CN101168495B - The synthetic method of 1-bromo-2,4,5-trifluorobenzene - Google Patents

Abstract

The invention relates to a synthesis method of 1-bromo-2,4,5-trifluorobenzene, adding iron powder and 1,2,4-trifluorobenzene into an organic solvent, adding liquid bromine at 43-48°C, 3 After ~4 hours, add azobisisobutyl cyanide to 62~68°C, stir evenly, and react completely at 82~102°C to obtain a reaction liquid, and purify the reaction liquid to obtain 1-bromo-2,4,5 -Trifluorobenzene, the molar ratio of said 1,2,4-trifluorobenzene: liquid bromine: iron powder: azobisisobutyl cyanide is 1: 0.5～1.5: 0.025～0.050: 0.002～0.006, The organic solvent is carbon tetrachloride or chloroform, and the volumetric usage of the organic solvent is 250-300ml/mol based on 1-bromo-2,4,5-trifluorobenzene. Compared with the existing synthesis method of 1-bromo-2,4,5-trifluorobenzene, the present invention has higher yield, low cost, simple process and less environmental pollution.

Description

The synthetic method of 1-bromo-2,4,5-trifluorobenzene

(1) Technical field

The invention discloses a new method for synthesizing 1-bromo-2,4,5-trifluorobenzene.

(2) Background technology

1-Bromo-2,4,5-trifluorobenzene is an important intermediate of broad-spectrum antibacterial quinolones. Its English name is: 1-bromo-2,4,5-trifluorobenzene. 19°C, boiling point 144°C, flash point 55°C, refractive index 1.4860, specific gravity 1.758. At present, the synthesis of 1-bromo-2,4,5-trifluorobenzene is carried out by using 1,2,4,5-tetrabromofluorobenzene, but its raw material price is relatively expensive, the synthesis process is complicated, and the purity of the obtained product is low , and not easy to separate and purify.

(3) Contents of the invention

The object of the present invention is to provide a method for synthesizing 1-bromo-2,4,5-trifluorobenzene with low cost and low pollution.

For achieving the purpose of the invention, the technical scheme adopted by the present invention is:

Add iron powder and 1,2,4-trifluorobenzene into the organic solvent, add liquid bromine at 43-48°C, add slowly in 3-4 hours, then raise the temperature to 62-68°C and add azobisisobutyronitrile, Stir well, and react completely at 82-102°C to obtain a reaction solution. After the reaction solution is purified, 1-bromo-2,4,5-trifluorobenzene is obtained. The 1,2,4-trifluorobenzene: liquid bromine : iron powder: the molar ratio of azobisisobutyronitrile is 1: 0.5～1.5: 0.025～0.050: 0.002～0.006, the organic solvent is carbon tetrachloride or chloroform, and the volume consumption of the organic solvent is 1 -Bromo-2,4,5-trifluorobenzene is calculated as 250 to 300 ml/mol.

The purification process of the present invention is to cool and filter the reaction solution to obtain a filtrate, and the obtained filtrate is washed with a sodium bisulfite solution with a concentration of 15 to 25%. The volumetric dosage of the sodium bisulfite solution is 1-bromo-2, 4,5-Trifluorobenzene is calculated at 250-350ml/mol, stirred and separated, and the organic layer is separated, and the organic layer is washed with 5-20% sodium hydroxide solution until the pH value is 7-9, and dried with a desiccant , filtered, and the filtrate was concentrated to obtain 1-bromo-2,4,5-trifluorobenzene. The desiccant is preferably anhydrous MgSO ₄ .

1,2,4-trifluorobenzene of the present invention: liquid bromine: iron powder: the molar ratio of azobisisobutyronitrile is preferably 1: 0.75～1.25: 0.029～0.045: 0.003～0.005, more preferably 1 :1:0.036:0.004.

The organic solvent of the present invention is preferably carbon tetrachloride.

The method of the present invention is preferably as follows: adding iron powder and 1,2,4-trifluorobenzene into the organic solvent, adding liquid bromine at 43-48°C, adding in 3-4 hours, heating up to 62-68°C and adding Azodiisobutyronitrile was stirred for 1-4 hours, reacted at 82-102°C for 3-5 hours to obtain a reaction solution, and the reaction solution was purified to obtain 1-bromo-2,4,5-trifluorobenzene. The organic solvent was carbon tetrachloride or chloroform.

The method recommended by the present invention specifically includes the following steps: adding iron powder and 1,2,4-trifluorobenzene to carbon tetrachloride, adding liquid bromine at 45°C for 4 hours, and adding azobisisobutylene at 65°C Nitrile (AIBN) was stirred for 2 hours, reacted at 90-95°C for 4 hours, cooled and filtered, and the resulting filtrate was washed with 20% sodium bisulfite solution, and the volume of sodium bisulfite solution was 1-bromo-2,4, The 5-trifluorobenzene is calculated as 300ml/mol, and the organic layer is separated, and the organic layer is washed with 10% sodium hydroxide to a pH value of 7-9, and the organic layer is taken with anhydrous _MgSO Drying, filtering, and concentrating the filtrate, That is, 1-bromo-2,4,5-trifluorobenzene; the molar ratio of said 1,2,4-trifluorobenzene: liquid bromine: iron powder: azobisisobutyronitrile is 1:1: 0.036:0.004; the volumetric usage of the carbon tetrachloride is 300ml/mol in terms of 1-bromo-2,4,5-trifluorobenzene.

Compared with the prior art, the present invention has the beneficial effects of high yield, low cost, simple process and little environmental pollution.

(4) Specific implementation methods

The present invention will be further described below in conjunction with the examples, but the protection scope of the present invention is not limited thereto.

Example 1.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.16g (2.857mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 12.0g (75mmol) dropwise, and drop it in 4 hours, heat up to 65°C, add 49mg (0.298mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 82°C, and react 3 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.1 g of the product was obtained, the purity of which was detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 57%.

Example 2.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.2g (3.571mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 12.0g (75mmol) dropwise, and drop it in 4 hours, then warm up to 65°C and add 66mg (0.402mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 92°C, and react 4 hours. Cool, add 20% sodium bisulfite solution 30ml, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide lotion until the pH value is 8, dry with MgSO ₄ , filter, and concentrate the filtrate to obtain The product was 13.9g, the purity was 99.2% by HPLC, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), it was 1-bromo-2, 4,5-Trifluorobenzene, the yield is 66%.

Example 3.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.25g (4.464mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 12.0g (75mmol) dropwise, drop it over in 4 hours, heat up to 65°C, add 82mg (0.499mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 102°C, and react 5 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 13.4g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 64%.

Example 4.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.16g (2.857mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 16.0g (100mmol) dropwise, and drop it in 4 hours, then warm up to 65°C and add 49mg (0.298mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 82°C, and react 3 hours. Cool, add 20% sodium bisulfite 30ml, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide washing agent until the pH value is 8, dry with anhydrous MgSO ₄ , filter, and concentrate the filtrate, 12.8 g of the product was obtained, the purity of which was detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo-2 , 4,5-trifluorobenzene, the yield was 61%.

Example 5.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.2g (3.571mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 16.0g (100mmol) dropwise, and drop it in 4 hours, then warm up to 65°C, add 66mg (0.402mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 92°C, and react 4 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 14.7g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 70%.

Example 6

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.25g (4.464mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 16.0g (100mmol) dropwise, and drop it in 4 hours, then raise the temperature to 65°C, add 82mg (0.50mmol) of azobisisobutyronitrile and stir for 2 hours, raise the temperature to 102°C, and react 5 Hour. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 14.3g of the product was obtained, the purity of which was detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 68%.

Example 7.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.16g (2.857mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 20.0g (125mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then warm up to 65°C and add 49mg (0.298mol) of azobisisobutyronitrile, stir for 2 hours, heat up to 82°C, and react 3 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.2g of the product was obtained, the purity of which was detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 58%.

Example 8.

1,2,4-trifluorobenzene 13.2g (100mmol), CCl _25ml , iron powder 0.2g_(3.571mmol), mechanical stirring, heating to 45 ° C, adding a constant pressure titration funnel on the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 20.0g (125mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then warm up to 65°C and add 66mg (0.402mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 92°C, and react 4 hours. Cool, add 30ml of 20% sodium bisulfite, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide lotion until the pH value is 8, dry with _MgSO4 , filter, and concentrate the filtrate to obtain the product 13.9g, the purity detected by HPLC is 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), is 1-bromo-2,4 , 5-trifluorobenzene, the yield was 66%.

Example 9

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.2g (3.571mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 20.0 g (125 mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then add 82 mg (0.499 mmol) of azobisisobutyronitrile when the temperature rises to 65°C, stir for 2 hours, heat up to 102°C, and react 5 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.6g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 60%.

Example 10

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.16g (2.857mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Put a drying tube on the funnel, slowly add liquid bromine 16.0g (100mmol) dropwise, and drop it in 4 hours, then warm up to 65°C, add 66mg (0.402mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 92°C, React for 5 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 14.5g of the product was obtained, the purity of which was detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 69%.

Example 11

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.25g (4.464mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 16.0g (100mmol) dropwise, and drop it in 4 hours, then warm up to 65°C and add 49mg (0.298mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 82°C, and react 3 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 13.7g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 65%.

Example 12.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.2g (3.571mmol), mechanical stirring, heating to 45°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 12.0g (75mmol) dropwise, drop it over in 4 hours, heat up to 65°C, add 49mg (0.298mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 92°C, and react 3 hours. Cool, add 30ml of 20% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 10% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 13.0 g of the product was obtained, the purity of which was detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 62%.

Example 13.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 27ml, iron powder 0.14g (2.450mmol), mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Put a drying tube on the funnel, slowly add 8.0g (50mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then warm up to 68°C, add 98mg (0.608mmol) of azobisisobutyronitrile, stir for 1 hour, heat up to 82°C, and react 3 hours. Cool, add 30ml of 15% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 20% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.5g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 59%.

Example 14.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 27ml, iron powder 0.14g (2.450mmol), mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 8.0g (50mmol) of liquid bromine dropwise, and drop it in 4 hours, then warm up to 65°C, add 98mg (0.608mmol) of azobisisobutyronitrile, stir for 3 hours, heat up to 95°C, and react 3 hours. Cool, add 30ml of 15% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 5% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 13.2g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 63%.

Example 15.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 25ml, iron powder 0.14g (2.450mmol), mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 8.0g (50mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then warm up to 62°C and add 32mg (0.201mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 90°C, and react 4 hours. Cool, add 30ml of 25% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 20% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 13.4g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 64%.

Example 16.

1,2,4-Trifluorobenzene 13.2g (100mmol), CCl ₄ 30ml, iron powder 0.28g (5.013mmol), mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 24.0 g (150 mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then add 49 mg (0.298 mmol) of azobisisobutyronitrile when the temperature rises to 68°C, stir for 1 hour, heat up to 82°C, and react 5 hours. Cool, add 30ml of 15% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 20% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.6g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 60%.

Example 17.

1,2,4-Trifluorobenzene 13.2g (100mmol), CHCl ₃ 27ml, iron powder 0.14g (2.450mmol), mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Put a drying tube on the funnel, slowly add 8.0g (50mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then warm up to 68°C, add 98mg (0.608mmol) of azobisisobutyronitrile, stir for 1 hour, heat up to 82°C, and react 3 hours. Cool, add 30ml of 15% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 20% sodium hydroxide detergent until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.5g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 59%.

Example 18.

1,2,4-Trifluorobenzene 13.2g (100mmol), CHCl ₃ 27ml, iron powder 0.14g (2.450mmol), mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 8.0g (50mmol) of liquid bromine dropwise, and drop it in 4 hours, then warm up to 65°C, add 98mg (0.608mmol) of azobisisobutyronitrile, stir for 3 hours, heat up to 95°C, and react 3 hours. Cool, add 25ml of 15% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 5% sodium hydroxide lotion until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 13.0 g of the product was obtained, the purity of which was detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 62%.

Example 19.

13.2g (100mmol) of 1,2,4-trifluorobenzene, 25ml of CHCl _{3 ,} 0.14g (2.450mmol) of iron powder, mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 8.0g (50mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then warm up to 62°C and add 32mg (0.201mmol) of azobisisobutyronitrile, stir for 2 hours, heat up to 90°C, and react 4 hours. Cool, add 28ml of 25% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 20% sodium hydroxide lotion until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 13.6g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 64%.

Example 20.

13.2g (100mmol) of 1,2,4-trifluorobenzene, 30ml of CHCl ₃ , 0.28g (5.013mmol) of iron powder, mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add 24.0 g (150 mmol) of liquid bromine dropwise, and finish dropping in 4 hours, then add 49 mg (0.298 mmol) of azobisisobutyronitrile when the temperature rises to 68°C, stir for 1 hour, heat up to 82°C, and react 5 hours. Cool, add 25ml of 15% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 20% sodium hydroxide lotion until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.3g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 58%.

Example 20.

13.2g (100mmol) of 1,2,4-trifluorobenzene, 30ml of CHCl _{3 ,} 0.21g (3.601mmol) of iron powder, mechanical stirring, heating to 43°C, adding a constant pressure titration funnel to the reflux condenser, constant pressure titration Install a drying tube on the funnel, slowly add liquid bromine 16.0g (100mmol) dropwise, and drop it in 4 hours, then warm up to 68°C, add 66mg (0.402mmol) of azobisisobutyronitrile, stir for 1 hour, heat up to 82°C, and react 3 hours. Cool, add 30ml of 15% sodium bisulfite solution, stir for 10 minutes, separate the organic layer, wash with 20% sodium hydroxide lotion until the pH value is 8, dry with anhydrous _MgSO4 , filter, and concentrate the filtrate , 12.7g of the product was obtained, the purity detected by HPLC was 99.2%, 1H-NMR (CDCl ₃ ) δ: 7.38 (m, H, Ar-H), 7.02 (m, H, Ar-H), which was 1-bromo- 2,4,5-Trifluorobenzene, the yield is 60%.

Claims (8)

1. The synthetic method of 1.1-bromo-2,4,5-trifluorobenzene is characterized in that said method is: add iron powder and 1,2,4-trifluorobenzene in organic solvent, add liquid Bromine, after 3-4 hours, add azobisisobutyronitrile at 62-68°C, stir well, and react completely at 82-102°C to obtain a reaction liquid, which is purified to obtain 1-bromo-2,4 , 5-trifluorobenzene, the 1,2,4-trifluorobenzene: liquid bromine: iron powder: the molar ratio of azobisisobutyronitrile is 1: 0.5～1.5: 0.025～0.050: 0.002～0.006 , the organic solvent is carbon tetrachloride or chloroform, and the volumetric usage of the organic solvent is 250-300ml/mol based on 1-bromo-2,4,5-trifluorobenzene. 2. 1-bromo-2 as claimed in claim 1, 4, the synthetic method of 5-trifluorobenzene is characterized in that described purifying process is, the reaction solution is cooled and filtered to obtain filtrate, and the added concentration of gained filtrate is 15～2. Wash with 25% sodium bisulfite solution, the volume of the sodium bisulfite solution is 250-350ml/mol based on 1-bromo-2,4,5-trifluorobenzene, stir and separate the layers, and separate the organic layer , the organic layer was washed with 5-20% sodium hydroxide solution until the pH value was 7-9, dried with a desiccant, filtered, and the filtrate was concentrated to obtain 1-bromo-2,4,5-trifluorobenzene. 3. The synthesis method of 1-bromo-2,4,5-trifluorobenzene as claimed in claim 2, characterized in that the desiccant is anhydrous MgSO ₄ . 4. 1-bromo-2 as claimed in claim 1, the synthetic method of 4,5-trifluorobenzene is characterized in that described 1,2,4-trifluorobenzene: liquid bromine: iron powder: azo The molar ratio of diisobutyronitrile is 1:0.75-1.25:0.029-0.045:0.003-0.005. 5. synthetic method as claimed in claim 4 is characterized in that described 1,2,4-trifluorobenzene: liquid bromine: iron powder: the molar ratio of azobisisobutyronitrile substance is 1: 1: 0.036 : 0.004. 6. synthetic method as claimed in claim 1 is characterized in that described organic solvent is carbon tetrachloride. 7. The synthesis method as claimed in claim 1, characterized in that the method is: adding iron powder and 1,2,4-trifluorobenzene in an organic solvent, adding liquid bromine at 43-48°C, 3-4 After adding in 1 hour, heat up to 62-68°C, add azobisisobutyronitrile and stir for 1-4 hours, and react at 82-102°C for 3-5 hours to completely obtain the reaction solution, which is purified to obtain 1-bromo-2 , 4,5-Trifluorobenzene. 8. the synthetic method as claimed in claim 1 is characterized in that described method is: add iron powder and 1,2,4-trifluorobenzene in carbon tetrachloride, add liquid bromine with 4 hours at 45 ℃, Add azobisisobutyronitrile at 65°C and stir for 2 hours, react at 90-95°C for 4 hours, cool and filter, and the obtained filtrate is washed with 20% sodium bisulfite solution, the volume of sodium bisulfite solution is 1-Bromo-2,4,5-trifluorobenzene was calculated as 300ml/mol, the organic layer was separated, and the organic layer was washed with 10% sodium hydroxide solution until the pH value was 8, and the organic layer was dried with _anhydrous MgSO , filtered, and the filtrate was concentrated to obtain 1-bromo-2,4,5-trifluorobenzene; the amount of 1,2,4-trifluorobenzene: liquid bromine: iron powder: azobisisobutyronitrile The ratio is 1:1:0.036:0.004; the volume of carbon tetrachloride used is 300 ml/mol based on 1-bromo-2,4,5-trifluorobenzene.