A preparation method of 2-bromo-5-fluorobenzotrifluoride

Abstract

This invention belongs to the field of organic synthesis and discloses a method for preparing 2-bromo-5-fluorotrifluorotoluene, comprising: controlling the temperature at 5-20℃, mixing m-fluorotrifluorotoluene with sulfuric acid, adding a composite catalyst, and then adding NBS in batches. After the NBS addition is completed, the reaction is maintained at this temperature until the m-fluorotrifluorotoluene content is ≤1%, at which point the reaction is stopped; the reaction solution is allowed to stand and separate into layers to obtain crude 2-bromo-5-fluorotrifluorotoluene; the crude 2-bromo-5-fluorotrifluorotoluene is then subjected to alkali washing and water washing, followed by atmospheric distillation, collecting the fraction at 158-165℃ to obtain the 2-bromo-5-fluorotrifluorotoluene product; the composite catalyst is a mixture of elemental iodine, zinc bromide, and tetrabutylammonium bromide. This method involves only one reaction step, is simple to operate, has accurate reaction positioning, high raw material conversion rate, high reaction yield, easy product purification, and simple post-processing. The reaction yield can reach over 93.0%, and the purity is over 98.0%.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, relates to a synthesis method of a pesticide chemical product, and relates to a preparation method of 2-bromo-5-fluorotrifluorotoluene. Background Art

[0002] 2-Bromo-5-fluorobenzotrifluoride has a wide range of uses, mainly as a pharmaceutical and pesticide intermediate.

[0003] Patent CN114163294A uses m-fluorobenzotrifluoride as raw material, bromine as bromination reagent, hydrogen peroxide as oxidant, and quaternary ammonium salt composite catalyst to obtain 2-bromo-5-fluorobenzotrifluoride by bromination and reoxidation. This method has a good reaction effect, but the use of a large amount of hydrogen peroxide may cause the risk of explosion.

[0004] Patent application CN102951996A uses m-fluorobenzotrifluoride as a raw material, which is first nitrated in a nitric acid / sulfuric acid system to obtain 5-fluoro-2-nitrobenzotrifluoride, and then 5-fluoro-2-nitrobenzotrifluoride is reduced, diazotized, and brominated to synthesize 2-bromo-5-fluorobenzotrifluoride. This method has many synthesis steps, high cost, a large amount of three wastes, high treatment costs, and is not environmentally friendly.

[0005] Patent CN111362775A uses trifluorotoluene as raw material, first mixes trifluorotoluene with sulfuric acid, potassium bromide, cuprous bromide and catalyst, and performs bromination reaction to obtain 2-bromotrifluorotoluene; 2-bromotrifluorotoluene is added with potassium fluoride and KCoF4 in DMSO solvent for fluorination reaction to obtain 2-bromo-5-fluorotrifluorotoluene. This process will produce a large amount of heavy metal waste liquid, which is difficult to recycle and is not environmentally friendly. In addition, the bromination reaction requires the use of expensive Pd-containing catalysts, which is costly. Summary of the invention

[0006] The purpose of the present invention is to solve the deficiencies in the prior art and provide a new method for preparing 2-bromo-5-fluorobenzotrifluoride, which has cheap and readily available raw materials, high product yield and purity, and is easy to industrialize. The method uses meta-fluorobenzotrifluoride as a raw material, N-bromosuccinimide (NBS) as a brominating agent, and concentrated sulfuric acid as a reaction solvent. Under the action of a composite catalyst, 2-bromo-5-fluorobenzotrifluoride is generated by a low-temperature reaction.

[0007] The purpose of the present invention can be achieved by the following technical measures:

[0008] A method for preparing 2-bromo-5-fluorobenzotrifluoride, the synthetic route is as follows:

[0009]

[0010] The method comprises: controlling the temperature at 5-20 DEG C, mixing meta-fluorobenzotrifluoride with sulfuric acid, adding a composite catalyst, and then adding NBS in batches, and after the addition of NBS is completed, keeping the temperature for reaction, and stopping the reaction when the content of meta-fluorobenzotrifluoride is less than 1%; standing the reaction liquid for stratification to obtain a crude 2-bromo-5-fluorobenzotrifluoride product, and sequentially performing alkali washing and water washing on the crude 2-bromo-5-fluorobenzotrifluoride product, and then performing normal pressure distillation, and collecting a fraction at 158-165 DEG C to obtain a 2-bromo-5-fluorobenzotrifluoride product.

[0011] The weight ratio of the meta-fluorobenzotrifluoride to the sulfuric acid is 1:3.5 to 1:6.5, preferably 1:4.8.

[0012] The mass fraction of the sulfuric acid is 80-98%.

[0013] Preferably, the temperature is controlled at 8-10° C. to mix the m-fluorobenzotrifluoride and the sulfuric acid.

[0014] The weight ratio of the meta-fluorobenzotrifluoride to the composite catalyst is 1:0.001 to 1:0.05, preferably 1:0.002.

[0015] The composite catalyst is a mixture of elemental iodine (I2), zinc bromide and tetrabutylammonium bromide; the weight ratio of the elemental iodine, zinc bromide and tetrabutylammonium bromide is 4:(1-3):(1-3), preferably 4:3:3.

[0016] The weight ratio of the meta-fluorobenzotrifluoride to NBS is 1:1.1 to 1:1.3, preferably 1:1.1.

[0017] In order to avoid the generation of by-products by adding excessive NBS in a short time, and based on production efficiency and product yield, the NBS addition time is 9 to 12 hours, and the amount of NBS added each time is 1 / 25 to 1 / 15 of the total amount of NBS, preferably 1 / 22.

[0018] Preferably, when NBS is added, the temperature of the system is controlled at 5-20° C. Specifically, when NBS is added, the temperature of the system can be controlled at 5-7° C., 5-8° C., 5-10° C., 7-10° C., 15-18° C., or 15-20° C.

[0019] Preferably, after the addition of NBS is completed, the heat preservation reaction time is 1 to 3 hours, during which time the content of fluorobenzotrifluoride is ≤1%.

[0020] Preferably, the temperature of the heat preservation reaction is 8-10°C.

[0021] The standing temperature is 10-20°C and the standing time is 1-3h. The present invention can control the standing temperature to avoid unsatisfactory stratification due to too low temperature and new impurities generated due to too high temperature.

[0022] The alkaline washing is to use sodium hydroxide solution to adjust the pH value of the crude 2-bromo-5-fluorobenzotrifluoride to 7.

[0023] Specifically, the alkali washing and water washing are as follows: water is added to the crude 2-bromo-5-fluorobenzotrifluoride product according to a mass ratio of m-fluorobenzotrifluoride to water of 1:1, alkali washing is performed by adjusting the pH to 7 with a 10% sodium hydroxide solution, separating the aqueous phase, and water is added to the organic phase according to a mass ratio of m-fluorobenzotrifluoride to water of 1:1 for water washing, and the organic phase is separated to obtain the organic phase.

[0024] Specifically, a method for preparing 2-bromo-5-fluorobenzotrifluoride comprises the following steps:

[0025] Step a, adding sulfuric acid into the reaction device, controlling the temperature at 5-20° C., adding m-fluorobenzotrifluoride at one time, and adding the composite catalyst while stirring;

[0026] Step b, controlling the system temperature at 5-20°C, adding NBS in batches within 9-12 hours; after the addition of NBS, keeping the temperature for reaction for 1-3 hours;

[0027] Step c, standing at a temperature of 10 to 20° C. for 1 to 3 hours, layering, and taking the organic phase to obtain a crude 2-bromo-5-fluorobenzotrifluoride product;

[0028] Step d, the crude 2-bromo-5-fluorobenzotrifluoride product is sequentially washed with alkali and water, and then distilled under normal pressure, and the fraction at 158-165° C. is collected to obtain a 2-bromo-5-fluorobenzotrifluoride product. The purity of the 2-bromo-5-fluorobenzotrifluoride product reaches more than 98%, and the yield is as high as about 93%.

[0029] Beneficial effects of the present invention:

[0030] The invention adopts meta-fluorobenzotrifluoride and NBS as raw materials and uses a composite catalyst to improve product selectivity, especially using iodine element to significantly improve product yield, and the composite catalyst is used in a small amount and has low cost.

[0031] The method of the invention has only one step of reaction, is easy to operate, has accurate reaction positioning, has high raw material conversion rate, high reaction yield, is easy to purify the product, has simple post-processing, and the reaction yield can reach more than 93.0% and the purity can reach more than 98.0%.

[0032] The raw materials used in the invention are easily available and inexpensive, so the prepared 2-bromo-5-fluorobenzotrifluoride is more competitive in the market.

[0033] The waste acid produced by the present invention can be recycled.

[0034] The invention has good economic and social benefits. DETAILED DESCRIPTION

[0035] The following examples are used to further illustrate the technical solution of the present invention so that those skilled in the art can better understand the present invention. However, the examples do not limit the scope of protection of the present invention in any way. Improvements and adjustments made by those skilled in the art within the scope of the claims of the present invention should also belong to the scope of protection of the present invention.

[0036] Example 1

[0037] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of a composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches over about 9 hours (5g is added each time, and added in 22 times), and after the addition is completed, keep the reaction at a temperature of 8-10°C, take samples and analyze during the reaction, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride in the raw material is ≤1%, terminate the reaction; let it stand at a temperature of 10-15°C The crude product of 2-bromo-5-fluorobenzotrifluoride was transferred to a 500mL three-necked flask, 100g of water was added under stirring, 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing, the aqueous phase was separated, and 100g of water was added to the organic phase for washing with water, and the organic phase was separated to obtain 147g of a crude product with a 2-bromo-5-fluorobenzotrifluoride content of 96.8%. The crude product was subjected to atmospheric distillation, and the fractions at 158-165°C were collected to obtain 141.4g of a 2-bromo-5-fluorobenzotrifluoride product with a content of 98.2% as detected by gas chromatography and a yield of 93.8%.

[0038] Example 2

[0039] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 1g of composite catalyst (0.4g of iodine, 0.3g of zinc bromide, and 0.3g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), and after the addition is completed, keep the reaction at a temperature of 8-10°C, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, the reaction is terminated; let stand at a temperature of 10-15°C for 1 hour to separate layers , separate the bottom acid, take the organic layer, and obtain the crude 2-bromo-5-fluorobenzotrifluoride; transfer the crude 2-bromo-5-fluorobenzotrifluoride to a 500mL three-necked flask, add 100g of water under stirring, add 10% sodium hydroxide solution dropwise to adjust the pH to 7 for alkaline washing, separate the aqueous phase, add 100g of water to the organic phase, wash with water, separate the liquid, take the organic phase, and obtain 146.9g of a crude product with a 2-bromo-5-fluorobenzotrifluoride content of 97.2%. The crude product is subjected to atmospheric distillation, and the fraction at 158-165°C is collected to obtain 140.7g of a 2-bromo-5-fluorobenzotrifluoride product, with a gas chromatography content of 98.2% and a yield of 93.4%.

[0040] Example 3

[0041] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 5g of composite catalyst (2g of iodine, 1.5g of zinc bromide, and 1.5g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add 110g of NBS in batches within about 9 hours (5g is added each time, and added in 22 times), after the addition is completed, keep the reaction at a temperature of 8-10°C, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, the reaction is terminated; stand at a temperature of 10-15°C for 1 hour to separate the layers, separate the bottom acid, take the organic layer, and obtain the crude 2-bromo-5-fluorobenzotrifluoride; transfer the crude 2-bromo-5-fluorobenzotrifluoride to a 500mL three-necked flask, add 100g of water under stirring, drop by drop, 10% sodium hydroxide solution was added to adjust the pH to 7 for alkaline washing, the aqueous phase was separated, and 100g of water was added to the organic phase for water washing. The organic phase was separated to obtain 146.8g of a crude product with a 2-bromo-5-fluorobenzotrifluoride content of 96.3%. The crude product was distilled at atmospheric pressure, and the fractions at 158-165°C were collected to obtain 140.1g of 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.3% as determined by gas chromatography, and the yield was 93.1%.

[0042] Example 4

[0043] Add 380g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), and after the addition is completed, keep the reaction at a temperature of 8-10°C, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let it stand at a temperature of 10-15°C for 1 hour. The mixture was separated into layers, the bottom acid was separated, and the organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing, the aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and the crude product 146.9 g with a 2-bromo-5-fluorobenzotrifluoride content of 96.2% was obtained. The crude product was subjected to atmospheric distillation, and the fraction at 158-165° C. was collected to obtain 139.9 g of a 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.4% as detected by gas chromatography, and the yield was 93.0%.

[0044] Example 5

[0045] Add 650g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), after the addition is completed, keep the reaction at 8-10°C, take samples for analysis, after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let stand at 10-15°C for 1 hour The mixture was separated into layers, the bottom acid was separated, and the organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing, the aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and the crude product 146.8 g of 2-bromo-5-fluorobenzotrifluoride content was 96.2%. The crude product was subjected to atmospheric distillation, and the fraction at 158-165° C. was collected to obtain 140.0 g of 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.5% as detected by gas chromatography, and the yield was 93.2%.

[0046] Example 6

[0047] Add 480g of 80% sulfuric acid by mass into a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) into the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches within about 9 hours (5g is added each time, and added in 22 times), after the addition is completed, keep the reaction at a temperature of 8-10°C, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let stand at a temperature of 10-15°C for 1 hour The layers were separated at a certain time, and the bottom acid was separated. The organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, and a 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing. The aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and the 2-bromo-5-fluorobenzotrifluoride content was 96.3%. 146.8 g of a crude product was obtained, and the crude product was distilled at normal pressure. The fractions at 158-165° C. were collected to obtain 139.6 g of a 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.3% as detected by gas chromatography, and the yield was 92.7%.

[0048] Example 7

[0049] Add 480g of 98% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), and after the addition is completed, keep the reaction at 8-10°C, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let stand at 10-15°C for 1 hour. The mixture was separated into layers, the bottom acid was separated, and the organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing, the aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and the crude product 146.8 g of 2-bromo-5-fluorobenzotrifluoride content was 96.6%. The crude product was subjected to atmospheric distillation, and the fraction at 158-165° C. was collected to obtain 140.2 g of 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.4% as detected by gas chromatography, and the yield was 93.2%.

[0050] Example 8

[0051] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 5-8°C, add a total of 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), and after the addition is completed, keep the reaction at 8-10°C, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let stand at 10-15°C for 1 hour The layers were separated at a certain time, and the bottom acid was separated. The organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, and a 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing. The aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and the 2-bromo-5-fluorobenzotrifluoride content was 96.8%. 147.1 g of a crude product was obtained, and the crude product was distilled at normal pressure. The fractions at 158 ​​to 165° C. were collected to obtain 139.9 g of a 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.3% as determined by gas chromatography, and the yield was 92.9%.

[0052] Example 9

[0053] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 15-20°C, add a total of 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), after the addition is completed, keep the reaction at 8-10°C, take samples for analysis, after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let stand at 10-15°C for 1 hour The layers were separated at a certain time, and the bottom acid was separated. The organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, and a 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing. The aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and the 2-bromo-5-fluorobenzotrifluoride content was 95.9%. 147.3 g of a crude product was obtained, and the crude product was distilled at normal pressure. The fractions at 158-165° C. were collected to obtain 140.3 g of a 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.1% as detected by gas chromatography, and the yield was 93.0%.

[0054] Example 10

[0055] Recycling of waste acid: Take 200g of the bottom acid separated in Example 1, put it into a 1000mL four-necked flask, then put in 280g of fresh sulfuric acid with a mass fraction of 96%, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) into the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches within about 9 hours (5g is added each time, and added in 22 times), and then keep the reaction at a temperature of 8-10°C, take samples for analysis, and after reacting for 1 hour, the content of meta-fluorobenzotrifluoride is ≤1%, and the reaction is terminated. The mixture was allowed to stand for 1 hour at a temperature of 10 to 15° C. to separate the layers, and the bottom acid was separated. The organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, and a 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing. The aqueous phase was separated, and 100 g of water was added to the organic phase for washing with water. The organic phase was separated to obtain 146.6 g of a crude product having a 2-bromo-5-fluorobenzotrifluoride content of 96.4%. The crude product was subjected to atmospheric distillation, and the fraction at 158 ​​to 165° C. was collected to obtain 140.3 g of a 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.3% as determined by gas chromatography, and the yield was 93.2%.

[0056] Comparative Example 1

[0057] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches within about 3 hours (11g each time, added in 10 times), after the addition is completed, keep the reaction at 8-10°C, take samples for analysis, react for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let stand at 10-15°C for 1 hour. The crude product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkali washing, the aqueous phase was separated, and 100 g of water was added to the organic phase for washing with water. The organic phase was separated to obtain 147 g of a crude product with a 2-bromo-5-fluorobenzotrifluoride content of 84.7%. The crude product was distilled at atmospheric pressure, and the fractions at 158 ​​to 165° C. were collected to obtain 120.9 g of a 2-bromo-5-fluorobenzotrifluoride product with a gas chromatography content of 98.3% and a yield of 80.3%.

[0058] Comparative Example 2

[0059] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, control the system temperature at 7-10°C, add a total of 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), keep the reaction at 8-10°C after the addition is completed, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, stand at 10-15°C for 1 hour to separate the layers, separate the bottom acid, and take the organic layer to obtain 2-bromo-5-fluorotrifluoroform The crude product of benzene was transferred to a 500mL three-necked flask, 100g of water was added under stirring, 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkali washing, the aqueous phase was separated, and 100g of water was added to the organic phase for water washing, liquid separation, and the organic phase was taken to obtain 146.9g of a crude product with a 2-bromo-5-fluorotrifluorotoluene content of 85.3%. The crude product was subjected to atmospheric distillation, and the fraction at 158-165°C was collected to obtain 123.0g of 2-bromo-5-fluorotrifluorotoluene product, the content of which was 98.3% as detected by gas chromatography, and the yield was 81.7%.

[0060] Comparative Example 3

[0061] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.6g of composite catalyst (0.3g of zinc bromide and 0.3g of tetrabutylammonium bromide) to the flask, control the system temperature at 7-10°C, add a total of 110g of NBS in batches over about 9 hours (5g each time, added in 22 times), keep the reaction at 8-10°C after the addition is completed, take samples for analysis, after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, let stand at 10-15°C for 1 hour to separate layers, The bottom acid was separated, and the organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing, the aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and the crude product of 147 g with a 2-bromo-5-fluorobenzotrifluoride content of 87.8% was obtained. The crude product was subjected to atmospheric distillation, and the fractions at 158-165° C. were collected to obtain 126.6 g of 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.1% as detected by gas chromatography, and the yield was 83.9%.

[0062] Comparative Example 4

[0063] Add 480g of 96% sulfuric acid to a 1000mL four-necked flask, control the temperature at 8-10°C, start stirring, add 100g of meta-fluorobenzotrifluoride at one time, then add 0.2g of composite catalyst (0.08g of iodine, 0.06g of zinc bromide, and 0.06g of tetrabutylammonium bromide) to the flask, control the system temperature at 30-40°C, add a total of 110g of NBS in batches within about 9 hours (5g is added each time, and added in 22 times), keep the reaction at 8-10°C, take samples for analysis, and after reacting for 1 hour, if the content of meta-fluorobenzotrifluoride is ≤1%, terminate the reaction, and let stand at 10-15°C for 1 hour The layers were separated at a certain time, and the bottom acid was separated. The organic layer was taken to obtain a crude 2-bromo-5-fluorobenzotrifluoride product. The crude 2-bromo-5-fluorobenzotrifluoride product was transferred to a 500 mL three-necked flask, 100 g of water was added under stirring, and a 10% sodium hydroxide solution was added dropwise to adjust the pH to 7 for alkaline washing. The aqueous phase was separated, and 100 g of water was added to the organic phase for water washing. The organic phase was separated and 147 g of a crude product with a 2-bromo-5-fluorobenzotrifluoride content of 83.3% was obtained. The crude product was subjected to atmospheric distillation, and the fractions at 158 ​​to 165° C. were collected to obtain 118.3 g of a 2-bromo-5-fluorobenzotrifluoride product. The content of the product was 98.3% as detected by gas chromatography, and the yield was 78.6%.

Claims

1. A method for preparing 2-bromo-5-fluorobenzotrifluoride, characterized in that: include: The temperature is controlled at 8 to 10° C., meta-fluorobenzotrifluoride and sulfuric acid are mixed, a composite catalyst is added, the temperature of the system is controlled at 5 to 20° C., NBS is added in batches, the NBS addition time is 9 to 12 hours, and the amount of NBS added each time is 1 / 25 to 1 / 15 of the total amount of NBS. After the addition of NBS is completed, the reaction is kept warm at 8 to 10° C., and the reaction is stopped when the meta-fluorobenzotrifluoride content is ≤1%. The reaction solution is allowed to stand for stratification at a temperature of 10 to 20° C. to obtain a crude 2-bromo-5-fluorobenzotrifluoride product, and the crude 2-bromo-5-fluorobenzotrifluoride product is sequentially The product is washed with alkali and water, and then distilled under normal pressure to collect the fraction at 158-165° C. to obtain a 2-bromo-5-fluorobenzotrifluoride product; wherein the mass fraction of the sulfuric acid is 80-98%; the weight ratio of the meta-fluorobenzotrifluoride to the composite catalyst is 1:0.001-1:0.05; the composite catalyst is a mixture of elemental iodine, zinc bromide and tetrabutylammonium bromide, and the weight ratio of the elemental iodine, zinc bromide and tetrabutylammonium bromide is 4:(1-3):(1-3); the weight ratio of the meta-fluorobenzotrifluoride to NBS is 1:1.1-1:1.

3.

2. The method for preparing 2-bromo-5-fluorobenzotrifluoride according to claim 1, characterized in that: The weight ratio of the meta-fluorobenzotrifluoride to the sulfuric acid is 1:3.5 to 1:6.

5.

3. The method for preparing 2-bromo-5-fluorobenzotrifluoride according to claim 1, characterized in that: The weight ratio of the meta-fluorobenzotrifluoride to the composite catalyst is 1:0.

002.

4. The method for preparing 2-bromo-5-fluorobenzotrifluoride according to claim 1, characterized in that: 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, characterized in that: The weight ratio of the meta-fluorobenzotrifluoride to NBS is 1:1.1.

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