Synthesis of m-trifluoromethylphenol

Abstract

The application belongs to the field of organic synthesis and particularly relates to a synthesis method of meta-trifluoromethyl phenol, which comprises the following steps: (1) in a solvent, a Williamson reaction is carried out on meta-chlorotrifluoromethyl benzene and tert-butyl alcohol under the catalysis of sodium hydride and a metal acetate salt to prepare an intermediate meta-trifluoromethyl phenyl tert-butyl ether; and (2) in a solvent, the meta-trifluoromethyl phenyl tert-butyl ether prepared in step (1) is subjected to tert-butyl group removal under the action of ZSM-5 molecular sieve to prepare trifluoromethyl phenol. The synthesis method is simple in steps, low in cost and relatively environmentally friendly.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing m-trifluoromethylphenol. Background Technology

[0002] m-Trifluoromethylphenol is an important chemical product used as an intermediate in pesticides, pharmaceuticals, and dyes. Since the 1980s, a large number of pesticides, herbicides, and insect pheromones have been developed based on m-trifluoromethylphenol, as well as chemical drugs used for anticonvulsants, antidepressants, anti-arthritis agents, and anti-HIV protease agents. Currently, the main industrial synthesis method for m-trifluoromethylphenol is the diazotization hydrolysis method, which causes serious environmental pollution. The ether hydrolysis method, however, uses inexpensive and readily available raw materials, has mild reaction conditions, and produces products with high yield and purity. This invention uses m-chlorotrifluorotoluene as a raw material. Under the catalysis of sodium hydride and different metal acetates, it first undergoes a Williamson reaction with tert-butanol to synthesize the intermediate m-trifluoromethylphenyl tert-butyl ether. Then, the tert-butyl group is hydrolyzed using an acidic cation exchange resin to synthesize the target product, m-trifluoromethylphenol. This synthesis method is mild, simple to operate, has a high yield, and avoids environmental pollution, making it a green and environmentally friendly synthesis method. Summary of the Invention

[0003] This invention addresses the shortcomings of existing technologies by providing a low-cost, highly safe, and environmentally friendly method for preparing m-trifluoromethylphenol.

[0004] To achieve the objectives of this invention, the technical solution adopted is as follows:

[0005] A method for preparing m-trifluoromethylphenol includes the following steps:

[0006] (1) In a solvent, m-chlorotrifluorotoluene and tert-butanol undergo the Williamson reaction in the presence of sodium hydride and metal acetate to prepare the intermediate m-trifluoromethylphenyl tert-butyl ether.

[0007] (2) In a solvent, the m-trifluoromethylbenzene tert-butyl ether obtained in step (1) is detert-butylated under the action of ZSM-5 molecular sieve to prepare trifluoromethylphenol.

[0008] The trifluoromethylphenol described in this invention has the following structure:

[0009]

[0010] Preferably, in the preparation method of the present invention, the metal acetate in step (1) is any one of sodium acetate, magnesium acetate, ferric acetate, zinc acetate, copper acetate, potassium acetate, manganese acetate and cobalt acetate.

[0011] Preferably, the solvent in step (1) is selected from one or more of tetrahydrofuran, N,N-dimethylformamide, N-methylpyrrolidone, petroleum ether, cyclohexane, benzene, toluene and ethylbenzene.

[0012] Preferably, the Williamson reaction in step (1) is carried out at a temperature of 0-200°C for 1-36 hours.

[0013] Preferably, the solvent in step (2) is selected from one or more of tetrahydrofuran, dichloromethane, 1,2-dichloroethane, ethyl acetate, petroleum ether and cyclohexane.

[0014] Preferably, the temperature for the detert-butylation reaction in step (2) is 20-80℃ and the reaction time is 1-12 hours.

[0015] As a preferred embodiment, the preparation method of trifluoromethylphenol is specifically defined, including the following steps:

[0016] (1) Dissolve m-chlorotrifluorotoluene and tert-butanol in a solvent, add sodium hydride and metal acetate. The molar ratio of m-chlorotrifluorotoluene to tert-butanol is 1:1-1:3, the molar ratio of tert-butanol to sodium hydride is 1:1-1:2, and the molar percentage of metal acetate in m-chlorotrifluorotoluene is 0.1-10%. After the Williamson reaction is complete, evaporate the solvent under reduced pressure, pour the reactants into ice-cold dilute hydrochloric acid, extract with ethyl acetate, and evaporate the toluene under reduced pressure to obtain m-trifluoromethylphenyl tert-butyl ether.

[0017] (2) Dissolve the m-trifluoromethylphenyl tert-butyl ether obtained in step (1) in a solvent, add 0.5-10% of ZSM-5 molecular sieve equivalent to the mass of m-trifluoromethylphenyl tert-butyl ether, after the reaction is complete, filter, evaporate the solvent under reduced pressure, and continue distillation to obtain m-trifluoromethylphenol.

[0018] Compared with existing technologies, the advantages of this invention are: simple synthesis steps, low cost, and relatively environmentally friendly process. Attached Figure Description

[0019] Figure 1 This is a reaction route diagram for the preparation method of trifluoromethylphenol according to the present invention. Detailed Implementation

[0020] This invention is not limited to the specific embodiments listed below. Those skilled in the art can implement this invention using various other specific embodiments based on the content disclosed herein. Any modifications or alterations made to the design structure and concept of this invention fall within the protection scope of this invention. It should be noted that, unless otherwise specified, the embodiments and features described in this invention can be combined with each other.

[0021] The present invention will be further described in detail below with reference to the embodiments:

[0022] Example 1

[0023] (1) Preparation of m-trifluoromethylphenyl tert-butyl ether

[0024]

[0025] 180 g (1.0 mol) of m-chlorotrifluorotoluene and 148.2 g (2.0 mol) of tert-butanol were dissolved in 600 mL of tetrahydrofuran, and 36.0 g (1.5 mol) of sodium hydride and 2.0 g (0.01 mol) of copper acetate were added. The reaction was carried out at 80 °C for 12 hours. After the reaction was completed, the solvent was evaporated under reduced pressure. The reactants were poured into 1500 mL of ice-cold 10% dilute hydrochloric acid, extracted with ethyl acetate, and the toluene was evaporated under reduced pressure to give 192.6 g of m-trifluoromethylphenyl tert-butyl ether, with a yield of 88.3%.

[0026] (2) Preparation of m-trifluoromethylphenol

[0027]

[0028] 218.2 g (1.0 mol) of m-trifluoromethylphenyl tert-butyl ether was dissolved in 500 mL of dichloromethane, and 10.9 g of ZSM-5 molecular sieve was added. The reaction was carried out at room temperature for 6 hours. After the reaction was completed, the mixture was filtered, the solvent was removed by vacuum distillation, and further distillation was carried out to obtain 138.7 g of m-trifluoromethylphenol with a purity of 99.8% (GC) and a yield of 85.6%.

[0029] Example 2

[0030] (1) Preparation of m-trifluoromethylphenyl tert-butyl ether

[0031] 180 g (1.0 mol) of m-chlorotrifluorotoluene and 111.2 g (1.5 mol) of tert-butanol were dissolved in 600 mL of tetrahydrofuran, and 48.0 g (2.0 mol) of sodium hydride and 2.0 g (0.01 mol) of copper acetate were added. The reaction was carried out at 80 °C for 24 hours. After the reaction was completed, the solvent was removed by vacuum distillation. The reactants were poured into 1500 mL of ice-cold 10% dilute hydrochloric acid, extracted with ethyl acetate, and the toluene was removed by vacuum distillation to give 188.7 g of m-trifluoromethylphenyl tert-butyl ether, with a yield of 86.5%.

[0032] (2) Preparation of m-trifluoromethylphenol

[0033] 218.2 g (1.0 mol) of m-trifluoromethylphenyl tert-butyl ether was dissolved in 500 mL of dichloromethane, and 17.5 g of ZSM-5 molecular sieve was added. The reaction was carried out at room temperature for 12 hours. After the reaction was completed, the mixture was filtered, the solvent was removed by vacuum distillation, and further distillation was carried out to obtain 149.6 g of m-trifluoromethylphenol with a purity of 99.2% (GC) and a yield of 92.3%.

[0034] Example 3

[0035] (1) Preparation of m-trifluoromethylphenyl tert-butyl ether

[0036] 180 g (1.0 mol) of m-chlorotrifluorotoluene and 89.0 g (1.2 mol) of tert-butanol were dissolved in 600 mL of tetrahydrofuran, and 48.0 g (2.0 mol) of sodium hydride and 4.0 g (0.02 mol) of copper acetate were added. The reaction was carried out at 80 °C for 18 hours. After the reaction was completed, the solvent was evaporated under reduced pressure. The reactants were poured into 1500 mL of ice-cold 10% dilute hydrochloric acid, extracted with ethyl acetate, and the toluene was evaporated under reduced pressure to give 179.5 g of m-trifluoromethylphenyl tert-butyl ether, with a yield of 82.3%.

[0037] (2) Preparation of m-trifluoromethylphenol

[0038] 218.2 g (1.0 mol) of m-trifluoromethylphenyl tert-butyl ether was dissolved in 500 mL of dichloromethane, and 6.5 g of ZSM-5 molecular sieve was added. The reaction was carried out at room temperature for 12 hours. After the reaction was completed, the mixture was filtered, the solvent was removed by vacuum distillation, and further distillation was carried out to obtain 132.3 g of m-trifluoromethylphenol with a purity of 99.3% (GC) and a yield of 81.6%.

[0039] Example 4: Investigation on the Reuse of Molecular Sieves

[0040] The molecular sieve in Example 1 was dried at 200°C for 5 hours. It was used for the detert-butylation reaction in this example.

[0041] 218.2 g (1.0 mol) of m-trifluoromethylphenyl tert-butyl ether was dissolved in 500 mL of dichloromethane, and 8.5 g of ZSM-5 molecular sieve was added. The reaction was carried out at room temperature for 12 hours. After the reaction was completed, the mixture was filtered, the solvent was removed by vacuum distillation, and further distillation was carried out to obtain 130.0 g of m-trifluoromethylphenol with a purity of 99.3% (GC) and a yield of 80.2%.

[0042] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing m-trifluoromethylphenol, characterized in that: Includes the following steps: (1) In a solvent, m-chlorotrifluorotoluene and tert-butanol undergo the Williamson reaction in the presence of sodium hydride and metal acetate to prepare the intermediate m-trifluoromethylphenyl tert-butyl ether. The Williamson reaction temperature is 0-200℃. (2) In a solvent, the m-trifluoromethylphenyl tert-butyl ether obtained in step (1) is detert-butylated under the action of ZSM-5 molecular sieve to prepare trifluoromethylphenol. The temperature of the detert-butylation reaction is 20-80℃. Step (1) is as follows: dissolve m-chlorotrifluorotoluene and tert-butanol in a solvent, add sodium hydride and metal acetate, the molar ratio of m-chlorotrifluorotoluene and tert-butanol is 1:1-1:3, the molar ratio of tert-butanol and sodium hydride is 1:1-1:2, and the molar percentage of metal acetate in m-chlorotrifluorotoluene is 0.1-10%. After the Williamson reaction is complete, evaporate the solvent under reduced pressure, pour the reactants into ice-cold dilute hydrochloric acid, extract with ethyl acetate, and evaporate the toluene under reduced pressure to obtain m-trifluoromethylphenyl tert-butyl ether. Step (2) is as follows: dissolve the m-trifluoromethyl tert-butyl ether obtained in step (1) in a solvent, add 0.5-10% of ZSM-5 molecular sieve equivalent to the mass of m-trifluoromethyl tert-butyl ether, after the reaction is complete, filter, evaporate the solvent under reduced pressure, and continue distillation to obtain m-trifluoromethylphenol. The metal acetate mentioned in step (1) is any one of sodium acetate, magnesium acetate, ferric acetate, zinc acetate, copper acetate, potassium acetate, manganese acetate, and cobalt acetate; The solvent mentioned in step (1) is selected from one or more of tetrahydrofuran, N,N-dimethylformamide, N-methylpyrrolidone, petroleum ether, cyclohexane, benzene, toluene and ethylbenzene; The solvent used in step (2) is selected from one or more of tetrahydrofuran, dichloromethane, 1,2-dichloroethane, ethyl acetate, petroleum ether and cyclohexane.

2. The method for preparing m-trifluoromethylphenol according to claim 1, characterized in that: The Williamson reaction described in step (1) lasts 1-36 hours.

3. The method for preparing m-trifluoromethylphenol according to claim 1, characterized in that: The detert-butylation reaction time in step (2) is 1-12 hours.

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