CN116854633B - Application of silicon carbide micro-channel reactor and preparation method of 2-chloro-3-aminopyridine - Google Patents
Application of silicon carbide micro-channel reactor and preparation method of 2-chloro-3-aminopyridine Download PDFInfo
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- CN116854633B CN116854633B CN202311126200.7A CN202311126200A CN116854633B CN 116854633 B CN116854633 B CN 116854633B CN 202311126200 A CN202311126200 A CN 202311126200A CN 116854633 B CN116854633 B CN 116854633B
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- MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 title claims abstract description 35
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229910010271 silicon carbide Inorganic materials 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 claims abstract description 80
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 64
- 238000006243 chemical reaction Methods 0.000 claims abstract description 63
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 19
- 238000002156 mixing Methods 0.000 claims abstract description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 32
- 238000001914 filtration Methods 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 239000012074 organic phase Substances 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 239000012071 phase Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 239000006227 byproduct Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 238000004821 distillation Methods 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 238000004811 liquid chromatography Methods 0.000 description 12
- XNYFAJZQMFNULQ-UHFFFAOYSA-N pyridin-1-ium-3-amine;chloride Chemical compound Cl.NC1=CC=CN=C1 XNYFAJZQMFNULQ-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 7
- IWJLGRUFXOYQPO-UHFFFAOYSA-N 2-chloro-1h-pyridin-2-amine Chemical compound NC1(Cl)NC=CC=C1 IWJLGRUFXOYQPO-UHFFFAOYSA-N 0.000 description 6
- 239000012295 chemical reaction liquid Substances 0.000 description 6
- 230000006837 decompression Effects 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000005886 Chlorantraniliprole Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- PSOVNZZNOMJUBI-UHFFFAOYSA-N chlorantraniliprole Chemical compound CNC(=O)C1=CC(Cl)=CC(C)=C1NC(=O)C1=CC(Br)=NN1C1=NC=CC=C1Cl PSOVNZZNOMJUBI-UHFFFAOYSA-N 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 1
- 229960004633 pirenzepine Drugs 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- 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
Abstract
The invention provides an application of a silicon carbide microchannel reactor and a preparation method of 2-chloro-3-aminopyridine, belonging to the field of chemical synthesis. The preparation method provided by the invention comprises the following steps: and dissolving 3-aminopyridine in hydrochloric acid, introducing the obtained solution and hydrogen peroxide into a silicon carbide microchannel reactor, and mixing for chlorination reaction to obtain the 2-chloro-3-aminopyridine. According to the invention, the silicon carbide micro-channel reactor is used for synthesizing the 2-chloro-3-aminopyridine, and the silicon carbide in the silicon carbide micro-channel reactor has good mass and heat transfer effects, so that the silicon carbide micro-channel reactor can well remove heat released by the chlorination reaction, the phenomenon of local temperature runaway is avoided, and the materials are mixed more uniformly, thereby solving the problems of more byproducts and low reaction yield, and improving the purity and yield of the 2-chloro-3-aminopyridine.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to application of a silicon carbide microchannel reactor and a preparation method of 2-chloro-3-aminopyridine.
Background
The 2-chloro-3-aminopyridine is an important fine chemical product, is a synthetic intermediate of pesticides such as chlorantraniliprole and the like, and is also a key intermediate for synthesizing pirenzepine, so that the 2-chloro-3-aminopyridine has wide application in the fields of medicines, pesticide intermediates and the like. The 2-chloro-3-aminopyridine and its derivatives can be used as raw materials of food additives and other substances, and can also be directly used as medicines and analytical detection reagents.
The method is characterized in that 3-aminopyridine is used as a raw material, chlorination reaction is carried out under the action of hydrogen peroxide and hydrochloric acid, and after the reaction is finished, refining post-treatments such as extraction, concentration, separation and the like are carried out to obtain the 2-chloro-3-aminopyridine. However, the process adopts the batch operation of the traditional kettle reaction, and the purity and the yield of the produced 3-aminopyridine are low to be improved.
Disclosure of Invention
The invention aims to provide an application of a silicon carbide microchannel reactor and a preparation method of 2-chloro-3-aminopyridine, wherein the purity and the yield of the 3-aminopyridine prepared by the method are high.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an application of a silicon carbide microchannel reactor in preparation of 2-chloro-3-aminopyridine.
The invention also provides a preparation method of the 2-chloro-3-aminopyridine, which comprises the following steps:
and dissolving 3-aminopyridine in hydrochloric acid, introducing the obtained 3-aminopyridine solution and hydrogen peroxide into a silicon carbide microchannel reactor, and mixing for chlorination reaction to obtain the 2-chloro-3-aminopyridine.
Preferably, the mass ratio of the 3-aminopyridine to the hydrochloric acid is 1:8-15;
the mass concentration of the hydrochloric acid is 30-36%.
Preferably, the 3-aminopyridine is mixed with H in hydrogen peroxide 2 O 2 The molar ratio of (2) is 1:1-1.5.
Preferably, the introducing speed of the 3-aminopyridine solution is 11-19 mL/min; the hydrogen peroxide is introduced at a speed of 1.2-2.2 mL/min.
Preferably, the temperature of the chlorination reaction is 0-50 ℃.
Preferably, the number of the reaction modules in the silicon carbide micro-channel reactor is 2-5.
Preferably, the chlorination reaction comprises a stage reaction carried out in each reaction module in sequence; the reaction time of the stages is independently 2-10 min.
Preferably, after the chlorination reaction, the method further comprises: extracting the obtained chlorination reaction product to obtain an organic phase and a water phase; and removing the extractant from the organic phase, and filtering and drying the obtained residue to obtain a pure 2-chloro-3-aminopyridine product.
Preferably, the extracting agent comprises one or more of ethyl acetate, diethyl ether, toluene and chloroform.
The invention provides a preparation method of 2-chloro-3-aminopyridine, which comprises the following steps: and dissolving 3-aminopyridine in hydrochloric acid, introducing the obtained 3-aminopyridine solution and hydrogen peroxide into a silicon carbide microchannel reactor, and mixing for chlorination reaction to obtain the 2-chloro-3-aminopyridine. According to the invention, the silicon carbide micro-channel reactor is used for synthesizing the 2-chloro-3-aminopyridine, and the silicon carbide in the silicon carbide micro-channel reactor has good mass and heat transfer effects, so that the silicon carbide micro-channel reactor can well remove heat released by the chlorination reaction, the phenomenon of local temperature runaway is avoided, and the materials are mixed more uniformly, thereby solving the problems of more byproducts and low reaction yield, and improving the purity and yield of the 2-chloro-3-aminopyridine. The example results show that the yield of the 2-chloro-3-aminopyridine prepared by the method is 95.2-97.5% and the purity is 99.1-99.6%.
Furthermore, the invention utilizes the silicon carbide microchannel reactor to synthesize the 2-chloro-3-aminopyridine, effectively solves the problem of long reaction time, reduces energy consumption, can realize continuous production of reaction, improves production efficiency, is convenient to operate and is suitable for industrial production.
Drawings
FIG. 1 is a diagram of an apparatus used in an embodiment of the present invention.
Detailed Description
The invention provides an application of a silicon carbide microchannel reactor in preparation of 2-chloro-3-aminopyridine.
The invention also provides a preparation method of the 2-chloro-3-aminopyridine, which comprises the following steps:
and dissolving 3-aminopyridine in hydrochloric acid, introducing the obtained 3-aminopyridine solution and hydrogen peroxide into a silicon carbide microchannel reactor, and mixing for chlorination reaction to obtain the 2-chloro-3-aminopyridine.
In the invention, the mass ratio of the 3-aminopyridine to the hydrochloric acid is preferably 1:8-15, more preferably 1:9-12; the mass concentration of the hydrochloric acid is preferably 30-36%, more preferably 32-35%.
In the invention, H in the 3-aminopyridine and hydrogen peroxide 2 O 2 The molar ratio of (2) is preferably 1:1-1.5, more preferably 1:1.1-1.2; the mass concentration of the hydrogen peroxide is preferably 27-35%, more preferably 28-32%.
In the invention, the 3-aminopyridine solution and hydrogen peroxide are preferably introduced into a silicon carbide microchannel reactor through a first plunger pump and a second plunger pump; the 3-aminopyridine solution is preferably introduced at a speed of 11-19 mL/min, more preferably 12-15 mL/min; the hydrogen peroxide is introduced at a speed of 1.2-2.2 mL/min, more preferably 1.5-2 mL/min.
In the present invention, the temperature of the chlorination reaction is preferably 0 to 50 ℃, more preferably 25 to 35 ℃.
In the invention, the number of the reaction modules in the silicon carbide micro-channel reactor is preferably 2-5; the chlorination reaction includes a stage reaction performed in each reaction module in sequence; the reaction time in the stages is preferably independently 2 to 10min, more preferably 4 to 7min. In the invention, the model of the silicon carbide micro-channel reactor is preferably S5-30.
In the present invention, each of the reaction modules is constituted by an inverted 6-shaped reaction unit.
In the present invention, it is preferable that after the chlorination reaction, the method further comprises: extracting the obtained chlorination reaction product to obtain an organic phase and a water phase; and removing the extractant from the organic phase, and filtering and drying the obtained residue to obtain a pure 2-chloro-3-aminopyridine product.
In the present invention, the extractant for extraction preferably includes one or more of ethyl acetate, diethyl ether, toluene and chloroform, more preferably chloroform.
In the present invention, the means for removing the extractant preferably comprises distillation; the pressure of the distillation is preferably normal pressure, and the temperature is preferably 70 ℃; the temperature of the drying is preferably 70 ℃.
The application of the silicon carbide microchannel reactor and the preparation method of 2-chloro-3-aminopyridine provided by the invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the invention.
The device used in the embodiment of the invention is shown in fig. 1:1. the device comprises a first plunger pump, a second plunger pump, a first reaction module, a second reaction module, a centrifugal extractor and a receiving bottle, wherein the first plunger pump, the second plunger pump, the first reaction module, the second reaction module, the centrifugal extractor and the receiving bottle are arranged in sequence.
In an embodiment, the silicon carbide microchannel reactor is model S5-30.
Example 1
Preparing 3-aminopyridine and hydrochloric acid with the mass concentration of 36% according to the mass ratio of 1:10, detecting the content of the raw material 3-aminopyridine by using liquid chromatography after the preparation, and then using a first plunger pump and a second plunger pump to mix the 3-aminopyridine hydrochloride solution with hydrogen peroxide with the mass concentration of 35% (H in the 3-aminopyridine and the hydrogen peroxide) 2 O 2 The molar ratio of (1:1.1) is conveyed to a first reaction module, the volume flow rate of the 3-aminopyridine hydrochloride solution conveyed by a first plunger pump is 14mL/min, and the volume flow rate of the 35% hydrogen peroxide conveyed by a second plunger pump is 1.6mL/min; then the reaction solution enters a second reaction module for reaction, the reaction temperature is 25 ℃, the residence time of each reaction module is 7min, and the total residence time is 14min;
after the reaction is finished, the reaction liquid enters a centrifugal extractor for extraction, chloroform is selected as an extracting agent, then separation distillation is carried out at the temperature of 70 ℃ under normal pressure, along with the distillation of the chloroform as the extracting agent, the target product 2-chloro-aminopyridine is separated out and becomes solid, then normal-temperature decompression filtration is carried out, the solid and the liquid are separated, a filter cake obtained after filtration is dried at the temperature of 70 ℃, and finally the dried 2-chloro-3 aminopyridine is obtained; the content was 99.2% by liquid chromatography and the yield was 95.2%.
Example 2
Preparing 3-aminopyridine and hydrochloric acid with the mass concentration of 36% according to the mass ratio of 1:10, detecting the content of the raw material 3-aminopyridine by using liquid chromatography after the preparation, and then using a first plunger pump and a second plunger pump to mix the 3-aminopyridine hydrochloride solution with hydrogen peroxide with the mass concentration of 35% (H in the 3-aminopyridine and the hydrogen peroxide) 2 O 2 The molar ratio of (1:1.1) is conveyed to a first reaction module, the volume flow rate of the 3-aminopyridine hydrochloride solution conveyed by a first plunger pump is 14mL/min, the volume flow rate of the 35% hydrogen peroxide conveyed by a second plunger pump is 1.6mL/min, then the reaction solution enters a second reaction module for reaction, the reaction temperature is 35 ℃, the residence time of each reaction module is 7min, and the total residence time is 14min;
after the reaction is finished, the reaction liquid enters a centrifugal extractor for extraction, chloroform is selected as an extracting agent, then separation distillation is carried out at the temperature of 70 ℃ under normal pressure, along with the distillation of the chloroform as the extracting agent, the target product 2-chloro-aminopyridine is separated out and becomes solid, then normal-temperature decompression filtration is carried out, the solid and the liquid are separated, a filter cake obtained after filtration is dried at the temperature of 70 ℃, and finally the dried 2-chloro-3 aminopyridine is obtained; the content was 99.6% by liquid chromatography and the yield was 97.5%.
Example 3
Preparing 3-aminopyridine and hydrochloric acid with the mass concentration of 36% according to the mass ratio of 1:10, detecting the content of the 3-aminopyridine in the raw material by using liquid chromatography after the preparation, and then using a first plunger pump and a second plunger pump to mix the 3-aminopyridine hydrochloride solution with the mass concentration of 35% of hydrogen peroxide (H in the 3-aminopyridine and the hydrogen peroxide 2 O 2 The molar ratio of (1:1.1) is conveyed to a first reaction module, the volume flow rate of the 3-aminopyridine hydrochloride solution conveyed by a first plunger pump is 14mL/min, the volume flow rate of the 35% hydrogen peroxide conveyed by a second plunger pump is 1.6mL/min, then the reaction solution enters a second reaction module for reaction, the reaction temperature is 45 ℃, the residence time of each reaction module is 7min, and the total residence time is 14min;
after the reaction is finished, the reaction liquid enters a centrifugal extractor for extraction, chloroform is selected as an extracting agent, then separation distillation is carried out at the temperature of 70 ℃ under normal pressure, along with the distillation of the chloroform as the extracting agent, the target product 2-chloro-aminopyridine is separated out and becomes solid, then normal-temperature decompression filtration is carried out, the solid and the liquid are separated, a filter cake obtained after filtration is dried at the temperature of 70 ℃, and finally the dried 2-chloro-3 aminopyridine is obtained; the content was 99.5% and the yield was 96.8% by liquid chromatography.
Example 4
Preparing 3-aminopyridine and hydrochloric acid with the mass concentration of 36% according to the mass ratio of 1:10, detecting the content of the raw material 3-aminopyridine by using liquid chromatography after the preparation, and then using a first plunger pump and a second plunger pump to mix the 3-aminopyridine hydrochloride solution with hydrogen peroxide with the mass concentration of 35% (H in the 3-aminopyridine and the hydrogen peroxide) 2 O 2 The molar ratio of (1:1.1) is conveyed to a first reaction module, the volume flow rate of the 3-aminopyridine hydrochloride solution conveyed by a first plunger pump is 14mL/min, the volume flow rate of the 35% hydrogen peroxide conveyed by a second plunger pump is 1.6mL/min, then the reaction solution enters a second reaction module for reaction, the reaction temperature is 55 ℃, the residence time of each reaction module is 7min, and the total residence time is 14min;
after the reaction is finished, the reaction liquid enters a centrifugal extractor for extraction, chloroform is selected as an extracting agent, then separation distillation is carried out at the temperature of 70 ℃ under normal pressure, along with the distillation of the chloroform as the extracting agent, the target product 2-chloro-aminopyridine is separated out and becomes solid, then normal-temperature decompression filtration is carried out, the solid and the liquid are separated, a filter cake obtained after filtration is dried at the temperature of 70 ℃, and finally the dried 2-chloro-3 aminopyridine is obtained; the content was 99.1% by liquid chromatography and the yield was 96%.
Example 5
Preparing 3-aminopyridine and hydrochloric acid with the mass concentration of 36% according to the mass ratio of 1:10, detecting the content of the raw material 3-aminopyridine by using liquid chromatography after the preparation, and then using a first plunger pump and a second plunger pump to mix the 3-aminopyridine hydrochloride solution with hydrogen peroxide with the mass concentration of 35% (H in the 3-aminopyridine and the hydrogen peroxide) 2 O 2 The molar ratio of (2) is 1:1.1 The solution is conveyed to a first reaction module, the volume flow rate of the solution of 3-aminopyridine hydrochloride conveyed by a first plunger pump is 19mL/min, the volume flow rate of 35% hydrogen peroxide conveyed by a second plunger pump is 2.2mL/min, then the reaction solution enters a second reaction module for reaction, the reaction temperature is 35 ℃, the residence time of each reaction module is 5min, and the total residence time is 10min;
after the reaction is finished, the reaction liquid enters a centrifugal extractor for extraction, chloroform is selected as an extracting agent, then separation distillation is carried out at the temperature of 70 ℃ under normal pressure, along with the distillation of the chloroform as the extracting agent, the target product 2-chloro-aminopyridine is separated out and becomes solid, then normal-temperature decompression filtration is carried out, the solid and the liquid are separated, a filter cake obtained after filtration is dried at the temperature of 70 ℃, and finally the dried 2-chloro-3 aminopyridine is obtained; the content was 99.4% and the yield was 96.6% by liquid chromatography.
Example 6
Preparing 3-aminopyridine and hydrochloric acid with the mass concentration of 36% according to the mass ratio of 1:10, detecting the content of the raw material 3-aminopyridine by using liquid chromatography after the preparation, and then using a first plunger pump and a second plunger pump to mix the 3-aminopyridine hydrochloride solution with hydrogen peroxide with the mass concentration of 35% (H in the 3-aminopyridine and the hydrogen peroxide) 2 O 2 The molar ratio of (1:1.1) is conveyed to a first reaction module, the volume flow rate of the 3-aminopyridine hydrochloride solution conveyed by a first plunger pump is 11mL/min, the volume flow rate of the 35% hydrogen peroxide conveyed by a second plunger pump is 1.2mL/min, then the reaction solution enters a second reaction module for reaction, the reaction temperature is 35 ℃, the residence time of each reaction module is 9min, and the total residence time is 18min;
after the reaction is finished, the reaction liquid enters a centrifugal extractor for extraction, chloroform is selected as an extracting agent, then separation distillation is carried out at the temperature of 70 ℃ under normal pressure, along with the distillation of the chloroform as the extracting agent, the target product 2-chloro-aminopyridine is separated out and becomes solid, then normal-temperature decompression filtration is carried out, the solid and the liquid are separated, a filter cake obtained after filtration is dried at the temperature of 70 ℃, and finally the dried 2-chloro-3 aminopyridine is obtained; the content was 99.2% by liquid chromatography and the yield was 97%.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (3)
1. The preparation method of the 2-chloro-3-aminopyridine is characterized by comprising the following steps:
dissolving 3-aminopyridine in hydrochloric acid, introducing the obtained 3-aminopyridine solution and hydrogen peroxide into a silicon carbide microchannel reactor for mixing and carrying out chlorination reaction, and extracting the obtained chlorination reaction product to obtain an organic phase and a water phase; filtering and drying the residue after the extractant is removed from the organic phase to obtain a pure 2-chloro-3-aminopyridine product;
h in the 3-aminopyridine and hydrogen peroxide 2 O 2 The molar ratio of (2) is 1:1.1;
the temperature of the chlorination reaction is 35 ℃;
the introducing speed of the 3-aminopyridine solution is 14mL/min; the hydrogen peroxide is introduced at a speed of 1.6mL/min;
the number of the reaction modules in the silicon carbide micro-channel reactor is 2;
the chlorination reaction includes a stage reaction performed in each reaction module in sequence; the time of the stage reaction was independently 7min.
2. The preparation method of claim 1, wherein the mass ratio of the 3-aminopyridine to the hydrochloric acid is 1:8-15;
the mass concentration of the hydrochloric acid is 30-36%.
3. The method of claim 1, wherein the extracted extractant comprises one or more of ethyl acetate, diethyl ether, toluene, and chloroform.
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