CN119080580B - Preparation method of 2-bromo-5-fluorobenzotrifluoride - Google Patents
Preparation method of 2-bromo-5-fluorobenzotrifluoride Download PDFInfo
- Publication number
- CN119080580B CN119080580B CN202411249553.0A CN202411249553A CN119080580B CN 119080580 B CN119080580 B CN 119080580B CN 202411249553 A CN202411249553 A CN 202411249553A CN 119080580 B CN119080580 B CN 119080580B
- Authority
- CN
- China
- Prior art keywords
- fluorobenzotrifluoride
- bromo
- reaction
- crude product
- temperature
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/12—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
-
- 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
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
-
- 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
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/138—Halogens; Compounds thereof with alkaline earth metals, magnesium, beryllium, zinc, cadmium or mercury
-
- 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
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0239—Quaternary ammonium compounds
-
- 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
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
-
- 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
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of organic synthesis, and discloses a preparation method of 2-bromo-5-fluorobenzotrifluoride, which comprises the steps of controlling the temperature to be 5-20 ℃, mixing m-fluorobenzotrifluoride and sulfuric acid, adding a compound catalyst, adding NBS in batches, carrying out heat preservation reaction after the NBS is added, stopping the reaction when the m-fluorobenzotrifluoride content is less than or equal to 1%, standing and layering reaction liquid to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, sequentially carrying out alkaline washing and water washing on the 2-bromo-5-fluorobenzotrifluoride crude product, rectifying at normal pressure, and collecting fractions at 158-165 ℃ to obtain a 2-bromo-5-fluorobenzotrifluoride product, wherein the compound catalyst is a mixture of elemental iodine, zinc bromide and tetrabutylammonium bromide. The method has the advantages of one-step reaction, simple and convenient operation, accurate reaction positioning, higher raw material conversion rate, high reaction yield, easy purification of products, simple post-treatment, and high reaction yield of more than 93.0 percent and purity of more than 98.0 percent.
Description
Technical Field
The invention belongs to the field of organic synthesis, relates to a synthesis method of pesticide chemical products, and relates to a preparation method of 2-bromo-5-fluorobenzotrifluoride.
Background
The 2-bromo-5-fluorobenzotrifluoride has wide application, and is mainly used as an intermediate of medicines and pesticides.
Patent CN114163294A uses m-fluorobenzotrifluoride as raw material, bromine as brominating agent and hydrogen peroxide as oxidant, uses quaternary ammonium salt compound catalyst, and uses bromination reoxidation method to obtain 2-bromo-5-fluorobenzotrifluoride. The method has good reaction effect, but the use of a large amount of hydrogen peroxide can cause explosion risk.
The patent application CN102951996A uses m-fluorobenzotrifluoride as a raw material, 5-fluoro-2-nitrobenzotrifluoride is obtained by nitration in a nitric acid/sulfuric acid system, and the 5-fluoro-2-nitrobenzotrifluoride is synthesized into 2-bromo-5-fluorobenzotrifluoride by reduction, diazotization and bromination.
The patent CN111362775A uses benzotrifluoride as raw material, firstly mixes benzotrifluoride with sulfuric acid, potassium bromide, cuprous bromide and catalyst, makes bromination reaction to obtain 2-bromobenzotrifluoride, and makes 2-bromobenzotrifluoride in DMSO solvent, and adds potassium fluoride and KCoF 4 to make fluorination reaction so as to obtain 2-bromo-5-benzotrifluoride. This process produces a large amount of heavy metal waste liquid, is difficult to recover, is environmentally unfriendly, and requires expensive Pd-containing catalysts for the bromination reaction, which is costly.
Disclosure of Invention
The invention aims to solve the defects in the prior art, provides a novel preparation method of 2-bromo-5-fluorobenzotrifluoride, which has the advantages of low cost and easy acquisition of raw materials, high product yield and purity and easy industrialization, the method takes m-fluorobenzotrifluoride as a raw material, N-bromosuccinimide (NBS) as a brominating agent and concentrated sulfuric acid as a reaction solvent, and the 2-bromo-5-fluorobenzotrifluoride is generated by low-temperature reaction under the action of a composite catalyst.
The aim of the invention can be achieved by the following technical measures:
The preparation method of the 2-bromo-5-fluorobenzotrifluoride comprises the following synthetic route:
The preparation method comprises the steps of controlling the temperature to be 5-20 ℃, mixing m-fluorotoluene and sulfuric acid, adding a composite catalyst, adding NBS in batches, carrying out heat preservation reaction after the NBS is added, stopping the reaction until the m-fluorotoluene content is less than or equal to 1%, standing and layering reaction liquid to obtain a 2-bromo-5-fluorotoluene crude product, sequentially carrying out alkali washing and water washing on the 2-bromo-5-fluorotoluene crude product, rectifying under normal pressure, and collecting fractions of 158-165 ℃ to obtain a 2-bromo-5-fluorotoluene product.
The weight ratio of the m-fluorobenzotrifluoride to the sulfuric acid is 1:3.5-1:6.5, and is preferably 1:4.8.
The mass fraction of the sulfuric acid is 80-98%.
Preferably, the temperature is controlled to be 8-10 ℃, and the m-fluorobenzotrifluoride is mixed with sulfuric acid.
The weight ratio of the m-fluorobenzotrifluoride to the composite catalyst is 1:0.001-1:0.05, and is preferably 1:0.002.
The composite catalyst is a mixture of elemental iodine (I 2), zinc bromide and tetrabutylammonium bromide, wherein the weight ratio of the elemental iodine to the zinc bromide to the tetrabutylammonium bromide is 4 (1-3), and is preferably 4:3:3.
The weight ratio of the m-fluorobenzotrifluoride to the NBS is 1:1.1-1:1.3, and is preferably 1:1.1.
To avoid the formation of byproducts by adding an excessive amount of NBS in a short period of time, and to take into account production efficiency and product yield. The time for adding NBS is 9-12 hours, and the amount of NBS added each time is 1/25-1/15 of the total amount of NBS, preferably 1/22.
Preferably, when NBS is added, the temperature of the system is controlled to be 5-20 ℃. Specifically, when NBS is added, the temperature of the control system can be 5-7 ℃, 5-8 ℃, 5-10 ℃, 7-10 ℃, 15-18 ℃ and 15-20 ℃.
Preferably, after NBS is added, the time of the heat preservation reaction is 1-3 h, and the content of fluorine benzotrifluoride is less than or equal to 1%.
Preferably, the temperature of the heat preservation reaction is 8-10 ℃.
The standing temperature is 10-20 ℃, and the standing time is 1-3 h. By controlling the standing temperature, the invention can avoid the unsatisfactory layering effect caused by too low temperature and avoid generating new impurities caused by too high temperature.
The alkaline washing is to adjust the pH=7 of the crude 2-bromo-5-fluorobenzotrifluoride product by sodium hydroxide solution.
In particular. The alkaline washing and water washing steps are that water is added into the 2-bromo-5-fluorobenzotrifluoride crude product according to the mass ratio of the m-fluorobenzotrifluoride to the water of 1:1, 10% sodium hydroxide solution is adopted to adjust pH=7 for alkaline washing, water phase is separated, water is added into the organic phase according to the mass ratio of the m-fluorobenzotrifluoride to the water of 1:1 for water washing, liquid separation is carried out, and the organic phase is taken.
Specifically, the preparation method of the 2-bromo-5-fluorobenzotrifluoride comprises the following steps:
step a, sulfuric acid is added into a reaction device, the temperature is controlled to be 5-20 ℃, m-fluorobenzotrifluoride is added at one time, and a composite catalyst is added while stirring;
B, controlling the temperature of the system at 5-20 ℃, and adding NBS in batches within 9-12 hours, wherein after the NBS is added, the temperature is kept for reaction for 1-3 hours;
c, standing for 1-3 hours at the temperature of 10-20 ℃, layering, and taking an organic phase to obtain a crude product of 2-bromo-5-fluorobenzotrifluoride;
And d, sequentially performing alkali washing and water washing on the 2-bromo-5-fluorobenzotrifluoride crude product, rectifying at normal pressure, and collecting fractions at 158-165 ℃ to obtain a 2-bromo-5-fluorobenzotrifluoride product, wherein the purity of the 2-bromo-5-fluorobenzotrifluoride product reaches more than 98%, and the yield reaches about 93%.
The invention has the beneficial effects that:
The invention adopts m-fluorobenzotrifluoride and NBS as raw materials, and uses the composite catalyst, thereby improving the selectivity of the product, especially using iodine simple substance, and remarkably improving the yield of the product.
The method has the advantages of one-step reaction, simple and convenient operation, accurate reaction positioning, higher raw material conversion rate, high reaction yield, easy purification of products, simple post-treatment, and high reaction yield of more than 93.0 percent and purity of more than 98.0 percent.
The raw materials used in the invention are easy to purchase and have low price, so that the prepared 2-bromo-5-fluorobenzotrifluoride has more market competitiveness.
The waste acid produced by the invention can be recycled.
The invention has good economic and social benefits.
Detailed Description
The technical solutions of the present invention will be further described by the following examples, so that those skilled in the art can better understand the present invention. The examples are not intended to limit the scope of the invention in any way. Modifications and adaptations of the invention within the scope of the claims will be within the scope of the invention.
Example 1
480G of 96% sulfuric acid with the mass fraction of 8-10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.2g of a compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is added into the flask, 110g of NBS is added in batches within about 9 hours (5 g is added for each time and 22 times of adding) with the mass fraction of 7-10 ℃ is controlled, the temperature is kept at 8-10 ℃ after the adding is completed, the reaction is carried out in a sampling analysis mode, the m-fluorobenzotrifluoride content of the raw material is less than or equal to 1% after the reaction is carried out for 1 hour, and the reaction is terminated; standing for 1 hour at the temperature of 10-15 ℃ for layering, separating out bottom acid, taking an upper organic phase to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkaline washing, separating out a water phase, adding 100g of water into the organic phase for water washing, separating liquid, taking the organic phase to obtain 147g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 96.8%, rectifying the crude product at normal pressure, collecting 158-165 ℃ fractions to obtain 141.4g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.2% and the yield to 93.8%.
Example 2
480G of 96% sulfuric acid with the mass fraction of 8-10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorotoluene is added at one time, then 1g of a composite catalyst (0.4 g of elemental iodine, 0.3g of zinc bromide and 0.3g of tetrabutylammonium bromide) is added into the flask, 110g of NBS is added in batches within about 9 hours (5 g is added for each time and 22 times are added for each time), the reaction is carried out after the addition is completed, the temperature is kept at 8-10 ℃, sampling analysis is carried out, the m-fluorotoluene content is less than or equal to 1% after the reaction is carried out for 1 hour, and the reaction is terminated; standing for 1 hour at the temperature of 10-15 ℃ for layering, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkaline washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating liquid, taking the organic phase to obtain 146.9g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 97.2%, rectifying the crude product at normal pressure, and collecting 158-165 ℃ fractions to obtain 140.7g of the 2-bromo-5-fluorobenzotrifluoride product, wherein the gas chromatography detection content is 98.2%, and the yield is 93.4%.
Example 3
Adding 480g of 96% sulfuric acid by mass fraction into a 1000mL four-necked flask, controlling the temperature to 8-10 ℃, starting stirring, adding 100g of m-fluorobenzotrifluoride at one time, adding 5g of a compound catalyst (2 g of elemental iodine, 1.5g of zinc bromide and 1.5g of tetrabutylammonium bromide) into the flask, controlling the system temperature to 7-10 ℃, adding 110g of NBS in batches within about 9 hours (5 g for each time, 22 times of adding), after the adding is completed, carrying out heat preservation reaction at 8-10 ℃, sampling analysis, reacting for 1 hour, and then, keeping the m-fluorobenzotrifluoride content to be less than or equal to 1%, terminating the reaction, standing for 1 hour at the temperature of 10-15 ℃, layering, separating out a bottom acid, taking an organic layer, obtaining a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-necked flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for a water phase to carry out alkali phase, separating out the water phase, adding 100.8-fluorobenzotrifluoride content to be less than or equal to 1.8%, carrying out a liquid chromatography to 1.98%, and carrying out a gas chromatography to obtain a liquid chromatography with the 3-3.98%, wherein the fluorine content is equal to 1.8-3%, and the fluorine content is equal to 1.98%, and the product is obtained by a normal pressure, and the product is obtained after the liquid phase is subjected to 3.98% to a normal pressure, and a phase is obtained.
Example 4
Adding 380g of sulfuric acid with the mass fraction of 96% into a 1000mL four-neck flask, controlling the temperature to be 8-10 ℃, starting stirring, adding 100g of m-fluorobenzotrifluoride at one time, then adding 0.2g of a compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) into the flask, controlling the temperature of the system to be 7-10 ℃, adding 110g of NBS (5 g for each time and 22 times of adding) in batches within about 9 hours, keeping the temperature at 8-10 ℃ after the addition is finished, sampling and analyzing, keeping the m-fluorobenzotrifluoride content to be less than or equal to 1% after the reaction for 1 hour, stopping the reaction, standing for 1 hour and layering at the temperature of 10-15 ℃, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkali washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 146.9g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 96.2%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 139.9g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.4% with the yield of 93.0%.
Example 5
Adding 650g of 96% sulfuric acid with mass fraction at 8-10 ℃ into a 1000mL four-neck flask, starting stirring, adding 100g of m-fluorobenzotrifluoride at one time, then adding 0.2g of a compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) into the flask, controlling the temperature of the system at 7-10 ℃, adding 110g of NBS (5 g for each time and 22 times of adding) in batches within about 9 hours, keeping the temperature at 8-10 ℃ after the addition is finished, sampling and analyzing, keeping the m-fluorobenzotrifluoride content less than or equal to 1% after the reaction for 1 hour, stopping the reaction, standing for 1 hour at 10-15 ℃ for layering, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkali washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 146.8g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 96.2%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 140.0g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to be 98.5%, wherein the yield is 93.2%.
Example 6
480G of 80% sulfuric acid with the mass fraction of 80% is added into a 1000mL four-neck flask, the temperature is controlled to be 8-10 ℃, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.2g of compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is added into the flask, the temperature of the system is controlled to be 7-10 ℃, 110g of NBS is added in batches in about 9 hours (5 g is added for each time and 22 times of adding) respectively, after the adding is finished, the temperature is kept at 8-10 ℃, the temperature is kept at 8 ℃ for reaction, sampling analysis is carried out, the m-fluorobenzotrifluoride content is less than or equal to 1% after 1 hour of reaction, the reaction is stopped, the mixture is kept stand for 1 hour at the temperature of 10-15 ℃, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkali washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 146.8g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 96.3%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 139.6g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.3% with the yield of 92.7%.
Example 7
480G of 98 percent sulfuric acid with the mass fraction of 8 to 10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.2g of compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is added into the flask, 110g of NBS is added in batches within about 9 hours (5 g is added for each time and 22 times of adding) with the mass fraction of 7 to 10 ℃ is controlled, the temperature is kept at 8 to 10 ℃ after the addition is finished, sampling analysis is carried out, the m-fluorobenzotrifluoride content is less than or equal to 1 percent after the reaction is carried out for 1 hour, the reaction is stopped, the mixture is kept stand for 1 hour at the temperature of 10 to 15 ℃, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkali washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 146.8g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 96.6%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 140.2g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.4% with the yield of 93.2%.
Example 8
480G of 96% sulfuric acid with the mass fraction of between 8 and 10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.2g of a compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is added into the flask, 110g of NBS is added in batches within about 9 hours (5 g is added for each time and 22 times of adding) at the temperature of between 5 and 8 ℃ respectively, after the adding is completed, the reaction is carried out at the temperature of between 8 and 10 ℃ in a heat preservation mode, sampling analysis is carried out, after the reaction is carried out for 1 hour, the m-fluorobenzotrifluoride content is less than or equal to 1%, the reaction is stopped, the reaction is carried out for 1 hour at the temperature of between 10 and 15 ℃ in a static mode, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkali washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 147.1g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 96.8%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 139.9g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.3% with the yield of 92.9%.
Example 9
480G of 96% sulfuric acid with the mass fraction of between 8 and 10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.2g of a compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is added into the flask, 110g of NBS is added in batches within about 9 hours (5 g is added for each time and 22 times of adding) at the temperature of between 8 and 10 ℃ after the addition, the reaction is carried out at the temperature of between 8 and 10 ℃ in a heat preservation mode, sampling analysis is carried out, the m-fluorobenzotrifluoride content is less than or equal to1 percent after the reaction is carried out for 1 hour, the reaction is stopped, the mixture is kept stand for 1 hour at the temperature of between 10 and 15 ℃, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkali washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 147.3g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 95.9%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 140.3g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.1% with the yield of 93.0%.
Example 10
Recycling waste acid: 200g of the bottom acid separated in the embodiment 1 is taken and put into a 1000mL four-neck flask, 280g of fresh sulfuric acid with the mass fraction of 96% is put into the flask, the temperature is controlled to be 8-10 ℃, stirring is started, 100g of m-fluorobenzotrifluoride is put into the flask at one time, 0.2g of a composite catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is then put into the flask, the temperature of the system is controlled to be 7-10 ℃, 110g of NBS is put into the flask in batches within about 9 hours (5 g are put into each time and 22 times are put into each time), then the mixture is subjected to heat preservation reaction at the temperature of 8-10 ℃, sampling analysis is carried out, the m-fluorobenzotrifluoride content is less than or equal to 1% after the reaction is carried out for 1 hour, the reaction is stopped, standing for 1 hour at the temperature of 10-15 ℃ for layering, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkaline washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating liquid, taking the organic phase to obtain 146.6g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 96.4%, rectifying the crude product at normal pressure, and collecting 158-165 ℃ fractions to obtain 140.3g of the 2-bromo-5-fluorobenzotrifluoride product, wherein the gas chromatography detection content is 98.3%, and the yield is 93.2%.
Comparative example 1
480G of 96% sulfuric acid with the mass fraction of between 8 and 10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.2g of a compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is added into the flask, 110g of NBS is added in batches within about 3 hours (11 g is added for each time and 10 times of adding) at the temperature of between 8 and 10 ℃ respectively, the reaction is carried out after the addition, the sampling analysis is carried out, the m-fluorobenzotrifluoride content is less than or equal to 1 percent after the reaction is carried out for 1 hour, the reaction is stopped, the mixture is kept stand for 1 hour at the temperature of between 10 and 15 ℃, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkaline washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 147g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 84.7%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 120.9g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.3% with the yield of 80.3%.
Comparative example 2
Adding 480g of 96% sulfuric acid in mass fraction into a 1000mL four-neck flask, controlling the temperature to be 8-10 ℃, starting stirring, adding 100g of m-fluorotoluene at one time, controlling the temperature of the system to be 7-10 ℃, adding 110g of NBS in batches in about 9 hours (5 g is added each time and 22 times are added each time), carrying out heat preservation reaction at the temperature of 8-10 ℃ after the addition is completed, sampling and analyzing, reacting for 1 hour, wherein the m-fluorotoluene content is less than or equal to 1%, terminating the reaction, standing for 1 hour at the temperature of 10-15 ℃ for layering, separating out bottom acid, taking an organic layer, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkaline washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out a liquid, taking the organic phase to obtain 146.9g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 85.3%, rectifying the crude product under normal pressure, and collecting fractions at 158-165 ℃ to obtain 123.0g of the 2-bromo-5-fluorobenzotrifluoride product, wherein the detection content of gas chromatography is 98.3%, and the yield is 81.7%.
Comparative example 3
480G of 96% sulfuric acid with the mass fraction of between 8 and 10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.6g of compound catalyst (zinc bromide 0.3g and tetrabutylammonium bromide 0.3 g) is added into the flask, the temperature of the system is controlled between 7 and 10 ℃, 110g of NBS is added in batches within about 9 hours (5 g is added for each time and 22 times of addition), the reaction is carried out after the addition is completed, the temperature is kept at 8 to 10 ℃ for reaction, sampling analysis is carried out, the m-fluorobenzotrifluoride content is less than or equal to 1% after the reaction is carried out for 1 hour, the reaction is stopped, the mixture is stood for 1 hour and layered at the temperature of between 10 and 15 ℃, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkaline washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 147g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 87.8%, rectifying the crude product under normal pressure, collecting fractions at 158-165 ℃ to obtain 126.6g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to be 98.1% and the yield to be 83.9%.
Comparative example 4
480G of 96% sulfuric acid with the mass fraction of between 8 and 10 ℃ is added into a 1000mL four-neck flask, stirring is started, 100g of m-fluorobenzotrifluoride is added at one time, then 0.2g of a compound catalyst (0.08 g of elemental iodine, 0.06g of zinc bromide and 0.06g of tetrabutylammonium bromide) is added into the flask, the temperature of the system is controlled between 30 and 40 ℃, 110g of NBS is added in batches within about 9 hours (5 g is added for each time and 22 times of addition) completely, the temperature is kept at 8 to 10 ℃ for reaction, sampling analysis is carried out, the m-fluorobenzotrifluoride content is less than or equal to 1% after 1 hour of reaction, the reaction is stopped, the mixture is stood for 1 hour and layered at the temperature of between 10 and 15 ℃, separating out bottom acid, taking an organic layer to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, transferring the 2-bromo-5-fluorobenzotrifluoride crude product into a 500mL three-neck flask, adding 100g of water under stirring, dropwise adding 10% sodium hydroxide solution to adjust pH=7 for alkaline washing, separating out a water phase, adding 100g of water into an organic phase, washing with water, separating out liquid, taking the organic phase to obtain 147g of the crude product with the 2-bromo-5-fluorobenzotrifluoride content of 83.3%, rectifying the crude product under normal pressure, collecting 158-165 ℃ fractions to obtain 118.3g of the 2-bromo-5-fluorobenzotrifluoride product, and detecting the content by gas chromatography to 98.3% and the yield to 78.6%.
Claims (5)
1. A preparation method of 2-bromo-5-fluorobenzotrifluoride is characterized by comprising the steps of controlling the temperature to be 8-10 ℃, mixing m-fluorobenzotrifluoride with sulfuric acid, adding a composite catalyst, controlling the temperature of a system to be 5-20 ℃, adding NBS in batches for 9-12 hours, wherein the amount of NBS added each time is 1/25-1/15 of the total amount of NBS, after the NBS is added, carrying out heat preservation reaction, the temperature of the heat preservation reaction is 8-10 ℃, the m-fluorobenzotrifluoride content is less than or equal to 1%, stopping the reaction, standing and layering the reaction solution, wherein the standing temperature is 10-20 ℃, so as to obtain a 2-bromo-5-fluorobenzotrifluoride crude product, sequentially carrying out alkali washing and water washing on the 2-bromo-5-fluorobenzotrifluoride crude product, and carrying out normal pressure rectification, collecting fractions of 158-165 ℃, so as to obtain a 2-bromo-5-fluorobenzotrifluoride product, wherein the sulfuric acid mass fraction is 80-98%, the ratio of m-fluorobenzotrifluoride to the tetra-1.1:1.0.001 is mixed with the zinc bromide in a ratio of 1-1.1:1.1 by weight of the m-fluorobenzotrifluoride to the zinc bromide.
2. The method for preparing 2-bromo-5-fluorobenzotrifluoride according to claim 1, wherein the weight ratio of m-fluorobenzotrifluoride to sulfuric acid is 1:3.5-1:6.5.
3. The method for preparing 2-bromo-5-fluorobenzotrifluoride according to claim 1, wherein the weight ratio of m-fluorobenzotrifluoride to the composite catalyst is 1:0.002.
4. The method for preparing 2-bromo-5-fluorobenzotrifluoride according to claim 1, wherein the weight ratio of elemental iodine, zinc bromide and tetrabutylammonium bromide is 4:3:3.
5. The method for preparing 2-bromo-5-fluorobenzotrifluoride according to claim 1, wherein the weight ratio of m-fluorobenzotrifluoride to NBS is 1:1.1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411249553.0A CN119080580B (en) | 2024-09-06 | 2024-09-06 | Preparation method of 2-bromo-5-fluorobenzotrifluoride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411249553.0A CN119080580B (en) | 2024-09-06 | 2024-09-06 | Preparation method of 2-bromo-5-fluorobenzotrifluoride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN119080580A CN119080580A (en) | 2024-12-06 |
| CN119080580B true CN119080580B (en) | 2025-02-18 |
Family
ID=93660330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202411249553.0A Active CN119080580B (en) | 2024-09-06 | 2024-09-06 | Preparation method of 2-bromo-5-fluorobenzotrifluoride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN119080580B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105152853A (en) * | 2015-09-25 | 2015-12-16 | 江苏永创医药科技股份有限公司 | Method for preparing 2-bromine-5-fluorobenzotrifluoride |
| CN107337576A (en) * | 2017-06-17 | 2017-11-10 | 盐城师范学院 | Constant temperature catalyzing synthesizes the fluoride trifluoro toluene of 2 bromine 5 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0819007B2 (en) * | 1988-01-29 | 1996-02-28 | 宇部興産株式会社 | Method for halogenating aromatic compounds |
| JP2010013388A (en) * | 2008-07-03 | 2010-01-21 | Central Glass Co Ltd | Method for producing 3-chloro-4-fluorobenzotrifluoride |
| CN114437062B (en) * | 2020-04-30 | 2024-05-17 | 成都海博为药业有限公司 | Compound capable of being used as sodium channel regulator and application thereof |
-
2024
- 2024-09-06 CN CN202411249553.0A patent/CN119080580B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105152853A (en) * | 2015-09-25 | 2015-12-16 | 江苏永创医药科技股份有限公司 | Method for preparing 2-bromine-5-fluorobenzotrifluoride |
| CN107337576A (en) * | 2017-06-17 | 2017-11-10 | 盐城师范学院 | Constant temperature catalyzing synthesizes the fluoride trifluoro toluene of 2 bromine 5 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN119080580A (en) | 2024-12-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112010733B (en) | Preparation method of 3,4, 5-trifluorobromobenzene | |
| CN112457153B (en) | Industrial preparation method of 2,4, 5-trifluoro-phenylacetic acid | |
| US20220024850A1 (en) | Method for preparing 2-ethyl-4-fluoro-1-nitrobenzene | |
| CN111517931A (en) | Method for synthesizing 2, 4-difluorobenzaldehyde by using microchannel reactor | |
| CN119080580B (en) | Preparation method of 2-bromo-5-fluorobenzotrifluoride | |
| CN112794787B (en) | Method for continuously preparing 3,3, 3-trifluoro-2- (trifluoromethyl) -1-propylene in gas phase | |
| CN114085163B (en) | Method for synthesizing 2, 3-tetrafluoro-2- (trifluoromethyl) propionitrile by gas phase catalytic fluorination | |
| CN108002976B (en) | Preparation method of 1-fluoro-2-bromo-3-iodobenzene | |
| CN107337576B (en) | Catalytic Synthesis of 2-Bromo-5-Fluorotrifluorotoluene at Room Temperature | |
| JPH01301636A (en) | Production of 1,2,2,2-tetrafluoroethyl difluoromethyl ether | |
| CN110590497B (en) | Method for synthesizing m-dichlorobenzene | |
| CN105085158B (en) | A kind of synthetic method of p-methylbenzotrifluoride | |
| CN111389424A (en) | Catalyst, preparation method and application in hexafluoropropylene oligomerization reaction | |
| CN101128412B (en) | Synthesis of fluorinated ethers | |
| CN107641067B (en) | Alpha-bromination method of o-diketone | |
| CN112094171B (en) | Method for synthesizing m-chlorotoluene through isomerization reaction | |
| CN102675148B (en) | The preparation method of p-hydroxybenzonitrile | |
| CN110642720B (en) | Preparation method of 2, 4-difluoro-3, 5-dichloronitrobenzene | |
| CN108530301A (en) | A kind of synthetic method of tri- fluorin benzyl amines of 2,4,6- | |
| EP1468983B1 (en) | Process for producing 2,5-bis(trifluoromethyl)nitrobenzene | |
| CN109761743B (en) | Preparation method of 2-methyl-3, 4, 5-trifluorobromobenzene | |
| CN114907232B (en) | Synthesis process of 2-nitro-4-trifluoromethyl benzonitrile | |
| CN111620876A (en) | Synthetic method of Rudesiwei key intermediate | |
| CN115521232B (en) | Preparation method of high-purity perfluoroalkyl sulfonyl bromide | |
| CN114751807B (en) | Preparation process of 2,3,5, 6-tetrafluorobenzyl alcohol |
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 |