CN113582817A - Method for synthesizing m-trifluoromethyl phenol - Google Patents
Method for synthesizing m-trifluoromethyl phenol Download PDFInfo
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- CN113582817A CN113582817A CN202110934868.9A CN202110934868A CN113582817A CN 113582817 A CN113582817 A CN 113582817A CN 202110934868 A CN202110934868 A CN 202110934868A CN 113582817 A CN113582817 A CN 113582817A
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- C07—ORGANIC CHEMISTRY
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- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
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- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing m-trifluoromethyl phenol, which comprises the following steps: (1) in a solvent, carrying out Williams' reaction on m-chlorotrifluorotoluene and tert-butyl alcohol under the catalysis of sodium hydride and metal acetate to prepare an intermediate m-trifluoromethylbenzene tert-butyl ether; (2) in a solvent, removing tert-butyl from m-trifluoromethyl benzene tert-butyl ether prepared in the step (1) under the action of a ZSM-5 molecular sieve to prepare the trifluoromethyl phenol. The invention has simple synthesis steps, low cost and environment-friendly process.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing m-trifluoromethyl phenol.
Background
M-trifluoromethylphenol is an important chemical product and is used as an intermediate of pesticides, medicaments and dyes. Since the 80's of the 20 th century, a large number of agricultural chemicals used as insecticides, herbicides, insect pheromones, etc., and chemical drugs used for anticonvulsant, anti-depressive, anti-arthritic, anti-aids protease, etc., have been developed mainly with m-trifluoromethylphenol. At present, the industrial synthesis method of m-trifluoromethyl phenol is mainly a diazotization hydrolysis method, and the environmental pollution is serious. Wherein, the raw materials used by the ether hydrolysis method are cheap and easy to obtain, the reaction condition is mild, and the yield and the purity of the product are high. The invention takes m-chlorotrifluoromethylene as a raw material, firstly carries out Williams' reaction with tert-butyl alcohol (tert-butyl) under the catalysis of sodium hydride and different metal acetates to synthesize intermediate m-trifluoromethylbenzene tert-butyl ether, and then hydrolyzes and removes tert-butyl by using acid type cation exchange resin to synthesize the target product m-trifluoromethylphenol. The synthesis method has the advantages of mild conditions, simple operation, high yield and no environmental pollution, and is a green and environment-friendly synthesis method.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of m-trifluoromethylphenol, which has the advantages of low cost, high safety and environment-friendly process.
In order to realize the purpose of the invention, the adopted technical scheme is as follows:
a preparation method of m-trifluoromethyl phenol comprises the following steps:
(1) in a solvent, carrying out Williams' reaction on m-chlorotrifluorotoluene and tert-butyl alcohol under the catalysis of sodium hydride and metal acetate to prepare an intermediate m-trifluoromethylbenzene tert-butyl ether;
(2) in a solvent, removing tert-butyl from m-trifluoromethyl benzene tert-butyl ether prepared in the step (1) under the action of a ZSM-5 molecular sieve to prepare the trifluoromethyl phenol.
The structure of the trifluoromethyl phenol is as follows:
preferably, in the preparation method of the present invention, the metal acetate in step (1) is any one of sodium acetate, magnesium acetate, iron acetate, zinc acetate, copper acetate, potassium acetate, manganese acetate, and cobalt acetate.
Preferably, the solvent in step (1) is one or more selected from tetrahydrofuran, N-dimethylformamide, N-methylpyrrolidone, petroleum ether, cyclohexane, benzene, toluene and ethylbenzene.
Preferably, the Williams reaction temperature in step (1) is 0-200 ℃ for 1-36 hours.
Preferably, the solvent in step (2) is one or more selected from tetrahydrofuran, dichloromethane, 1, 2-dichloroethane, ethyl acetate, petroleum ether and cyclohexane.
Preferably, the temperature of the tert-butyl removal reaction in the step (2) is 20 to 80 ℃ and the reaction time is 1 to 12 hours.
As a preference, a process for the preparation of trifluoromethylphenol is specifically defined, comprising the steps of:
(1) dissolving m-chlorotrifluoromethylene and tert-butyl alcohol in a solvent, adding sodium hydride and metal acetate, wherein the molar ratio of the m-chlorotrifluoromethylene to the tert-butyl alcohol is 1:1-1:3, the molar ratio of the tert-butyl alcohol to the sodium hydride is 1:1-1:2, the molar percentage of the metal acetate in the m-chlorotrifluoromethylene is 0.1-10%, evaporating the solvent under reduced pressure after the Williams reaction is finished, pouring reactants into ice dilute hydrochloric acid, extracting ethyl acetate, and evaporating toluene under reduced pressure to obtain m-trifluoromethylbenzene tert-butyl ether.
(2) Dissolving the m-trifluoromethyl benzene tert-butyl ether prepared in the step (1) in a solvent, adding a ZSM-5 molecular sieve which accounts for 0.5-10% of the mass of the m-trifluoromethyl benzene tert-butyl ether, filtering after the reaction is finished, evaporating the solvent under reduced pressure, and continuously rectifying to obtain the m-trifluoromethyl phenol.
Compared with the prior art, the invention has the advantages that: the synthesis steps are simple, the cost is low, and the process is environment-friendly.
Drawings
FIG. 1 is a reaction scheme of a process for preparing trifluoromethylphenol according to the present invention.
Detailed Description
The present invention is not limited to the following embodiments, and those skilled in the art can implement the present invention in other embodiments according to the disclosure of the present invention, or make simple changes or modifications on the design structure and idea of the present invention, and fall into the protection scope of the present invention. It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The invention is described in more detail below with reference to the following examples:
example 1
(1) Preparation of m-trifluoromethyl benzene tert-butyl ether
180 g (1.0mol) of m-chlorotrifluorotoluene and 148.2 g (2.0mol) of tert-butanol are dissolved in 600 ml of tetrahydrofuran, and 36.0 g (1.5mol) of sodium hydride and 2.0 g (0.01mol) of copper acetate are added. Reacting at 80 ℃ for 12 hours, and evaporating the solvent under reduced pressure after the reaction is finished. The reaction mixture was poured into 1500 ml of ice, 10% diluted hydrochloric acid, extracted with ethyl acetate, and the toluene was distilled off under reduced pressure to give 192.6 g of m-trifluoromethylbenzene tert-butyl ether in 88.3% yield.
(2) Preparation of m-trifluoromethylphenol
Dissolving 218.2 g (1.0mol) of m-trifluoromethyl benzene tert-butyl ether in 500 ml of dichloromethane, adding 10.9 g of ZSM-5 molecular sieve, reacting for 6 hours at normal temperature, filtering, evaporating the solvent under reduced pressure, and continuing to rectify to obtain 138.7 g of m-trifluoromethyl phenol with the purity of 99.8% (GC) and the yield of 85.6%.
Example 2
(1) Preparation of m-trifluoromethyl benzene tert-butyl ether
180 g (1.0mol) of m-chlorotrifluoromethylene and 111.2 g (1.5mol) of tert-butanol are dissolved in 600 ml of tetrahydrofuran, and 48.0 g (2.0mol) of sodium hydride and 2.0 g (0.01mol) of copper acetate are added. Reacting at 80 ℃ for 24 hours, and evaporating the solvent under reduced pressure after the reaction is finished. The reaction mixture was poured into 1500 ml of ice, 10% diluted hydrochloric acid, extracted with ethyl acetate, and the toluene was distilled off under reduced pressure to give 188.7 g of m-trifluoromethylbenzene tert-butyl ether in 86.5% yield.
(2) Preparation of m-trifluoromethylphenol
Dissolving 218.2 g (1.0mol) of m-trifluoromethyl benzene tert-butyl ether in 500 ml of dichloromethane, adding 17.5 g of ZSM-5 molecular sieve, reacting for 12 hours at normal temperature, filtering, evaporating the solvent under reduced pressure, and continuing to rectify to obtain 149.6 g of m-trifluoromethyl phenol with the purity of 99.2% (GC) and the yield of 92.3%.
Example 3
(1) Preparation of m-trifluoromethyl benzene tert-butyl ether
180 g (1.0mol) of m-chlorotrifluoromethylene and 89.0 g (1.2mol) of tert-butanol are dissolved in 600 ml of tetrahydrofuran, and 48.0 g (2.0mol) of sodium hydride and 4.0 g (0.02mol) of copper acetate are added. Reacting at 80 ℃ for 18 hours, and evaporating the solvent under reduced pressure after the reaction is finished. The reaction mass was poured into 1500 ml of ice 10% diluted hydrochloric acid, extracted with ethyl acetate, and the toluene was distilled off under reduced pressure to obtain 179.5 g of m-trifluoromethylbenzene tert-butyl ether with a yield of 82.3%.
(2) Preparation of m-trifluoromethylphenol
Dissolving 218.2 g (1.0mol) of m-trifluoromethyl benzene tert-butyl ether in 500 ml of dichloromethane, adding 6.5 g of ZSM-5 molecular sieve, reacting for 12 hours at normal temperature, filtering, evaporating the solvent under reduced pressure, and continuing to rectify to obtain 132.3 g of m-trifluoromethyl phenol with the purity of 99.3% (GC) and the yield of 81.6%.
Example 4 molecular sieve recycle study
The molecular sieve of example 1 was baked at 200 ℃ for 5 hours. The de-tert-butyl reaction used in this example.
Dissolving 218.2 g (1.0mol) of m-trifluoromethyl benzene tert-butyl ether in 500 ml of dichloromethane, adding 8.5 g of ZSM-5 molecular sieve, reacting for 12 hours at normal temperature, filtering, evaporating the solvent under reduced pressure, and continuing to rectify to obtain 130.0 g of m-trifluoromethyl phenol with the purity of 99.3% (GC) and the yield of 80.2%.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and their concepts should be equivalent or changed within the technical scope of the present invention.
Claims (7)
1. A preparation method of m-trifluoromethyl phenol is characterized in that: the method comprises the following steps:
(1) in a solvent, carrying out Williams' reaction on m-chlorotrifluorotoluene and tert-butyl alcohol under the catalysis of sodium hydride and metal acetate to prepare an intermediate m-trifluoromethylbenzene tert-butyl ether;
(2) in a solvent, removing tert-butyl from m-trifluoromethyl benzene tert-butyl ether prepared in the step (1) under the action of a ZSM-5 molecular sieve to prepare the trifluoromethyl phenol.
2. The process for producing m-trifluoromethylphenol according to claim 1, wherein: the metal acetate in the step (1) is any one of sodium acetate, magnesium acetate, iron acetate, zinc acetate, copper acetate, potassium acetate, manganese acetate and cobalt acetate.
3. The process for producing m-trifluoromethylphenol according to claim 1, wherein: in the step (1), the solvent is one or more selected from tetrahydrofuran, N-dimethylformamide, N-methylpyrrolidone, petroleum ether, cyclohexane, benzene, toluene and ethylbenzene.
4. The process for producing m-trifluoromethylphenol according to claim 1, wherein: the Williams reaction temperature in the step (1) is 0-200 ℃ for 1-36 hours.
5. The process for producing m-trifluoromethylphenol according to claim 1, wherein: in the step (2), the solvent is one or more selected from tetrahydrofuran, dichloromethane, 1, 2-dichloroethane, ethyl acetate, petroleum ether and cyclohexane.
6. The process for producing m-trifluoromethylphenol according to claim 1, wherein: the temperature of the tert-butyl removal reaction in the step (2) is 20-80 ℃, and the reaction time is 1-12 hours.
7. The process for producing m-trifluoromethylphenol according to claim 1, wherein:
the step (1) is specifically as follows: dissolving m-chlorotrifluoromethane and tert-butyl alcohol in a solvent, adding sodium hydride and metal acetate, wherein the molar ratio of the m-chlorotrifluoromethane to the tert-butyl alcohol is 1:1-1:3, the molar ratio of the tert-butyl alcohol to the sodium hydride is 1:1-1:2, the molar percentage of the metal acetate in the m-chlorotrifluoromethane is 0.1-10%, evaporating the solvent under reduced pressure after the Williams reaction is finished, pouring reactants into ice dilute hydrochloric acid, extracting ethyl acetate, and evaporating toluene under reduced pressure to obtain m-trifluoromethylbenzene tert-butyl ether;
the step (2) is specifically as follows: dissolving the m-trifluoromethyl benzene tert-butyl ether prepared in the step (1) in a solvent, adding a ZSM-5 molecular sieve which accounts for 0.5-10% of the mass of the m-trifluoromethyl benzene tert-butyl ether, filtering after the reaction is finished, evaporating the solvent under reduced pressure, and continuously rectifying to obtain the m-trifluoromethyl phenol.
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Citations (6)
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|---|---|---|---|---|
| GB2017095A (en) * | 1978-03-23 | 1979-10-03 | Lilly Co Eli | Preparation of trifluoromethylphenols and trifluoromethylphenyl nezyl ether intermediates |
| CN1994990A (en) * | 2006-12-29 | 2007-07-11 | 天津市筠凯化工科技有限公司 | Process for preparing trifloro methyl phenol |
| CN107686440A (en) * | 2016-08-04 | 2018-02-13 | 辽宁天予化工有限公司 | A kind of preparation method of m-trifluoromethyl phenol |
| WO2019148005A1 (en) * | 2018-01-26 | 2019-08-01 | Nurix Therapeutics, Inc. | Inhibitors of cbl-b and methods of use thereof |
| CN111362782A (en) * | 2020-03-16 | 2020-07-03 | 内蒙古大中实业化工有限公司 | Method for preparing m-trifluoromethylphenol |
| CN111646881A (en) * | 2020-05-23 | 2020-09-11 | 盐城师范学院 | Synthesis method of m-trifluoromethylphenol |
-
2021
- 2021-08-16 CN CN202110934868.9A patent/CN113582817A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2017095A (en) * | 1978-03-23 | 1979-10-03 | Lilly Co Eli | Preparation of trifluoromethylphenols and trifluoromethylphenyl nezyl ether intermediates |
| JPS54135737A (en) * | 1978-03-23 | 1979-10-22 | Lilly Co Eli | Manufacture of trifluoromethylphenols |
| CA1134841A (en) * | 1978-03-23 | 1982-11-02 | Eli Lilly And Company | Method of preparing trifluoromethylphenols |
| CN1994990A (en) * | 2006-12-29 | 2007-07-11 | 天津市筠凯化工科技有限公司 | Process for preparing trifloro methyl phenol |
| CN107686440A (en) * | 2016-08-04 | 2018-02-13 | 辽宁天予化工有限公司 | A kind of preparation method of m-trifluoromethyl phenol |
| WO2019148005A1 (en) * | 2018-01-26 | 2019-08-01 | Nurix Therapeutics, Inc. | Inhibitors of cbl-b and methods of use thereof |
| CN111362782A (en) * | 2020-03-16 | 2020-07-03 | 内蒙古大中实业化工有限公司 | Method for preparing m-trifluoromethylphenol |
| CN111646881A (en) * | 2020-05-23 | 2020-09-11 | 盐城师范学院 | Synthesis method of m-trifluoromethylphenol |
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| 徐玲等: ""碱处理法制备微孔－介孔ＺＳＭ－５分子筛及其"", 《吉林大学学报（理学版）》 * |
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