CN117886700A - Preparation method of 2-methyl-3-trifluoromethyl aniline - Google Patents

Abstract

The invention relates to a preparation method of 2-methyl-3-trifluoromethyl aniline, which comprises the following steps of: 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent, a phase transfer catalyst, a hydrogenation catalyst and water are put into a reaction kettle, and hydrogen atmosphere is introduced to carry out high-pressure hydrogenation reaction, so that 2-methyl-3-trifluoromethyl aniline is obtained. According to the technical scheme, water is used as a reaction solvent in the hydrogenation reaction, calcium hydroxide or magnesium oxide or triethylamine is used as an acid-binding agent, and a phase transfer catalyst is also added, so that the hydrogenation reaction speed can be increased, the reaction time can be shortened, the production efficiency can be improved, meanwhile, the separation and purification steps of the 2-methyl-3-trifluoromethyl aniline are simple, and the salt generated in the reaction is a related product, so that the method has economic value.

Description

Preparation method of 2-methyl-3-trifluoromethyl aniline

Technical Field

The application relates to the field of fluoride engineering, in particular to a preparation method of 2-methyl-3-trifluoromethyl aniline.

Background

2-methyl-3-trifluoromethylaniline (2-methyl-3-trifluoromethyl-aniline) is abbreviated as MTA, CAS [54396-44-0 ]]Molecular formula C ₈ H ₈ F ₃ N, molecular weight 175, melting point 40 ℃, boiling point 198 ℃. MTA is an important intermediate of medicines and pesticides, is mainly used for synthesizing tranquilizers, anti-inflammatory and analgesic drugs and herbicides, such as- (2-methyl-3-trifluoromethyl) anilino nicotinic acid and N- (2-methyl-3-trifluoromethyl phenyl) anthranilic acid, and has good anti-inflammatory and analgesic effects. MTA is a key intermediate for preparing flunixin, and the chemical name of flunixin is 2- [ [ 2-methyl-3- (trifluoromethyl) phenyl 1 amino group]-3-acids, which are potent analgesics, are particularly suitable for parenteral administration.

In the 2004 5-phase of China chemical abstracts of China, 3, 4-dichlorotoluene is used as a raw material, and a target product 2-methyl-3-trifluoromethyl aniline is obtained through trichloromethylation, displacement fluorination, nitration and reduction. The last hydrogenation reduction reaction in the literature adopts 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene as a starting material, sodium acetate as an acid binding agent, ethanol as a solvent and palladium carbon as a catalyst, the hydrogenation reaction time is 30-36 hours, the time is long, the obtained mixed salt of sodium chloride and sodium acetate after the reaction is finished, the separation is inconvenient, and the three-waste treatment pressure is high. Meanwhile, the ethanol is inflammable liquid, so that hidden danger of safety and environmental protection exists in the reaction process, distillation recovery treatment is needed to be carried out on the ethanol after the reaction is finished, the post-treatment procedure is complex, and the production efficiency is low.

Disclosure of Invention

In view of the problems, the preparation method of 2-methyl-3-trifluoromethyl aniline, which is simple in process raw materials, simple to operate, short in reaction time, simple and feasible in post-treatment, less in three wastes, high in economic benefit and suitable for industrial popularization, takes 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene as a starting raw material.

The preparation method provided by the application comprises the following steps:

hydrogenation reaction: 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent, a phase transfer catalyst, a hydrogenation catalyst and a reaction solvent are put into a reaction kettle, and hydrogen atmosphere is introduced to carry out high-pressure hydrogenation reaction to obtain 2-methyl-3-trifluoromethyl aniline; the reaction solvent is water, and the phase transfer catalyst is one or more of quaternary ammonium salt, polyethylene glycol and crown ether compounds; the acid binding agent is calcium hydroxide or magnesium oxide or triethylamine.

Compared with the prior art, the technical scheme adopts water as a reaction solvent in the hydrogenation reaction, calcium hydroxide or magnesium oxide or triethylamine as an acid-binding agent, and a phase transfer catalyst is also added, so that the hydrogenation reaction speed can be increased, the reaction time can be shortened, the production efficiency can be improved, meanwhile, the separation and purification steps of the 2-methyl-3-trifluoromethyl aniline are simple, the salt generated in the reaction is a single salt (calcium chloride, magnesium chloride or triethylamine hydrochloride), and the product can be prepared into a joint product, thereby having economic value. The technical proposal has the advantages of easily obtained raw materials, low price, simple steps of separation and purification, small impurity content in the product, high yield, less three wastes, reduction of the cost of three wastes treatment and contribution to the industrialized production of the product.

Further, the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the reaction solvent is 1:2-10.

Further, the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the phase transfer catalyst is 1000:5-250.

Further, the molar ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the calcium hydroxide is 10:10 to 18.

Further, the molar ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the magnesium oxide is 10:10 to 18.

Further, the molar ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the triethylamine is 10:20 to 35.

Further, the hydrogenation catalyst comprises palladium carbon, platinum carbon, raney nickel or a mixture thereof.

Further, the hydrogenation reaction temperature is 40-150 ℃, the pressure is 0.3-2.0 MPa, and the time is 5-16 hours; after the hydrogenation reaction is completed, removing hydrogen in the reaction kettle to obtain a first mixture; and separating and purifying the first mixture to obtain the 2-methyl-3-trifluoromethyl aniline.

Further, the separation and purification comprises the following steps:

1) Standing and layering the first mixture, and collecting a first organic phase;

2) And distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline.

Further, the separation and purification comprises the following steps:

1) Standing and layering the first mixture, and collecting a first organic phase and a first aqueous phase;

2) Distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline;

3) Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, and decoloring by using active carbon to obtain a second water phase;

4) Concentrating the second aqueous phase under reduced pressure to obtain a first concentrate;

5) Adding methanol into the first concentrate, and filtering to obtain a filter cake;

6) And (5) drying the filter cake in vacuum to obtain a related product.

The type of the associated product is related to the acid binding agent. Calcium hydroxide is used as an acid binding agent, and the associated product is calcium chloride; magnesium oxide is used as an acid binding agent, and the associated product is magnesium calcium chloride; triethylamine is used as an acid binding agent, and the related product is triethylamine hydrochloride. The above are all soluble salts, and the separation and purification process is simple and the cost is low.

Further, in the step 5), after methanol is added, stirring is started, the temperature is raised to 50-55 ℃ to stir and break up the first concentrate, so that organic impurities in the first concentrate can be fully dissolved in the methanol; and the content of related products can be increased by cooling to 20-25 ℃ and filtering.

Further, the method also comprises the steps of trichloromethylation, fluorination and nitration, wherein the trichloromethylation reaction comprises the following steps: 3, 4-dichloro toluene reacts with carbon tetrachloride and aluminum trichloride to obtain 3, 4-dichloro-6-trichloromethyl toluene;

fluorination reaction: carrying out fluorination reaction on the 3, 4-dichloro-6-trichloromethyl toluene and anhydrous hydrogen fluoride to obtain 3, 4-dichloro-6-trifluoromethyl toluene;

nitration reaction: and (3) performing nitration reaction on the 3, 4-dichloro-6-trifluoromethyl toluene and nitric acid and sulfuric acid to obtain the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene.

The whole technical route is as follows:

the foregoing summary is merely an overview of the present application, and is provided to enable one of ordinary skill in the art to make and use the present application and to enable one of ordinary skill in the art to make and use the present application.

Detailed Description

In order to describe the technical content, constructional features, achieved objects and effects of the technical solution in detail, the following description is made in detail with reference to specific embodiments.

In order to describe the possible application scenarios, technical principles, practical embodiments, and the like of the present application in detail, the following description is made with reference to the specific embodiments listed below. The embodiments described herein are only used to more clearly illustrate the technical solutions of the present application, and are therefore only used as examples and are not intended to limit the scope of protection of the present application.

Reference herein to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the present application. The appearances of the phrase "in various places in the specification are not necessarily all referring to the same embodiment, nor are they particularly limited to independence or relevance from other embodiments. In principle, in the present application, as long as there is no technical contradiction or conflict, the technical features mentioned in the embodiments may be combined in any manner to form a corresponding implementable technical solution.

Unless defined otherwise, technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application pertains; the use of related terms herein is for the description of specific embodiments only and is not intended to limit the present application.

In the description of the present application, the term "and/or" is a representation for describing a logical relationship between objects, which means that there may be three relationships, e.g., a and/or B, representing: there are three cases, a, B, and both a and B. In addition, the character "/" herein generally indicates that the front-to-back associated object is an "or" logical relationship.

In this application, terms such as "first" and "second" are used merely to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual number, order, or sequence of such entities or operations.

Without further limitation, the use of the terms "comprising," "including," "having," or other like terms in this application is intended to cover a non-exclusive inclusion, such that a process, method, or article of manufacture that comprises a list of elements does not include additional elements but may include other elements not expressly listed or inherent to such process, method, or article of manufacture.

As in the understanding of the "examination guideline," the expressions "greater than", "less than", "exceeding", and the like are understood to exclude the present number in this application; the expressions "above", "below", "within" and the like are understood to include this number. Furthermore, in the description of the embodiments of the present application, the meaning of "a plurality of" is two or more (including two), and similarly, the expression "a plurality of" is also to be understood as such, for example, "a plurality of groups", "a plurality of" and the like, unless specifically defined otherwise.

In the embodiment, 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene is taken as a hydrogenation raw material, a reaction solvent is water, an acid binding agent is calcium hydroxide, magnesium oxide or triethylamine, and a phase transfer catalyst is quaternary ammonium salt TBAB, polyethylene glycol PEG400 or crown ether compound 18 crown 6 (C1) ₂ H ₂₄ O ₆ ) The acid-binding agent is calcium hydroxide or magnesium oxide or triethylamine, and the hydrogenation catalyst is palladium carbon or platinum carbon or Raney nickel.

Sequentially adding 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent (calcium hydroxide or magnesium oxide with the molar quantity of 1.1-1.8 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) and water (with the molar quantity of 2.0-3.5 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene), a hydrogenation catalyst (with the molar quantity of 0.002-0.15 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene), a phase transfer catalyst (with the mass of 0.005-0.25 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) into a high-pressure reaction kettle, stirring uniformly after the addition, covering a kettle cover, vacuumizing the system to the vacuum degree of < -0.096MPa, performing three nitrogen displacement, introducing hydrogen into the kettle for a slow reaction time ranging from 0.005-0.25 MPa to the temperature of between 0.5 and 150 ℃ after the three nitrogen displacement, and the reaction kettle is completed, and the reaction time is adjusted to the reaction time of between the temperature and between 0.0 and 150 ℃ and the pressure of the reaction kettle; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; distilling the first organic phase at 100-130 deg.c and vacuum degree below-0.95 MPa to obtain 2-methyl-3-trifluoro methylaniline product.

The purity of the 2-methyl-3-trifluoromethyl aniline obtained in the embodiment is 93.2% -99.6%, and the reaction yield is 96.0% -98.7%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding activated carbon (0.01 times of the mass of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) for 60min for decoloring, and filtering the activated carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding methanol (1.0-10.0 times of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene) into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain a related product (calcium chloride or magnesium chloride or triethylamine hydrochloride).

Example 12 preparation of methyl-3-trifluoromethylaniline (purity 99.6%, yield 97.1%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.4g (0.1 mol) of calcium hydroxide, 0.0548g (0.002 times mass) of palladium carbon, 0.137g (0.005 times mass) of TBAB and 274g (10 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 40-50 ℃ and a pressure of 0.3-0.5 MPa for 16 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.1g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 99.6%, and the yield is 97.1%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.5g of calcium chloride as a related product.

Example 2 2 preparation of methyl-3-trifluoromethylaniline (purity 98.6%, yield 98.7%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 13.3g (0.18 mol) of calcium hydroxide, 4.11g (0.15 times mass) of palladium-carbon, 6.85g (0.25 times mass) of TBAB and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 140-150 ℃ and a pressure of 1.8-2.0 MPa for 5 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.5g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.6%, and the yield is 98.7%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.8g of calcium chloride as a related product.

Example 3 2 preparation of methyl-3-trifluoromethylaniline (purity 98.4%, yield 97.1%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 4.0g (0.1 mol) of magnesium oxide, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 54.8g (2 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, reacting at a temperature of 40-50 ℃ and a pressure of 0.3-0.5 MPa, and reacting for 13 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.4%, and the yield is 97.1%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 8.8g of calcium chloride as a related product.

Example 4 2 preparation of methyl-3-trifluoromethylaniline (purity 98.2%, yield 97.7%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.2g (0.18 mol) of magnesium oxide, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 54.8g (2 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, reacting at a temperature of 80-90 ℃ and a pressure of 0.6-0.8 MPa, and reacting for 8 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.1g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.2%, and the yield is 97.7%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 9.1g of calcium chloride as a related product.

Example 5 2 preparation of methyl-3-trifluoromethylaniline (purity 98.4%, yield 96.0%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 20.2g (0.2 mol) of triethylamine, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 60-80 ℃ and a pressure of 0.3-0.5 MPa for 10 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 16.8g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.4%, and the yield is 96.0%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 23.6g of triethylamine hydrochloride which is a related product. Example 6 2 preparation of methyl-3-trifluoromethylaniline (purity 98.8%, yield 97.7%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 35.35g (0.35 mol) of triethylamine, 0.137g (0.005 times mass) of palladium-carbon, 0.274g (0.01 times mass) of TBAB and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 60-80 ℃ and a pressure of 0.3-0.5 MPa for 10 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.1g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.8%, and the yield is 97.7%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 25.8g of triethylamine hydrochloride which is a related product. Example 7 2 preparation of methyl-3-trifluoromethylaniline (purity 98.5%, yield 96.6%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 9.6g (0.13 mol) of calcium hydroxide, 0.137g (0.005 times mass) of palladium-carbon, 4000.137g (0.005 times mass) of PEG and 137g (5 times mass) of water into a high-pressure reaction kettle, uniformly stirring after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 70-90 ℃ under a pressure of 0.7-0.9 MPa for 8 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, thus obtaining 16.9g of 2-methyl-3-trifluoromethyl aniline with the purity of 98.5 percent and the yield of 96.6 percent.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 13.6g of calcium chloride as a related product.

Example 8 2 preparation of methyl-3-trifluoromethylaniline (purity 98.7%, yield 97.1%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.4g (0.1 mol) of calcium hydroxide, 0.274g (0.01 times mass) of Raney nickel, 6.85g (0.25 times mass) of PEG4006.85g (5 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle after the substitution is finished, and reacting at a temperature of 70-90 ℃ under a pressure of 0.7-0.9 MPa for 8 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.7%, and the yield is 97.1%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.9g of calcium chloride as a related product.

Example 9 2 preparation of methyl-3-trifluoromethylaniline (purity 98.2%, yield 98.3%)

Sequentially adding 27.4g (0.1 mol) of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, 7.4g (0.1 mol) of calcium hydroxide, 4.11g (0.15 times mass) of Raney nickel, 0.274g (0.01 times mass) of 18 crown and 164.4g (6 times mass) of water into a high-pressure reaction kettle, stirring uniformly after the material addition is finished, covering a kettle cover, vacuumizing the system, vacuumizing to a vacuum degree of < -0.096MPa, performing three times of nitrogen substitution and three times of hydrogen substitution, slowly introducing hydrogen into the high-pressure kettle, and reacting at a temperature of 80-100 ℃ and a pressure of 0.6-0.8 MPa for 9 hours; sampling and controlling until the raw materials and the intermediate state are completely reacted, cooling to 20-30 ℃ after the reaction is finished, slowly opening an autoclave emptying valve, discharging unreacted hydrogen in the reaction kettle to a safe place, then performing nitrogen replacement for three times, and opening a kettle cover to obtain a first mixture; standing the first mixture for 30min for layering, and collecting a first organic phase and a first aqueous phase; the first organic phase is distilled at 100-130 ℃ and the vacuum degree is less than-0.95 MPa, 17.2g of 2-methyl-3-trifluoromethyl aniline is obtained, the purity is 98.2%, and the yield is 98.3%.

Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, adding 0.274g (0.01 times of the mass) of active carbon for 60min for decoloration, and filtering the active carbon to obtain a second water phase; concentrating the second water phase under reduced pressure at 60-100 ℃ and vacuum degree of < -0.9MPa, and concentrating until the second water phase is dried to obtain a first concentrate; adding 137g (5 times mass) of methanol into the first concentrate, heating to 50-55 ℃, stirring for 60min, cooling to 20-25 ℃, and filtering to obtain a filter cake; and (3) vacuum drying the filter cake at 80-120 ℃ to obtain 10.3g of calcium chloride as a related product.

The technical scheme adopted by the embodiment has the advantages of easily obtained raw materials, low price, high product selectivity and easy separation of products, and the obtained 2-methyl-3-trifluoromethyl aniline has small impurity, high yield, purity up to 99.6 percent and reaction yield up to 98.7 percent. Meanwhile, the hydrogenation reaction time can be shortened from 30-36 hours to 5-16 hours, the reaction time is shortened, the reaction efficiency is greatly improved, the production efficiency of the product is improved, single salt related products can be obtained, the generated three wastes are less, the three-waste treatment cost is reduced, and the industrial production of the product is facilitated.

Finally, it should be noted that, although the foregoing embodiments have been described in the text of the present application, the scope of the patent protection of the present application is not limited thereby. All technical schemes generated by replacing or modifying equivalent structures or equivalent processes based on the essential idea of the application and by directly or indirectly implementing the technical schemes of the embodiments in other related technical fields and the like are included in the patent protection scope of the application.

Claims (10)

1. The preparation method of the 2-methyl-3-trifluoromethyl aniline is characterized by comprising the following steps of: hydrogenation reaction: 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene, an acid binding agent, a phase transfer catalyst, a hydrogenation catalyst and a reaction solvent are put into a reaction kettle, and hydrogen atmosphere is introduced to carry out high-pressure hydrogenation reaction to obtain 2-methyl-3-trifluoromethyl aniline; the reaction solvent is water, and the phase transfer catalyst is one or more of quaternary ammonium salt, polyethylene glycol and crown ether compounds; the acid binding agent is calcium hydroxide or magnesium oxide or triethylamine.

2. The preparation method according to claim 1, wherein the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the reaction solvent is 1:2-10.

3. The preparation method according to claim 1, wherein the mass ratio of the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to the phase transfer catalyst is 1000:5-250.

4. The method according to claim 1, wherein the molar ratio of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to calcium hydroxide is 10:10 to 18.

5. The method according to claim 1, wherein the molar ratio of 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene to magnesium oxide is 10:10 to 18.

6. The method according to claim 1, wherein the molar ratio of 2-nitro-3, 4-dichloro-6-trifluoromethyltoluene to triethylamine is 10:20 to 35.

7. The preparation method according to claim 1, wherein the hydrogenation reaction temperature is 40-150 ℃, the pressure is 0.3-2.0 MPa, and the time is 5-16 hours; after the hydrogenation reaction is completed, removing hydrogen in the reaction kettle to obtain a first mixture; and separating and purifying the first mixture to obtain the 2-methyl-3-trifluoromethyl aniline.

8. The method of claim 7, wherein the separation and purification comprises the steps of:

1) Standing and layering the first mixture, and collecting a first organic phase;

2) And distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline.

9. The method of claim 8, wherein the separation and purification comprises the steps of:

1) Standing and layering the first mixture, and collecting a first organic phase and a first aqueous phase;

2) Distilling the first organic phase to obtain 2-methyl-3-trifluoromethyl aniline;

3) Dropwise adding hydrochloric acid into the first water phase until the pH value is 6.5-7.5, and decoloring by using activated carbon to obtain a second water phase;

4) Concentrating the second aqueous phase under reduced pressure to obtain a first concentrate;

5) Adding methanol into the first concentrate, and filtering to obtain a filter cake;

6) And (5) drying the filter cake in vacuum to obtain a related product.

10. The method of claim 1, further comprising the steps of trichloromethylation, fluorination, and nitration:

trichloromethylation reaction: 3, 4-dichloro toluene reacts with carbon tetrachloride and aluminum trichloride to obtain 3, 4-dichloro-6-trichloromethyl toluene;

fluorination reaction: carrying out fluorination reaction on the 3, 4-dichloro-6-trichloromethyl toluene and anhydrous hydrogen fluoride to obtain 3, 4-dichloro-6-trifluoromethyl toluene;

nitration reaction: and (3) performing nitration reaction on the 3, 4-dichloro-6-trifluoromethyl toluene and nitric acid and sulfuric acid to obtain the 2-nitro-3, 4-dichloro-6-trifluoromethyl toluene.