Method for synthesizing 2-methyl-3, 4, 5-trifluorophenol

Abstract

The invention relates to the technical field of intermediate synthesis, and provides a method for synthesizing 2-methyl-3, 4, 5-trifluorophenol, which comprises the following steps: S1, carrying out chloromethylation reaction on 3, 4, 5-trifluorobromobenzene serving as a raw material under the action of paraformaldehyde and chlorosulfonic acid to obtain 2-chloromethyl-3, 4, 5-trifluorobromobenzene; s2, the 2-chloromethyl-3, 4, 5-trifluorobromobenzene is subjected to a reduction reaction, and 2-methyl-3, 4, 5-trifluorobromobenzene is obtained; s3, 2-methyl-3, 4, 5-trifluorobromobenzene is subjected to a substitution reaction, hydrolysis, crystallization and filtration, and 2-methyl-3, 4, 5-trifluorophenylboronic acid is obtained; s4, 2-methyl-3, 4, 5-trifluorophenylboronic acid is subjected to an oxidation reaction, and 2-methyl-3, 4, 5-trifluorophenol is obtained; the crystallization solvent is composed of an ether solvent and water. According to the technical scheme, the problems of high cost and low yield in synthesis of 2-methyl-3, 4, 5-trifluorophenol in related technologies are solved.

Description

Technical Field

[0001] The invention relates to the technical field of intermediate synthesis, and in particular to a method for synthesizing 2-methyl-3,4,5-trifluorophenol. Background Art

[0002] 2-Methyl-3,4,5-trifluorophenol, as an important fluorinated benzene compound, has a wide range of applications in the field of liquid crystal materials. This compound can form liquid crystal compositions, which have low rotational viscosity and large elastic constants, thereby showing a shorter response time, which can improve the display effect and display quality. Generally, 3,4,5-trifluorophenol is required as a raw material for the synthesis of 2-methyl-3,4,5-trifluorophenol, but the existing supply of 3,4,5-trifluorophenol on the market is insufficient and the price is inflated; the synthesis of 2-methyl-3,4,5-trifluorophenol also uses iodomethane with high price and low boiling point, and the production conditions require ultra-low temperature reaction. The production conditions are harsh and the cost is difficult to control. Therefore, the development of a low-cost and high-yield synthesis method for 2-methyl-3,4,5-trifluorophenol is a problem that needs to be solved at present. Summary of the invention

[0003] The invention provides a method for synthesizing 2-methyl-3,4,5-trifluorophenol, which solves the problems of high cost and low yield in synthesizing 2-methyl-3,4,5-trifluorophenol in the related art.

[0004] The technical solution of the present invention is as follows: The present invention provides a method for synthesizing 2-methyl-3,4,5-trifluorophenol, comprising the following steps: S1. Using 3,4,5-trifluorobromobenzene as a raw material, chloromethylation reaction is carried out under the action of paraformaldehyde and chlorosulfonic acid to obtain 2-chloromethyl-3,4,5-trifluorobromobenzene; S2, 2-chloromethyl-3,4,5-trifluorobromobenzene is subjected to reduction reaction to obtain 2-methyl-3,4,5-trifluorobromobenzene; S3, 2-methyl-3,4,5-trifluorobromobenzene under the action of tributyl borate and n-butyl lithium, through substitution reaction, hydrolysis, crystallization and filtration to obtain 2-methyl-3,4,5-trifluorophenylboric acid; S4, 2-methyl-3,4,5-trifluorophenylboronic acid is subjected to oxidation reaction to obtain 2-methyl-3,4,5-trifluorophenol; The crystallization solvent consists of ether solvent and water.

[0005] As a further technical solution, in S1, 3,4,5-trifluorobromobenzene is used as a raw material, and under the action of polyformaldehyde and chlorosulfonic acid, after chloromethylation reaction, hydrolysis, phase separation, extraction, washing, and reduced pressure distillation are performed to obtain 2-chloromethyl-3,4,5-trifluorobromobenzene.

[0006] As a further technical solution, the molar ratio of the 3,4,5-trifluorobromobenzene, paraformaldehyde and chlorosulfonic acid is 1:1.5~1.8:1.1~1.2.

[0007] As a further technical solution, the molar ratio of the 3,4,5-trifluorobromobenzene, paraformaldehyde and chlorosulfonic acid is 1:1.6~1.7:1.1~1.2.

[0008] As a further technical solution, the temperature of the chloromethylation reaction in S1 is 35-45° C., and the time of the chloromethylation reaction is 2-6 hours.

[0009] As a further technical solution, the 2-chloromethyl-3,4,5-trifluorobromobenzene in S2 is subjected to reduction reaction, filtration, extraction, washing and atmospheric distillation under the action of glacial acetic acid and zinc powder to obtain 2-methyl-3,4,5-trifluorobromobenzene.

[0010] As a further technical solution, the molar ratio of the 2-chloromethyl-3,4,5-trifluorobromobenzene to the zinc powder is 1:1.6-1.75.

[0011] As a further technical solution, the mass volume ratio of the 2-chloromethyl-3,4,5-trifluorobromobenzene and glacial acetic acid is 1 g:2 mL.

[0012] As a further technical solution, the temperature of the reduction reaction in S2 is 30-40° C., and the time of the reduction reaction is 4-6 hours.

[0013] As a further technical solution, the molar ratio of 2-methyl-3,4,5-trifluorobromobenzene, n-butyl lithium and tributyl borate in S3 is 1:1.1:1.2~1.3.

[0014] As a further technical solution, the temperature of the substitution reaction is -50~-65°C, and the time of the substitution reaction is 1~2h.

[0015] As a further technical solution, the reagent used for the hydrolysis is hydrochloric acid.

[0016] As a further technical solution, the volume ratio of the ether solvent to water is 1-3:1.

[0017] As a further technical solution, the ether solvent includes one or two of petroleum ether and ethylene glycol methyl ether acrylate.

[0018] As a further technical solution, the 2-methyl-3,4,5-trifluorobromobenzene in S3 is subjected to substitution reaction, hydrolysis, addition of a first crystallization solvent for a first crystallization, addition of a second crystallization solvent for a second crystallization, and filtration to obtain 2-methyl-3,4,5-trifluorophenylboric acid under the action of tributyl borate and n-butyl lithium.

[0019] In the present invention, by performing crystallization twice, the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid are further improved, thereby improving the yield and purity of 2-methyl-3,4,5-trifluorophenol.

[0020] As a further technical solution, the crystallization temperature is -5~0°C.

[0021] As a further technical solution, the first crystallization solvent consists of petroleum ether and water, and the second crystallization solvent is ethylene glycol methyl ether acrylate.

[0022] In the present invention, by limiting the first crystallization solvent to consist of petroleum ether and water and the second crystallization solvent to ethylene glycol methyl ether acrylate, the yield and purity of 2-methyl-3,4,5-trifluorophenol are further improved.

[0023] As a further technical solution, the volume ratio of petroleum ether, water and ethylene glycol methyl ether acrylate is 1:1:1.

[0024] As a further technical solution, the oxidant for the oxidation reaction in S4 is hydrogen peroxide.

[0025] As a further technical solution, the temperature of the oxidation reaction is 65-85° C., and the time of the oxidation reaction is 3-4 hours.

[0026] As a further technical solution, the mass volume ratio of the 2-methyl-3,4,5-trifluorophenylboric acid and hydrogen peroxide is 1 g:1.5 mL.

[0027] As a further technical solution, the 2-methyl-3,4,5-trifluorophenylboric acid in S4 is subjected to an oxidation reaction, phase separation, washing, distillation and crystallization to obtain 2-methyl-3,4,5-trifluorophenol.

[0028] As a further technical solution, the washing solvent includes one or both of a sodium sulfite aqueous solution and a saturated sodium chloride aqueous solution.

[0029] As a further technical solution, the temperature of the distillation and collection fraction is 122-124°C.

[0030] The working principle and beneficial effects of the present invention are: In the invention, 3,4,5-trifluorobromobenzene, which is easily available and has low cost, is used as a raw material, and 2-methyl-3,4,5-trifluorophenol is obtained through chloromethylation reaction, reduction reaction, substitution reaction and oxidation reaction. The reaction operation is simple and the conditions are mild. By using ether solvent and water as crystallization solvents, the yield and purity of 2-methyl-3,4,5-trifluorophenol are further improved, so that the purity of 2-methyl-3,4,5-trifluorophenol reaches more than 99% and the yield reaches more than 85%, thereby solving the problems of high cost and low yield in preparing 2-methyl-3,4,5-trifluorophenol. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0032] Figure 1 This is the gas chromatography detection spectrum for the purity determination of 2-methyl-3,4,5-trifluorophenol in Example 12. DETAILED DESCRIPTION

[0033] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] In the following embodiments and comparative examples: Paraformaldehyde, molecular weight: 30, CAS: 30525-89-4.

[0035] Example 1 A method for synthesizing 2-methyl-3,4,5-trifluorophenol comprises the following steps: S1. Add 300g 3,4,5-trifluorobromobenzene and 68.25g paraformaldehyde into a three-necked flask, start stirring, cool to about 20°C, add 198.77g chlorosulfonic acid dropwise, control the temperature at 35°C for 6h, after the reaction, pour the reaction solution into 800g ice water for hydrolysis for 10min, pour into a separating funnel, stand and separate, 2-chloromethyl-3,4,5-trifluorobromobenzene is located at the lower layer, the aqueous phase is extracted once with 600mL dichloromethane, the organic phases are combined, washed twice with 800mL water, washed once with 800mL 5wt% sodium bicarbonate water, the aqueous phase is removed, the solvent is removed by rotation, the temperature is controlled at -0.096MPa, and the fraction above 100°C is distilled under reduced pressure to obtain 334.73g 2-chloromethyl-3,4,5-trifluorobromobenzene. Purity: 99.14%. Yield: 84.92%.

[0036] S2. Add 300g 2-chloromethyl-3,4,5-trifluorobromobenzene and 600mL glacial acetic acid into a three-necked flask and start stirring. After the brine is cooled to 10°C, add 113.45g zinc powder and react at 30°C for 6h. After the reaction is completed, add 200mL water to the reaction solution and stir until the white solid is dissolved. Filter to remove excess zinc powder, add 2L water to the filtrate, pour into a separatory funnel, let stand to separate, 2-methyl-3,4,5-trifluorobromobenzene is in the lower layer, extract the aqueous phase twice with 350mL dichloromethane, combine the organic phases, wash twice with 1200mL water, wash once with 1000mL 5wt% sodium carbonate water, and wash again with 1000mL water, remove the solvent by rotation, distill at atmospheric pressure, collect the fraction at 168~170°C, and obtain 213.97g 2-methyl-3,4,5-trifluorobromobenzene. Purity: 99.7%, yield: 86.91%.

[0037] S3. In a three-necked flask, 200 g of 2-methyl-3,4,5-trifluorobromobenzene, 245.33 g of tributyl borate and 600 mL of tetrahydrofuran were added, the temperature was lowered to -50 °C under nitrogen protection, 391 mL of n-butyl lithium (2.5 M) was added dropwise, and the temperature was naturally raised to -20 °C to obtain a reaction solution. 120 g (concentration 31%) of hydrochloric acid and 240 g of deionized water were mixed evenly, and then dropped into the reaction solution. The mixture was hydrolyzed and stirred for 10 min. The organic phase was separated, and the organic phase was washed once with 240 mL of deionized water. The aqueous phase was removed and the solid was dried to obtain 188 g of solid. 600 mL of crystallization solvent (the volume ratio of petroleum ether to water was 2:1) was added. The temperature was controlled at -5 °C, stirred for 1 h, filtered and dried to obtain 135.08 g of 2-methyl-3,4,5-trifluorophenylboric acid with a purity of 99.52% and a yield of 80.02%.

[0038] S4, put 120g 2-methyl-3,4,5-trifluorophenylboric acid and 300mL deionized water into a three-necked flask, heat it in a water bath to 60℃, add 180mL hydrogen peroxide (30wt%) dropwise, control the temperature to 65℃ for 4h after the addition, separate the liquid, extract the aqueous phase twice with 200mL dichloromethane, combine the organic phases, wash once with 200mL 5wt% sodium bisulfite aqueous solution, wash once with saturated sodium chloride water, remove the aqueous phase, spin-dry the solvent, collect the fraction of 122~124℃ under -0.084MPa and nitrogen protection, and crystallize after standing to obtain 87.75g 2-methyl-3,4,5-trifluorophenol. Purity: 99.71%, yield: 85.6%.

[0039] Example 2 S1. Add 300g 3,4,5-trifluorobromobenzene and 63.98g paraformaldehyde into a three-necked flask, start stirring, cool to about 20°C, add 182.20g chlorosulfonic acid dropwise, control the temperature at 40°C and react for 4h. After the reaction, pour the reaction solution into 800g ice water for hydrolysis for 10min, pour into a separating funnel, stand and separate, 2-chloromethyl-3,4,5-trifluorobromobenzene is located in the lower layer, the aqueous phase is extracted once with 600mL dichloromethane, the organic phase is combined, washed twice with 800mL water, washed once with 800mL 5wt% sodium bicarbonate water, the aqueous phase is removed, and the solvent is removed by spinning to obtain 396g liquid. Control -0.096MPa, distill under reduced pressure, collect the fraction above 100°C, and obtain 335.73g 2-chloromethyl-3,4,5-trifluorobromobenzene. Purity: 99.14%. Yield: 83.54%.

[0040] S2. Add 300g 2-chloromethyl-3,4,5-trifluorobromobenzene and 600mL glacial acetic acid to a three-necked flask, start stirring, cool the brine to 10°C, add 124.09g zinc powder, control the temperature at 35°C and react for 5h. After the reaction is completed, add 200mL water to the reaction solution, stir until the white solid dissolves, filter to remove excess zinc powder, add 2L water to the filtrate, pour into a separatory funnel, let stand to separate, 2-methyl-3,4,5-trifluorobromobenzene is in the lower layer, extract the aqueous phase twice with 350mL dichloromethane, combine the organic phases, wash twice with 1200mL water, wash once with 1000mL 5wt% sodium carbonate water, and wash once again with 1000mL water. The pH is about 7, spin off the solvent to obtain 279g liquid, distill at atmospheric pressure, collect the fraction of 168~170°C, and obtain 214.71g 2-methyl-3,4,5-trifluorobromobenzene. Purity: 99.73%, yield: 87.24%.

[0041] S3. In a three-necked flask, 200 g of 2-methyl-3,4,5-trifluorobromobenzene, 255.56 g of tributyl borate and 600 mL of tetrahydrofuran were added, the temperature was lowered to -60 ° C under nitrogen protection, 391 mL of n-butyl lithium (2.5 M) was added dropwise, and the temperature was naturally raised to -20 ° C to obtain a reaction solution. 120 g (concentration 31%) of hydrochloric acid and 240 g of deionized water were mixed evenly, and then dropped into the reaction solution. The mixture was hydrolyzed and stirred for 10 min. The organic phase was separated, and the organic phase was washed once with 240 mL of deionized water. The aqueous phase was removed and the solid was dried to obtain 190 g of solid. 600 mL of crystallization solvent (the volume ratio of petroleum ether to water was 1:1) was added. The temperature was controlled at 0 ° C, stirred for 2 h, and filtered and dried to obtain 136.89 g of 2-methyl-3,4,5-trifluorophenylboric acid with a purity of 99.58% and a yield of 81.14%.

[0042] S4, put 120g 2-methyl-3,4,5-trifluorophenylboric acid and 300mL deionized water into a three-necked flask, heat it in a water bath to 60℃, add 180mL hydrogen peroxide (30wt%) dropwise, control the temperature at 75℃ to react for 4h after the addition, separate the liquids, extract the aqueous phase twice with 200mL dichloromethane, combine the organic phases, wash once with 200mL 5wt% sodium bisulfite aqueous solution, wash once with saturated sodium chloride water, separate the water, spin-dry the solvent, control -0.084Mpa, under nitrogen protection, collect the fraction of 122~124℃ by vacuum distillation, and crystallize after standing to obtain 88.31g 2-methyl-3,4,5-trifluorophenol. Purity: 99.79%, yield: 86.21%.

[0043] Example 3 S1. Add 300g 3,4,5-trifluorobromobenzene and 76.78g paraformaldehyde into a three-necked flask, start stirring, cool to about 20°C, add 182.20g chlorosulfonic acid dropwise, control the temperature at 45°C and react for 2h. After the reaction, pour the reaction solution into 800g ice water for hydrolysis for 10min, pour into a separating funnel, stand and separate, 2-chloromethyl-3,4,5-trifluorobromobenzene is located at the lower layer, extract the aqueous phase once with 600mL dichloromethane, combine the organic phases, wash twice with 800mL water, wash once with 800mL 5wt% sodium bicarbonate water, remove the aqueous phase, spin-dry the solvent, control -0.096MPa, distill under reduced pressure, collect the fraction above 100°C, and obtain 336.61g 2-chloromethyl-3,4,5-trifluorobromobenzene. Purity: 99.21%. Yield: 85.41%.

[0044] S2. Add 300g 2-chloromethyl-3,4,5-trifluorobromobenzene and 600mL glacial acetic acid to a three-necked flask, start stirring, cool the brine to 10°C, add 113.45g zinc powder, control the temperature at 40°C and react for 4h. After the reaction is completed, add 200mL water to the reaction solution, stir until the white solid dissolves, filter to remove excess zinc powder, add 2L water to the filtrate, pour into a separatory funnel, let stand and separate, 2-methyl-3,4,5-trifluorobromobenzene is in the lower layer, separate the product, extract the aqueous phase twice with 350mL dichloromethane, combine the organic phases, wash twice with 1200mL water, wash once with 1000mL 5wt% sodium carbonate water, and wash once again with 1000mL water. The pH is about 7, spin off the solvent, distill at atmospheric pressure, collect the fraction at 168~170°C, and obtain 214.48g 2-methyl-3,4,5-trifluorobromobenzene. Purity: 99.71%, yield: 87.13%.

[0045] S3. In a three-necked flask, 200 g of 2-methyl-3,4,5-trifluorobromobenzene, 265.78 g of tributyl borate and 600 mL of tetrahydrofuran were added, the temperature was lowered to -65 ° C under nitrogen protection, 391 mL of n-butyl lithium (2.5 M) was added dropwise, and the temperature was naturally raised to -20 ° C to obtain a reaction solution. 120 g (concentration 31%) of hydrochloric acid and 240 g of deionized water were mixed evenly, and then dropped into the reaction solution. The mixture was hydrolyzed and stirred for 10 min. The organic phase was separated, and the organic phase was washed once with 240 mL of deionized water. The aqueous phase was removed and the solid was dried to obtain 190 g of solid. 600 mL of crystallization solvent (the volume ratio of petroleum ether to water was 3:1) was added. The temperature was controlled at 0 ° C, stirred for 2 h, and filtered and dried to obtain 136.70 g of 2-methyl-3,4,5-trifluorophenylboric acid with a purity of 99.61% and a yield of 81.05%.

[0046] S4, put 120g 2-methyl-3,4,5-trifluorophenylboric acid and 300mL deionized water into a three-necked flask, heat it in a water bath to 60℃, add 180mL hydrogen peroxide (30wt%) dropwise, control the temperature at 85℃ for 3h after the addition, separate the liquids, extract the aqueous phase twice with 200mL dichloromethane, combine the organic phases, wash once with 200mL 5wt% sodium bisulfite aqueous solution, wash once with saturated sodium chloride water, separate the water, spin-dry the solvent, collect the fraction of 122~124℃ under -0.084Mpa and nitrogen protection, and crystallize after standing to obtain 88.42g 2-methyl-3,4,5-trifluorophenol. Purity: 99.81%, yield: 86.34%.

[0047] The difference between Examples 4 to 8 and Example 1 is only that the molar ratios of 3,4,5-trifluorobromobenzene, paraformaldehyde and chlorosulfonic acid in step S1 are different (the amount of 3,4,5-trifluorobromobenzene added is the same as that in Example 1). The yield and purity of 2-chloromethyl-3,4,5-trifluorobromobenzene are shown in Table 1.

[0048] Table 1 Purity and yield of 2-chloromethyl-3,4,5-trifluorobromobenzene in Examples 4 to 8

[0049] Example 9 The only difference between this embodiment and embodiment 1 is that the petroleum ether in the crystallization solvent in step S3 is replaced by an equal amount of ethylene glycol methyl ether acrylate.

[0050] Result: 138.86 g of 2-methyl-3,4,5-trifluorophenylboric acid was obtained. Purity: 99.62%, yield: 82.34%.

[0051] Example 10 The only difference between this embodiment and embodiment 1 is that the petroleum ether in the crystallization solvent in step S3 is replaced by equal amounts of petroleum ether and ethylene glycol methyl ether acrylate in a mass ratio of 1:1.

[0052] Result: 141.97 g of 2-methyl-3,4,5-trifluorophenylboric acid was obtained. Purity: 99.73%, yield: 84.28%.

[0053] Embodiment 11 The difference between this embodiment and embodiment 10 is that in step S3, 400 mL of crystallization solvent (the volume ratio of ethylene glycol methyl ether acrylate to water is 1:1) is first added and mixed evenly, and then 200 mL of petroleum ether is added for crystallization.

[0054] Result: 144.69 g of 2-methyl-3,4,5-trifluorophenylboric acid was obtained with a purity of 99.82% and a yield of 85.97%.

[0055] Example 12 The difference between this embodiment and embodiment 10 is that in step S3, 400 mL of crystallization solvent (the volume ratio of petroleum ether to water is 1:1) is first added and mixed evenly, and then 200 mL of ethylene glycol methyl ether acrylate is added for crystallization.

[0056] Result: 146.99 g of 2-methyl-3,4,5-trifluorophenylboric acid was obtained with a purity of 99.95% and a yield of 87.45%.

[0057] The gas chromatography detection spectrum of the purity determination of 2-methyl-3,4,5-trifluorophenol in this embodiment is as follows Figure 1 shown.

[0058] Embodiment 13 The only difference between this embodiment and embodiment 12 is that the ethylene glycol methyl ether acrylate in the crystallization solvent in step S3 is replaced by an equal amount of ethylene glycol dimethyl ether.

[0059] Result: 141.54 g of 2-methyl-3,4,5-trifluorophenylboric acid was obtained. Purity: 99.87%, yield: 84.14%.

[0060] Comparative Example 1 The only difference between this comparative example and Example 1 is that the petroleum ether in the crystallization solvent in step S3 is replaced by an equal amount of ethyl acetate.

[0061] Result: 121.20 g of 2-methyl-3,4,5-trifluorophenylboric acid was obtained. Purity: 97.38%, yield: 70.25%.

[0062] Comparative Example 2 The only difference between this comparative example and Example 1 is that the amount of zinc powder added in step S2 is 70.91 g.

[0063] Result: 160.98 g of 2-methyl-3,4,5-trifluorobromobenzene was obtained. Purity: 95.45%, yield: 62.60%.

[0064] Comparative Example 3 The comparative example is different from Example 1 only in that, in step S3, a magnesium bar is added to a three-necked flask, heated to 70° C., 200 mL of tetrahydrofuran is added, 1 grain of iodine is added, and the temperature is lowered to below 20° C. under nitrogen protection, 200 g of 2-methyl-3,4,5-trifluorobromobenzene is dissolved in 200 mL of tetrahydrofuran, and the mixture is added dropwise to the above solution for about 1.5 hours, the temperature is controlled at 35° C., the reaction is stirred for 1 hour, and the mixture is allowed to stand for standby use.

[0065] In another three-necked flask, add 245.33g tri-n-butyl borate and 200mL tetrahydrofuran, under nitrogen protection, stir and cool to -20℃, filter the Grignard reagent to remove excess magnesium chips, slowly drip, control the temperature at -10℃, leave overnight, control the temperature below 10℃ and drip into a mixed solution of 120g hydrochloric acid (31%) and 240g water, stir for 10min, pour into a separatory funnel, separate the water phase, wash once with 240mL deionized water, spin dry to obtain 144g solid, add 600mL crystallization solvent (volume ratio of petroleum ether to water is 2:1), control the temperature at -5℃, stir for 1h, filter and dry to obtain 123.24g 2-methyl-3,4,5-trifluorophenylboric acid. Purity: 98.23%, yield: 72.06%.

[0066] Compared with Example 1, Examples 4 to 8 change the molar ratio of 3,4,5-trifluorobromobenzene, paraformaldehyde, and chlorosulfonic acid in step S1. As a result, the yield and purity of 2-chloromethyl-3,4,5-trifluorobromobenzene in Example 1 are higher than those in Examples 4 to 8, indicating that when the molar ratio of 3,4,5-trifluorobromobenzene, paraformaldehyde, and chlorosulfonic acid is 1:1.6:1.2, the yield and purity of 2-chloromethyl-3,4,5-trifluorobromobenzene can be improved, thereby improving the yield of 2-methyl-3,4,5-trifluorophenol.

[0067] Compared with Example 1, Comparative Example 2 changes the equivalent of zinc powder in step S2. As a result, the yield and purity of 2-methyl-3,4,5-trifluorobromobenzene in Comparative Example 2 are lower than those in Example 1, indicating that when the molar ratio of 2-chloromethyl-3,4,5-trifluorobromobenzene to zinc powder is 1:1.6, the yield and purity of 2-methyl-3,4,5-trifluorobromobenzene can be improved, and the yield of 2-methyl-3,4,5-trifluorophenol can be further improved.

[0068] Compared with Example 1, in Comparative Example 3, n-butyllithium in step S3 is replaced by a Grignard reagent. As a result, the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid in Comparative Example 3 are lower than those in Example 1, indicating that 2-methyl-3,4,5-trifluorobromobenzene undergoes a substitution reaction with tributyl borate under the action of n-butyllithium, which can further improve the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid.

[0069] Compared with Example 1, Comparative Example 1 changes the composition of the crystallization solvent in step S3. As a result, the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid in Comparative Example 1 are lower than those in Example 1, indicating that the use of a crystallization solvent composed of an ether solvent and water can improve the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid, and further improve the yield and purity of 2-methyl-3,4,5-trifluorophenol.

[0070] Compared with Example 1, Examples 9 and 10 changed the composition of the ether solvent in the crystallization solvent. As a result, the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid in Example 10 were higher than those in Examples 1 and 9, indicating that when the ether solvent consisted of petroleum ether and ethylene glycol methyl ether acrylate, the yield and purity of 2-methyl-3,4,5-trifluorophenol could be further improved.

[0071] Compared with Example 10, Examples 11-12 changed the order of adding the crystallization solvents. As a result, the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid in Example 12 were higher than those in Examples 10 and 11, indicating that adding petroleum ether and water first and then adding ethylene glycol methyl ether acrylate for crystallization can further improve the yield and purity of 2-methyl-3,4,5-trifluorophenol.

[0072] Compared with Example 12, in Example 13, ethylene glycol methyl ether acrylate was replaced with ethylene glycol dimethyl ether. As a result, the yield and purity of 2-methyl-3,4,5-trifluorophenylboric acid in Example 12 were higher than those in Example 13, indicating that the use of ethylene glycol methyl ether acrylate as a crystallization solvent can better improve the yield and purity of 2-methyl-3,4,5-trifluorophenol.

[0073] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 2-methyl-3,4,5-trifluorophenol, characterized in that: The following steps are involved: S1. Using 3,4,5-trifluorobromobenzene as a raw material, chloromethylation reaction is carried out under the action of paraformaldehyde and chlorosulfonic acid to obtain 2-chloromethyl-3,4,5-trifluorobromobenzene; S2, 2-chloromethyl-3,4,5-trifluorobromobenzene is subjected to reduction reaction to obtain 2-methyl-3,4,5-trifluorobromobenzene; S3, 2-methyl-3,4,5-trifluorobromobenzene under the action of tributyl borate and n-butyl lithium, through substitution reaction, hydrolysis, crystallization and filtration to obtain 2-methyl-3,4,5-trifluorophenylboric acid; S4, 2-methyl-3,4,5-trifluorophenylboronic acid is subjected to oxidation reaction to obtain 2-methyl-3,4,5-trifluorophenol; The crystallization solvent consists of ether solvent and water.

2. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 1, characterized in that: The volume ratio of the ether solvent to water is 1-3:

1.

3. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 1, characterized in that: The ether solvent includes one or two of petroleum ether and ethylene glycol methyl ether acrylate.

4. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 1, characterized in that: The 2-methyl-3,4,5-trifluorobromobenzene in S3 is subjected to substitution reaction, hydrolysis, addition of a first crystallization solvent for first crystallization, addition of a second crystallization solvent for second crystallization, and filtration to obtain 2-methyl-3,4,5-trifluorophenylboric acid under the action of tributyl borate and n-butyl lithium.

5. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 4, characterized in that: The first crystallization solvent consists of petroleum ether and water, and the second crystallization solvent is ethylene glycol methyl ether acrylate.

6. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 1, characterized in that: The oxidant for the oxidation reaction in S4 is hydrogen peroxide.

7. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 1, characterized in that: The temperature of the chloromethylation reaction in S1 is 35-45° C., and the time of the chloromethylation reaction is 2-6 hours.

8. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 1, characterized in that: The molar ratio of 2-methyl-3,4,5-trifluorobromobenzene, n-butyl lithium and tributyl borate in S3 is 1:1.1:1.2-1.

3.

9. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 1, characterized in that: After the 2-methyl-3,4,5-trifluorophenylboric acid in S4 undergoes oxidation reaction, phase separation, washing, distillation and crystallization are performed to obtain 2-methyl-3,4,5-trifluorophenol.

10. A method for synthesizing 2-methyl-3,4,5-trifluorophenol according to claim 9, characterized in that: The washing solvent includes one or both of a sodium sulfite aqueous solution and a saturated sodium chloride aqueous solution.

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