Method for preparing m-fluorophenol based on m-fluoroanisole

Abstract

The invention discloses a method for preparing m-fluorophenol based on m-fluoroanisole, and relates to the technical field of organic synthesis, and the method comprises the following steps: adding m-fluoroanisole, hydrobromic acid and a catalyst into a reaction container, carrying out heating reflux reaction, tracking the reaction until the raw materials are completely reacted, and terminating the reaction; and standing and layering the reaction liquid, collecting an organic phase, extracting the organic phase by adopting an organic solvent, and finally rectifying to obtain the m-fluorophenol. The method disclosed by the invention is low in raw material cost, mild in reaction condition, small in waste liquid generation amount in the reaction process, high in product purity and yield and suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for preparing m-fluorophenol based on m-fluoroanisole. Background Art

[0002] m-Fluorophenol is a colorless to light yellow liquid or a low melting point solid at room temperature. It is slightly soluble in water and easily soluble in organic solvents such as ethanol, ether, and acetone. It is not only used for synthesizing fluorine-containing drugs such as antibiotics and anti-tumor agents, but also can be used as a building block for fluorine-containing pesticides such as herbicides and insecticides. In addition, m-fluorophenol can also be used for preparing fluorine-containing polymer materials.

[0003] At present, the synthesis methods of m-fluorophenol mainly include the following several: First, the diazonium salt hydrolysis method: using m-fluoroaniline as a raw material, reacting with sodium nitrite and acid at low temperature to generate a diazonium salt, and then hydrolyzing to obtain m-fluorophenol; Second, the fluorination reaction: through halogen exchange. For the above method one, a large amount of waste acid is generated during the reaction process, and the raw material m-fluoroaniline is expensive, and the treatment of the diazonium mother liquor is difficult; for the above method two, the reaction needs to be carried out under high temperature and high pressure conditions, the conditions are relatively harsh, and the energy consumption is large. Therefore, it is of great significance to provide a more economical and environmentally friendly method for synthesizing m-fluorophenol. Summary of the Invention

[0004] The technical problem to be solved by the present invention is: aiming at the deficiencies existing in the prior art, to provide a method for preparing m-fluorophenol based on m-fluoroanisole, which has low raw material cost, mild reaction conditions, less waste liquid generated during the reaction process, high product purity and yield, and is suitable for industrial production.

[0005] To solve the above technical problem, the technical solution of the present invention is: A method for preparing m-fluorophenol based on m-fluoroanisole, comprising the following steps: Adding m-fluoroanisole, hydrobromic acid, and a catalyst into a reaction vessel, heating to reflux for reaction, tracking the reaction until the raw materials react completely, and terminating the reaction; Let the above reaction solution stand for stratification, collect the organic phase, extract the organic phase with an organic solvent, and finally rectify to obtain m-fluorophenol.

[0006] Preferably, the reaction vessel is a reaction kettle.

[0007] Preferably, the temperature of the heating to reflux reaction is 102 - 107 °C.

[0008] Preferably, the concentration of the hydrobromic acid is 40 - 50 wt%, and the molar ratio of m-fluoroanisole to hydrobromic acid is 1:(3 - 5.2).

[0009] Preferably, terminating the reaction is achieved by cooling the reaction system to room temperature.

[0010] Preferably, the catalyst is an iodide, and the addition amount of the catalyst is 0.5-1% of the mass of m-fluorophenol.

[0011] Preferably, when using an organic solvent to extract the organic phase, the organic solvent used is one of toluene and dichloromethane.

[0012] Preferably, the conditions for rectification are: the kettle temperature is 110±5°C, the top temperature is 95±5°C, and the pressure is -0.095 Mpa.

[0013] Due to the adoption of the above technical solution, the present invention has at least the following beneficial effects: The present invention provides a method for synthesizing m-fluorophenol. Using m-fluorophenol as a raw material, a catalyst and hydrobromic acid are added for reaction. First, H⁺ in the hydrobromic acid combines with the methoxy oxygen atom of m-fluorophenol to form a protonated ether intermediate, weakening the C-O bond. The bromide ion, as a nucleophile, attacks the methylene carbon atom connected to the oxygen in the protonated ether intermediate, resulting in the cleavage of the C-O bond, thereby obtaining m-fluorophenol. Moreover, the catalyst iodide generates I⁻ with higher activity in the reaction, which has stronger nucleophilicity and polarization ability, and can significantly accelerate the cleavage of the methoxy group and promote the smooth progress of the reaction.

[0014] The hydrobromic acid of the present invention is both an acidic medium and a nucleophile participating in the cleavage of the ether bond. Without the need to additionally use a solvent, it reduces the generation of waste liquid in the reaction and reduces the preparation cost of the product. The present invention also optimizes the addition amount of hydrobromic acid, the addition amount of the catalyst, and other process conditions to obtain m-fluorophenol with high purity, and the yield is also significantly improved.

[0015] The method of the present invention has mild conditions, avoids high-temperature and high-pressure processes, has low raw material costs, generates less three wastes during the reaction process, has low energy consumption, and is suitable for industrial applications. Detailed Embodiments

[0016] In order to more clearly understand the above objects, features, and advantages of the present invention, the solution of the present invention will be further described below. It should be noted that, without conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

[0017] Many specific details are set forth in the following description in order to fully understand the present invention, but the present invention can also be implemented in other ways different from those described herein; obviously, the embodiments in the specification are only a part of the embodiments of the present invention, rather than all the embodiments.

[0018] In order to further understand the present invention, the preferred embodiments of the present invention will be described below in conjunction with embodiments. However, it should be understood that these descriptions are only for further explaining the features and advantages of the present invention, rather than limiting the claims of the present invention.

[0019] The calculation method of the effective yield of the product is as follows: Effective yield (%) = [(Actual output of product × Purity of product) / Theoretical output of product] × 100%. Example

[0020] A method for preparing m-fluorophenol based on m-fluoroanisole, comprising the following steps: (1) Add 126 g of m-fluoroanisole, 1600 g of 45 wt% hydrobromic acid, and 1 g of potassium iodide to the reaction kettle, start stirring, heat up to 105 °C, carry out reflux reaction, track the reaction until the m-fluoroanisole reacts completely, cool the reaction solution to room temperature, and terminate the reaction; Let the reaction solution stand for liquid separation, collect the organic phase, extract the organic phase with dichloromethane, and rectify the extracted organic phase under the conditions of a kettle temperature of 110 °C, a top temperature of 95 °C, and a pressure of -0.095 Mpa to obtain 103.5 g of m-fluorophenol with a purity of 99.5% and an effective yield of 92%. Example

[0021] A method for preparing m-fluorophenol based on m-fluoroanisole, comprising the following steps: (1) Add 126 g of m-fluoroanisole, 1550 g of 45 wt% hydrobromic acid, and 1 g of potassium iodide to the reaction kettle, start stirring, heat up to 105 °C, carry out reflux reaction, track the reaction until the m-fluoroanisole reacts completely, cool the reaction solution to room temperature, and terminate the reaction; Let the reaction solution stand for liquid separation, collect the organic phase, extract the organic phase with dichloromethane, and rectify the extracted organic phase under the conditions of a kettle temperature of 112 °C, a top temperature of 95 °C, and a pressure of -0.095 Mpa to obtain 102.2 g of m-fluorophenol with a purity of 99.2% and an effective yield of 90.5%. Example

[0022] A method for preparing m-fluorophenol based on m-fluoroanisole, comprising the following steps: (1) Add 126 g of m-fluoroanisole, 1600 g of 45 wt% hydrobromic acid, and 0.8 g of potassium iodide to the reaction kettle, start stirring, heat up to 106 °C, carry out reflux reaction, track the reaction until the m-fluoroanisole reacts completely, cool the reaction solution to room temperature, and terminate the reaction; Let the reaction solution stand for liquid separation, collect the organic phase, extract the organic phase with toluene or dichloromethane, and rectify the extracted organic phase under the conditions of a kettle temperature of 113 °C, a top temperature of 96 °C, and a pressure of -0.095 Mpa to obtain 102.4 g of m-fluorophenol with a purity of 99.4% and an effective yield of 90.9%. Example

[0023] A method for preparing m-fluorophenol based on m-fluoroanisole, comprising the following steps: (1) Add 126 g of m-fluoroanisole, 1580 g of 45 wt% hydrobromic acid, and 0.9 g of potassium iodide into a reaction kettle, start stirring, heat up to 105 °C, reflux and react, track the reaction until the m-fluoroanisole reaction is complete, cool the reaction solution to room temperature, and terminate the reaction; Let the reaction solution stand for liquid separation, collect the organic phase, extract the organic phase with dichloromethane, and rectify the extracted organic phase under the conditions of a kettle temperature of 112 °C, a top temperature of 94 °C, and a pressure of -0.095 Mpa to obtain 102.5 g of m-fluorophenol with a purity of 99.4% and an effective yield of 91.0%.

[0024] In order to verify that the method of the present invention has better effects, the following takes Example 1 as a reference and combines several comparative examples for detailed description.

[0025] Comparative Example 1 The difference between this comparative example and Example 1 is that the dosage of potassium iodide is 0.5 g, and other operations are the same as those in Example 1, obtaining 97.8 g of m-fluorophenol with a purity of 99.5% and an effective yield of 86.9%.

[0026] Comparative Example 2 The difference between this comparative example and Example 1 is that the dosage of potassium iodide is 1.5 g, and other operations are the same as those in Example 1, obtaining 103.5 g of m-fluorophenol with a purity of 98.2% and an effective yield of 90.7%.

[0027] Comparative Example 3 The difference between this comparative example and Example 1 is that the addition amount of hydrobromic acid is 920 g, and other operations are the same as those in Example 1, obtaining 96.1 g of m-fluorophenol with a purity of 90.7% and an effective yield of 77.8%.

[0028] Comparative Example 4 The difference between this comparative example and Example 1 is that the addition amount of hydrobromic acid is 1700 g, and other operations are the same as those in Example 1, obtaining 105 g of m-fluorophenol with a purity of 91.1% and an effective yield of 85.4%.

[0029] In summary, under the combined action of acidic conditions and a catalyst, by optimizing the dosages of hydrobromic acid, catalyst and other conditions, the prepared m-fluorophenol not only has high purity, but also has high yield.

[0030] In this article, specific examples are used to elaborate on the principles and implementation modes of the present invention. The descriptions of the above embodiments are only used to help understand the method and its core idea of the present invention, including the best mode, and also enable any person skilled in the art to practice the present invention, including manufacturing and using any device or system, and implementing any combined method. It should be noted that for those of ordinary skill in the art in this technical field, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention. The protection scope of the present invention is defined by the claims and may include other embodiments that can be conceived by those skilled in the art. If these other embodiments have structural elements similar to the literal description of the claims, or if they include equivalent structural elements that have no substantial difference from the literal description of the claims, then these other embodiments should also be included within the scope of the claims.

Claims

1. A method for preparing m-fluorophenol based on m-fluoroanisole, characterized in that, It includes the following steps: Add m-fluoroanisole, hydrobromic acid, and a catalyst into a reaction vessel, heat to reflux for reaction, monitor the reaction until the raw materials are completely reacted, and terminate the reaction; Let the above reaction solution stand for liquid separation, collect the organic phase, extract the organic phase with an organic solvent, and finally perform rectification to obtain m-fluorophenol.

2. The method for preparing m-fluorophenol based on m-fluoroanisole according to claim 1, wherein The reaction vessel is a reaction kettle.

3. A method for preparing m-fluorophenol based on m-fluoroanisole according to claim 1, characterized in that, The temperature for the reflux reaction is 102 - 107 °C.

4. A method for preparing m-fluorophenol based on m-fluoroanisole according to claim 1, characterized in that, The concentration of the hydrobromic acid is 40 - 50 wt%, and the molar ratio of m-fluoroanisole to hydrobromic acid is 1:(3 - 5.2).

5. A method for preparing m-fluorophenol based on m-fluoroanisole according to claim 1, characterized in that, The termination of the reaction is achieved by cooling the reaction system to room temperature.

6. A method for preparing m-fluorophenol based on m-fluoroanisole according to claim 1, characterized in that, The catalyst is an iodide, and the addition amount of the catalyst is 0.5 - 1% of the mass of m-fluoroanisole.

7. A method for preparing m-fluorophenol based on m-fluoroanisole according to claim 1, characterized in that, When extracting the organic phase with an organic solvent, the organic solvent used is one of toluene and dichloromethane.

8. A method for preparing m-fluorophenol based on m-fluoroanisole according to claim 1, characterized in that, The conditions for rectification are: kettle temperature 110 ± 5 °C, top temperature 95 ± 5 °C, and pressure -0.095 Mpa.