Method for preparing 5-fluoro-2-bromobenzotrifluoride through bromination

Abstract

The invention relates to a method for preparing 5-fluoro-2-bromobenzotrifluoride through bromination, and relates to the technical field of organic synthesis.The method comprises the following steps that fluorobenzotrifluoride, an acid medium and a catalyst are added into a solvent, bromine is added at the temperature of-10 DEG C to 60 DEG C, the dropwise adding time is 1-6 h, heat preservation is conducted, a bromination reaction is conducted for 2-24 h, and reaction liquid is obtained; the acid medium comprises chlorosulfonic acid; the solvent comprises any one or two of dichloromethane, dichloroethane, trichloromethane and tetrachloromethane; the catalyst comprises any one or two of sulfur, sodium sulfide and potassium sulfide; filtering the reaction liquid, and standing and separating the filtrate to obtain an organic phase; the filter cake is a catalyst and can be repeatedly used; distilling and concentrating the organic phase to obtain a concentrated solution; and carrying out rectification separation on the concentrated solution to obtain the 5-fluoro-2-bromobenzotrifluoride. The method has the advantages of few reaction steps, simplicity in operation and environmental friendliness, and the product has high yield and high purity.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and in particular to a method for preparing 5-fluoro-2-bromotrifluorotoluene by bromination. Background Art

[0002] As a key pharmaceutical and pesticide intermediate, 5-fluoro-2-bromobenzotrifluoride has a wide range of applications in these fields. 5-fluoro-2-bromobenzotrifluoride can be used to synthesize the non-steroidal antitumor drug bicalutamide, which plays an important role in cancer treatment. It can also be used to synthesize the isopropyltriazole pesticide fungicide clofonate-butyl, which is of great significance for pest and disease control in agricultural production. With the continuous development of the pharmaceutical and pesticide industries, the demand for 5-fluoro-2-bromobenzotrifluoride is increasing. Therefore, the development of efficient and environmentally friendly preparation methods has important economic and social value. At the same time, market requirements for its yield and quality are also gradually increasing, prompting researchers to continuously explore new preparation processes.

[0003] Currently, the preparation methods of 5-fluoro-2-bromobenzotrifluoride are mainly divided into two categories. The first category is to obtain the product through the conversion of multiple functional groups. This type of method usually involves multi-step reactions, such as nitration, reduction, and diazotization halogenation. For example, the related technology uses o-aminobenzotrifluoride or m-fluorobenzotrifluoride as the starting material, and finally obtains the target product through a series of complex reaction steps. The other category uses m-fluorobenzotrifluoride as the starting material and obtains the product through a one-step bromination reaction, such as carrying out the bromination reaction in a medium such as concentrated sulfuric acid or acetic acid, or carrying out the bromination reaction under the catalysis of iron powder or ferric tribromide.

[0004] Existing preparation methods have many defects. The first type of method has many reaction steps and complicated operations. It requires the use of multiple reaction materials and solvents, resulting in the generation of a large amount of "three wastes", which puts great pressure on the environment. Although the second type of method has relatively few reaction steps and simple operation, it also has problems such as a large amount of "three wastes" and low bromine utilization rate. For example, bromination reaction in concentrated sulfuric acid will produce a large amount of waste acid that is difficult to handle; the method using acetic acid and hydrogen peroxide has a large variety of materials and more "three wastes"; the method using iron powder or ferric tribromide as a catalyst has a low bromine utilization rate. These problems limit the large-scale industrial application of existing preparation methods. Therefore, it is necessary to provide a method for preparing 5-fluoro-2-bromotrifluorotoluene with few reaction steps, simple operation, and environmental friendliness. Summary of the Invention

[0005] In order to improve the preparation efficiency of 5-fluoro-2-bromobenzotrifluoride, the present application provides a method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination.

[0006] The present application provides a method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination using the following technical solution: A method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination comprises the following steps: S1. Adding m-fluorobenzotrifluoride, an acid medium and a catalyst to a solvent, adding bromine at -10-60°C for 1-6 hours, and carrying out a bromination reaction by heat preservation for 2-24 hours to obtain a reaction solution; the acid medium comprises chlorosulfonic acid; the solvent comprises any one or two of dichloromethane, dichloroethane, chloroform, and tetrachloromethane; the catalyst comprises any one or two of sulfur, sodium sulfide, and potassium sulfide; S2. Filter the reaction solution, let the filtrate stand, separate the liquids, and obtain an organic phase; the filter cake is a catalyst and can be reused; S3. Distilling and concentrating the organic phase to obtain a concentrated solution; and separating the concentrated solution by rectification to obtain 5-fluoro-2-bromotrifluorotoluene.

[0007] By dissolving m-fluorobenzotrifluoride, chlorosulfonic acid and a sulfur-based catalyst in a specific chlorinated hydrocarbon solvent, controlling the reaction temperature and reaction time, and utilizing the strong acidity of chlorosulfonic acid to cooperate with the surface active sites of the sulfur-based catalyst, bromine is efficiently activated to generate electrophilic bromide cations, thereby directionally driving the ortho-bromine substitution reaction of m-fluorobenzotrifluoride; after the reaction, the solid catalyst is filtered and recovered, and combined with liquid separation, distillation and rectification processes, the solvent recycling and high-precision separation of the product are achieved; this preparation process simplifies the process through one-step bromination, optimizes mass transfer and reaction selectivity, reduces the generation of by-products and waste liquid, and has the characteristics of high yield, high purity and environmental friendliness.

[0008] Preferably, the solvent in S1 includes one of dichloromethane and dichloroethane.

[0009] Dichloromethane or dichloroethane can effectively dissolve aromatic ring substrates such as m-fluorotrifluorotoluene, while stabilizing the bromide cation intermediate through the solvation effect, promoting the electrophilic substitution reaction of bromine under the catalysis of chlorosulfonic acid; the high boiling point and thermal stability of dichloroethane can maintain the reaction homogeneous system and avoid side reactions caused by local temperature fluctuations; the rapid volatility of dichloromethane is conducive to subsequent solvent recovery and product purification; both can inhibit the unintended interaction between the sulfur catalyst and bromine through the inert environment, while reducing the solvent decomposition side reaction that may be caused by strong nucleophilic reagents, ultimately taking into account both process safety and economy while ensuring high yield and purity.

[0010] Preferably, the solvent in S1 comprises dichloromethane and dichloroethane in a mass ratio of 1:(1-2).

[0011] The mixed solvent of dichloromethane and dichloroethane forms a dynamic dissolution medium through fine-tuning of polarity, which not only enhances the solubility of m-fluorotrifluorotoluene, but also stabilizes the bromide cation intermediate through intermolecular dipole interaction, promoting the positional selectivity of the electrophilic substitution reaction; the mixed solvent system can circumvent the defects of a single solvent, improve mass transfer efficiency, and inhibit the formation of polybrominated by-products through the solvation effect, ultimately achieving the stable preparation of high-yield and high-purity products.

[0012] Preferably, the catalyst comprises sulfur.

[0013] Sulfur can decompose in the chlorosulfonic acid system to produce sulfur radicals. These radicals trigger a chain reaction by grabbing the bromine atoms in bromine to generate bromine radicals, thereby promoting the radical addition pathway of the aromatic ring of meta-fluorotrifluorotoluene; the polysulfides formed on the sulfur surface can limit the excessive attack of bromine on the ortho position of the aromatic ring through the steric effect, preferentially guiding the formation of 5-position brominated products; the weak reducing property of sulfur can also inhibit the dibromination by-products that may be generated during the reaction, and its synergistic effect with chlorosulfonic acid further stabilizes the electrophilic substitution activity of the bromide cation, forming a reaction network with parallel electrophilic-radical dual pathways; sulfur, as a heterogeneous catalyst, can be filtered to achieve efficient recovery, avoiding the interference of metal catalyst residues on the subsequent distillation process, while ensuring product purity and improving green environmental protection.

[0014] Preferably, the catalyst comprises sulfur and sodium sulfide in a mass ratio of (11-13):1.

[0015] Sulfur acts as the main catalyst, adsorbing bromine molecules through lattice defect sites and generating sulfur free radicals, triggering the dissociation of bromine into bromine free radicals, and then initiating the free radical addition pathway of the aromatic ring; sodium sulfide acts as a co-catalyst, releasing S 2 - ions form a thiosulfate intermediate with the sulfur surface, which can reduce the reaction activation energy and enhance the electrophilic substitution activity of the bromide cation; the introduction of sodium sulfide can neutralize the hydrogen bromide by-product generated in the reaction, avoiding the polybromination side reaction caused by the acidic environment. At the same time, the electron density distribution of sulfur is adjusted through interfacial charge transfer, enhancing the exposure of catalytic active sites, and further improving the catalytic efficiency and product purity.

[0016] Preferably, the molar ratio of the intermediate fluorobenzotrifluoride, bromine, acid medium and catalyst in S1 is 1:(0.5-1):(0.5-2):(0.02-0.1).

[0017] Preferably, the molar ratio of the intermediate fluorobenzotrifluoride, bromine, acid medium and catalyst in S1 is 1: (0.5-0.7): (0.5-1): (0.02-0.05).

[0018] Bromination according to the above molar ratio is carried out to prepare 5-fluoro-2-bromotrifluorotoluene, which can effectively improve the yield and purity of the product.

[0019] Preferably, the acid medium further comprises ferric chloride.

[0020] Ferric chloride, as a Lewis acid, complements the strong proton acid properties of chlorosulfonic acid: chlorosulfonic acid protonates bromine to generate a bromide ion, while ferric chloride coordinates with bromine through its empty orbital to form a complex, synergistically enhancing the electrophilic activity of the bromide ion while reducing the electron cloud density of the aromatic ring and promoting the selective substitution of the 2-position of m-fluorotrifluorotoluene. In addition, the presence of ferric chloride can inhibit the side reactions caused by the strong acidity of chlorosulfonic acid, and its weak oxidizing property can also regulate the free radical generation rate of the sulfur catalyst, balancing the electrophilic substitution and free radical addition pathways, avoiding the formation of polybrominated byproducts, and thus improving the yield and purity of 5-fluoro-2-bromotrifluorotoluene.

[0021] Preferably, the molar ratio of chlorosulfonic acid to ferric chloride in the acid medium is 1:(0.05-0.1).

[0022] The acid medium prepared according to the above molar ratio can effectively improve the yield and purity of the product.

[0023] Preferably, the bromination reaction temperature in step S1 is 5-40° C., and the bromination reaction time is 6-18 h.

[0024] The above reaction temperature and reaction time regulate the kinetic and thermodynamic equilibrium of the bromination reaction, synergistically optimize the reaction conditions, inhibit the occurrence of side reactions, maintain good reaction activity and mass transfer efficiency, and improve the yield and purity of the product.

[0025] In summary, this application includes at least one of the following beneficial technical effects: 1. By dissolving m-fluorobenzotrifluoride, chlorosulfonic acid, and a sulfur-based catalyst in a specific chlorinated hydrocarbon solvent, controlling the reaction temperature and reaction time, and utilizing the strong acidity of chlorosulfonic acid to cooperate with the surface active sites of the sulfur-based catalyst, bromine is efficiently activated to generate electrophilic bromide cations, thereby directionally driving the ortho-bromine substitution reaction of m-fluorobenzotrifluoride. After the reaction, the solid catalyst is filtered and recovered, and combined with liquid separation, distillation, and rectification processes, the solvent is recycled and the product is separated with high precision. This preparation process simplifies the process through one-step bromination, optimizes mass transfer and reaction selectivity, reduces the generation of by-products and waste liquid, and has the characteristics of high yield, high purity, and environmental friendliness.

[0026] 2. The mixed solvent of dichloromethane and dichloroethane forms a dynamic dissolution medium through fine-tuning of polarity, which not only enhances the solubility of m-fluorotrifluorotoluene, but also stabilizes the bromide cation intermediate through intermolecular dipole interactions, promoting the site-specific selectivity of the electrophilic substitution reaction. The mixed solvent system can circumvent the defects of a single solvent, improve mass transfer efficiency, and inhibit the formation of polybrominated byproducts through the solvation effect, ultimately achieving the stable preparation of high-yield and high-purity products.

[0027] 3. Sulfur acts as the main catalyst, adsorbing bromine molecules through lattice defect sites and generating sulfur free radicals, triggering the dissociation of bromine into bromine free radicals, and then initiating the free radical addition pathway of the aromatic ring; sodium sulfide acts as a co-catalyst, releasing S 2 - ions form a thiosulfate intermediate with the sulfur surface, which can reduce the reaction activation energy and enhance the electrophilic substitution activity of the bromide cation; the introduction of sodium sulfide can neutralize the hydrogen bromide by-product generated in the reaction, avoiding the polybromination side reaction caused by the acidic environment. At the same time, the electron density distribution of sulfur is adjusted through interfacial charge transfer, enhancing the exposure of catalytic active sites, and further improving the catalytic efficiency and product purity. DETAILED DESCRIPTION

[0028] The present application discloses a method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination. The raw materials used in the present application can be obtained from commercially available raw materials unless otherwise specified. The present application is further described in detail below in conjunction with the examples: Ingredients: m-Fluorobenzotrifluoride (CAS No. 401-80-9), bromine (CAS No. 7726-95-6), chlorosulfonic acid (CAS No. 7790-94-5), sulfur (CAS No. 7704-34-9), dichloromethane (CAS No. 75-09-2), dichloroethane (CAS No. 107-06-2), sodium sulfide (CAS No. 1313-82-2).

[0029] Example 1 The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is sulfur.

[0030] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0031] Example 2 The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.5:1:0.05, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is sulfur.

[0032] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at 200 rpm. The addition is completed within 6 hours, and the reaction temperature is maintained at 5°C. After the addition is completed, the reaction is maintained at 5°C. During the reaction, samples are taken to monitor the content of m-fluorobenzotrifluoride. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 18 hours to obtain a reaction solution. S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0033] Example 3 The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.55:0.7:0.031, the solvent is dichloromethane, the mass ratio of dichloromethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is sulfur.

[0034] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at 200 rpm. The addition is completed within 3 hours, and the reaction temperature is maintained at 25° C. After the addition is completed, the reaction is maintained at 25° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 12 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0035] Example 4 The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.6:0.75:0.035, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is sulfur.

[0036] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at 200 rpm. The addition is completed within 3.5 hours, and the reaction temperature is maintained at 40° C. After the addition is completed, the reaction is maintained at 25° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0037] Example 5 Example 5 is based on Example 1. The only difference between Example 5 and Example 1 is that in Example 5, the solvent is replaced by dichloromethane and dichloroethane in a mass ratio of 1:1.

[0038] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is composed of a mixture of dichloromethane and dichloroethane in a mass ratio of 1:1, the mass ratio of the solvent to meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is sulfur.

[0039] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0040] Example 6 Example 6 is based on Example 1. The only difference between Example 6 and Example 1 is that in Example 6, the solvent is replaced by dichloromethane and dichloroethane in a mass ratio of 1:2.

[0041] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is composed of a mixture of dichloromethane and dichloroethane in a mass ratio of 1:2, the mass ratio of the solvent to meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is sulfur.

[0042] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0043] Example 7 Example 7 is based on Example 1. The only difference between Example 7 and Example 1 is that in Example 7, the solvent is replaced by dichloromethane and dichloroethane in a mass ratio of 1:1.5.

[0044] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is composed of a mixture of dichloromethane and dichloroethane in a mass ratio of 1:1.5, the mass ratio of the solvent to meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is sulfur.

[0045] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0046] Example 8 Example 8 is based on Example 7. The only difference between Example 8 and Example 7 is that in Example 8, the solvent is replaced by dichloromethane and dichloroethane in a mass ratio of 1:0.5.

[0047] Example 9 Example 9 is based on Example 7. The only difference between Example 9 and Example 7 is that in Example 9, the solvent is replaced by dichloromethane and dichloroethane in a mass ratio of 1:2.5.

[0048] Example 10 Example 10 is based on Example 1. The only difference between Example 10 and Example 1 is that in Example 10, the catalyst is replaced by sulfur and sodium sulfide in a mass ratio of 11:1.

[0049] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is composed of a mixture of sulfur and sodium sulfide in a mass ratio of 11:1.

[0050] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0051] Example 11 Example 11 is based on Example 1. The only difference between Example 11 and Example 1 is that in Example 11, the catalyst is replaced by sulfur and sodium sulfide in a mass ratio of 13:1.

[0052] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is composed of a mixture of sulfur and sodium sulfide in a mass ratio of 13:1.

[0053] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0054] Example 12 Example 12 is based on Example 1. The only difference between Example 12 and Example 1 is that in Example 12, the catalyst is replaced by sulfur and sodium sulfide in a mass ratio of 12:1.

[0055] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is chlorosulfonic acid, and the catalyst is composed of a mixture of sulfur and sodium sulfide in a mass ratio of 12:1.

[0056] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0057] Example 13 Example 13 is based on Example 12. The only difference between Example 13 and Example 12 is that in Example 13, the catalyst is replaced by sulfur and sodium sulfide in a mass ratio of 10:1.

[0058] Example 14 Example 14 is based on Example 12. The only difference between Example 14 and Example 12 is that in Example 14, the catalyst is replaced by sulfur and sodium sulfide in a mass ratio of 14:1.

[0059] Example 15 Example 15 is based on Example 1. The only difference between Example 15 and Example 1 is that in Example 15, the molar ratio of fluorotrifluorotoluene, bromine, acid medium and catalyst is 1:0.3:1.5:0.02.

[0060] Example 16 Example 16 is based on Example 1. The only difference between Example 16 and Example 1 is that the molar ratio of fluorotrifluorotoluene, bromine, acid medium and catalyst in Example 16 is 1:1:0.3:0.02.

[0061] Example 17 Example 17 is based on Example 1. The only difference between Example 17 and Example 1 is that the molar ratio of fluorotrifluorotoluene, bromine, acid medium and catalyst in Example 17 is 1:0.7:0.5:0.01.

[0062] Example 18 Example 18 is based on Example 1. The only difference between Example 18 and Example 1 is that the molar ratio of fluorotrifluorotoluene, bromine, acid medium and catalyst in Example 18 is 1:0.7:0.5:0.1.

[0063] Example 19 Example 19 is based on Example 1. The only difference between Example 19 and Example 1 is that the acid medium in Example 19 further includes ferric chloride, and the mass ratio of chlorosulfonic acid to ferric chloride in the acid medium is 1:0.05.

[0064] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is composed of chlorosulfonic acid and ferric chloride in a mass ratio of 1:0.05, and the catalyst is sulfur.

[0065] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0066] Example 20 Example 20 is based on Example 1. The only difference between Example 20 and Example 1 is that the acid medium in Example 20 further includes ferric chloride, and the mass ratio of chlorosulfonic acid to ferric chloride in the acid medium is 1:0.1.

[0067] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is composed of chlorosulfonic acid and ferric chloride in a mass ratio of 1:0.1, and the catalyst is sulfur.

[0068] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0069] Example 21 Example 21 is based on Example 1. The only difference between Example 21 and Example 1 is that the acid medium in Example 21 further includes ferric chloride, and the mass ratio of chlorosulfonic acid to ferric chloride in the acid medium is 1:0.075.

[0070] The molar ratio of meta-fluorobenzotrifluoride, bromine, acid medium and catalyst is 1:0.7:0.5:0.02, the solvent is dichloroethane, the mass ratio of dichloroethane and meta-fluorobenzotrifluoride is 3:1, the acid medium is composed of chlorosulfonic acid and ferric chloride in a mass ratio of 1:0.075, and the catalyst is sulfur.

[0071] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium, and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 35° C. After the addition is completed, the reaction is maintained at 35° C., and the content of m-fluorobenzotrifluoride is monitored by sampling during the reaction. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 6 hours to obtain a reaction solution; S2. Filter the reaction solution, let the filtrate stand, and separate the liquid to obtain an organic phase; the filter cake is the catalyst and can be reused; S3. Distill and concentrate the organic phase, recover the solvent dichloroethane, and obtain a concentrated solution; and separate the concentrated solution through a distillation tower to obtain 5-fluoro-2-bromotrifluorotoluene.

[0072] Example 22 Example 22 is based on Example 21. The only difference between Example 22 and Example 21 is that the mass ratio of chlorosulfonic acid and ferric chloride in the acid medium in Example 22 is 1:0.02.

[0073] Example 23 Example 23 is based on Example 21. The only difference between Example 23 and Example 21 is that the mass ratio of chlorosulfonic acid to ferric chloride in the acid medium in Example 23 is 1:0.13.

[0074] Example 24 Example 24 is based on Example 1. The only difference between Example 24 and Example 1 is that the bromination reaction conditions in step S1 are changed in Example 24.

[0075] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 0°C. After the addition is completed, the reaction is maintained at 0°C. During the reaction, sampling is performed to monitor the content of m-fluorobenzotrifluoride. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 22 hours to obtain a reaction solution.

[0076] Example 25 Example 25 is based on Example 1. The only difference between Example 25 and Example 1 is that the bromination reaction conditions in step S1 are changed in Example 25.

[0077] S1. Add a solvent, m-fluorobenzotrifluoride, an acid medium and a catalyst to a reaction flask, and add bromine dropwise under stirring at a speed of 200 rpm. The addition is completed within 2 hours, and the reaction temperature is maintained at 45°C. After the addition is completed, the reaction is maintained at 45°C. During the reaction, samples are taken to monitor the content of m-fluorobenzotrifluoride. The reaction is stopped when the content is less than 0.1%. The total reaction time is about 4 hours to obtain a reaction solution.

[0078] Comparative Example 1 The molar ratio of m-fluorobenzotrifluoride, concentrated sulfuric acid and bromine is 1:4.2:0.8, and the concentrated sulfuric acid has a mass fraction of 98%.

[0079] S1. Add m-fluorobenzotrifluoride and concentrated sulfuric acid to a four-necked flask, stir at 200 rpm, heat to 15° C., add bromine dropwise over 6 hours, maintain the reaction temperature at 15° C., stir and react at 15° C. for 4 hours after the addition is complete, take samples regularly and monitor the content of m-fluorobenzotrifluoride by gas chromatography until the content is lower than 0.5%, and stop the reaction to obtain a reaction solution; S2. Transfer the reaction solution to a separatory funnel, let it stand and separate into layers, discard the lower aqueous phase, and obtain the organic phase; S3. Wash the organic phase twice with a 10% aqueous sodium carbonate solution, shaking for 5 minutes each time, allowing it to stand for stratification, discarding the aqueous phase, and washing with deionized water until neutral; add anhydrous magnesium sulfate to the washed organic phase and dry it for 2 hours. After filtering to remove the desiccant, distill it to obtain 5-fluoro-2-bromotrifluorotoluene.

[0080] Performance testing Yield and purity test: The mass of the product was weighed and the yield was calculated. The purity of the product was tested by gas chromatography. Each sample was tested three times and the average value was taken after measurement. The results are recorded in Table 1.

[0081] Table 1 Yield and purity test results of 5-fluoro-2-bromobenzotrifluoride As shown in Table 1, the yields of Examples 1-4 are greater than 94.3% and the purities are greater than 99.5%. This shows that the method for preparing 5-fluoro-2-bromotrifluorotoluene by bromination of the present application has high yield and high purity, improves the preparation efficiency, and is environmentally friendly.

[0082] As can be seen from Table 1, the only difference between Examples 5-9 and Example 1 is that the solvent in Examples 5-9 is replaced with a mixed solvent of dichloromethane and dichloroethane. Compared with Example 1, the yield and purity of the product in Example 7 are increased. This is because within the optimal ratio, efficient mass transfer can be maintained, thereby improving the reaction efficiency. Examples 8 and 9 destroy the optimal ratio, and the yield and purity decrease.

[0083] As shown in Table 1, the only difference between Examples 10-14 and Example 1 is that the catalyst in Examples 10-15 is replaced with a catalyst composed of sulfur and sodium sulfonate. Compared with Example 1, the yield and purity of Examples 10-12 are improved. This is because the catalyst has a good synergistic effect and high catalytic activity within the specified ratio. The yield and purity of Examples 13 and 14 are reduced because the optimal ratio is destroyed.

[0084] As can be seen from Table 1, the only difference between Examples 15-18 and Example 1 is that the amount of bromine and acid medium in Examples 15 and 16 destroys the optimal ratio. Too little bromine or acid medium will have an impact, resulting in a decrease in performance. The molar ratio of the catalyst in Examples 17 and 18 destroys the optimal ratio, affecting the catalytic activity and causing a decrease in the product and yield.

[0085] As can be seen from Table 1, the only difference between Examples 19-23 and Example 1 is that in Examples 19-21, the acid medium uses ferric chloride and chlorosulfonic acid as the compound, and the product and yield are increased. This is because the compounding of the two can improve the activation efficiency, thereby increasing the yield and purity. Examples 22 and 23 destroy the optimal ratio of the acid medium, and the improvement effect is reduced.

[0086] As can be seen from Table 1, the only difference between Examples 24 and 25 and Example 1 is that the optimal reaction temperature and time are destroyed in Examples 24 and 25. Compared with Example 1, the products and yields of Examples 24 and 25 are reduced. This is because the destruction of the optimal reaction temperature and time will affect the reaction process, making it difficult to balance the yield and purity.

[0087] As can be seen from Table 1, the only difference between Comparative Example 1 and Example 1 is that the conventional direct bromination preparation process is used in Comparative Example 1, and the yield of the product is significantly reduced, and the preparation efficiency is reduced. It can be seen that the method for preparing 5-fluoro-2-bromotrifluorotoluene by bromination of the present application can efficiently carry out the reaction, and has the advantages of fewer reaction steps, simple operation, and environmental friendliness.

[0088] This specific embodiment is merely an explanation of the present application and does not limit the present application. Based on the above description, relevant personnel can make various changes and modifications without departing from the technical scope of the present application. The technical scope of the present application is not limited to the contents of the specification and must be determined according to the scope of the claims.

Claims

1. A method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination, characterized in that: The following steps are involved: S1. Adding m-fluorobenzotrifluoride, an acid medium and a catalyst to a solvent, adding bromine at -10-60°C for 1-6 hours, and carrying out a bromination reaction by heat preservation for 2-24 hours to obtain a reaction solution; the acid medium comprises chlorosulfonic acid; the solvent comprises any one or two of dichloromethane, dichloroethane, chloroform, and tetrachloromethane; the catalyst comprises any one or two of sulfur, sodium sulfide, and potassium sulfide; S2. Filter the reaction solution, let the filtrate stand, separate the liquids, and obtain an organic phase; the filter cake is a catalyst and can be reused; S3. Distilling and concentrating the organic phase to obtain a concentrated solution; and separating the concentrated solution by rectification to obtain 5-fluoro-2-bromotrifluorotoluene.

2. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 1, wherein: The solvent in S1 includes one of dichloromethane and dichloroethane.

3. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 1, wherein: The solvent in S1 includes dichloromethane and dichloroethane in a mass ratio of 1:(1-2).

4. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 1, wherein: The catalyst includes sulfur.

5. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 1, wherein: The catalyst comprises sulfur and sodium sulfide in a mass ratio of (11-13):

1.

6. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 1, wherein: The molar ratio of the intermediate fluorobenzotrifluoride, bromine, acid medium and catalyst in S1 is 1: (0.5-1): (0.5-2): (0.02-0.1).

7. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 6, characterized in that: The molar ratio of the intermediate fluorobenzotrifluoride, bromine, acid medium and catalyst in S1 is 1: (0.5-0.7): (0.5-1): (0.02-0.05).

8. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 1, wherein: The acid medium also includes ferric chloride.

9. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 8, characterized in that: The molar ratio of chlorosulfonic acid to ferric chloride in the acid medium is 1:(0.05-0.1).

10. The method for preparing 5-fluoro-2-bromobenzotrifluoride by bromination according to claim 1, wherein: In step S1, the bromination reaction temperature is 5-40° C., and the bromination reaction time is 6-18 hours.

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