Preparation method of 1,2,4-trifluorobenzene

A technology for trifluorobenzene and difluoroaniline, which is applied in the field of chemical drug preparation, can solve the problems of harsh operating conditions, high production cost, expensive raw materials, etc., and achieves the effects of low production cost, easy operation and low requirement for reaction conditions

Inactive Publication Date: 2012-08-22
Jiangsu Shimeikang Pharmaceutical Co Ltd
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Technical problem to be solved: In order to solve the problems of expensive raw materials, high production cost, harsh operating conditions and low yield o

Method used

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  • Preparation method of 1,2,4-trifluorobenzene
  • Preparation method of 1,2,4-trifluorobenzene
  • Preparation method of 1,2,4-trifluorobenzene

Examples

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Effect test

Embodiment 1

[0026] Embodiment 1: Preparation of diazonium fluoroborate.

[0027] Add 1760g 30% fluoroboric acid aqueous solution (fluoroboric acid content: 6mol) in a 3000ml four-neck flask, add 258g (2mol) 2,4-difluoroaniline dropwise at room temperature, the reaction is exothermic, continue to stir at room temperature for 1 hour after dropping, and then lower the temperature To -5 ~ 0 ℃. Add dropwise a solution made of 145g (2.1mol) sodium nitrite and 340g water, exothermic reaction, control the rate of addition, keep the reaction temperature not exceeding 5°C, continue the reaction at 0-5°C for 2 hours after the addition, filter, The solid was washed successively with 300ml of water precooled to 0°C and 200ml of ethanol, and after drying, 410g of diazonium fluoroborate was obtained with a yield of 90%.

Embodiment 2

[0028] Embodiment 2: Preparation of diazonium fluoroborate.

[0029] Add 1760g 20% ​​fluoroboric acid aqueous solution (fluoroboric acid content: 4mol) in a 3000ml four-neck flask, add 258g (2mol) 2,4-difluoroaniline dropwise at room temperature, the reaction is exothermic, continue to stir at room temperature for 1 hour after dropping, and then lower the temperature To -5 ~ 0 ℃. Add dropwise a solution made of 141g (2.04mol) sodium nitrite and 340g water, exothermic reaction, control the rate of addition, keep the reaction temperature not exceeding 5°C, and continue the reaction at -10--5°C for 4 hours after the addition is complete. After filtering, the solid was washed successively with 300ml of water and 200ml of ethanol precooled to 0°C, and after drying, 415g of diazonium fluoroborate was obtained, with a yield of 91%.

Embodiment 3

[0030] Embodiment 3: Preparation of diazonium fluoroborate.

[0031] Add 2200g 40% fluoboric acid solution (fluoboric acid content: 10mol) in a 3000ml four-neck flask, add 258g (2mol) 2,4-difluoroaniline dropwise at room temperature, the reaction is exothermic, continue to stir at room temperature for 1 hour after dropping, and then lower the temperature To -5 ~ 0 ℃. Add dropwise a solution made of 152g (2.2mol) sodium nitrite and 360g water, exothermic reaction, control the rate of addition, keep the reaction temperature not exceeding 5°C, and continue the reaction at -20~-10°C for 6 hours after the addition is complete. After filtering, the solid was washed successively with 300ml of water and 200ml of ethanol precooled to 0°C.

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Abstract

The invention provides a preparation method of 1,2,4-trifluorobenzene, which comprises the following steps: 1) preparation of fluoboric acid diazonium salt: carrying out diazo-reaction on 2,4-difluoroaniline and sodium nitrate in fluoboric acid to obtain a fluoboric acid diazonium salt intermediate; and 2) preparation of 1,2,4-trifluorobenzene: heating to 100-300 DEG C to decompose the fluoboric acid diazonium salt intermediate while emitting nitrogen gas and boron trifluoride gas. The preparation technique provided by the invention is simple to operate, and has the advantages of low cost, high yield, high product quality and the like; and meanwhile, the quality of the byproduct boron trifluoride organic solvent solution is high, the production cost is greatly lowered, the emission of three wastes is reduced, and thus, the invention is suitable for industrial application.

Description

technical field [0001] The invention relates to a preparation method of chemical medicine, especially a preparation method of 1,2,4-trifluorobenzene. Background technique [0002] 1,2,4-Trifluorobenzene is an important pharmaceutical raw material, which can be used to produce the hypoglycemic drug sitagliptin phosphate. [0003] Various preparation methods of 1,2,4-trifluorobenzene have been disclosed at home and abroad. CN101817724A discloses a process for preparing 1,2,4-trifluorobenzene by diazotization and thermal decomposition using 3,4-difluoroaniline as a raw material. The raw materials used in this process are relatively expensive and the production cost is relatively high; US2011171112 discloses a method of using 1,2,4-trichlorobenzene as a raw material and reacting with anhydrous potassium fluoride in a high-boiling point solvent, but this method requires a very expensive catalyst; TetrahedronLetters, 2010, vol: 51(14), 1906-1909 reported the process of using 2,5...

Claims

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Application Information

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IPC IPC(8): C07C25/13C07C17/00
Inventor 刘一超王秀云王俊华
Owner Jiangsu Shimeikang Pharmaceutical Co Ltd
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