CN116332732A - Preparation method of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride - Google Patents
Preparation method of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride Download PDFInfo
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- CN116332732A CN116332732A CN202111545858.2A CN202111545858A CN116332732A CN 116332732 A CN116332732 A CN 116332732A CN 202111545858 A CN202111545858 A CN 202111545858A CN 116332732 A CN116332732 A CN 116332732A
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- trichlorophenoxy
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- ethyl chloride
- trichlorophenol
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- YNJGVSWHTYTTDC-UHFFFAOYSA-N 1,3,5-trichloro-2-(2-chloroethoxy)benzene Chemical compound ClCCOC1=C(Cl)C=C(Cl)C=C1Cl YNJGVSWHTYTTDC-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 75
- 239000000463 material Substances 0.000 claims abstract description 71
- LINPIYWFGCPVIE-UHFFFAOYSA-N 2,4,6-trichlorophenol Chemical compound OC1=C(Cl)C=C(Cl)C=C1Cl LINPIYWFGCPVIE-UHFFFAOYSA-N 0.000 claims abstract description 32
- 239000003513 alkali Substances 0.000 claims abstract description 30
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims abstract description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 39
- 238000005406 washing Methods 0.000 claims description 29
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 23
- 239000000243 solution Substances 0.000 claims description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000006266 etherification reaction Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 9
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 239000012670 alkaline solution Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 abstract description 20
- 239000002994 raw material Substances 0.000 abstract description 14
- 238000004090 dissolution Methods 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000007788 liquid Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 12
- 239000006227 byproduct Substances 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 238000004811 liquid chromatography Methods 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000007865 diluting Methods 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000005820 Prochloraz Substances 0.000 description 5
- 238000005352 clarification Methods 0.000 description 5
- TVLSRXXIMLFWEO-UHFFFAOYSA-N prochloraz Chemical compound C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl TVLSRXXIMLFWEO-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000003899 bactericide agent Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- -1 2,4, 6-trichlorophenoxy Chemical group 0.000 description 1
- 241000235349 Ascomycota Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002888 effect on disease Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
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- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/36—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/38—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of preparation of pharmaceutical intermediates, and provides a preparation method of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride. The organic alkali is mixed with the organic system of the 2,4, 6-trichlorophenol and the dichloroethane to serve as a first material, so that the organic alkali can promote the dissolution of the 2,4, 6-trichlorophenol serving as a reaction raw material while ensuring the alkaline environment of the organic phase; meanwhile, the reaction is carried out with inorganic alkali solution through micro-channel reaction equipment, so that the wettability of the alkali environment can be improved, and the reaction efficiency of raw materials is further improved; the inorganic alkali solution as a second material can react with the raw material 2,4, 6-trichlorophenol to make the raw material become salt; meanwhile, the reaction area of the microchannel reactor is large, the contact area of raw materials can be increased, and the reaction efficiency is improved. The data of the examples show that: the preparation method provided by the invention has the advantage that the yield of the obtained 2- (2, 4, 6-trichlorophenoxy) ethyl chloride reaches 91.9%.
Description
Technical Field
The invention relates to the technical field of preparation of drug intermediates, in particular to a preparation method of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
Background
Prochloraz is used as an important variety in imidazole bactericides, and has obvious control effect on diseases of various crops caused by ascomycetes and deuteromycetes. The prochloraz can keep better effect when being mixed with most pesticides, bactericides and herbicides. In addition, prochloraz is also used for multiple purposes such as seed soaking treatment, soil treatment, fruit and vegetable fresh-keeping and the like, and is one of common bactericides in the market.
The main production route of the (2, 4, 6-trichlorophenoxy) ethyl chloride as an intermediate of prochloraz serving as a bactericide is that 2,4, 6-trichlorophenol is taken as a raw material, alkoxide is formed by the raw material and inorganic salt, the alkoxide and dichloroethane generate 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, the 2,4, 6-trichlorophenoxy) ethyl chloride is reacted in two steps, the reaction can be completed after 5 to 6 hours at the temperature of more than 100 ℃, and then the prochloraz is prepared by alkaline washing, water washing and dichloroethane removal processes. In this method, the yield of (2, 4, 6-trichlorophenoxy) ethyl chloride is low.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for producing 2- (2, 4, 6-trichlorophenoxy) ethyl chloride. The yield of the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride obtained by the preparation method provided by the invention reaches 91.9%.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, which comprises the following steps:
taking a mixed solution of 2,4, 6-trichlorophenol, organic alkali and dichloroethane as a first material, and taking inorganic alkali solution as a second material;
and (3) carrying out etherification reaction on the first material and the second material in micro-channel reaction equipment to obtain the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
Preferably, the organic base is one of methylamine, ethylamine and triethylamine.
Preferably, the mass ratio of the 2,4, 6-trichlorophenol, the organic base and the dichloroethane in the first material is 1: (0.2-1.5): (3-10).
Preferably, the concentration of the inorganic alkali solution is 0.5-5 mol/L.
Preferably, the inorganic base in the inorganic base solution is one of sodium hydroxide, sodium carbonate, potassium carbonate and sodium bicarbonate.
Preferably, the flow ratio of the first material to the second material is 1: (1-2).
Preferably, the temperature of the etherification reaction is 150-200 ℃, and the pressure controlled by a back pressure valve of the micro-channel reaction equipment is 8-15 bar.
Preferably, after the etherification reaction, the etherification reaction system is sequentially subjected to alkali washing, water washing and desolventizing to obtain the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
Preferably, the microchannel reaction device comprises a microchannel mixer and a microchannel reactor; the microchannel mixer is heart-shaped.
Preferably, the inner diameter of the micro-channel in the micro-channel reaction device is 0.01 mm-0.1 mm.
The invention provides a preparation method of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, which comprises the following steps: taking a mixed solution of 2,4, 6-trichlorophenol, organic alkali and dichloroethane as a first material, and taking inorganic alkali solution as a second material; and (3) carrying out etherification reaction on the first material and the second material in micro-channel reaction equipment to obtain the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
The preparation method of the invention adopts organic alkali and inorganic alkali to provide alkali environment for the reaction system respectively, the organic alkali is mixed with the organic system of 2,4, 6-trichlorophenol and dichloroethane, and as a first material, the organic alkali can promote the dissolution of the reaction raw material 2,4, 6-trichlorophenol while ensuring the alkaline environment of the organic phase; meanwhile, the alkali solution and the inorganic alkali solution are subjected to etherification reaction through micro-channel reaction equipment, so that the wettability of the alkali environment can be improved, and the reaction efficiency of raw materials is further improved; the inorganic alkali solution as a second material can react with the raw material 2,4, 6-trichlorophenol to make the raw material become salt; meanwhile, the reaction area of the microchannel reactor is large, the contact area of raw materials can be increased, and the reaction efficiency is improved; finally, the yield of the obtained 2- (2, 4, 6-trichlorophenoxy) ethyl chloride is improved.
The data of the examples show that: the yield of the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride obtained by the preparation method provided by the invention reaches 91.9%.
Drawings
FIG. 1 is a schematic diagram of a microchannel mixer;
FIG. 2 is a flow chart for preparing 2- (2, 4, 6-trichlorophenoxy) ethyl chloride using a microchannel reactor apparatus.
Detailed Description
The invention provides a preparation method of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, which comprises the following steps:
taking a mixed solution of 2,4, 6-trichlorophenol, organic alkali and dichloroethane as a first material, and taking inorganic alkali solution as a second material;
and (3) carrying out etherification reaction on the first material and the second material in micro-channel reaction equipment to obtain the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
In the present invention, the raw materials used in the present invention are preferably commercially available products unless otherwise specified.
In the invention, the mass ratio of the 2,4, 6-trichlorophenol, the organic base and the dichloroethane in the first material is preferably 1: (0.2-1.5): (3 to 10), more preferably 1: (0.8-1.4): (3-6), more preferably 1: (0.98-1.5): (3-4). In the present invention, the organic base is preferably one of methylamine, ethylamine and triethylamine, and more preferably ethylamine.
In the present invention, the molar concentration of the inorganic alkali solution is preferably 0.5 to 5mol/L, more preferably 0.9 to 2mol/L, and still more preferably 0.9 to 1.5mol/L. In the present invention, the inorganic base in the inorganic alkaline solution is preferably one of sodium hydroxide, sodium carbonate, potassium carbonate and sodium bicarbonate, and more preferably sodium carbonate.
In the present invention, the flow ratio of the first material to the second material is preferably 1: (1-2), more preferably 1:1.5. in the present invention, the flow rate of the first material is preferably 5 to 20g/min, and more preferably 11g/min.
In the present invention, the temperature of the etherification reaction is preferably 150 to 200 ℃, more preferably 160 to 190 ℃, still more preferably 170 to 180 ℃; the back pressure valve of the microchannel reactor is preferably controlled to a pressure of 8 to 15bar, more preferably 11 to 14bar.
In the present invention, the microchannel reaction apparatus includes a microchannel mixer and a microchannel reactor. In the present invention, the microchannel mixer is preferably an loving type, and the structure is shown in fig. 1.
In the present invention, the inner diameter of the micro-channel reaction apparatus is preferably 0.01mm to 0.1mm, more preferably 0.011mm to 0.021mm.
The reaction process of the first material and the second material in the microchannel reaction equipment is particularly preferably as follows:
the first material and the second material respectively enter a micro-channel mixer in the micro-channel reaction equipment through two inlets to be mixed, and then flow into the micro-channel reactor to carry out etherification reaction. The temperature and pressure of the etherification reaction defined above in the present invention refer to the conditions under which the stable reaction is carried out in the microchannel reactor.
After the etherification reaction, the invention preferably further comprises the steps of sequentially carrying out alkali washing, water washing and desolventizing on the etherification reaction feed liquid to obtain the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
In the invention, the alkaline washing reagent is preferably sodium hydroxide solution, and the mass concentration of the sodium hydroxide solution is preferably 1-10%; the number of the alkali washing is preferably 2 to 10, more preferably 3 to 6; preferably, after the alkaline washing, an aqueous phase and an organic phase are obtained; the organic phase is subjected to a subsequent water wash. In the present invention, the alkaline washing can remove unreacted raw materials.
In the present invention, the number of times of the washing with water is preferably 2 to 8 times, more preferably 4 times; preferably, after said washing with water, an aqueous phase and an organic phase are obtained; the organic phase is subjected to subsequent desolventization. In the present invention, the water washing can remove alkali.
In the present invention, the desolventizing operation is preferably extraction separation.
FIG. 2 is a flow chart for preparing 2- (2, 4, 6-trichlorophenoxy) ethyl chloride using a microchannel reactor apparatus.
The following is a detailed description of a method for preparing 2- (2, 4, 6-trichlorophenoxy) ethyl chloride according to the present invention, but it should not be construed as limiting the scope of the present invention.
Example 1
2,4, 6-trichlorophenol, ethylamine and 1 dichloroethane are mixed according to the mass ratio of 300:312:1100 stirring to fully dissolve and mix, standing until the mixture is clear and then taking the mixture as a first material; and taking sodium carbonate solution with the concentration of 1mol/L as a second material. The microchannel reactor of the microchannel reaction equipment was opened, the temperature of the microchannel reactor was set to 160 ℃, and the back pressure valve was adjusted to make the reaction pressure 13bar. The feed pump is turned on, and the feed pump is regulated so that the flow rate of the first material is 11g/min and the flow rate of the second material is 13g/min. After reacting for 10min in a microchannel reactor, extracting reaction feed liquid in the microchannel reactor, washing the reaction feed liquid with 5% sodium hydroxide aqueous solution for 5 times, washing the obtained organic phase with water for 4 times successively, extracting and separating the obtained organic phase, removing the solvent, taking 3.89g of crude product, diluting with ethanol for 1000 times, and obtaining 3.64g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 0.20g of 2,4, 6-trichlorophenol and 0.05g of byproduct through liquid chromatography, wherein the conversion rate is 2.80/3=93.2%, and the selectivity is 3.64/3.69=98.6%; yield 93.2% ×98.6% =91.9%; the inner diameter of the micro-channel in the micro-channel reaction equipment is 0.015mm; the shape of the microchannel mixer is an loving heart type.
Example 2
2,4, 6-trichlorophenol, ethylamine and dichloroethane are mixed according to the mass ratio of 300:80:1100 stirring to fully dissolve and mix, standing until the mixture is clear and then taking the mixture as a first material; sodium carbonate solution with the concentration of 1mol/L is used as a second material. The microchannel reactor of the microchannel reaction equipment was opened, the temperature of the microchannel reactor was set to 160 ℃, and the back pressure valve was adjusted to make the reaction pressure 13bar. The feed pump is turned on, and the feed pump is regulated so that the flow rate of the first material is 11g/min and the flow rate of the second material is 13g/min. After reacting for 10min in a microchannel reactor, extracting reaction feed liquid in the microchannel reactor, washing the reaction feed liquid with 5% sodium hydroxide aqueous solution for 5 times, washing the obtained organic phase with water for 4 times successively, extracting and separating the obtained organic phase, removing the solvent, taking 3.89g of crude product, diluting 1000 times with ethanol, obtaining 1.72g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 1.91g of 2,4, 6-trichlorophenol, 0.26g of byproduct and 1.45/3.36=43.2 percent of conversion rate through liquid chromatography; selectivity was 1.72/1.98=86.9%; yield 43.2% ×86.9% =37.54%; the inner diameter of the micro-channel in the micro-channel reaction equipment is 0.15mm; the shape of the microchannel mixer is an loving heart type.
Example 3
2,4, 6-trichlorophenol, ethylamine and dichloroethane are mixed according to the mass ratio of 300:120:1100 is stirred to be fully dissolved and mixed, and is left to stand for clarification to be used as a first material. Sodium carbonate solution with the concentration of 1mol/L is used as a second material. The microchannel reactor of the microchannel reaction equipment was opened, the temperature of the microchannel reactor was set to 160 ℃, and the back pressure valve was adjusted to make the reaction pressure 13bar. The feed pump is turned on, and the feed pump is regulated so that the flow rate of the first material is 11g/min and the flow rate of the second material is 13g/min. After reacting for 10min in a microchannel reactor, extracting reaction feed liquid in the microchannel reactor, washing the reaction feed liquid with 5% sodium hydroxide aqueous solution for 5 times, washing the obtained organic phase with water for 4 times successively, extracting and separating the obtained organic phase, removing the solvent, taking 3.89g of crude product, diluting with ethanol for 1000 times, and obtaining 2.85g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 0.77g of 2,4, 6-trichlorophenol and 0.27g of byproduct by liquid chromatography, wherein the conversion rate is 2.38/3.15=75.6%; selectivity was 2.85/3.12=91.3%; yield 75.6% ×91.3% = 69.02%; the inner diameter of the micro-channel in the micro-channel reaction equipment is 0.015mm; the shape of the microchannel mixer is an loving heart type.
Example 4
2,4, 6-trichlorophenol, ethylamine and dichloroethane are mixed according to the mass ratio of 300:129:1100 is stirred to be fully dissolved and mixed, and is left to stand for clarification to be used as a first material. Sodium bicarbonate solution with the concentration of 1mol/L is used as a second material. The microchannel reactor of the microchannel reaction equipment was opened, the temperature of the microchannel reactor was set to 160 ℃, and the back pressure valve was adjusted to make the reaction pressure 13bar. The feed pump is turned on, and the feed pump is regulated so that the flow rate of the first material is 11g/min and the flow rate of the second material is 13g/min. After reaction in a microchannel reactor for 10min, extracting reaction feed liquid in the microchannel reactor, washing the reaction feed liquid with 5% sodium hydroxide aqueous solution for 5 times, washing the obtained organic phase with water for 4 times successively, extracting and separating the obtained organic phase, removing the solvent, taking 3.89g of crude product, diluting 1000 times with ethanol, obtaining 2.67g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 0.98g of 2,4, 6-trichlorophenol and 0.24g of byproduct by liquid chromatography, wherein the conversion rate is 2.20/3.18=69.2%; selectivity was 2.67/2.91=91.8%; yield 69.2% ×91.8% = 63.53%; the inner diameter of the micro-channel in the micro-channel reaction equipment is 0.015mm; the shape of the microchannel mixer is an loving heart type.
Example 5
2,4, 6-trichlorophenol, ethylamine and dichloroethane are mixed according to the mass ratio of 300:120:1100 is stirred to be fully dissolved and mixed, and is left to stand for clarification to be used as a first material. A potassium carbonate solution with a concentration of 1mol/L is used as a second material. The microchannel reactor of the microchannel reaction equipment was opened, the temperature of the microchannel reactor was set to 160 ℃, and the back pressure valve was adjusted to make the reaction pressure 11bar. The feed pump is turned on, and the feed pump is regulated so that the flow rate of the first material is 11g/min and the flow rate of the second material is 13g/min. After reacting for 10min in a microchannel reactor, extracting reaction feed liquid in the microchannel reactor, washing the reaction feed liquid with 5% sodium hydroxide aqueous solution for 5 times, washing the obtained organic phase with water for 4 times successively, extracting and separating the obtained organic phase, removing the solvent, taking 3.89g of crude product, diluting 1000 times with ethanol, obtaining 1.54g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 1.93g of 2,4, 6-trichlorophenol, 0.42g of byproduct and 1.49/3.42=43.6 percent of conversion rate through liquid chromatography; selectivity was 1.54/1.96=78.6%; yield 43.6% ×78.6% = 34.27%; the inner diameter of the micro-channel in the micro-channel reaction equipment is 0.015mm; the shape of the microchannel mixer is an loving heart type.
Example 6
2,4, 6-trichlorophenol, ethylamine and dichloroethane are mixed according to the mass ratio of 300:120:1100 stirring to fully dissolve and mix, standing until the mixture is clear and then taking the mixture as a first material; taking sodium carbonate aqueous solution with the concentration of 1mol/L as a second material, stirring to fully dissolve the second material, and standing the second material after the second material is clarified. The microchannel reactor of the microchannel reaction equipment was opened, the temperature of the microchannel reactor was set to 150 ℃, and the back pressure valve was adjusted to make the reaction pressure 13bar. The feed pump is turned on, and the feed pump is regulated so that the flow of the first material is 11g/min and the flow of the second material is 15g/min. After reaction in a microchannel reactor for 10min, extracting reaction feed liquid in the microchannel reactor, washing the reaction feed liquid with 5% sodium hydroxide aqueous solution for 5 times, washing the obtained organic phase with water for 4 times successively, extracting and separating the obtained organic phase, removing the solvent, taking 3.89g of crude product, diluting 1000 times with ethanol, obtaining 2.52g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 0.94g of 2,4, 6-trichlorophenol and 0.43g of byproduct through liquid chromatography, wherein the conversion rate is 2.24/3.18=70.4%; selectivity was 2.52/2.95=85.4%; yield 70.4% ×85.4% = 60.12%; the inner diameter of the micro-channel in the micro-channel reaction equipment is 0.015mm; the shape of the microchannel mixer is an loving heart type.
Example 7
2,4, 6-trichlorophenol, ethylamine and dichloroethane are mixed according to the mass ratio of 300:120:1100 is stirred to be fully dissolved and mixed, and is left to stand for clarification to be used as a first material. And taking sodium hydroxide solution with the concentration of 1mol/L as a second material. The microchannel reactor of the microchannel reaction equipment was opened, the temperature of the microchannel reactor was set to 140 ℃, and the back pressure valve was adjusted to make the reaction pressure 13bar. The feed pump is turned on, and the feed pump is regulated so that the flow rate of the first material is 11g/min and the flow rate of the second material is 13g/min. After reacting for 10min in a microchannel reactor, extracting reaction feed liquid in the microchannel reactor, washing the reaction feed liquid with 5% sodium hydroxide aqueous solution for 5 times, washing the obtained organic phase with water for 4 times successively, extracting and separating the obtained organic phase, removing the solvent, taking 3.89g of crude product, diluting with ethanol for 1000 times, and obtaining 2.03g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 1.36g of 2,4, 6-trichlorophenol, 0.50g of byproduct and 1.91/3.27=58.4% of conversion rate through liquid chromatography; selectivity was 2.03/2.53=80.2%; yield 58.4% ×80.2% = 46.84%; the inner diameter of the micro-channel in the micro-channel reaction equipment is 0.015mm; the shape of the microchannel mixer is an loving heart type.
Comparative example 1
The differences from example 1 are: 2,4, 6-trichlorophenol and dichloroethane according to the mass ratio of 300:1100 is stirred to be fully dissolved and mixed, and is left to stand for clarification to be used as a first material. Ethylamine, anhydrous sodium carbonate and pure water are mixed according to a mass ratio of 312:500:1000, stirring to fully dissolve the mixture, and standing the mixture until the mixture is clarified to obtain a second material.
3.89g of crude product is diluted 1000 times by ethanol, and 1.09g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 1.85g of 2,4, 6-trichlorophenol and 0.95g of byproduct can be obtained through liquid chromatography, wherein the conversion rate is 1.54/3.39=45.4%, and the selectivity is 1.09/2.04=53.4%; yield was 45.4% ×53.4% =24.24%.
Comparative example 2
The differences from example 2 are: the flow of the first material is 11g/min, and the flow of the second material is 30g/min.
3.89g of crude product is diluted 1000 times by ethanol, and 1.07g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 2.46g of 2,4, 6-trichlorophenol and 0.36g of byproduct can be obtained through liquid chromatography, wherein the conversion rate is 1.08/3.54=30.5%, and the selectivity is 1.07/1.43=74.8%; yield was 30.5% ×74.8% =22.8%.
Comparative example 3
The differences from example 2 are: the flow of the first material is 11g/min, and the flow of the second material is 60g/min.
3.89g of crude product is diluted 1000 times by ethanol, 0.49g of 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, 3.19g of 2,4, 6-trichlorophenol and 0.21g of byproduct can be obtained through liquid chromatography, the conversion rate is 0.53/3.72=14.2%, and the selectivity is 0.49/0.7=70.0%; yield was 14.2% ×70% =9.94%.
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 (10)
1. The preparation method of the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride is characterized by comprising the following steps:
taking a mixed solution of 2,4, 6-trichlorophenol, organic alkali and dichloroethane as a first material, and taking inorganic alkali solution as a second material;
and (3) carrying out etherification reaction on the first material and the second material in micro-channel reaction equipment to obtain the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
2. The method according to claim 1, wherein the organic base is one of methylamine, ethylamine and triethylamine.
3. The preparation method according to claim 1, wherein the mass ratio of the 2,4, 6-trichlorophenol, the organic base and the dichloroethane in the first material is 1: (0.2-1.5): (3-10).
4. The method according to claim 1, wherein the concentration of the inorganic alkaline solution is 0.5 to 5mol/L.
5. The method according to claim 1 or 4, wherein the inorganic base in the inorganic alkali solution is one of sodium hydroxide, sodium carbonate, potassium carbonate and sodium bicarbonate.
6. The method of claim 1, wherein the flow ratio of the first material to the second material is 1: (1-2).
7. The method according to claim 1, wherein the etherification reaction temperature is 150 to 200 ℃, and the back pressure valve of the microchannel reaction apparatus controls the pressure to 8 to 15bar.
8. The method according to claim 1, further comprising subjecting the etherification reaction system to alkali washing, water washing and desolventizing in this order to obtain the 2- (2, 4, 6-trichlorophenoxy) ethyl chloride.
9. The method of claim 1, wherein the microchannel reaction device comprises a microchannel mixer and a microchannel reactor; the microchannel mixer is heart-shaped.
10. The method according to claim 1 or 9, wherein the inner diameter of the microchannel in the microchannel reactor is 0.01mm to 0.1mm.
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| PCT/CN2021/139660 WO2023108677A1 (en) | 2021-12-16 | 2021-12-20 | Method for preparing 2-(2,4,6-trichlorophenoxy)ethyl chloride |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101402608A (en) * | 2008-11-25 | 2009-04-08 | 乐斯化学有限公司 | Method for producing bactericide prochloraz |
| CN101851167A (en) * | 2010-06-12 | 2010-10-06 | 温州大学 | Method for synthesizing prochloraz intermediate |
| CN107226777A (en) * | 2016-08-03 | 2017-10-03 | 沈阳金久奇科技有限公司 | Synthesis method of 1, 2-diphenoxyl ethane thermosensitive sensitizer |
| CN111233771A (en) * | 2020-03-30 | 2020-06-05 | 江西汇和化工有限公司 | Process for continuously synthesizing prochloraz and intermediate acylate of prochloraz raw material |
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2021
- 2021-12-16 CN CN202111545858.2A patent/CN116332732A/en active Pending
- 2021-12-20 WO PCT/CN2021/139660 patent/WO2023108677A1/en unknown
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101402608A (en) * | 2008-11-25 | 2009-04-08 | 乐斯化学有限公司 | Method for producing bactericide prochloraz |
| CN101851167A (en) * | 2010-06-12 | 2010-10-06 | 温州大学 | Method for synthesizing prochloraz intermediate |
| CN107226777A (en) * | 2016-08-03 | 2017-10-03 | 沈阳金久奇科技有限公司 | Synthesis method of 1, 2-diphenoxyl ethane thermosensitive sensitizer |
| CN111233771A (en) * | 2020-03-30 | 2020-06-05 | 江西汇和化工有限公司 | Process for continuously synthesizing prochloraz and intermediate acylate of prochloraz raw material |
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