirring vigorously for 20 hours (stirring speed of 1000r/min) at normal temperature (30-35 ℃).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 60 minutes at room temperature, and absorbing the exhausted gas by saturated sodium hydroxide solution. And then adding the materials into a vacuum filtration device, and collecting filtrate and filter residues. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 15.6 g, with a yield of 85%.
Example 5:
step one, adding 3.5mL of water into 120mL of dioxane solution, shaking up, adding into a reactor, then dropwise adding 17mL of thionyl chloride, dropwise adding 0.2mL of triethylamine and 0.1mL of pyridine, stirring and mixing uniformly (stirring speed 1000r/min), finally adding 12 g of serine sample, and continuously stirring for 20 hours (stirring speed 1000r/min) at normal temperature (30-35 ℃).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 60 minutes at room temperature, and absorbing the exhausted gas by saturated sodium hydroxide solution. And then adding the materials into a vacuum filtration device, and collecting filtrate and filter residues. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 14.6 g, with a yield of 80%.
Example 6:
step one, adding 2.2mL of water into 122mL of dioxane solution, shaking uniformly, adding into a reactor, then dropwise adding 19mL of thionyl chloride, dropwise adding 0.05mL of triethylamine and 0.2mL of dimethylformamide, stirring and mixing (stirring speed is 1000r/min), finally adding 12 g of serine sample, and continuously stirring for 28 hours (stirring speed is 1000r/min) at normal temperature (30-35 ℃).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 60 minutes at room temperature, and absorbing the exhausted gas by saturated sodium hydroxide solution. And then adding the materials into a vacuum filtration device, and collecting filtrate and filter residues. The filtrate is used for the next cycle. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 15.2 g, with a yield of 84%.
Example 7
Step one, adding 1mL of water into 60mL of dioxane solution, shaking up, adding into a reactor, then dropwise adding 8mL of thionyl chloride, and stirring uniformly (stirring speed 800 r/min); 0.5mL of pyridine is added dropwise, stirring is continued (stirring speed 800r/min), and finally 6 g of serine sample is added, and stirring is continued for 20 hours (stirring speed 800r/min) at normal temperature (30-35 ℃).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 30 minutes at room temperature, and absorbing the extracted waste gas by saturated sodium hydroxide solution. And then adding the materials into a vacuum filtration device, and collecting filtrate and filter residues. The filtrate is used for the next cycle. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 8.8 g, with a yield of 97%.
45mL of the filtrate collected in step two was used, then 15mL of dioxane solution and 6mL of thionyl chloride were supplemented, and finally 6 g of serine sample was added, and stirring was continued vigorously at room temperature (30-35 ℃) for 20 hours (stirring speed 800 r/min).
After completion of the stirring reaction, the treatment in step two was repeated to finally obtain 8.0 g of 3-chloro-alanine hydrochloride in a yield of 88%.
Example 8:
step one, adding 2.2mL of water into 120mL of dioxane solution, shaking uniformly, adding into a reactor, then dropwise adding 19mL of thionyl chloride, dropwise adding 0.05mL of triethylamine and 0.2mL of dimethylformamide, stirring and mixing (stirring speed is 1000r/min), finally adding 12 g of serine sample, and continuously stirring for 20 hours at 5 ℃ (stirring speed is 1000 r/min).
And step two, after the stirring reaction is finished, vacuumizing the reaction material for 30 minutes at room temperature, and absorbing the extracted waste gas by saturated sodium hydroxide solution. And then adding the materials into a vacuum filtration device, and collecting filtrate and filter residues. The filtrate is used for the next cycle. The filter residue was 3-chloro-alanine hydrochloride, which was dried and weighed 12.6 g, with a yield of 70%.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A method for preparing 3-chloro-alanine hydrochloride by taking water as an auxiliary agent is characterized by comprising the following steps:
mixing dioxane, thionyl chloride, water, an organic small molecular catalyst and serine, and stirring; after the reaction is finished, carrying out solid-liquid separation on the obtained liquid material to obtain filter residue, namely 3-chloro-alanine hydrochloride.
2. The method of claim 1, wherein: the mass ratio of the dioxane to the water to the thionyl chloride is 30: (0.1-10): (1-30).
3. The method of claim 1, wherein: the organic small molecular catalyst is at least one of pyridine, dimethylformamide and triethylamine; the mass ratio of the organic micromolecule catalyst to water is (0.01-10): 1.
4. the production method according to claim 1, 2 or 3, characterized in that: the mass ratio of the serine to the dioxane is 1: (2-50).
5. The method of claim 1, wherein: the temperature of the stirring reaction is 0-45 ℃, and the stirring reaction time is 10-40 hours.
6. The method of claim 1, wherein: the temperature during the stirring reaction is 25-35 ℃, and the stirring reaction time is 20-30 hours.
7. The method of claim 1, wherein: and after the reaction is finished, vacuumizing the reaction materials, and absorbing the extracted waste gas by alkali liquor.
8. The method of claim 7, wherein: the vacuumizing temperature is room temperature, and the vacuumizing time is 30-60 minutes.
9. The method of claim 1, wherein: the filtrate collected after the solid-liquid separation is recycled; the solid-liquid separation is vacuum filtration or centrifugal separation.
10. A reaction apparatus for carrying out the method according to any one of claims 1 to 9, characterized in that: comprises a reaction system and a separation system; the reaction system comprises a reactor, a dioxane tank, a water tank, a thionyl chloride tank and a raw material tank; the separation system comprises a solid-liquid separation device, a solvent recovery tank, a buffer tank, an alkali liquor tank, a vacuum pump and a chemical pump;
the top of the reactor is provided with a solid material feeding hole and a solvent feeding pipe, the inside of the reactor is provided with a stirring paddle, and the bottom of the reactor is provided with a discharging hole; a discharge pipe at the bottom of the reactor is connected with a feed pipe orifice of the solid-liquid separation device; the solid-liquid separation device, the buffer tank, the lye tank and the vacuum pump are sequentially connected; the waste gas in the solid-liquid separation device flows through the buffer tank and enters the lye tank to be absorbed under the negative pressure effect generated by the vacuum pump; the feeding pipe orifice of the solvent recovery tank is connected with the liquid discharging pipe orifice of the solid-liquid separation device, the feeding pipe orifice of the chemical pump is connected with the discharging pipe orifice of the solvent recovery storage tank, the discharge port of the chemical pump is connected with the reactor, the recovered solvent enters the reaction system again through the chemical pump, and the solvent is recycled.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115872882A (en) * | 2021-09-27 | 2023-03-31 | 中国科学院大连化学物理研究所 | Synthetic method of 3-chloro-alanine |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294528A (en) * | 2015-11-26 | 2016-02-03 | 成都百事兴科技实业有限公司 | Preparation method for L-selenocysteine |
| CN106518695A (en) * | 2016-11-03 | 2017-03-22 | 安徽省诚联医药科技有限公司 | A synthetic method of (R)-methyl 2-amino-3-chloropropanoate hydrochloride |
| RU2015153332A (en) * | 2015-12-11 | 2017-06-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Пензенский государственный университет архитектуры и строительства" | METHOD FOR PRODUCING BIOLOGICALLY ACTIVE SUBSTANCE β-CHLORO-L-ALANINE |
| CN107879925A (en) * | 2017-09-21 | 2018-04-06 | 南京红太阳生物化学有限责任公司 | A kind of synthetic method of the chloropropionic acids of high-purity high-yield L 2 |
| CN110590587A (en) * | 2019-09-23 | 2019-12-20 | 湖北宇阳药业有限公司 | Synthetic method of 3-chloro-L-alanine methyl ester hydrochloride |
| WO2021098712A1 (en) * | 2019-11-21 | 2021-05-27 | 利尔化学股份有限公司 | Preparation method for chlorohomoserine alkyl ester |
-
2019
- 2019-12-27 CN CN201911373970.5A patent/CN111018728A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294528A (en) * | 2015-11-26 | 2016-02-03 | 成都百事兴科技实业有限公司 | Preparation method for L-selenocysteine |
| RU2015153332A (en) * | 2015-12-11 | 2017-06-16 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Пензенский государственный университет архитектуры и строительства" | METHOD FOR PRODUCING BIOLOGICALLY ACTIVE SUBSTANCE β-CHLORO-L-ALANINE |
| CN106518695A (en) * | 2016-11-03 | 2017-03-22 | 安徽省诚联医药科技有限公司 | A synthetic method of (R)-methyl 2-amino-3-chloropropanoate hydrochloride |
| CN107879925A (en) * | 2017-09-21 | 2018-04-06 | 南京红太阳生物化学有限责任公司 | A kind of synthetic method of the chloropropionic acids of high-purity high-yield L 2 |
| CN110590587A (en) * | 2019-09-23 | 2019-12-20 | 湖北宇阳药业有限公司 | Synthetic method of 3-chloro-L-alanine methyl ester hydrochloride |
| WO2021098712A1 (en) * | 2019-11-21 | 2021-05-27 | 利尔化学股份有限公司 | Preparation method for chlorohomoserine alkyl ester |
Non-Patent Citations (2)
| Title |
|---|
| 姜慧君等: "《医用化学》", 东南大学出版社, pages: 202 * |
| 巢峰等: "《上海经济区工业概貌》", 28 February 1986, 学林出版社, pages: 78 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115872882A (en) * | 2021-09-27 | 2023-03-31 | 中国科学院大连化学物理研究所 | Synthetic method of 3-chloro-alanine |
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