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Improved synthesis process of 5-fluorothiophene-2-formic acid

A synthesis process and fluorothiophene technology are applied in the field of synthesis technology of 5-fluorothiophene-2-carboxylic acid, and can solve the problems of unobtainable raw materials, complicated refining process and the like

Inactive Publication Date: 2012-10-17
NANJING COLLEGE OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0012] The purpose of this invention is to provide an improved synthesis process of 5-fluorothiophene-2-carboxylic acid, which reduces the requirements for low moisture content of raw materials, reduces the requirements for operating conditions and supporting equipment, and optimizes the product refining method , the operation is simple and convenient, and the two-step total yield is as high as 85%, which overcomes the shortcomings of the prior art, such as high requirements for process operating conditions and supporting equipment, difficult raw materials, and complicated refining processes.

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  • Improved synthesis process of 5-fluorothiophene-2-formic acid

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Embodiment 15

[0020] Synthesis of embodiment 15-fluorothiophene-2-carbonitrile

[0021] Potassium fluoride (23.2 g, 0.40 mol), catalyst tetraphenylphosphine bromide (4.2 g, 0.01 mol) were dissolved in sulfolane (200 ml), toluene (20 ml) was added, and heated to reflux for dehydration for 2 h. Cool to 80°C, add 5-nitrothiophene-2-carbonitrile (15.4g, 0.10mol), phthaloyl chloride (20.3g, 0.10mol), and heat at 180°C for 4h. Cool to 50°C, filter with suction, collect the filtrate, and distill to obtain transparent oily liquid 5-fluorothiophene-2-carbonitrile (11.44g, 0.09mol), yield: 90%. Boiling point: 171-173°C.

[0022] The synthesis of embodiment 25-fluorothiophene-2-formonitrile

[0023] Potassium fluoride (23.2g, 0.40mol), catalyst n-tetrabutylphosphine bromide (3.39g, 0.01mol) were dissolved in sulfolane (200ml), toluene (20ml) was added, and heated to reflux for dehydration for 2h. Cool to 80°C, add 5-nitrothiophene-2-carbonitrile (15.4g, 0.10mol), phthaloyl chloride (20.3g, 0.10mol)...

Embodiment 45

[0026] The synthesis of embodiment 45-fluorothiophene-2-carbonitrile

[0027] Potassium fluoride (23.2g, 0.40mol), catalyst n-tetrabutylphosphine chloride (2.95g, 0.01mol) were dissolved in sulfolane (200ml), toluene (20ml) was added, and heated to reflux for dehydration for 2h. Cool to 80°C, add 5-nitrothiophene-2-carbonitrile (15.4g, 0.10mol), phthaloyl chloride (20.3g, 0.10mol), and heat at 180°C for 4h. Cool to 50°C, filter with suction, collect the filtrate, and distill to obtain transparent oily liquid 5-fluorothiophene-2-carbonitrile (5.09g, 0.04mol), yield: 40%. Boiling point: 171-173°C.

[0028] Synthesis of Example 55-fluorothiophene-2-carbonitrile

[0029] Potassium fluoride (23.2g, 0.40mol), catalyst triphenylbenzylphosphine bromide (4.33g, 0.01mol) were dissolved in sulfolane (200ml), benzene (100ml) was added, and heated to reflux for dehydration for 2h. Cool to 80°C, add 5-nitrothiophene-2-carbonitrile (15.4g, 0.10mol), phthaloyl chloride (20.3g, 0.10mol), an...

Embodiment 85

[0034] Synthesis of Example 85-fluorothiophene-2-carbonitrile

[0035] Potassium fluoride (19.17g, 0.33mol), catalyst tetraphenylphosphine bromide (4.2g, 0.01mol) were dissolved in sulfolane (200ml), dichloroethane (50ml) was added, and heated under reflux for dehydration for 2h. Cool to 80°C, add 5-nitrothiophene-2-carbonitrile (15.4g, 0.10mol), phthaloyl chloride (20.3g, 0.10mol), and heat at 200°C for 10h. Cool to 50°C, filter with suction, collect the filtrate, and distill to obtain transparent oily liquid 5-fluorothiophene-2-carbonitrile (3.81 g, 0.03 mol), yield: 30%. Boiling point: 171-173°C.

[0036] Synthesis of Example 95-fluorothiophene-2-carboxylic acid

[0037] 5-fluorothiophene-2-carbonitrile (11.44g, 0.09mol), 1.0mol / L NaOH (25ml, 0.19mol) aqueous solution, heated to reflux for 3h. Cool, adjust pH=1 with 1 mol / L hydrochloric acid, filter to obtain a solid, and recrystallize with petroleum ether to obtain a light yellow solid 5-fluorothiophene-2-carboxylic aci...

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Abstract

The invention provides an improved synthesis process of 5-fluorothiophene-2-formic acid, which comprises the steps of mixing a dehydrating agent A, catalyst B, solvent sulfolane with raw material potassium fluoride; heating, refluxing and dehydrating; then cooling to 80 DEG C, then adding raw material 5-nitrothiophene-2-formonitrile and o-phthaloyl chloride; heating and reacting for 1-10 hours at 150-220 DEG C; filtering and distilling reaction liquid to obtain 5-fluorothiophene-2-formonitrile; heating and refluxing and reacting for 3 hours for 5-fluorothiophene-2-formonitrile and sodium hydroxide aqueous solution; then acidizing and filtering and recrystalizing with petroleum ether to obtain 5-fluorothiophene-2-formic acid. The process reduces the requirement of low water ratio to raw materials, reduces the requirements on operating condition and corollary equipment, optimizes the refining method of product, is simple and convenient to operate, and has the total yield of 85% in two steps. The prepared 5-fluorothiophene-2-formic acid can be used as an intermediate for medical and organic photoelectric materials.

Description

technical field [0001] The invention relates to the industrial production of a fluorinated five-membered ring medicine and an organic photoelectric material intermediate, in particular to an improved synthesis process of 5-fluorothiophene-2-carboxylic acid. technical background [0002] 5-fluorothiophene-2-carboxylic acid can be used as an important pharmaceutical intermediate. In addition, 5-fluorothiophene-2-carboxylic acid can also be used as an intermediate in the synthesis of organic optoelectronic materials due to the electron-rich properties of the thiophene group. [0003] At present, there are mainly three kinds of synthetic techniques of 5-fluorothiophene-2-carboxylic acid reported in the literature: [0004] 1. Using thiophene as raw material, react with butyl lithium ether solution at low temperature to obtain 2-thiophene lithium, and then react with perfluorinated chloride to obtain 2-fluorothiophene, and then undergo acetylation and oxidation reactions to obta...

Claims

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Application Information

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IPC IPC(8): C07D333/40
Inventor 刘山杨小燕王世娟许宁关琦
Owner NANJING COLLEGE OF CHEM TECH