A process for the preparation of 2-methyl-3-trifluoromethylaniline

Abstract

The present application relates to a preparation method of 2-methyl-3-trifluoromethylaniline, comprising the following steps: hydrogenation reaction: 2-nitro-3,4-dichloro-6-trifluoromethyl toluene, acid binding agent, phase transfer catalyst, hydrogenation catalyst, water are put into a reaction kettle, hydrogen gas atmosphere is introduced, high pressure hydrogenation reaction is carried out, and 2-methyl-3-trifluoromethylaniline is obtained. The above technical scheme uses water as the reaction solvent in the hydrogenation reaction, uses calcium hydroxide or magnesium oxide or triethylamine as the acid binding agent, and further adds the phase transfer catalyst, so that the hydrogenation reaction speed can be accelerated, the reaction time can be shortened, the production efficiency can be improved, the separation and purification steps of 2-methyl-3-trifluoromethylaniline are simple, and the salt generated in the reaction is the associated product and has economic value.

Description

Technical Field

[0001] This application relates to the field of fluorochemicals, and in particular to a method for preparing 2-methyl-3-trifluoromethylaniline. Background Technology

[0002] 2-Methyl-3-trifluoromethylaniline (MTA), CAS [54396-44-0], molecular formula C8H8F3N, molecular weight 175, melting point 40℃, boiling point 198℃. MTA is an important pharmaceutical and pesticide intermediate, mainly used in the synthesis of sedatives, anti-inflammatory analgesics, and herbicides, such as 2-(2-methyl-3-trifluoromethyl)anilinenicotinic acid and N-(2-methyl-3-trifluoromethylphenyl)o-aminobenzoic acid, both of which have good anti-inflammatory and analgesic effects. MTA is a key intermediate in the preparation of flunixin, whose chemical name is 2-[[2-methyl-3-(trifluoromethyl)phenyl-1-amino]-3-acid, an effective analgesic, particularly suitable for parenteral administration.

[0003] The May 2004 issue of *China Chemical* described a process using 3,4-dichlorotoluene as a raw material, followed by trichloromethylation, substitution fluorination, nitration, and reduction to obtain the target product 2-methyl-3-trifluoromethylaniline. The final hydrogenation reduction step in the literature used 2-nitro-3,4-dichloro-6-trifluoromethyltoluene as the starting material, sodium acetate as the acid-binding agent, ethanol as the solvent, and palladium on carbon as the catalyst. The hydrogenation reaction took 30-36 hours, which was lengthy. Furthermore, the reaction yielded a mixed salt of sodium chloride and sodium acetate, which was difficult to separate, resulting in significant waste treatment challenges. Additionally, ethanol is a flammable liquid, posing safety and environmental hazards during the reaction. Moreover, the ethanol required for distillation recovery after the reaction was complex, leading to low production efficiency. Summary of the Invention

[0004] In view of the above problems, this application provides a method for preparing 2-methyl-3-trifluoromethylaniline from 2-nitro-3,4-dichloro-6-trifluoromethyltoluene as a starting material. This method is simple in terms of raw materials, operation, reaction time, post-treatment, and waste, and has high economic benefits and is suitable for industrial promotion.

[0005] The preparation method provided in this application includes the following steps:

[0006] Hydrogenation reaction: 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, an acid-binding agent, a phase transfer catalyst, a hydrogenation catalyst, and a reaction solvent are added to a reaction vessel, and a high-pressure hydrogenation reaction is carried out under a hydrogen atmosphere to obtain 2-methyl-3-trifluoromethylaniline; the reaction solvent is water, the phase transfer catalyst is one or more of quaternary ammonium salts, polyethylene glycol, and crown ether compounds; the acid-binding agent is calcium hydroxide, magnesium oxide, or triethylamine.

[0007] Unlike existing technologies, the above-mentioned technical solution uses water as the reaction solvent in the hydrogenation reaction, and calcium hydroxide, magnesium oxide, or triethylamine as the acid-binding agent. A phase transfer catalyst is also added, which accelerates the hydrogenation reaction, shortens the reaction time, and improves production efficiency. Furthermore, the separation and purification steps for 2-methyl-3-trifluoromethylaniline are simple, and the salt produced is a single salt (calcium chloride, magnesium chloride, or triethylamine hydrochloride), which can be used as a co-product, making it economically valuable. This technical solution uses readily available and inexpensive raw materials, has simple separation and purification steps, produces products with low impurities and high yields, generates less waste, reduces waste treatment costs, and is conducive to the industrial production of the product.

[0008] Furthermore, the mass ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to the reaction solvent is 1:2 to 10.

[0009] Furthermore, the mass ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to the phase transfer catalyst is 1000:5 to 250.

[0010] Furthermore, the molar ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to calcium hydroxide is 10:10 to 18.

[0011] Furthermore, the molar ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to magnesium oxide is 10:10 to 18.

[0012] Furthermore, the molar ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to triethylamine is 10:20-35.

[0013] Furthermore, the hydrogenation catalyst comprises palladium on carbon, platinum on carbon, Raney nickel, or a mixture thereof.

[0014] Furthermore, the hydrogenation reaction is carried out at a temperature of 40–150°C, a pressure of 0.3–2.0 MPa, and a time of 5–16 hours. After the hydrogenation reaction is completed, the hydrogen gas in the reactor is removed to obtain a first mixture. The first mixture is then separated and purified to obtain 2-methyl-3-trifluoromethylaniline.

[0015] Furthermore, the separation and purification includes the following steps:

[0016] 1) Allow the first mixture to stand and separate into layers, and collect the first organic phase;

[0017] 2) The first organic phase was distilled to obtain 2-methyl-3-trifluoromethylaniline.

[0018] Furthermore, the separation and purification includes the following steps:

[0019] 1) Allow the first mixture to stand and separate into layers, and collect the first organic phase and the first aqueous phase;

[0020] 2) The first organic phase was distilled to obtain 2-methyl-3-trifluoromethylaniline;

[0021] 3) Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5-7.5, and then activated carbon was used for decolorization to obtain the second aqueous phase;

[0022] 4) The second aqueous phase is concentrated under reduced pressure to obtain the first concentrate;

[0023] 5) Add methanol to the first concentrate and filter to obtain a filter cake;

[0024] 6) The filter cake is vacuum dried to obtain the associated product.

[0025] The types of associated products are related to the acid-binding agent. Calcium hydroxide, when used as an acid-binding agent, produces calcium chloride; magnesium oxide, produces calcium magnesium chloride; and triethylamine, produces triethylamine hydrochloride. All of these are soluble salts, making separation and purification processes simple and low-cost.

[0026] Furthermore, in step 5), after adding methanol, stirring is started, and the temperature is raised to 50-55℃ to stir and disperse the first concentrate, so that the organic impurities in the first concentrate can be fully dissolved in methanol; while cooling to 20-25℃ and filtering can increase the content of related products.

[0027] Furthermore, it also includes trichloromethylation, fluorination and nitration steps. The trichloromethylation reaction is: 3,4-dichlorotoluene is reacted with carbon tetrachloride and aluminum trichloride to obtain 3,4-dichloro-6-trichloromethyltoluene.

[0028] Fluorination reaction: The 3,4-dichloro-6-trichloromethyltoluene was fluorinated with anhydrous hydrogen fluoride to obtain 3,4-dichloro-6-trifluoromethyltoluene;

[0029] Nitration reaction: 3,4-dichloro-6-trifluoromethyltoluene is nitrated with nitric acid and sulfuric acid to obtain 2-nitro-3,4-dichloro-6-trifluoromethyltoluene.

[0030] The overall technical roadmap is as follows:

[0031]

[0032] The above description of the invention is merely an overview of the technical solution of this application. In order to enable those skilled in the art to better understand the technical solution of this application and to implement it based on the textual description, and to make the above-mentioned objectives and other objectives, features and advantages of this application easier to understand, the following description is based on the specific embodiments of this application. Detailed Implementation

[0033] To explain in detail the technical content, structural features, objectives, and effects of the technical solution, the following detailed description is provided in conjunction with specific embodiments.

[0034] To illustrate the possible application scenarios, technical principles, implementable specific solutions, and achievable objectives and effects of this application in detail, the following description is provided in conjunction with the specific embodiments listed. The embodiments described herein are merely illustrative of the technical solutions of this application and are therefore intended only as examples, not as limiting the scope of protection of this application.

[0035] In this document, the term "embodiment" means that a specific feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The term "embodiment" appearing in various places throughout the specification does not necessarily refer to the same embodiment, nor does it specifically limit its independence or connection with other embodiments. In principle, in this application, as long as there are no technical contradictions or conflicts, the technical features mentioned in each embodiment can be combined in any way to form corresponding implementable technical solutions.

[0036] Unless otherwise defined, the technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains; the use of related terms herein is merely for the purpose of describing particular embodiments and is not intended to limit this application.

[0037] In the description of this application, the term "and / or" is used to describe the logical relationship between objects, indicating that three relationships can exist. For example, A and / or B means: A exists, B exists, and A and B exist simultaneously. Additionally, the character " / " in this document generally indicates that the preceding and following objects have an "or" logical relationship.

[0038] In this application, terms such as “first” and “second” are used only to distinguish one entity or operation from another, and do not necessarily require or imply any actual quantity, hierarchy or order relationship between these entities or operations.

[0039] Unless otherwise specified, the use of terms such as “comprising,” “including,” “having,” or other similar expressions in this application is intended to cover non-exclusive inclusion, which does not exclude the presence of additional elements in a process, method, or product that includes the stated elements, such that a process, method, or product that includes a list of elements may include not only those defined elements but also other elements not expressly listed, or elements inherent to such a process, method, or product.

[0040] Similar to the understanding in the Examination Guidelines, in this application, expressions such as "greater than," "less than," and "exceeding" are understood to exclude the stated number; expressions such as "above," "below," and "within" are understood to include the stated number. Furthermore, in the description of the embodiments in this application, "multiple" means two or more (including two), and similar expressions related to "multiple" are also understood in this way, such as "multiple groups" and "multiple times," unless otherwise explicitly specified.

[0041] In this embodiment, 2-nitro-3,4-dichloro-6-trifluoromethyltoluene is used as the hydrogenation feedstock, water is used as the reaction solvent, calcium hydroxide, magnesium oxide, or triethylamine is used as the acid-binding agent, and quaternary ammonium salt TBAB, polyethylene glycol PEG400, or crown ether compound 18-crown-6 (C12H) is used as the phase transfer catalyst. 24 O6), the acid-binding agent is calcium hydroxide or magnesium oxide or triethylamine, and the hydrogenation catalyst is palladium on carbon or platinum on carbon or Raney nickel.

[0042] 2-Nitro-3,4-dichloro-6-trifluoromethyltoluene, acid-binding agent (calcium hydroxide or magnesium oxide, 1.1–1.8 times the molar weight of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, triethylamine, 2.0–3.5 times the molar weight of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene), hydrogenation catalyst (0.002–0.15 times the mass of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene), phase transfer catalyst (0.005–0.25 times the mass of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene), and water (2–10 times the mass of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene) were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and a vacuum was applied to the system until the required vacuum level was reached. <-0.096MPa, then perform three nitrogen purgings and three hydrogen purgings. After the purgings are completed, slowly introduce hydrogen into the autoclave, adjust the temperature to 40-150℃ and the pressure to 0.3-2.0MPa for the reaction time of 5-16 hours; take samples to control the reaction until the raw materials and intermediates are completely reacted. After the reaction is completed, cool down to 20-30℃, slowly open the autoclave vent valve to release the unreacted hydrogen to a safe location, then perform three nitrogen purgings, open the autoclave lid, and obtain the first mixture; let the first mixture stand for 30 minutes to separate the layers, and collect the first organic phase and the first aqueous phase; distill the first organic phase at 100-130℃ and a vacuum of <-0.95MPa to obtain the 2-methyl-3-trifluoromethylaniline product.

[0043] The 2-methyl-3-trifluoromethylaniline obtained in this embodiment has a purity of 93.2% to 99.6% and a reaction yield of 96.0% to 98.7%.

[0044] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. Activated carbon (0.01 times the mass of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene) was added for decolorization for 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. Methanol (1.0–10.0 times the mass of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene) was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain the associated product (calcium chloride, magnesium chloride, or triethylamine hydrochloride).

[0045] Example 1: Preparation of 2-methyl-3-trifluoromethylaniline (purity 99.6%, yield 97.1%)

[0046]

[0047] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 7.4 g (0.1 mol) of calcium hydroxide, 0.0548 g (0.002 times the mass) of palladium on carbon, 0.137 g (0.005 times the mass) of TBAB, and 274 g (10 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum level < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the reaction was carried out at a temperature of 40–50 °C and a pressure of 0.3–0.5 MPa for 16 hours. Sampling was conducted to monitor the reaction until the raw materials and intermediates had completely reacted. After the reaction is complete, the temperature is lowered to 20-30℃, and the vent valve of the autoclave is slowly opened to release the unreacted hydrogen gas in the autoclave to a safe location. Then, nitrogen purging is performed three times, and the autoclave lid is opened to obtain the first mixture. The first mixture is allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase are collected. The first organic phase is distilled at 100-130℃ under a vacuum of <-0.95MPa to obtain 17.1g of 2-methyl-3-trifluoromethylaniline with a purity of 99.6% and a yield of 97.1%.

[0048] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. 0.274 g (0.01 times the mass) of activated carbon was added for decolorization over 60 min, and the activated carbon was filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times the mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 10.5 g of the associated product, calcium chloride.

[0049] Example 2: Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.6%, yield 98.7%)

[0050]

[0051] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 13.3 g (0.18 mol) of calcium hydroxide, 4.11 g (0.15 times the mass) of palladium on carbon, 6.85 g (0.25 times the mass) of TBAB, and 137 g (5 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum level < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the reaction was carried out at a temperature of 140–150 °C and a pressure of 1.8–2.0 MPa for 5 hours. Samples were taken to monitor the reaction until the raw materials and intermediates were completely reacted. After the reaction is complete, the temperature is lowered to 20-30℃, and the vent valve of the high-pressure reactor is slowly opened to release the unreacted hydrogen gas in the reactor to a safe location. Then, nitrogen purging is performed three times, the reactor lid is opened, and the first mixture is obtained. The first mixture is allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase are collected. The first organic phase is distilled at 100-130℃ and a vacuum degree <-0.95MPa to obtain 17.5g of 2-methyl-3-trifluoromethylaniline with a purity of 98.6% and a yield of 98.7%.

[0052] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. 0.274 g (0.01 times the mass) of activated carbon was added for decolorization over 60 min, and the activated carbon was filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times the mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 10.8 g of the associated product, calcium chloride.

[0053] Example 3: Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.4%, yield 97.1%)

[0054]

[0055] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 4.0 g (0.1 mol) of magnesium oxide, 0.137 g (0.005 times the mass) of palladium on carbon, 0.274 g (0.01 times the mass) of TBAB, and 54.8 g (2 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum degree < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the reaction was carried out at a temperature of 40–50 °C and a pressure of 0.3–0.5 MPa for 13 hours. Sampling was conducted to monitor the reaction until the raw materials and intermediates had completely reacted. After the reaction is complete, the temperature is lowered to 20-30℃, and the vent valve of the high-pressure reactor is slowly opened to release the unreacted hydrogen gas in the reactor to a safe location. Then, nitrogen purging is performed three times, the reactor lid is opened, and the first mixture is obtained. The first mixture is allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase are collected. The first organic phase is distilled at 100-130℃ and a vacuum degree <-0.95MPa to obtain 17g of 2-methyl-3-trifluoromethylaniline with a purity of 98.4% and a yield of 97.1%.

[0056] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. 0.274 g (0.01 times the mass) of activated carbon was added for decolorization over 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times the mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 8.8 g of the associated product, calcium chloride.

[0057] Example 4: Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.2%, yield 97.7%)

[0058]

[0059] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 7.2 g (0.18 mol) of magnesium oxide, 0.137 g (0.005 times the mass) of palladium on carbon, 0.274 g (0.01 times the mass) of TBAB, and 54.8 g (2 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum degree < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the reaction was carried out at a temperature of 80–90 °C and a pressure of 0.6–0.8 MPa for 8 hours. Sampling was conducted to monitor the reaction until the raw materials and intermediates were completely reacted. After the reaction is complete, the temperature is lowered to 20-30°C, and the vent valve of the high-pressure reactor is slowly opened to release the unreacted hydrogen gas in the reactor to a safe location. Then, nitrogen purging is performed three times, the reactor lid is opened, and the first mixture is obtained. The first mixture is allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase are collected. The first organic phase is distilled at 100-130°C under a vacuum of <-0.95 MPa to obtain 17.1 g of 2-methyl-3-trifluoromethylaniline with a purity of 98.2% and a yield of 97.7%.

[0060] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. 0.274 g (0.01 times the mass) of activated carbon was added for decolorization over 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times the mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 9.1 g of the associated product, calcium chloride.

[0061] Example 5: Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.4%, yield 96.0%)

[0062]

[0063] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 20.2 g (0.2 mol) of triethylamine, 0.137 g (0.005 times the mass) of palladium on carbon, 0.274 g (0.01 times the mass) of TBAB, and 137 g (5 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum level < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the reaction was carried out at a temperature of 60–80 °C and a pressure of 0.3–0.5 MPa for 10 hours. Samples were taken to monitor the reaction until the raw materials and intermediates had completely reacted. After the reaction is complete, the temperature is lowered to 20-30℃, and the vent valve of the high-pressure reactor is slowly opened to release the unreacted hydrogen gas in the reactor to a safe location. Then, nitrogen purging is performed three times, the reactor lid is opened, and the first mixture is obtained. The first mixture is allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase are collected. The first organic phase is distilled at 100-130℃ and a vacuum degree <-0.95MPa to obtain 16.8g of 2-methyl-3-trifluoromethylaniline with a purity of 98.4% and a yield of 96.0%.

[0064] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. Then, 0.274 g (0.01 times its mass) of activated carbon was added for decolorization over 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times its mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 23.6 g of the associated product, triethylamine hydrochloride. Example 6: Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.8%, yield 97.7%).

[0065]

[0066] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 35.35 g (0.35 mol) of triethylamine, 0.137 g (0.005 times the mass) of palladium on carbon, 0.274 g (0.01 times the mass) of TBAB, and 137 g (5 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum level < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the reaction was carried out at a temperature of 60–80 °C and a pressure of 0.3–0.5 MPa for 10 hours. Samples were taken to monitor the reaction until the raw materials and intermediates had completely reacted. After the reaction is complete, the temperature is lowered to 20-30°C, and the vent valve of the high-pressure reactor is slowly opened to release the unreacted hydrogen gas in the reactor to a safe location. Then, nitrogen purging is performed three times, the reactor lid is opened, and the first mixture is obtained. The first mixture is allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase are collected. The first organic phase is distilled at 100-130°C under a vacuum of <-0.95 MPa to obtain 17.1 g of 2-methyl-3-trifluoromethylaniline with a purity of 98.8% and a yield of 97.7%.

[0067] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. Then, 0.274 g (0.01 times its mass) of activated carbon was added for decolorization over 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times its mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 25.8 g of the associated product, triethylamine hydrochloride. Example 7: Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.5%, yield 96.6%).

[0068]

[0069] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 9.6 g (0.13 mol) of calcium hydroxide, 0.137 g (0.005 times the mass) of palladium on carbon, 0.137 g (0.005 times the mass) of PEG400, and 137 g (5 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum level of <-0.096 MPa. Then, nitrogen purging and hydrogen purging were performed three times. After the purging was completed, hydrogen was slowly introduced into the high-pressure reactor, and the temperature was adjusted to 70-90℃ and the pressure to 0. The reaction was carried out within the range of 7–0.9 MPa for 8 hours. Sampling was conducted until the reactants and intermediates were completely reacted. After the reaction, the temperature was lowered to 20–30 °C, and the vent valve of the autoclave was slowly opened to release any unreacted hydrogen gas to a safe location. Then, nitrogen purging was performed three times. The autoclave lid was opened to obtain the first mixture. The first mixture was allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase were collected. The first organic phase was distilled at 100–130 °C under a vacuum of <-0.95 MPa to obtain 16.9 g of 2-methyl-3-trifluoromethylaniline with a purity of 98.5% and a yield of 96.6%.

[0070] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. 0.274 g (0.01 times its mass) of activated carbon was added for decolorization over 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times its mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 13.6 g of the associated product, calcium chloride.

[0071] Example 8 Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.7%, yield 97.1%)

[0072]

[0073] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 7.4 g (0.1 mol) of calcium hydroxide, 0.274 g (0.01 times the mass) of Raney nickel, 6.85 g (0.25 times the mass) of PEG400, and 137 g (5 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred thoroughly, the reactor lid was closed, and a vacuum was applied to the system until the vacuum level was < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the temperature was adjusted to 70–90 °C and the pressure to 0.7 mmol / L. The reaction was carried out within a pressure range of ~0.9 MPa for 8 hours. Sampling was conducted until the raw materials and intermediates were completely reacted. After the reaction, the temperature was lowered to 20-30°C, and the vent valve of the high-pressure reactor was slowly opened to release any unreacted hydrogen gas to a safe location. Then, nitrogen purging was performed three times. The reactor lid was opened to obtain the first mixture. The first mixture was allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase were collected. The first organic phase was distilled at 100-130°C under a vacuum of <-0.95 MPa to obtain 17 g of 2-methyl-3-trifluoromethylaniline with a purity of 98.7% and a yield of 97.1%.

[0074] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. 0.274 g (0.01 times the mass) of activated carbon was added for decolorization over 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times the mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 10.9 g of the associated product, calcium chloride.

[0075] Example 9 Preparation of 2-methyl-3-trifluoromethylaniline (purity 98.2%, yield 98.3%)

[0076]

[0077] 27.4 g (0.1 mol) of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, 7.4 g (0.1 mol) of calcium hydroxide, 4.11 g (0.15 times the mass) of Raney nickel, 0.274 g (0.01 times the mass) of 18-crown 6, and 164.4 g (6 times the mass) of water were sequentially added to a high-pressure reactor. After the addition was complete, the mixture was stirred evenly, the reactor lid was closed, and the system was evacuated to a vacuum level < -0.096 MPa. Then, three nitrogen purgings and three hydrogen purgings were performed. After the purgings were completed, hydrogen was slowly introduced into the high-pressure reactor, and the reaction was carried out at a temperature of 80–100℃ and a pressure of 0.6–0.8 MPa for 9 hours. Sampling was conducted to monitor the reaction until the raw materials and intermediates had completely reacted. After the reaction is complete, the temperature is lowered to 20-30℃, and the vent valve of the high-pressure reactor is slowly opened to release the unreacted hydrogen gas in the reactor to a safe location. Then, nitrogen purging is performed three times, the reactor lid is opened, and the first mixture is obtained. The first mixture is allowed to stand for 30 minutes to separate into layers, and the first organic phase and the first aqueous phase are collected. The first organic phase is distilled at 100-130℃ and a vacuum degree <-0.95MPa to obtain 17.2g of 2-methyl-3-trifluoromethylaniline with a purity of 98.2% and a yield of 98.3%.

[0078] Hydrochloric acid was added dropwise to the first aqueous phase until the pH reached 6.5–7.5. 0.274 g (0.01 times the mass) of activated carbon was added for decolorization over 60 min. The activated carbon was then filtered off to obtain the second aqueous phase. The second aqueous phase was concentrated under reduced pressure at 60–100 °C and a vacuum degree < -0.9 MPa until dry to obtain the first concentrate. 137 g (5 times the mass) of methanol was added to the first concentrate, and the mixture was heated to 50–55 °C and stirred for 60 min. The mixture was then cooled to 20–25 °C and filtered to obtain a filter cake. The filter cake was dried under vacuum at 80–120 °C to obtain 10.3 g of the associated product, calcium chloride.

[0079] The technical solution adopted in this implementation plan uses readily available and inexpensive raw materials, exhibits high product selectivity, and facilitates product separation. The resulting 2-methyl-3-trifluoromethylaniline has low impurity content, high yield, and a purity that can reach up to 99.6%, with a reaction yield of up to 98.7%. Simultaneously, the hydrogenation reaction time can be shortened from 30-36 hours to 5-16 hours, significantly improving reaction efficiency and production efficiency. It also yields a single salt-related product, generates less waste, reduces waste treatment costs, and is beneficial for the industrial production of the product.

[0080] Finally, it should be noted that although the above embodiments have been described in the description of this application, this should not limit the scope of patent protection of this application. Any technical solutions that are based on the essential concept of this application, utilize the content described in this application's description to make equivalent structural or procedural substitutions or modifications, or directly or indirectly implement the technical solutions of the above embodiments in other related technical fields, are all included within the scope of patent protection of this application.

Claims

1. A method for preparing 2-methyl-3-trifluoromethylaniline, characterized in that, Includes the following steps: Hydrogenation reaction: 2-nitro-3,4-dichloro-6-trifluoromethyltoluene, an acid-binding agent, a phase transfer catalyst, a hydrogenation catalyst, and a reaction solvent are added to a reaction vessel, and a high-pressure hydrogenation reaction is carried out under a hydrogen atmosphere to obtain 2-methyl-3-trifluoromethylaniline; the reaction solvent is water, the phase transfer catalyst is one or more of quaternary ammonium salts, polyethylene glycol, and crown ether compounds; the acid-binding agent is calcium hydroxide, magnesium oxide, or triethylamine; the 2-nitro-3,4- The mass ratio of dichloro-6-trifluoromethyltoluene to the phase transfer catalyst is 1000:5-250; the molar ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to calcium hydroxide is 10:10-18; the molar ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to magnesium oxide is 10:10-18; and the molar ratio of 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to triethylamine is 10:20-35.

2. The preparation method according to claim 1, characterized in that, The mass ratio of the 2-nitro-3,4-dichloro-6-trifluoromethyltoluene to the reaction solvent is 1:2 to 10.

3. The preparation method according to claim 1, characterized in that, The hydrogenation reaction is carried out at a temperature of 40–150°C, a pressure of 0.3–2.0 MPa, and a time of 5–16 hours. After the hydrogenation reaction is completed, the hydrogen gas in the reactor is removed to obtain a first mixture. The first mixture is then separated and purified to obtain 2-methyl-3-trifluoromethylaniline.

4. The preparation method according to claim 3, characterized in that, The separation and purification process includes the following steps: 1) Allow the first mixture to stand and separate into layers, and collect the first organic phase; 2) The first organic phase was distilled to obtain 2-methyl-3-trifluoromethylaniline.

5. The preparation method according to claim 4, characterized in that, The separation and purification process includes the following steps: 1) Allow the first mixture to stand and separate into layers, and collect the first organic phase and the first aqueous phase; 2) The first organic phase was distilled to obtain 2-methyl-3-trifluoromethylaniline; 3) Add hydrochloric acid dropwise to the first aqueous phase until the pH reaches 6.5-7.5, and decolorize with activated carbon to obtain the second aqueous phase; 4) The second aqueous phase is concentrated under reduced pressure to obtain the first concentrate; 5) Add methanol to the first concentrate and filter to obtain a filter cake; 6) The filter cake is vacuum dried to obtain the associated product.

6. The preparation method according to claim 1, characterized in that, It also includes trichloromethylation, fluorination, and nitration steps: Trichloromethylation reaction: 3,4-dichlorotoluene is reacted with carbon tetrachloride and aluminum trichloride to obtain 3,4-dichloro-6-trichloromethyltoluene; Fluorination reaction: The 3,4-dichloro-6-trichloromethyltoluene was fluorinated with anhydrous hydrogen fluoride to obtain 3,4-dichloro-6-trifluoromethyltoluene; Nitration reaction: 3,4-dichloro-6-trifluoromethyltoluene is nitrated with nitric acid and sulfuric acid to obtain 2-nitro-3,4-dichloro-6-trifluoromethyltoluene.

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