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Method for preparing o-fluorophenol by one-pot method

A technology of o-fluorophenol and chlorofluorobenzene, which is applied in the field of preparation of o-fluorophenol, can solve the problems of strong toxicity of fluorine-containing reagents, unstable diazotization, and explosives, and avoid fluorinated reagents and unstable diazonium Chemical reaction, process efficiency, no isomer effect

Pending Publication Date: 2021-04-13
甘肃瀚聚药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] A is to synthesize o-fluorophenol by fluorination of phenol, such as CN110950739A, etc., the cost is relatively low, but direct fluorination will produce isomers, the difficulty of purification increases, and the toxicity of fluorine-containing reagents is relatively strong, and the amount of post-treatment wastewater is large
[0005] B is obtained through the oxidation of o-fluorophenylboronic acid to obtain o-fluorophenol, which has the advantages of high yield and no isomers. The disadvantage is that the finished product is high, and the price of o-fluorophenylboronic acid is much higher than that of the obtained o-fluorophenol
[0006] C is fluorinated by the Sandmeyer reaction of o-aminophenol, but the fluorinating reagent is more expensive, waste water, diazotization is unstable, explosive and other potential risk factors

Method used

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  • Method for preparing o-fluorophenol by one-pot method
  • Method for preparing o-fluorophenol by one-pot method
  • Method for preparing o-fluorophenol by one-pot method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022]

[0023] Under the protection of nitrogen flow, put 13g (0.542mol) of magnesium metal, 8.6g (0.049mol) of o-bromofluorobenzene, 31.2g (0.736mol) of anhydrous lithium chloride and 150mL of 2-methyltetrahydrofuran into the reaction flask, and cool down to - 10°C, add 0.1g iodine and 1g dibromoethane to initiate, after the initiation, slowly add dropwise the remaining 77.4g o-bromofluorobenzene and 300mL 2-methyltetrahydrofuran mixed solution, after dropping, slowly raise the temperature to 25°C for reaction 2 Hours, sampling dilute hydrochloric acid quenched and organic solvent extraction, detection of raw materials without remaining, containing 3% benzene. Cool down to 0°C, control the flow rate and feed compressed air, keep it warm for 6 hours, slowly raise the temperature to 35°C and keep it warm for 2 hours, take a sample to detect the product purity is greater than 96%, cool down to 10°C, add dilute hydrochloric acid to quench, separate, and water phase Extract wi...

Embodiment 2

[0025]

[0026] Under the protection of nitrogen flow, put 65.3g (0.5mol) of o-bromofluorobenzene, 27.5g (0.736mol) of anhydrous lithium chloride and 180mL of tetrahydrofuran into the reaction bottle, lower the temperature and control it at -5°C, and slowly add 262mL of isopropyl Magnesium chloride / tetrahydrofuran solution (2.0mol / L), reacted at this temperature for 3 hours, raised the temperature to 15°C and reacted for 2 hours, sampled dilute hydrochloric acid to quench and extracted with organic solvent, no raw materials were detected, containing 1.5% benzene. Cool down to 0°C, control the flow rate and feed compressed air, keep it warm for 6 hours, slowly raise the temperature to 35°C and keep it warm for 2 hours, take a sample to test that the product purity is greater than 93%, cool down to 10°C, add acetic acid aqueous solution to quench, separate layers, and water phase Extract with ethyl acetate, combine the organic phases, add activated carbon and sodium thiosulfat...

Embodiment 3

[0028]

[0029] Under the protection of nitrogen flow, put 65.3g (0.5mol) of o-bromofluorobenzene, 27.5g (0.736mol) of anhydrous lithium chloride and 180mL of tetrahydrofuran into the reaction bottle, lower the temperature and control it at -5°C, and slowly add 261mL of ethylmagnesium chloride dropwise Tetrahydrofuran solution (2.0 mol / L), reacted at this temperature for 2 hours, raised the temperature to 15°C and reacted for 2 hours, sampled dilute hydrochloric acid to quench and extracted with organic solvent, no remaining raw materials were detected, containing 1.8% benzene. Cool down to 0°C, control the flow rate to feed oxygen, keep warm for 2 hours, slowly raise the temperature to 35°C and keep warm for 3 hours, take a sample to test the product purity is 92%, cool down to 10°C, add ammonium chloride aqueous solution to quench, separate layers, water phase acetic acid Extract with ethyl ester, combine the organic phases, add activated carbon and sodium thiosulfate, fil...

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Abstract

The invention discloses a method for preparing o-fluorophenol by a one-pot method, and belongs to the technical field of organic synthesis. O-bromine / chlorofluorobenzene is used as a raw material, a 2-fluorophenyl Grignard reagent is obtained through magnesium metal or Grignard reagent exchange in the presence of a stabilizer, and then oxygen or compressed air is introduced to obtain the o-fluorophenol. The method is simple and convenient in reaction operation, less in three wastes, high in yield and free of isomers, inhibits elimination of a Grignard reagent due to addition of the stabilizer, and accords with industrial amplification prospects.

Description

technical field [0001] The invention relates to a method for preparing o-fluorophenol in one pot, and belongs to the technical field of organic synthesis. Background technique [0002] O-fluorophenol, CAS 367-12-4, English name 2-Fluorophemol, is an important intermediate for the synthesis of new fluorine-containing antibacterial and anti-inflammatory drugs, insecticides, acaricides, herbicides and liquid crystals, and can also be used as a plastic and rubber additive. The new lipidity of the fluorine atom in the compound can improve the cell membrane permeability of the drug, thereby greatly improving the bioavailability of the drug. At the same time, the strong electronegativity of the fluorine atom will enhance the binding ability between the ligand and the target. It is used in the field of medicine widely. O-fluorophenol belongs to fluorine-containing phenol derivatives. However, many natural products contain phenol structures, which are of great significance as precur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C37/58C07C39/27C07F3/02
CPCC07C37/58C07F3/02C07C39/27
Inventor 杜景峰马飞鸿查正兴谭再佩
Owner 甘肃瀚聚药业有限公司
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