Preparation method of 2, 6-dichloro-4-trifluoromethylaniline

Abstract

The invention discloses a method for preparing 2, 6-dichloro-4-(trifluoromethyl) aniline and a preparation method of the 2, 6-dichloro-4-(trifluoromethyl) aniline. The preparation method comprises the following steps: carrying out aromatic ring chlorination reaction and side chain methyl chlorination reaction on N, N-dimethyl-4-trifluoromethylaniline, hydrochloric acid and hydrogen peroxide under an ultraviolet irradiation condition, and carrying out alkali washing treatment on a reaction solution in a sodium hydroxide solution to prepare the 2, 6-dichloro-4-trifluoromethylaniline. The preparation method is high in reaction efficiency, the reaction process is simple and convenient to operate, safe and controllable, the energy consumption and the raw material cost are low, and the prepared 2, 6-dichloro-4-trifluoromethylaniline has relatively high yield and purity.

Description

Technical Field

[0001] The present invention relates to a method for preparing 2,6-dichloro-4-trifluoromethylaniline. Background Art

[0002] 2,6-Dichloro-4-trifluoromethylaniline is an important organic compound and a key synthetic intermediate for the insecticide Fipronil. Its diazonium salt can be used in dye synthesis through condensation reactions and is widely used in the pesticide and dye industries. Its general structural formula is as follows:

[0003]

[0004] The following methods for synthesizing 2,6-dichloro-4-trifluoromethylaniline are reported in the literature: (1) The route reported in the literature (Chen Jun; Liu Jinting; Synthesis of 2,6-dichloro-4-trifluoromethylaniline [J]. Shandong Chemical Industry, 2007(03):17-1) is carried out in two steps. First, an aminolysis reaction is carried out on the chloro-trifluoromethyl benzene ring. The characteristics of the strong electron-withdrawing group trifluoromethyl at the para position make the aminolysis reaction easy to proceed, and the yield of this step is 74%; then chlorination and demethylation reactions are carried out; the total yield of 2,6-dichloro-4-trifluoromethylaniline is 71.8%.

[0005]

[0006] (2) Patent CN102643202A discloses a method for producing p-trifluoromethylaniline, wherein p-chlorobenzotrifluoride and liquid ammonia are reacted in the presence of alcohol and a catalyst to obtain p-trifluoromethylaniline; the catalyst is mainly composed of cuprous chloride and potassium fluoride, and the yield can reach 90%. Patent CN102633722A discloses a process for synthesizing 2,6-dichloro-4-trifluoromethylaniline by dissolving p-trifluoromethylaniline in hydrochloric acid and adding hydrogen peroxide to carry out an oxychlorination reaction.

[0007]

[0008] (3) Literature report (Zhang Lala, Han Xiangen. Synthesis of 2,6-dichloro-4-trifluoromethylaniline [J]. Chemical Intermediates, 2011, 8(6): 58-60) uses 3,4-dichlorobenzotrifluoride as the starting material, dimethylamine as the amination reagent, and azobisisobutyronitrile as the initiator instead of ultraviolet light. 2,6-dichloro-4-trifluoromethylaniline is synthesized in three steps via ammonialysis, aromatic ring and side chain methyl chlorination, and hydrolysis. The overall reaction yield is as high as 90%. This method achieves the simultaneous halogenation of the ring and side chain methyl in the same reactor under relatively mild conditions.

[0009]

[0010] During the development of a method for synthesizing 2,6-dichloro-4-trifluoromethylaniline using para-chlorobenzotrifluoride as a raw material, the inventors discovered that the aminolysis of para-chlorobenzotrifluoride to para-trifluoromethylaniline requires high temperatures and pressures, resulting in high catalyst consumption and low conversion rates. While amination to N,N-dimethyl-4-trifluoromethylaniline is easier, the chlorination of the nitrogen methyl group to 2,6-dichloro-4-trifluoromethylaniline is typically carried out using chlorine gas, requiring high reaction equipment requirements and poor safety. Summary of the Invention

[0011] In order to overcome the problem of acid contamination during the chlorination of the aromatic ring and the chlorination of the side chain methyl groups of N,N-dimethyl-4-trifluoromethylaniline, the present invention provides a method for preparing 2,6-dichloro-4-trifluoromethylaniline. The method uses hydrochloric acid and hydrogen peroxide to chlorinate the aromatic ring and the side chain methyl groups under ultraviolet irradiation conditions, and then performs alkaline washing in a sodium hydroxide solution. The reaction conditions are simple and safe, no expensive equipment is required, and the prepared 2,6-dichloro-4-trifluoromethylaniline has a high yield and purity.

[0012] The present invention solves the above technical problems through the following technical solutions:

[0013] The present invention provides a method for preparing 2,6-dichloro-4-trifluoromethylaniline as shown in formula b.

[0014] The synthesis method is as follows:

[0015]

[0016] The preparation method is carried out according to the following steps:

[0017] Dissolve N,N-dimethyl-4-trifluoromethylaniline as shown in formula a in a 21.5% to 30% (preferably 21.5%) hydrochloric acid aqueous solution, add an organic solvent, and add 30% hydrogen peroxide at 40 to 60° C. (preferably 50° C.) for 0.5 to 2 h (preferably 0.5 h). After the addition is complete, irradiate with ultraviolet light at 50 to 80° C. (preferably 60° C.) for 1 to 6 h (preferably 3 h). The obtained first reaction solution is allowed to stand and separate to obtain an acid phase and an organic phase. The lower organic phase is removed and filtered. The mixture is filtered, the filtrate is collected for desolventizing, an excess amount of sodium hydroxide solution having a mass concentration of 20% to 50% is added, and the mixture is stirred at room temperature for 0.5 to 3 hours for alkaline washing reaction. The obtained second reaction solution is subjected to post-treatment to obtain 2,6-dichloro-4-trifluoromethylaniline; the volume of the hydrogen peroxide is 1.78 to 2.66 mL / g based on the mass of the N,N-dimethyl-4-trifluoromethylaniline, and the volume of the hydrochloric acid aqueous solution is 14.1 to 14.5 mL / g based on the mass of the N,N-dimethyl-4-trifluoromethylaniline represented by formula a.

[0018] Furthermore, the organic solvent is one or more of chloroform, dichloromethane, dichloroethane, carbon tetrachloride, toluene, and cyclohexane.

[0019] Furthermore, the obtained first reaction solution was allowed to stand for stratification: the acid phase was extracted with dichloromethane to obtain an extract, the extract was combined with the organic phase and then filtered, and the filtrate was taken for desolventizing and put into the next alkaline washing reaction.

[0020] Furthermore, the post-treatment is as follows: adding dichloromethane to the second reaction solution for extraction, taking the extract and adding anhydrous magnesium sulfate for drying, filtering, and desolvating the filtrate to obtain 2,6-dichloro-4-trifluoromethylaniline.

[0021] Furthermore, the ultraviolet lamp used for the ultraviolet irradiation has a wavelength of 365nm and a power of 20W.

[0022] Further, a base having a mass concentration of 20% to 50% sodium hydroxide solution is added until the pH value of the solution of the reaction system reaches 10, and the addition of the base is stopped.

[0023] Furthermore, based on the mass of the N,N-dimethyl-4-trifluoromethylaniline, the volumetric dosage of the hydrogen peroxide is 2.14 mL / g.

[0024] Furthermore, based on the mass of the N,N-dimethyl-4-trifluoromethylaniline, the volume amount of the hydrochloric acid is 14.3 mL / g.

[0025] Furthermore, the concentration of the hydrochloric acid aqueous solution is 21.5%.

[0026] Furthermore, the mass percentage of the sodium hydroxide is 30%

[0027] On the basis of conforming to the common sense in this field, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0028] The reagents and raw materials used in the present invention are commercially available.

[0029] The positive progress effect of the present invention is:

[0030] 1) The process conditions are mild and no chlorine is required;

[0031] 2) After the reaction is completed, vacuum distillation is performed to obtain a 2,6-dichloro-4-trifluoromethylaniline product with a purity of ≥99.5%; the percentage is by mass.

[0032] 3) The amount of three wastes is small.

[0033] On the basis of conforming to the common sense in this field, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0034] The reagents and raw materials used in the present invention are commercially available.

[0035] Compared with the prior art, the advantages of the present invention are:

[0036] (1) It is more economical to synthesize 2,6-dichloro-4-trifluoromethylaniline using N,N-dimethyl-4-trifluoromethylaniline;

[0037] (2) A method for preparing 2,6-dichloro-4-trifluoromethylaniline by direct chlorination. The main by-product is caused by the hydrolysis reaction of the amino group on the benzene ring. The method provided by the present invention is to carry out a chlorination reaction of N,N-dimethyl-4-trifluoromethylaniline in a multiphase system, thereby reducing the generation of the hydrolysis reaction. Therefore, the by-product phenol is less, and the conversion rate of N,N-dimethyl-4-trifluoromethylaniline and the selectivity for producing 2,6-dichloro-4-trifluoromethylaniline are both extremely high;

[0038] (3) The method for preparing 2,6-dichloro-4-trifluoromethylaniline of the present invention uses a hydrochloric acid and hydrogen peroxide system for the aromatic ring chlorination step and the side chain methyl chlorination step, so the reaction conditions are mild, the three wastes are generated less, and the selectivity is good;

[0039] (4) The method for preparing 2,6-dichloro-4-trifluoromethylaniline of the present invention has a high yield and simple purification, so the production cost is lower than the traditional method. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 This is a gas chromatogram of the reaction liquid after the chlorination reaction in Example 26 is completed.

[0041] Figure 2 This is the gas chromatogram after 3 hours of alkali washing in Example 26. DETAILED DESCRIPTION

[0042] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0043] Comparative Example 1: Chlorination reaction occurs only in aqueous phase

[0044] This embodiment provides a method for preparing 2,6-dichloro-4-trifluoromethylaniline, comprising the following steps:

[0045] Chlorination reaction

[0046] Add 60mL of hydrochloric acid (21.5%) (the hydrochloric acid concentration is mass concentration, the same below) and 4.2g of N,N-dimethyl-4-trifluoromethylaniline to the reaction flask, stir and dissolve, heat to 50°C and add 9mL (7.2eq.) of 30% hydrogen peroxide dropwise within 0.5h. After the addition is complete, maintain the reaction temperature at 60°C, turn on the ultraviolet lamp with a wavelength of 365nm and a power of 20w, and react for 3h to obtain the first reaction solution. The first reaction solution was allowed to stand for stratification, and the lower organic phase was removed for filtration and desolvation. The GC content was 36.7%. (The gas chromatography detection content of the first reaction solution in the chlorination step is the peak area ratio of b, the same below)

[0047] Alkaline washing

[0048] 10g of 20% sodium hydroxide solution (the sodium hydroxide concentration is by mass, the same below) was slowly added dropwise to the product from the previous step while stirring. After the addition was complete, the mixture was stirred for 1 hour to obtain a second reaction solution. The second reaction solution was extracted three times with 10mL of dichloromethane. The extracts were combined, dried over anhydrous magnesium sulfate, filtered, and desolventized. This yielded crude 2,6-dichloro-4-trifluoromethylaniline with a GC content of 43.2% and a molar yield of 32.3%. (The peak area percentage of the content b in the second reaction solution from the alkali washing step was determined by gas chromatography, the same below.)

[0049]

[0050] Example 1-6: Chlorination step using a water-insoluble organic solvent to form a multiphase system reaction This example provides a method for preparing 2,6-dichloro-4-trifluoromethylaniline, comprising the following steps:

[0051] Chlorination reaction

[0052] To six reaction bottles, 60 mL of hydrochloric acid (21.5%) and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline were added, stirred and dissolved, and then 10 mL of dichloroethane, 10 mL of dichloromethane, 10 mL of chloroform, 10 mL of carbon tetrachloride, 10 mL of toluene, and 10 mL of cyclohexane (the following examples are given in order). After heating to 50°C, 9 mL (7.2 eq.) of 30% hydrogen peroxide was added dropwise over 0.5 h. After the addition was complete, the reaction temperature was maintained at 60°C, and a UV lamp with a wavelength of 365 nm and a power of 20 W was turned on for 3 h to obtain a first reaction solution. The first reaction solution was allowed to stand for demixing, and the lower organic phase was removed by filtration and desolvation. The GC contents were 86.2%, 74.2%, 84.5%, 83.6%, 63.2%, and 71.9%, respectively.

[0053] Alkaline washing

[0054] 10 g of 20% sodium hydroxide solution was slowly added dropwise to the product from the previous step while stirring. After the addition was complete, the mixture was stirred for 1 hour to obtain a second reaction solution. The second reaction solution was extracted three times with 10 mL of dichloromethane. The extracts were combined, dried over anhydrous magnesium sulfate, filtered, and desolventized. This afforded crude 2,6-dichloro-4-trifluoromethylaniline with GC contents of 93.4%, 77.2%, 90.8%, 89.3%, 66.2%, and 72.3%, respectively, and molar yields of 83.2%, 68.1%, 79.6%, 80.4%, 60.5%, and 62.6%, respectively.

[0055] Comparative Example 2-5: Chlorination step using a water-soluble organic solvent to form a homogeneous system reaction

[0056] This embodiment provides a method for preparing 2,6-dichloro-4-trifluoromethylaniline, comprising the following steps:

[0057] Chlorination reaction

[0058] To four reaction flasks, 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline were added, stirred and dissolved, and then 10 mL of methanol, 10 mL of ethanol, 10 mL of acetone, and 10 mL of tetrahydrofuran (Comparative Examples 2, 3, 4, and 5, respectively) were added. After heating to 50°C, 9 mL (7.2 eq.) of 30% hydrogen peroxide was added dropwise over 0.5 h. After the addition was complete, the reaction temperature was maintained at 60°C, and a UV lamp with a wavelength of 365 nm and a power of 20 W was turned on for 3 h to obtain a first reaction solution. The first reaction solution was allowed to stand for stratification, and the lower organic phase was removed by filtration and desolvation. The GC contents were 42.1%, 48.6%, 12.4%, and 26.2%, respectively.

[0059] Alkaline washing

[0060] 10 g of 20% sodium hydroxide solution was slowly added dropwise to the product from the previous step while stirring. After the addition was complete, the mixture was stirred for 1 hour to obtain a second reaction solution. The second reaction solution was extracted three times with 10 mL of dichloromethane. The extracts were combined, dried over anhydrous magnesium sulfate, filtered, and desolventized. This yielded crude 2,6-dichloro-4-trifluoromethylaniline with GC contents of 45.1%, 52.3%, 11.9%, and 27.8%, respectively, and molar yields of 36.8%, 57.2%, 8.8%, and 19.3%, respectively.

[0061] Experiments have shown that in the chlorination reaction step, N,N-dichloromethyl-2,6-dichloro-4-trifluoromethylaniline and N,N-(methyl,chloromethyl)-2,6-dichloro-4-trifluoromethylaniline will react with water to produce a large amount of by-product 2,6-dichloro-4-trifluoromethylphenol. Adding water-insoluble organic solvents such as dichloroethane can protect the product and reduce the occurrence of side reactions, while reflux controls the reaction temperature. Adding water-soluble organic solvents can accelerate the reaction, while increasing the number of by-products.

[0062] Comparative Example 6: Chlorination step without UV reaction

[0063] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C for 3 h to obtain the first reaction solution. The first reaction solution was allowed to stand for separation, and the lower organic phase was removed by filtration and solvent removal. The GC content was 1.3%.

[0064] Experiments have shown that nitrogen methyl is difficult to chlorinate without ultraviolet light irradiation.

[0065] Comparative Example 7: Selection of hydrogen peroxide addition equivalents for chlorination reaction

[0066] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 5 mL (4 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. Allow the first reaction solution to stand and separate. Remove the lower organic phase, filter, and desolventize. The GC content is 44.3%.

[0067] Example 7-9: Selection of hydrogen peroxide addition equivalents for chlorination reaction

[0068] To three reaction flasks, 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline were added, stirred to dissolve, and 10 mL of dichloroethane was added. After heating to 50°C, 7.5 mL (6 eq.), 9 mL (7.2 eq.), and 11.2 mL (8 eq.) of 30% hydrogen peroxide (described in Examples 7, 8, and 9, respectively) were added dropwise over 0.5 h. After the additions were complete, the reaction temperature was maintained at 60°C, a 365 nm UV lamp with a power of 20 W was turned on, and the reaction was continued for 3 h to obtain a first reaction solution. The first reaction solution was allowed to stand for demixing, and the lower organic phase was removed by filtration and solvent removal. The GC contents were 78.7%, 86.2%, and 86.6%, respectively.

[0069] Example 10-12: Chlorination reaction hydrogen peroxide addition time selection

[0070] To each of three reaction flasks, 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline were added, stirred to dissolve, and 10 mL of dichloroethane was added. After heating to 50°C, 9 mL (7.2 eq.) of 30% hydrogen peroxide was added dropwise over 0.5 h, 1 h, and 2 h (for Examples 10, 11, and 12, respectively). After the addition was complete, the reaction temperature was maintained at 60°C, and a UV lamp with a wavelength of 365 nm and a power of 20 W was used. The reaction was allowed to react for 3 h to obtain a first reaction solution. The first reaction solution was allowed to stand for stratification, and the lower organic phase was removed by filtration and desolvation. The GC contents were 86.6%, 85.4%, and 85.7%, respectively.

[0071] Example 13: Chlorination reaction hydrogen peroxide dropwise addition temperature selection

[0072] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 40°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. The first reaction solution was allowed to stand for separation, and the lower organic phase was removed, filtered, and desolvated. The GC content was 84.2%.

[0073] Example 14: Chlorination reaction hydrogen peroxide dropwise addition temperature selection

[0074] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 60°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. Allow the first reaction solution to stand and separate. Remove the lower organic phase, filter, and desolventize. The GC content is 81.6%.

[0075] Comparative Example 8: Selection of hydrochloric acid concentration for chlorination reaction

[0076] To a reaction flask, add 60 mL of 10% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. Allow the first reaction solution to stand and separate. Remove the lower organic phase, filter, and desolventize. The GC content is 0.3%.

[0077] Comparative Example 9: Selection of hydrochloric acid concentration for chlorination reaction

[0078] To a reaction flask, add 60 mL of 15% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. Allow the first reaction solution to stand and separate. Remove the lower organic phase, filter, and desolventize. The GC content is 3.5%.

[0079] Comparative Example 10: Selection of hydrochloric acid concentration for chlorination reaction

[0080] To a reaction flask, add 60 mL of 20% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. Allow the first reaction solution to stand and separate. Remove the lower organic phase, filter, and desolventize. The GC content is 40.8%.

[0081] Example 15: Selection of hydrochloric acid concentration for chlorination reaction

[0082] To a reaction flask, add 60 mL of 24% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. Allow the first reaction solution to stand and separate. Remove the lower organic phase, filter, and desolventize. The GC content is 72.6%.

[0083] Example 16: Selection of hydrochloric acid concentration for chlorination reaction

[0084] To a reaction flask, add 60 mL of 30% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 60°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp for 3 h to obtain a first reaction solution. Allow the first reaction solution to stand and separate. Remove the lower organic phase, filter, and desolventize. The GC content is 50.6%.

[0085] Experiments have shown that the concentration of hydrochloric acid in the chlorination reaction greatly affects the reaction yield. Low-concentration hydrochloric acid can only chlorinate the aromatic ring and can hardly chlorinate the nitrogen methyl group; a concentration of 21% is a watershed, exceeding which can greatly increase the reaction yield. However, high-concentration hydrochloric acid reactions make the temperature difficult to control and increase side reactions.

[0086] Example 17: Chlorination reaction time selection

[0087] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. After the addition is complete, maintain the reaction temperature at 60°C and turn on a 365 nm, 20 W UV lamp. Samples are taken at 1 h, 2 h, 3 h, 4 h, 5 h, and 6 h of reaction time for gas chromatography analysis. The GC contents are 77.4%, 84.9%, 86.2%, 86.3%, 84.2%, and 83.7%, respectively.

[0088] Example 18: Chlorination reaction temperature selection

[0089] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 50°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp. After 3 h of reaction, sample the mixture for gas chromatography, revealing a GC content of 64.3%.

[0090] Example 19: Chlorination reaction temperature selection

[0091] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 70°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp. After 3 h of reaction, sample the mixture for gas chromatography, revealing a GC content of 85.5%.

[0092] Example 20: Chlorination reaction temperature selection

[0093] To a reaction flask, add 60 mL of 21.5% hydrochloric acid and 4.2 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 10 mL of dichloroethane. After heating to 50°C, add 9 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. Maintain the reaction temperature at 80°C after the addition is complete. Turn on a 365 nm, 20 W UV lamp. After 3 h of reaction, sample the mixture for gas chromatography, revealing a GC content of 73.9%.

[0094] Example 21: Chlorination reaction amplification experiment

[0095] To a reaction flask, add 240 mL of 21.5% hydrochloric acid and 16.8 g of N,N-dimethyl-4-trifluoromethylaniline, stir to dissolve, and then add 40 mL of dichloroethane. After heating to 50°C, add 36 mL (7.2 eq.) of 30% hydrogen peroxide dropwise over 0.5 h. After the addition is complete, maintain the reaction temperature at 60°C and operate a 20W UV lamp at a wavelength of 365 nm for 3 h to obtain a first reaction solution. The first reaction solution was allowed to stand for separation, and the lower organic phase was removed by filtration and solvent removal. The GC content was 84.5%.

[0096] Examples 22-25: Selection of mass concentration and dosage of sodium hydroxide aqueous solution in alkali washing

[0097] The chlorination reaction product of Example 21 was divided into four equal parts and added to 10 g of 10% NaOH, 20% NaOH, 30% NaOH, and 50% NaOH at room temperature, respectively, with stirring for 1 hour (for Examples 22, 23, 24, and 25, respectively). The GC contents were 89.2%, 94.1%, 91.5%, and 74.6%, respectively, and the molar yields were 71.2%, 81.4%, 78.3%, and 72.5%, respectively.

[0098] Example 26: Alkali Washing Time Selection

[0099] Chlorination reaction

[0100] Add 60mL of hydrochloric acid (21.5%) and 4.2g of N,N-dimethyl-4-trifluoromethylaniline to the reaction flask, stir and dissolve, and add 10mL of dichloroethane. After heating to 50℃, add 9mL (7.2eq.) of 30% hydrogen peroxide dropwise within 0.5h. After the addition is complete, maintain the reaction temperature at 60℃, turn on the ultraviolet lamp with a wavelength of 365nm and a power of 20w, and react for 3h to obtain the first reaction solution. The first reaction solution is allowed to stand and separate, and the lower organic phase is removed by filtration and desolvation. The GC content is 84.7% (see the gas chromatogram). Figure 1 , peak table see Table 1).

[0101] Alkaline washing

[0102] The product of the previous step was slowly added dropwise to 10 g of sodium hydroxide solution (20%) while stirring. After the addition was completed, gas phase samples were taken for detection at 0.5 h, 1 h, 2 h, and 3 h of stirring reaction. The GC contents were 91.3%, 94.8%, 94.7%, and 95.1%, respectively (see gas chromatogram). Figure 2 , peak table see Table 2).

[0103] Gas phase detection method: chromatographic column model SHIMADZU SK-17010.25um*0.25um*30m;

[0104] MYJ-40(2)-260(6).20.M.

[0105] In particular, the target product 2,6-dichloro-4-trifluoromethylaniline was obtained at a retention time of 10.85 min.

[0106] Table 1

[0107] <Peak table>

[0108] FID1

[0109] Peak Retention time area high concentration Concentration unit mark 1 9.038 1764 164 0.044 V 2 10.158 113726 45214 2.833 SV 3 10.442 2371 904 0.059 T 4 10.574 72265 13740 1.800 V 5 10.858 3401549 1577324 84.749 M 6 11.326 1074 425 0.027 7 11.378 1459 363 0.036 V 8 11.940 3305 622 0.082 V 9 12.050 116463 65265 2.902 V 10 12.098 155241 66736 3868 V 11 12.398 68690 14006 1.711 V 12 12.652 1316 479 0.033 V 13 12.806 12886 2133 0.321 V 14 12.935 4633 1500 0.115 V 15 12.999 4172 713 0.104 V 16 13.157 1528 593 0.038 V 17 13.209 2956 1115 0.074 V 18 13.379 4431 1575 0.110 V 19 13.517 1703 519 0.042 20 13.986 1337 348 0.033 V 21 14.091 1250 296 0.031 V 22 14.280 1571 177 0.039 V

[0110] Table 2

[0111] <Peak table>

[0112] FID1

[0113] Peak Retention time area high concentration Concentration unit mark 1 8.914 8106 555 0.191 M 2 10.171 42586 13544 1.003 S 3 10.543 5467 605 0.129 T 4 10.721 1251 161 0.029 TV 5 10.863 4036449 1911986 95.075 M 6 11.325 1121 281 0.026 7 11.973 1941 421 0.046 M 8 12.389 106303 24229 2.504 S 9 12.984 5525 1112 0.130 TV 10 13.548 3868 689 0.091 TV 11 13.977 2187 646 0.052 12 14.024 1087 528 0.026 V 13 14.103 3142 647 0.074 V 14 14.201 1569 335 0.037 V 15 14.354 4560 868 0.107 V 16 14.416 2514 586 0.059 V 17 14.976 14510 4724 0.342 V 18 16.029 3342 340 0.079 M total 4245528 1962256

Claims

1. A method for preparing 2,6-dichloro-4-trifluoromethylaniline as shown in formula b, It is characterized in that The preparation method is carried out according to the following steps: The N, N-dimethyl-4-trifluoromethylaniline shown in formula a is dissolved in a 21.5% to 30% hydrochloric acid aqueous solution, an organic solvent is added, and a 30% hydrogen peroxide solution is added dropwise at 40 to 60° C. within 0.5 to 2 h. After the addition is completed, the reaction solution is irradiated with ultraviolet light at 50 to 80° C. for 1 to 6 h. The obtained first reaction solution is allowed to stand and separate to obtain an acid phase and an organic phase. The lower organic phase is filtered, the filtrate is taken for desolvation, and an excess of 2% by mass of the reaction solution is added. 0% to 50% sodium hydroxide solution, stirring at room temperature for 0.5 to 3 hours to carry out alkaline washing reaction, and the obtained second reaction liquid is post-treated to obtain 2,6-dichloro-4-trifluoromethylaniline; the volume of the hydrogen peroxide is 1.78 to 2.66 mL / g based on the mass of the N,N-dimethyl-4-trifluoromethylaniline, and the volume of the hydrochloric acid aqueous solution is 14.1 to 14.5 mL / g based on the mass of the N,N-dimethyl-4-trifluoromethylaniline represented by formula a.

2. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein The organic solvent is one or more of chloroform, dichloromethane, dichloroethane, carbon tetrachloride, toluene and cyclohexane.

3. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein After the obtained first reaction solution was allowed to stand and separate into layers, the acid phase was extracted with dichloromethane to obtain an extract, the extract was combined with the organic phase and filtered, and the filtrate was taken for desolventizing and then put into alkaline washing reaction.

4. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein The post-treatment is as follows: adding dichloromethane to the second reaction solution for extraction, taking the extract and adding anhydrous magnesium sulfate for drying, filtering, and desolvating the filtrate to obtain 2,6-dichloro-4-trifluoromethylaniline.

5. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein The ultraviolet lamp used for the ultraviolet irradiation has a wavelength of 365nm and a power of 20W.

6. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein Add a base having a mass concentration of 20% to 50% sodium hydroxide solution until the pH value of the solution of the reaction system reaches 10, and stop adding the base.

7. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein The volume of the hydrogen peroxide solution is calculated based on the mass of the N,N-dimethyl-4-trifluoromethylaniline to be 2.14 mL / g.

8. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein The volume of the hydrochloric acid aqueous solution is 14.3 mL / g based on the mass of the N,N-dimethyl-4-trifluoromethylaniline.

9. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein The concentration of the hydrochloric acid aqueous solution is 21.5%.

10. The method for preparing 2,6-dichloro-4-trifluoromethylaniline according to claim 1, wherein The mass percentage of the sodium hydroxide is 30%.