CN110577491B - Method for preparing 2-chloro-5-chloromethyl pyridine - Google Patents
Method for preparing 2-chloro-5-chloromethyl pyridine Download PDFInfo
- Publication number
- CN110577491B CN110577491B CN201910989343.8A CN201910989343A CN110577491B CN 110577491 B CN110577491 B CN 110577491B CN 201910989343 A CN201910989343 A CN 201910989343A CN 110577491 B CN110577491 B CN 110577491B
- Authority
- CN
- China
- Prior art keywords
- chloro
- chloromethylpyridine
- pressure
- noble metal
- catalyst
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- C07D213/61—Halogen atoms or nitro radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a method for preparing 2-chloro-5-chloromethyl pyridine, which comprises the steps of carrying out selective hydrogenation dechlorination reaction on 2-chloro-5-trichloromethylpyridine serving as a raw material to prepare 2-chloro-5-chloromethyl pyridine; the catalyst is a noble metal catalyst taking active carbon or alumina as a carrier, and the mass percentage of noble metal in the noble metal catalyst is 1-10%; the mass of the noble metal catalyst is 0.1-0.5 percent of that of the 2-chloro-5-trichloromethyl pyridine; the acid-binding agent is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium phosphate, triethylamine, triethanolamine, 2-hydroxyethylamine or ammonia gas; the organic solvent is toluene, xylene, methyl acetate, ethyl acetate or 2-methyltetrahydrofuran. The yield of the 2-chloro-5-chloromethylpyridine is over 82 percent, the purity is over 98 percent, the process control is simple, the generated industrial three wastes are less, and the synthetic method is green and environment-friendly.
Description
Technical Field
The invention belongs to the technical field of pesticide intermediate synthesis, and particularly relates to a method for preparing 2-chloro-5-chloromethyl pyridine.
Background
2-chloro-5-chloromethyl pyridine is an important fine chemical raw material, and is widely applied to the synthesis process of pyridine series insecticides, such as imidacloprid, thiacloprid, acetamiprid, nitenpyram and the like. The synthesis methods of the 2-chloro-5-chloromethylpyridine disclosed at present are many, and mainly comprise a directional cyclization method and a chlorination synthesis method, wherein the directional cyclization method mainly comprises a 2-chloro-5-aminomethylpyridine diazo-chlorination method, a morpholine-propionaldehyde method, a cyclopentadiene-acrolein method, a benzylamine-propionaldehyde method, a 2-methylpyridine-fuming sulfuric acid reduction method and a 2-chloro-2-chloromethyl 4-cyanobutanal cyclization method. Although the directional cyclization method has the advantages of high product quality and the like, a large amount of waste water, waste gas and waste residues are generated in the production process, so that great influence is caused on environmental management, factory cost control and the like.
The chlorination synthesis method mainly comprises the step of taking 3-methylpyridine or 2-chloro-5-methylpyridine which is a byproduct of industrial pyridine synthesis as a main starting material, and carrying out chlorination reaction to generate the 2-chloro-5-chloromethylpyridine, wherein the method has less industrial three wastes, and greatly relieves the environmental protection pressure of the traditional production process of the 2-chloro-5-methylpyridine. However, the methods for synthesizing 2-chloro-5-methylpyridine from 3-methylpyridine or 2-chloro-5-methylpyridine reported in the prior art generate a large amount of 2-chloro-5-trichloromethylpyridine which is an unwanted by-product, and have problems of poor selectivity of chlorination reaction, low yield of target products, and the like.
Disclosure of Invention
The technical problem to be solved by the present invention is to provide a method for preparing 2-chloro-5-chloromethylpyridine, which aims at overcoming the defects of the prior art. The method takes 2-chloro-5-trichloromethylpyridine as a raw material as a byproduct of chlorination of 3-methylpyridine, the 2-chloro-5-trichloromethylpyridine is three wastes, the conversion of the 2-chloro-5-trichloromethylpyridine into useful 2-chloro-5-chloromethylpyridine can effectively realize cyclic utilization of resources, and has important economic and social values, the catalytic reaction is relatively thorough, the yield of the 2-chloro-5-chloromethylpyridine exceeds 82%, and the purity is more than 98%.
In order to solve the technical problems, the invention adopts the technical scheme that: the method for preparing 2-chloro-5-chloromethylpyridine is characterized in that 2-chloro-5-trichloromethylpyridine is used as a raw material to carry out selective hydrogenation dechlorination reaction to prepare 2-chloro-5-chloromethylpyridine;
the catalyst for the selective hydrogenation and dechlorination reaction is a noble metal catalyst taking active carbon or alumina as a carrier, the mass percentage of noble metal in the noble metal catalyst is 1-10%, and the noble metal is palladium or palladium and platinum; the mass of the noble metal catalyst is 0.1-0.5% of that of the 2-chloro-5-trichloromethylpyridine;
the acid-binding agent for the selective hydrogenation dechlorination reaction is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium phosphate, triethylamine, triethanolamine, 2-hydroxyethylamine or ammonia gas; the amount of the acid-binding agent is 0.5 to 2.5 times of that of the 2-chloro-5-trichloromethylpyridine;
the organic solvent of the selective hydrogenation dechlorination reaction is toluene, xylene, methyl acetate, ethyl acetate or 2-methyltetrahydrofuran.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized by comprising the following steps:
adding 2-chloro-5-trichloromethylpyridine, a noble metal catalyst, an acid-binding agent, water and an organic solvent into a high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen, and then introducing hydrogen for replacement;
secondly, reacting for 3 to 12 hours under the conditions that the hydrogen pressure in the high-pressure reaction kettle is between 0.1 and 3.0MPa and the temperature is between 30 and 100 ℃, and cooling to the room temperature;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 2 to 4 times;
step four, performing pressure filtration on the solid-liquid mixture in the high-pressure reaction kettle after nitrogen replacement to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase;
putting the organic phase obtained in the fifth step into an evaporator, and evaporating at 80-120 ℃ for 4-6 h to obtain organic solvent steam and a crude product;
and seventhly, decompressing and rectifying the crude product in the step six to obtain the 2-chloro-5-chloromethylpyridine.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that the mass of the organic solvent is 1.2 to 2.5 times of that of 2-chloro-5-trichloromethylpyridine.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that the amount of the acid-binding agent is 1.1 times of the amount of the 2-chloro-5-trichloromethylpyridine, and the acid-binding agent is ammonia gas.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that the organic solvent is methyl acetate.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that the mass of the noble metal catalyst is 0.3% of that of 2-chloro-5-trichloromethylpyridine, the mass percentage of the noble metal in the noble metal catalyst is 5%, the noble metal is palladium, and the carrier is activated carbon.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that the times of nitrogen replacement and hydrogen replacement in the first step are 2 to 4 times.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that in the second step, the hydrogen pressure is 0.6MPa to 1.0MPa, the temperature is 30 ℃ to 60 ℃, and the reaction time is 6h to 9 h.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that the pressure of the filter pressing in the fourth step is 0.1MPa to 0.3 MPa.
The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that the pressure of the reduced pressure distillation in the seventh step is-0.095 MPa to-0.1 MPa, and the time of the reduced pressure distillation is 5h to 8 h.
The reaction equation of the method for preparing 2-chloro-5-chloromethylpyridine of the invention is as follows:
compared with the prior art, the invention has the following advantages:
1. the method takes 2-chloro-5-trichloromethylpyridine as a raw material to carry out selective hydrogenation and dechlorination reaction, the 2-chloro-5-trichloromethylpyridine is a byproduct of chlorination of 3-methylpyridine, the three wastes are generated, and the 2-chloro-5-trichloromethylpyridine is converted into useful 2-chloro-5-chloromethylpyridine through selective hydrogenation and dechlorination, so that the recycling of resources can be effectively realized, and the method has important economic and social values.
2. The method for preparing the 2-chloro-5-chloromethylpyridine has the advantages of relatively thorough reaction, yield of the 2-chloro-5-chloromethylpyridine exceeding 82 percent, purity of over 98 percent, simple process control, less generated industrial three wastes and green and environment-friendly synthetic method.
3. According to the invention, 2-chloro-5-trichloromethylpyridine, a noble metal catalyst, an acid-binding agent, water and an organic solvent are reacted under a high-pressure condition, so that the 2-chloro-5-trichloromethylpyridine can be effectively promoted to be subjected to selective dehydrochlorination, and the 2-chloro-5-chloromethylpyridine is obtained.
4. The organic solvent of the invention is preferably methyl acetate, which can effectively improve the selective dechlorination and hydrogenation performances of the raw material 2-chloro-5-trichloromethylpyridine and improve the reaction rate and selectivity; the acid-binding agent is preferably ammonia gas, so that the reaction rate and selectivity can be effectively improved, and the reaction cost is controlled.
5. The invention also comprises the steps of recovering and recycling the noble metal catalyst and the organic solvent steam, wherein the recycling frequency can reach 6 times, and the yield and the purity of the 2-chloro-5-chloromethylpyridine are basically unchanged in the recycling process.
The technical solution of the present invention is further described in detail with reference to the following examples.
Detailed Description
Example 1
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is Pd/C catalyst, the Pd/C catalyst comprises carrier activated carbon and noble metal palladium loaded on the carrier activated carbon, and the mass percentage of the noble metal Pd in the Pd/C catalyst is 3%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is sodium phosphate;
the organic solvent of the selective hydrogenation dechlorination reaction is methyl acetate;
the preparation method comprises the following steps:
step one, dissolving sodium phosphate in water to obtain a sodium phosphate aqueous solution with the mass content of 30%, placing 1300g of methyl acetate in a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 5g of Pd/C catalyst and 1600g of the sodium phosphate aqueous solution into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 3 times, and then introducing hydrogen for replacing the nitrogen for 3 times;
continuously introducing hydrogen into the high-pressure reaction kettle, reacting for 4 hours at the pressure of 1.5MPa and the temperature of 50-60 ℃ in the reaction kettle, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 3 times;
step four, under the condition that the pressure is 0.1MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating at the temperature of 120 ℃ for 4 hours to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure distillation is-0.1 MPa, and the time of the reduced pressure distillation is 8 h;
step eight, condensing and recovering the organic solvent steam obtained in the step six at the temperature of 0-5 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 87.3%, and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.5%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 2
This example is the same as example 1 except that the acid scavenger for the selective hydrodechlorination reaction is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, triethylamine, triethanolamine, 2-hydroxyethylamine or ammonia gas.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 87.1% to 87.3%, and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.4% to 98.5%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 3
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is Pd/C catalyst, the Pd/C catalyst comprises carrier activated carbon and noble metal palladium loaded on the carrier activated carbon, and the mass percentage of the noble metal Pd in the Pd/C catalyst is 10%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is triethanolamine;
the organic solvent of the selective hydrogenation dechlorination reaction is ethyl acetate;
the preparation method comprises the following steps:
placing 2500g of ethyl acetate into a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 1g of Pd/C catalyst, 552g of triethanolamine and 400g of pure water into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 2 times, and then introducing hydrogen to replace the nitrogen for 2 times;
step two, continuously introducing hydrogen into the high-pressure reaction kettle until the pressure of the hydrogen is 3MPa, reacting for 12 hours under the conditions that the pressure in the reaction kettle is 3MPa and the temperature is 30-35 ℃, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 4 times;
step four, under the condition that the pressure is 0.2MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating at the temperature of 80 ℃ for 6 hours to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure rectification is-0.098 MPa, and the time of the reduced pressure rectification is 5 h;
step eight, condensing and recovering the organic solvent steam obtained in the step six at the temperature of 0-5 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 87.2% and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.3%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 4
This example is the same as example 3, except that the acid scavenger for the selective hydrodechlorination reaction is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium phosphate, triethylamine, 2-hydroxyethylamine or ammonia gas.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 87.0% to 87.2%, and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.1% to 98.3%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 5
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation dechlorination reaction is Pd/Al2O3Catalyst of said Pd/Al2O3The catalyst comprises carrier alumina and noble metal palladium, Pd/Al loaded on the carrier alumina2O3The mass percentage of the noble metal Pd in the catalyst is 3 percent;
the acid-binding agent for the selective hydrogenation dechlorination reaction is 2-hydroxyethylamine;
the organic solvent of the selective hydrogenation dechlorination reaction is ethyl acetate;
the preparation method comprises the following steps:
step one, 1500g of ethyl acetate is placed in a high-pressure reaction kettle, and 1000g of 2-chloro-5-trichloromethylpyridine and 5g of Pd/Al are put into the high-pressure reaction kettle2O3The catalyst, 942g 2-hydroxyethylamine and 400g pure water, replacing the air in the high-pressure reaction kettle with nitrogen for 3 times, and then introducing hydrogen to replace the nitrogen for 3 times;
step two, continuously introducing hydrogen into the high-pressure reaction kettle, reacting for 8 hours under the conditions that the pressure of the hydrogen in the reaction kettle is 1.2MPa and the temperature is 30-35 ℃, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 3 times;
step four, under the condition that the pressure is 0.1MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating at the temperature of 120 ℃ for 4 hours to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure rectification is-0.1 MPa, and the time of the reduced pressure rectification is 8 h;
step eight, condensing and recovering the organic solvent steam obtained in the step six at the temperature of 0-5 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 87.2% and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.3%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 6
This example is the same as example 5 except that the acid-binding agent for the selective hydrodechlorination reaction is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium phosphate, triethylamine, triethanolamine or ammonia gas.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 87.0% to 87.2%, and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.2% to 98.3%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 7
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is Pd/C catalyst, the Pd/C catalyst comprises carrier activated carbon and noble metal palladium loaded on the carrier activated carbon, and the mass percentage of the noble metal Pd in the Pd/C catalyst is 5%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is ammonia gas, and the ammonia gas is dissolved in water to prepare ammonia water with the mass concentration of 28%;
the organic solvent of the selective hydrogenation dechlorination reaction is toluene;
the preparation method comprises the following steps:
putting 1500g of toluene into a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 3g of Pd/C catalyst, 600g of 28 mass percent ammonia water and 400g of pure water into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 3 times, and then introducing hydrogen to replace the nitrogen for 3 times;
step two, continuously introducing hydrogen into the high-pressure reaction kettle, reacting for 5 hours under the conditions that the pressure of the hydrogen in the reaction kettle is 1.0MPa and the temperature is 60-65 ℃, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 3 times;
step four, under the condition that the pressure is 0.3MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating for 5 hours at the temperature of 100 ℃ to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure rectification is-0.095 MPa, and the time of the reduced pressure rectification is 6 h;
step eight, condensing and recovering the organic solvent steam in the step six at the temperature of-10 to-5 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 82.1% and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.2%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 8
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is a Pd-Pt/C catalyst, the Pd-Pt/C catalyst comprises carrier activated carbon and noble metals such as palladium and platinum loaded on the carrier activated carbon, and the mass percentage content of the noble metals such as Pd-Pt in the Pd-Pt/C catalyst is 5%, wherein Pd is 4% and Pt is 1%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is sodium hydroxide;
the organic solvent of the selective hydrodechlorination reaction is xylene;
the preparation method comprises the following steps:
step one, dissolving sodium hydroxide in water to obtain a sodium hydroxide aqueous solution with the mass content of 30%, placing 1500g of dimethylbenzene in a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 2g of Pd-Pt/C catalyst and 1200g of the sodium hydroxide aqueous solution into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 3 times, and then introducing hydrogen for replacing the nitrogen for 3 times;
step two, continuously introducing hydrogen into the high-pressure reaction kettle, reacting for 4 hours under the conditions that the pressure of the hydrogen in the reaction kettle is 1.2MPa, the pressure in the reaction kettle is 1.2MPa and the temperature is 60-65 ℃, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 3 times;
step four, under the condition that the pressure is 0.2MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating at the temperature of 80 ℃ for 6 hours to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure distillation is-0.1 MPa, and the time of the reduced pressure distillation is 5 h;
step eight, condensing and recovering the organic solvent steam in the step six at the temperature of-5-0 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 85.3%, and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.3%. In this example, the number of times of recycling the recovered catalyst was 4, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 9
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is Pd/C catalyst, the Pd/C catalyst comprises carrier activated carbon and noble metal palladium loaded on the carrier activated carbon, and the mass percentage of the noble metal Pd in the Pd/C catalyst is 5%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is ammonia gas, and the ammonia gas is dissolved in water to prepare ammonia water with the mass concentration of 25%;
the organic solvent of the selective hydrogenation dechlorination reaction is methyl acetate;
the preparation method comprises the following steps:
putting 1500g of methyl acetate into a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 3g of Pd/C catalyst, 420g of 25% ammonia water and 400g of pure water into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 3 times, and then introducing hydrogen to replace the nitrogen for 3 times;
step two, continuously introducing hydrogen into the high-pressure reaction kettle, reacting for 9 hours under the conditions that the pressure of the hydrogen in the reaction kettle is 0.6MPa, the pressure in the reaction kettle is 0.6MPa and the temperature is 30-35 ℃, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 3 times;
step four, under the condition that the pressure is 0.2MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating for 5 hours at the temperature of 100 ℃ to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure rectification is-0.095 MPa, and the time of the reduced pressure rectification is 6 h;
step eight, condensing and recovering the organic solvent steam in the step six at the temperature of-5-0 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 88.2% and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.9%. In this example, the number of times of recycling the recovered catalyst was 6, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 10
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is Pd/C catalyst, the Pd/C catalyst comprises carrier activated carbon and noble metal palladium loaded on the carrier activated carbon, and the mass percentage of the noble metal Pd in the Pd/C catalyst is 5%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is ammonia gas, and the ammonia gas is dissolved in water to prepare ammonia water with the mass concentration of 25%;
the organic solvent of the selective hydrogenation dechlorination reaction is methyl acetate;
the preparation method comprises the following steps:
putting 1500g of methyl acetate into a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 3g of Pd/C catalyst, 420g of 25% ammonia water and 400g of pure water into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 3 times, and then introducing hydrogen to replace the nitrogen for 3 times;
continuously introducing hydrogen into the high-pressure reaction kettle until the pressure of the hydrogen is 1MPa, reacting for 6 hours under the conditions that the pressure in the reaction kettle is 1MPa and the temperature is 40-45 ℃, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 3 times;
step four, under the condition that the pressure is 0.2MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating for 5 hours at the temperature of 100 ℃ to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure rectification is-0.095 MPa, and the time of the reduced pressure rectification is 6 h;
step eight, condensing and recovering the organic solvent steam in the step six at the temperature of-5-0 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 88.3%, and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.7%. In this example, the number of times of recycling the recovered catalyst was 6, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 11
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is Pd/C catalyst, the Pd/C catalyst comprises carrier activated carbon and noble metal palladium loaded on the carrier activated carbon, and the mass percentage of the noble metal Pd in the Pd/C catalyst is 5%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is ammonia gas, and the ammonia gas is dissolved in water to prepare ammonia water with the mass concentration of 25%;
the organic solvent of the selective hydrogenation dechlorination reaction is methyl acetate;
the preparation method comprises the following steps:
putting 1500g of methyl acetate into a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 3g of Pd/C catalyst, 420g of 25% ammonia water and 400g of pure water into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 3 times, and then introducing hydrogen to replace the nitrogen for 3 times;
continuously introducing hydrogen into the high-pressure reaction kettle, reacting for 7 hours at the pressure of 0.8MPa and the temperature of 55-60 ℃ in the reaction kettle, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 3 times;
step four, under the condition that the pressure is 0.2MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating for 5 hours at the temperature of 100 ℃ to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure rectification is-0.095 MPa, and the time of the reduced pressure rectification is 6 h;
step eight, condensing and recovering the organic solvent steam in the step six at the temperature of-5-0 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 88.6%, and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.8%, the number of times of recycling the recovered catalyst was 6 in this example, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
Example 12
In this example, 2-chloro-5-chloromethylpyridine was subjected to selective hydrodechlorination to obtain 2-chloro-5-chloromethylpyridine, using 2-chloro-5-trichloromethylpyridine as a raw material;
the catalyst for the selective hydrogenation and dechlorination reaction is Pd/C catalyst, the Pd/C catalyst comprises carrier activated carbon and noble metal palladium loaded on the carrier activated carbon, and the mass percentage of the noble metal Pd in the Pd/C catalyst is 1%;
the acid-binding agent for the selective hydrogenation dechlorination reaction is triethylamine;
the organic solvent for the selective hydrogenation dechlorination reaction is 2-methyltetrahydrofuran;
the preparation method comprises the following steps:
placing 1200g of 2-methyltetrahydrofuran in a high-pressure reaction kettle, adding 1000g of 2-chloro-5-trichloromethylpyridine, 3g of Pd/C catalyst, 687g of triethylamine and 400g of pure water into the high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen for 4 times, and then introducing hydrogen to replace the nitrogen for 4 times;
continuously introducing hydrogen into the high-pressure reaction kettle, reacting for 3 hours at the pressure of 0.1MPa and the temperature of 95-100 ℃ in the reaction kettle, and cooling to room temperature after the reaction is finished;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 2 times;
step four, under the condition that the pressure is 0.3MPa, filter-pressing the solid-liquid mixture in the high-pressure reaction kettle after the nitrogen replacement in the step three to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase; intermittently sampling in the reaction process, and stopping the reaction when the conversion rate of the 2-chloro-5-trichloromethyl pyridine is more than 98 percent through gas chromatography analysis;
putting the organic phase obtained in the step five into an evaporator, and evaporating for 5 hours at the temperature of 100 ℃ to obtain organic solvent steam and a crude product;
step seven, rectifying the crude product under reduced pressure to obtain 2-chloro-5-chloromethylpyridine; the pressure of the reduced pressure rectification is-0.095 MPa, and the time of the reduced pressure rectification is 6 h;
step eight, condensing and recovering the organic solvent steam in the step six at the temperature of-10 to-5 ℃ to obtain a recovered organic solvent, and recycling the recovered organic solvent;
and step nine, recovering the filter cake obtained in the step four to obtain the recovered catalyst.
In this example, the yield of 2-chloro-5-chloromethylpyridine was 87.0% and the gas chromatography purity of 2-chloro-5-chloromethylpyridine was 98.1%. In this example, the number of times of recycling the recovered catalyst was 5, and the yield and purity of 2-chloro-5-chloromethylpyridine were substantially unchanged during the recycling process.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and all simple modifications, changes and equivalent structural changes made to the above embodiment according to the technical spirit of the present invention still fall within the protection scope of the technical solution of the present invention.
Claims (10)
1. The method for preparing 2-chloro-5-chloromethylpyridine is characterized in that 2-chloro-5-trichloromethylpyridine is used as a raw material to carry out selective hydrogenation dechlorination reaction to prepare 2-chloro-5-chloromethylpyridine;
the catalyst for the selective hydrogenation and dechlorination reaction is a noble metal catalyst taking active carbon or alumina as a carrier, the mass percentage of noble metal in the noble metal catalyst is 1-10%, and the noble metal is palladium or palladium and platinum; the mass of the noble metal catalyst is 0.1-0.5% of that of the 2-chloro-5-trichloromethylpyridine;
the acid-binding agent for the selective hydrogenation dechlorination reaction is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium phosphate, triethylamine, triethanolamine, 2-hydroxyethylamine or ammonia gas; the amount of the acid-binding agent is 0.5 to 2.5 times of that of the 2-chloro-5-trichloromethylpyridine;
the organic solvent for the selective hydrogenation dechlorination reaction is toluene, xylene, methyl acetate, ethyl acetate or 2-methyltetrahydrofuran;
the selective hydrogenation dechlorination reaction comprises the step of reacting the 2-chloro-5-trichloromethylpyridine, the catalyst, the acid-binding agent, water and the organic solvent for 3 to 12 hours under the conditions that the hydrogen pressure is 0.1 to 3.0MPa and the temperature is 30 to 100 ℃.
2. The process for the preparation of 2-chloro-5-chloromethylpyridine according to claim 1, wherein said process comprises the steps of:
adding 2-chloro-5-trichloromethylpyridine, a noble metal catalyst, an acid-binding agent, water and an organic solvent into a high-pressure reaction kettle, replacing air in the high-pressure reaction kettle with nitrogen, and then introducing hydrogen for replacement;
secondly, reacting for 3 to 12 hours under the conditions that the hydrogen pressure in the high-pressure reaction kettle is between 0.1 and 3.0MPa and the temperature is between 30 and 100 ℃, and cooling to the room temperature;
step three, discharging the hydrogen in the high-pressure reaction kettle after being cooled in the step two, and replacing the hydrogen with nitrogen for 2 to 4 times;
step four, performing pressure filtration on the solid-liquid mixture in the high-pressure reaction kettle after nitrogen replacement to obtain a filter cake and filtrate;
step five, standing the filtrate obtained in the step four until a water phase is separated from an organic phase, and removing the water phase to obtain an organic phase;
putting the organic phase obtained in the fifth step into an evaporator, and evaporating at 80-120 ℃ for 4-6 h to obtain organic solvent steam and a crude product;
and seventhly, decompressing and rectifying the crude product in the step six to obtain the 2-chloro-5-chloromethylpyridine.
3. The method for preparing 2-chloro-5-chloromethylpyridine according to claim 1, wherein the mass of the organic solvent is 1.2 to 2.5 times that of the 2-chloro-5-trichloromethylpyridine.
4. The method for preparing 2-chloro-5-chloromethylpyridine as claimed in claim 3, wherein the acid scavenger is ammonia gas in an amount of 1.1 times the amount of 2-chloro-5-trichloromethylpyridine.
5. The process of claim 4, wherein the organic solvent is methyl acetate.
6. The method for preparing 2-chloro-5-chloromethylpyridine according to claim 1, wherein the mass of the noble metal catalyst is 0.3% of the mass of the 2-chloro-5-trichloromethylpyridine, the mass percentage of the noble metal in the noble metal catalyst is 5%, the noble metal is palladium, and the carrier is activated carbon.
7. The process according to claim 2, wherein the nitrogen substitution and the hydrogen substitution are performed 2 to 4 times in the first step.
8. The method for preparing 2-chloro-5-chloromethylpyridine according to claim 2, wherein the hydrogen pressure in step two is 0.6MPa to 1.0MPa, the temperature is 30 ℃ to 60 ℃, and the reaction time is 6h to 9 h.
9. The method for preparing 2-chloro-5-chloromethylpyridine according to claim 2, wherein the pressure of the pressure filtration in the fourth step is 0.1MPa to 0.3 MPa.
10. The method for preparing 2-chloro-5-chloromethylpyridine according to claim 2, wherein the pressure of the vacuum distillation in step seven is-0.095 MPa to-0.1 MPa, and the time of the vacuum distillation is 5h to 8 h.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910989343.8A CN110577491B (en) | 2019-10-17 | 2019-10-17 | Method for preparing 2-chloro-5-chloromethyl pyridine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910989343.8A CN110577491B (en) | 2019-10-17 | 2019-10-17 | Method for preparing 2-chloro-5-chloromethyl pyridine |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110577491A CN110577491A (en) | 2019-12-17 |
CN110577491B true CN110577491B (en) | 2021-01-08 |
Family
ID=68814978
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910989343.8A Active CN110577491B (en) | 2019-10-17 | 2019-10-17 | Method for preparing 2-chloro-5-chloromethyl pyridine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110577491B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112159350A (en) * | 2020-10-15 | 2021-01-01 | 山东省农药科学研究院 | Preparation method of 2-chloro-3-trifluoromethylpyridine |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0512436A1 (en) * | 1991-05-02 | 1992-11-11 | Ishihara Sangyo Kaisha, Ltd. | Method for producing substituted pyridine derivatives |
CN101348420A (en) * | 2008-09-12 | 2009-01-21 | 湖南利洁生物化工有限公司 | Hydrogenation dehalogenation method of halogenated alkyl phenol coumpound |
JP5320132B2 (en) * | 2009-03-31 | 2013-10-23 | 太平洋セメント株式会社 | Porous body, metal-ceramic composite material, and production method thereof |
CN110280239A (en) * | 2019-07-23 | 2019-09-27 | 西安凯立新材料股份有限公司 | A kind of synthesis 2,3- dichloropyridine catalyst and its preparation method and application |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3123815B2 (en) * | 1992-05-19 | 2001-01-15 | 広栄化学工業株式会社 | Method for producing 2-chloro-5-chloromethylpyridine and / or 2-chloro-5-dichloromethylpyridine |
-
2019
- 2019-10-17 CN CN201910989343.8A patent/CN110577491B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0512436A1 (en) * | 1991-05-02 | 1992-11-11 | Ishihara Sangyo Kaisha, Ltd. | Method for producing substituted pyridine derivatives |
CN101348420A (en) * | 2008-09-12 | 2009-01-21 | 湖南利洁生物化工有限公司 | Hydrogenation dehalogenation method of halogenated alkyl phenol coumpound |
JP5320132B2 (en) * | 2009-03-31 | 2013-10-23 | 太平洋セメント株式会社 | Porous body, metal-ceramic composite material, and production method thereof |
CN110280239A (en) * | 2019-07-23 | 2019-09-27 | 西安凯立新材料股份有限公司 | A kind of synthesis 2,3- dichloropyridine catalyst and its preparation method and application |
Non-Patent Citations (3)
Title |
---|
A Sorbitol Dehydrogenase Inhibitor of Exceptional in Vivo Potency with a Long Duration of Action:1-(R)-{4-[4-(4,6-Dimethyl[1,3,5]triazin-2-yl)-2R,6S-dimethylpiperazin-1-yl]pyrimidin-2-yl}ethanol;Banavara L. Mylari等;《J. Med. Chem.》;20020830;第45卷(第20期);第4400页流程图2、Supplementary Information第4页 * |
四氯化硅及四氯化碳的催化加氢脱氯反应;杨昭;《南昌大学硕士学位论文》;20190315;1-51 * |
脱卤反应研究进展;薛福玲等;《有机化学》;20131231;第33卷;2291~2297 * |
Also Published As
Publication number | Publication date |
---|---|
CN110577491A (en) | 2019-12-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101302190B (en) | Method for preparing 2,3-dichloropyridine | |
CN110759859B (en) | Method for preparing 2, 3-dichloropyridine by selective dechlorination of tetrachloropyridine | |
CN110577491B (en) | Method for preparing 2-chloro-5-chloromethyl pyridine | |
CN111072525B (en) | Preparation method of N-methyl sodium taurate | |
CN101903344A (en) | Process for preparing of N-methyl pyrrolidone | |
CN102731357A (en) | Preparation method of high purity N,N'-dicyclohexylthiourea | |
CN110526860B (en) | Method for preparing intermediate 2, 6-tetramethyl piperidine amine | |
CN111153779A (en) | Efficient synthesis method of m-fluoroanisole | |
CN111138351A (en) | Synthetic method of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine acetate | |
CN110563699A (en) | Post-treatment purification method of fluoro pranoprazan intermediate | |
CN113024389B (en) | Preparation method of substituted phenoxybenzylamine compound and pyrazole carboxamide compound | |
CN112939843B (en) | Synthesis method of N-hydroxymethyl-3, 4,5, 6-tetrahydrophthalimide | |
CN110255632B (en) | Method for preparing ruthenium trichloride from ruthenium-containing waste | |
CN113683558A (en) | Preparation method for increasing yield of 2, 3-dichloropyridine | |
CN113149911A (en) | Preparation method of high-purity 5-aminobenzimidazole ketone | |
CN110606827A (en) | One-step method for synthesizing methylaminopyridine compounds | |
CN110551062A (en) | Method for preparing 2,3, 5-trichloropyridine by adopting 2,3,5, 6-tetrachloropyridine | |
CN109651244A (en) | A kind of preparation method of niacin | |
CN110835296B (en) | Preparation process of 2,2, 4-trimethyl-3-hydroxypentanoic acid | |
CN114249352B (en) | Method for treating wastewater generated in production of 6-methoxy tetralone | |
CN114456057B (en) | Synthesis method of caronic acid | |
CN117886732A (en) | Preparation method of 1, 5-dimethyl-2-pyrrolidone | |
CN110590578B (en) | Method for preparing monoethanolamine and diethanolamine | |
CN110590572B (en) | Method for producing monoethanolamine and diethanolamine | |
CN110586171B (en) | Catalyst for producing monoethanolamine and diethanolamine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |