A method for preparing 2,5-dichloro-4-trifluoromethylaniline

Abstract

This invention discloses a method for preparing 2,5-dichloro-4-trifluoromethylaniline. Specifically, it includes the following steps: in a solvent, at a temperature of 130°C to 150°C, under the action of a monovalent copper salt, a ligand, and a base, 2,4,5-trichlorotrifluorotoluene undergoes an ammoniation reaction with ammonia as shown below; the ligand is selected from one or more of proline, 4-hydroxyproline, and 2-pyridinecarboxylic acid. Compared with existing methods, the method of this invention reduces the reaction temperature, reduces the formation of isomers, and improves the reaction yield.

Description

Technical Field

[0001] This invention belongs to the field of catalytic amination technology, specifically relating to a method for preparing 2,5-dichloro-4-trifluoromethylaniline. Background Technology

[0002] 2,4,5-Trichlorotrifluorotoluene is a co-product of the chlorination of 3,4-dichlorotrifluorotoluene to produce 3,4,5-trichlorotrifluorotoluene. Industrially, 2,4,5-trichlorotrifluorotoluene is aminated to produce 2,5-dichloro-4-trifluoromethylaniline, which is then further hydrogenated and dechlorinated to produce the high-value-added fine chemical intermediate p-trifluoromethylaniline. However, the aminated preparation of 2,5-dichloro-4-trifluoromethylaniline from 2,4,5-trichlorotrifluorotoluene requires a high temperature of 170-180°C and a pressure of 12 MPa, which poses a high reaction risk and is not conducive to safe and stable production. In addition, the proportion of the aminated isomer is only 10%, and the reaction yield is low, approximately 50%. Summary of the Invention

[0003] To address the shortcomings of existing methods for preparing 2,5-dichloro-4-trifluoromethylaniline, which require high temperature and high pressure reactions, posing safety risks, resulting in low yields and numerous isomers, this invention provides a method for preparing 2,5-dichloro-4-trifluoromethylaniline. Compared to existing methods, this method lowers the reaction temperature, reduces isomer formation, and improves the reaction yield.

[0004] This invention provides a method for preparing 2,5-dichloro-4-trifluoromethylaniline, comprising the following steps: in a solvent, at a temperature of 130°C to 150°C, under the action of a monovalent copper salt, a ligand, and a base, 2,4,5-trichlorotrifluorotoluene undergoes an ammoniation reaction with ammonia as shown below; wherein the ligand is selected from one or more of proline, 4-hydroxyproline, and 2-pyridinecarboxylic acid;

[0005]

[0006] In this invention, the ligand is preferably proline and / or 4-hydroxyproline, more preferably proline.

[0007] In this invention, the copper salt is a conventional monovalent copper salt used in such reactions in the art, preferably selected from one or more of cuprous iodide, cuprous bromide and cuprous chloride.

[0008] In this invention, the base is a conventional base for such reactions in the art, such as alkali metal or alkaline earth metal carbonates and / or alkali metal or alkaline earth metal hydroxides, preferably alkali metal carbonates (e.g., sodium carbonate and / or potassium carbonate).

[0009] In this invention, the ammonia can be used in a conventional form of ammonia, preferably in the form of ammonia solution. The mass fraction of ammonia in the ammonia solution is preferably 40% to 60%, for example, 50%. The ammonia solution is preferably obtained by introducing liquid ammonia into the reaction system.

[0010] In this invention, the solvent is a conventional solvent for such reactions in the art, such as water.

[0011] In this invention, in the amination reaction, the molar ratio of the copper salt to the 2,4,5-trichlorotrifluorotoluene is a conventional molar ratio for such reactions in the art, for example, 1:(5 to 30), preferably 1:20.

[0012] In this invention, in the amination reaction, the molar ratio of the ligand to the 2,4,5-trichlorotrifluorotoluene is a conventional molar ratio for such reactions in the art, for example 1:(10 to 40), preferably 1:20.

[0013] In this invention, in the amination reaction, the molar ratio of the base to the 2,4,5-trichlorotrifluorotoluene is a conventional molar ratio for such reactions in the art, for example, 1:(1 to 3), preferably 1:1.

[0014] In this invention, in the amination reaction, the volume molar ratio of the solvent to the 2,4,5-trichlorotrifluorotoluene is a conventional volume molar ratio for such reactions in the art, for example (100 to 200):1 ml / mol, preferably 125:1 ml / mol.

[0015] In this invention, the reaction system pressure of the amination reaction is the conventional reaction system pressure of such reactions in the art, for example, 8 to 12 MPa, preferably 10 MPa.

[0016] In this invention, the reaction time of the ammoniation reaction is the conventional reaction time for such reactions in the art, for example, 12 to 24 hours, preferably 18 to 24 hours, and more preferably 24 hours.

[0017] In this invention, the reaction temperature of the ammoniation reaction is preferably 140°C.

[0018] In this invention, the ammoniation reaction is preferably carried out under vacuum conditions.

[0019] In this invention, the amination reaction preferably includes the following post-processing steps: cooling, tail gas treatment (e.g., absorbing the tail gas with water after depressurization), settling and layering, washing (e.g., washing the organic phase with water), and distillation (e.g., vacuum distillation, or for example, first distilling at 100°C to recover 2,4,5-trichlorotrifluorotoluene, and then continuing distillation at 120°C to obtain 2,5-dichloro-4-trifluoromethylaniline).

[0020] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0021] The reagents and raw materials used in this invention are all commercially available.

[0022] The positive and progressive effects of this invention are as follows: compared with existing methods, the method of this invention reduces the reaction temperature, reduces the generation of isomers, and increases the reaction yield. Detailed Implementation

[0023] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0024] In the following examples, the yield is calculated as: moles of product / (moles of substrate × (1 - residual rate of feed)).

[0025] In the following embodiments, the GC-MS method used for molecular weight detection is as follows:

[0026] project parameter chromatographic column HP-INNOWAX Column length×column inner diameter×film thickness 30m × 0.25mm × 0.25μm vaporization chamber temperature / ℃ 230 Detector temperature / °C 250 Column oven temperature / ℃ 190 Injection volume / μL 0.1 carrier gas He Carrier gas flow rate (mL / min) 0.8 Flow split ratio 200:1 EI source / ℃ 230 Solvent delay / min 2

[0027] The central control method used for testing conversion rates is:

[0028]

[0029]

[0030] Example 1

[0031] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 11.5g of L-proline, 212g of sodium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distilling at 120℃ to obtain 361g of the product 2,5-dichloro-4-trifluoromethylaniline, with a yield of 92% and a purity of 99.5%.

[0032] The residual rate of the raw material, as measured by the central control method, was 15%. The conversion rate of the raw material to the product was 82%, and the conversion rate of the raw material to the isomers (2,4-dichloro-5-trifluoromethylaniline and 2-trifluoromethyl-4,5-dichloroaniline) was 3%. The retention time of the raw material was 3.45 min, the retention time of the product was 7.14 min, and the retention time of the isomers was 5.77-6.07 min.

[0033] The molecular weight of the product was determined by GC-MS to be 229. The gas chromatogram data of p-trifluoromethylaniline obtained after hydrogenation and dechlorination are shown in the table below. The peak position of p-trifluoromethylaniline is completely consistent with that of the standard p-trifluoromethylaniline at 2.81 min, which proves its structure.

[0034] Hydrogenation dechlorination method: Dissolve the product in methanol, add palladium on carbon, introduce hydrogen gas, maintain the temperature at 40-60℃ and the pressure at 0.6-1.2MPa, react for 6 hours, filter palladium on carbon, concentrate methanol to obtain p-trifluoromethylaniline.

[0035]

[0036] Example 2

[0037] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 14.2g of cuprous bromide, 11.5g of L-proline, 212g of sodium carbonate, and 250g of water. After vacuuming, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distilling at 120℃ to obtain 359g of the product 2,5-dichloro-4-trifluoromethylaniline, with a yield of 90% and a purity of 99.7%.

[0038] Example 3

[0039] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 19.0g of cuprous iodide, 11.5g of L-proline, 212g of sodium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distillation at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline with a yield of 91% and a purity of 99.5%.

[0040] Example 4

[0041] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 19.0g of cuprous iodide, 13.1g of L-proline, 212g of sodium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distillation at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline with a yield of 92% and a purity of 99.6%.

[0042] Example 5

[0043] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 11.5g of L-proline, 276g of potassium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distillation at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline with a yield of 93% and a purity of 99.5%.

[0044] Example 6

[0045] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 13.1g of 4-hydroxyproline, 212g of sodium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distillation at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline with a yield of 91% and a purity of 99.4%.

[0046] Example 7

[0047] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 12.3g of 2-pyridinecarboxylic acid, 212g of sodium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distillation at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline with a yield of 83% and a purity of 99.2%.

[0048] Comparative Example 1

[0049] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 10.0g of acetylacetone, 212g of sodium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 140℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distillation at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline, with a yield of 11% and a purity of 99.1%.

[0050] Comparative Example 2

[0051] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 11.5g of L-proline, 212g of sodium carbonate, and 250g of water. After evacuation, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 50%. Heat to about 120℃, maintain the pressure inside the reactor at about 10MPa, and react for 24 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distillation at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline, with a yield of 21% and a purity of 99.3%.

[0052] Comparative Example 3

[0053] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 11.5g of L-proline, 212g of sodium carbonate, and 250g of water. After vacuuming, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at about 60%. Heat to about 170℃, maintain the pressure inside the reactor at about 10MPa, and react for 12 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is allowed to stand and separate into layers, and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distilling at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline. The residual rate of the raw material was measured to be 3% by the central control method. The conversion rate of the raw material to the product was 87%, and the conversion rate of the raw material to the isomers (2,4-dichloro-5-trifluoromethylaniline and 2-trifluoromethyl-4,5-dichloroaniline) was 10%.

[0054] Comparative Example 4

[0055] Take 500g of 2,4,5-trichlorotrifluorotoluene, add 9.9g of cuprous chloride, 11.5g of L-proline, 212g of sodium carbonate, and 250g of water. After vacuuming, introduce liquid ammonia. Control the amount of liquid ammonia to maintain the ammonia concentration (mass fraction) at around 60%. Heat to about 160℃, maintain the pressure inside the reactor at about 10MPa, and react for 12 hours. Cool down and start depressurizing. Use water to absorb the tail gas to prepare ammonia water. After the reaction liquid is separated and washed with water, first distill at 100℃ to recover the raw material 2,4,5-trichlorotrifluorotoluene, and then continue distilling at 120℃ to obtain the product 2,5-dichloro-4-trifluoromethylaniline. The residual rate of the raw material was measured to be 12% by the central control method, the conversion rate of the raw material to the product was 79%, and the conversion rate of the raw material to the isomers (2,4-dichloro-5-trifluoromethylaniline and 2-trifluoromethyl-4,5-dichloroaniline) was 9%.

Claims

1. A method for preparing 2,5-dichloro-4-trifluoromethylaniline, comprising the following steps: In a solvent, 2,4,5-trichlorotrifluorotoluene reacts with ammonia in the presence of a monovalent copper salt, a ligand, and a base, as shown below; the reaction system pressure for the ammoniation reaction is 10 MPa; the reaction temperature for the ammoniation reaction is 140°C; the ligand is proline and / or 4-hydroxyproline; and the solvent is water. 。 2. The method as described in claim 1, characterized in that, It meets one or more of the following conditions: (1) The copper salt is selected from one or more of cuprous iodide, cuprous bromide and cuprous chloride; (2) The alkali is a carbonate and / or hydroxide; the carbonate is an alkali metal or alkaline earth metal carbonate; the hydroxide is an alkali metal or alkaline earth metal hydroxide; (3) The ammonia is in the form of ammonia water for the ammoniation reaction.

3. The method as described in claim 1, characterized in that, It meets one or more of the following conditions: (1) The ligand is proline; and, (2) The alkali is an alkali metal carbonate.

4. The method as described in claim 2, characterized in that, The alkali is sodium carbonate and / or potassium carbonate.

5. The method as described in claim 1, characterized in that, It meets one or more of the following conditions: (1) When the ammonia is used in the form of ammonia solution for the ammoniation reaction, the mass fraction of ammonia in the ammonia solution is 40% to 60%; and, (2) When the ammonia is in the form of ammonia water, the ammonia water is obtained by introducing liquid ammonia into the reaction system.

6. The method as described in claim 5, characterized in that, When the ammonia is used in the form of ammonia water for the ammoniation reaction, the mass fraction of ammonia in the ammonia water is 50%.

7. The method as described in claim 1, characterized in that, It meets one or more of the following conditions: (1) The molar ratio of the copper salt to the 2,4,5-trichlorotrifluorotoluene is 1:(5 to 30); (2) The molar ratio of the ligand to the 2,4,5-trichlorotrifluorotoluene is 1:(10 to 40); (3) The molar ratio of the alkali to the 2,4,5-trichlorotrifluorotoluene is 1:(1 to 3); and, (4) The volume molar ratio of the solvent to the 2,4,5-trichlorotrifluorotoluene is (100 to 200):1 ml / mol.

8. The method as described in claim 7, characterized in that, It meets one or more of the following conditions: (1) The molar ratio of the copper salt to the 2,4,5-trichlorotrifluorotoluene is 1:20; (2) The molar ratio of the ligand to the 2,4,5-trichlorotrifluorotoluene is 1:20; (3) The molar ratio of the alkali to the 2,4,5-trichlorotrifluorotoluene is 1:1; and, (4) The volume molar ratio of the solvent to the 2,4,5-trichlorotrifluorotoluene is 125:1 ml / mol.

9. The method as described in claim 1, characterized in that, The reaction time for the ammoniation reaction is 12 to 24 hours.

10. The method as described in claim 1, characterized in that, The reaction time for the ammoniation reaction is 18 to 24 hours.

11. The method as described in claim 1, characterized in that, The reaction time for the ammoniation reaction is 24 h.

12. The method as described in claim 1, characterized in that, The ammoniation reaction includes the following post-processing steps: cooling, tail gas treatment, settling and stratification, washing and distillation.

Images