A process for the preparation of 2,4,6-trichlorobenzoic acid

Abstract

The application provides a preparation method of 2,4,6-trichlorobenzoic acid, which comprises the following steps: 1) subjecting toluene to a chlorination reaction to obtain 1,3,5-trichloro-2-(trichloromethyl)benzene; and 2) subjecting the 1,3,5-trichloro-2-(trichloromethyl)benzene to an oxidation reaction to obtain 2,4,6-trichlorobenzoic acid. The method can obtain 2,4,6-trichlorobenzoic acid with a purity of up to 99.6% and a molar yield of up to 92.7%, the raw material is low in price, the process is simple, the preparation cost is low, the method is safe and environmentally friendly, and the method can be applied to large-scale production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and in particular to a method for preparing 2,4,6-trichlorobenzoic acid. Background Technology

[0002] 2,4,6-Trichlorobenzoic acid is an important pharmaceutical and pesticide intermediate. It can be used to manufacture immunosuppressants, as a reagent for analyzing the sensitivity of anticancer drugs for leukemia, and to synthesize insecticides and fungicides, with a wide range of applications.

[0003] Existing technologies have reported methods for preparing 2,4,6-trichlorobenzoic acid from substituted trichlorobenzene. Specifically, 2,4,6-trichlorobenzoic acid is prepared from 1,3,5-trichlorobenzene through Friedel-Crafts acylation, oxidation, and acidification reactions. This method is complex and uses expensive acylation reagents such as acetyl chloride, propionyl chloride, and butyryl chloride, thus limiting the large-scale production of 2,4,6-trichlorobenzoic acid.

[0004] Another method for preparing 2,4,6-trichlorobenzoic acid using 1,3,5-trichlorobenzene as a raw material involves reacting 1,3,5-trichlorobenzene with carbon tetrachloride under the catalysis of anhydrous aluminum chloride to obtain 2,4,6-trichlorotrichlorotoluene, which is then reacted with concentrated sulfuric acid to yield 2,4,6-trichlorobenzoic acid. While this method avoids the use of acylation reagents, the yield of 2,4,6-trichlorobenzoic acid is less than 75%, and the reaction process involves high toxicity. Furthermore, the raw materials are expensive, making this method unsuitable for large-scale production.

[0005] Therefore, there is an urgent need for a low-cost and relatively safe and environmentally friendly method for preparing 2,4,6-trichlorobenzoic acid, which is suitable for large-scale production. Summary of the Invention

[0006] To address the problems existing in the prior art, this invention provides a method for preparing 2,4,6-trichlorobenzoic acid. This method is simple, uses inexpensive raw materials, and yields 2,4,6-trichlorobenzoic acid with high purity and high yield. It is also safe and environmentally friendly, and suitable for large-scale production.

[0007] This invention provides a method for preparing 2,4,6-trichlorobenzoic acid, comprising:

[0008] 1) Chlorination of toluene yields 1,3,5-trichloro-2-(trichloromethyl)benzene;

[0009] 2) The 1,3,5-trichloro-2-(trichloromethyl)benzene is oxidized to obtain 2,4,6-trichlorobenzoic acid.

[0010] According to one embodiment of the present invention, step 1) includes: introducing chlorine gas into a system comprising the toluene and a chlorination catalyst to produce the chlorination reaction, thereby obtaining the 1,3,5-trichloro-2-(trichloromethyl)benzene;

[0011] The chlorination catalyst includes at least one of MoO2, MoO3, and MoCl5; the chlorine gas introduction rate is 5-10 g / min.

[0012] According to one embodiment of the present invention, the mass ratio of toluene to the chlorination catalyst is 1:(0.01-0.08).

[0013] According to one embodiment of the present invention, the temperature of the chlorination reaction is 50-70°C.

[0014] According to one embodiment of the present invention, after the chlorination reaction is completed, the pH of the chlorination reaction system is adjusted to 8-9, and then the system is washed with water and distilled to obtain the 1,3,5-trichloro-2-(trichloromethyl)benzene.

[0015] The distillation process is carried out at a pressure of 3-8 MPa and a temperature of 90-100℃.

[0016] According to one embodiment of the present invention, step 2) includes: adding an oxidant to water, and then adding the 1,3,5-trichloro-2-(trichloromethyl)benzene to undergo the oxidation reaction to obtain the 2,4,6-trichlorobenzoic acid;

[0017] The oxidant includes at least one of concentrated sulfuric acid and concentrated nitric acid; the mass ratio of the oxidant to the water is (6-9):1.

[0018] According to one embodiment of the present invention, the mass ratio of toluene to the oxidant is 1:(6-10).

[0019] According to one embodiment of the present invention, the addition rate of the 1,3,5-trichloro-2-(trichloromethyl)benzene is 3-6 g / min.

[0020] According to one embodiment of the present invention, the temperature of the oxidation reaction is 110-120°C.

[0021] According to one embodiment of the present invention, after the oxidation reaction is completed, the water and oxidant in the oxidation reaction system are recovered and cooled to 20-30°C. Sodium hydroxide aqueous solution is added to the crude product, and then an organic solvent is added for washing to obtain an aqueous phase. After filtering the aqueous phase, the pH of the aqueous phase is adjusted to 1.0 to obtain the 1,3,5-trichloro-2-(trichloromethyl)benzene.

[0022] This invention uses toluene as a raw material to obtain 1,3,5-trichloro-2-(trichloromethyl)benzene through a chlorination reaction, and then converts 1,3,5-trichloro-2-(trichloromethyl)benzene to 2,4,6-trichlorobenzoic acid through an oxidation reaction. This method has the advantages of simple process, inexpensive and readily available raw materials in small quantities, high molar yield and purity of 2,4,6-trichlorobenzoic acid, low preparation cost, and mild reaction conditions, eliminating the need for large amounts of corrosive, polluting, and hazardous reagents, making it relatively safe and environmentally friendly, and suitable for large-scale production. Attached Figure Description

[0023] Figure 1 The 1H NMR spectrum of the second product prepared in Example 1 of this invention. Detailed Implementation

[0024] To enable those skilled in the art to better understand the present invention, the present invention will be further described in detail below. The specific embodiments listed below are merely descriptions of the principles and features of the present invention, and the examples are only for explaining the present invention and are not intended to limit the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] This invention provides a method for preparing 2,4,6-trichlorobenzoic acid, comprising the following steps:

[0026] 1) Chlorination of toluene yields 1,3,5-trichloro-2-(trichloromethyl)benzene;

[0027] 2) Oxidize 1,3,5-trichloro-2-(trichloromethyl)benzene to give 2,4,6-trichlorobenzoic acid.

[0028] The above reaction process is illustrated below:

[0029]

[0030] This invention prepares 2,4,6-trichlorobenzoic acid from toluene via chlorination and oxidation reactions. Toluene is chosen as the raw material for several reasons: First, toluene exhibits a directing effect, readily substituting chlorine for hydrogens at the ortho and para positions rather than the meta position. Once chlorine substitution occurs at both the ortho and para positions, the meta position is difficult to substitutably, leading to chlorine substitution of the hydrogen on the methyl group. This results in a high yield and high purity of 1,3,5-trichloro-2-(trichloromethyl)benzene. Second, using toluene as a raw material avoids the introduction of additional solvents, facilitating product separation and purification. Furthermore, toluene is a stable and inexpensive source, reducing the preparation cost of 2,4,6-trichlorobenzoic acid. In step 2), the oxidation reaction is less likely to occur on the benzene ring, typically occurring at the trichloromethyl site in 1,3,5-trichloro-2-(trichloromethyl)benzene, minimizing the generation of byproducts and thus ensuring a high purity and high yield of 2,4,6-trichlorobenzoic acid. Therefore, this method has the advantages of simple process, low raw material cost, high yield and purity of 2,4,6-trichlorobenzoic acid, and does not require the use of highly toxic reagents such as carbon tetrachloride, making it relatively safe and environmentally friendly, and suitable for large-scale production.

[0031] It should be noted that after the chlorination reaction is completed, the 1,3,5-trichloro-2-(trichloromethyl)benzene obtained exists in the greening reaction system. Therefore, the chlorination reaction system obtained after the reaction needs to be post-processed before being used in the oxidation reaction of step 2) to improve the purity and yield of 2,4,6-trichlorobenzoic acid.

[0032] In step 2), after the oxidation reaction is completed, the 2,4,6-trichlorobenzoic acid obtained exists in the oxidation reaction system. By post-processing the oxidation reaction system, 2,4,6-trichlorobenzoic acid with high purity and high molar yield can be obtained.

[0033] Step 1) of the present invention includes: introducing chlorine gas (Cl2) into a system including toluene and a chlorination catalyst to produce a chlorination reaction, thereby obtaining 1,3,5-trichloro-2-(trichloromethyl)benzene; the chlorination catalyst includes at least one of molybdenum dioxide (MoO2), molybdenum trioxide (MoO3), and molybdenum pentachloride (MoCl5); the chlorine gas introduction rate is 5-10 g / min.

[0034] When introducing chlorine gas, it is necessary to introduce the chlorine gas below the surface of the toluene to increase the reaction rate and avoid wasting the chlorine gas.

[0035] When the chlorine gas introduction rate is too fast, impurities will be generated, which is not conducive to obtaining high-purity 1,3,5-trichloro-2-(trichloromethyl)benzene. Conversely, if the rate is too slow, the chlorination reaction is slow, requiring a longer time for the toluene to fully chlorinate, which is not conducive to reducing preparation costs. Therefore, this invention controls the chlorine gas introduction rate to 5-10 g / min, and more preferably, this rate is 7 g / min.

[0036] Since the present invention does not limit the amount of chlorine used, in the specific implementation process, the content of toluene can be detected by HPLC (high performance liquid chromatography) to track the chlorination reaction. When HPLC shows that the content of toluene is less than 0.2%, it indicates that the chlorination reaction is complete. Generally, the reaction can be completed in about 1 hour.

[0037] In practice, the mass ratio of toluene to chlorination catalyst is 1:(0.01-0.08).

[0038] When the mass of the chlorination catalyst is too high relative to toluene, it leads to an increase in byproducts, thereby reducing the purity of 1,3,5-trichloro-2-(trichloromethyl)benzene. Conversely, if the amount of catalyst is too low, it results in incomplete toluene conversion and a decrease in the yield of 1,3,5-trichloro-2-(trichloromethyl)benzene. Therefore, this invention controls the mass ratio of toluene to the chlorination catalyst to be 1:(0.01-0.08).

[0039] In this invention, the chlorination reaction temperature is 50-70℃.

[0040] Under these temperature conditions, 1,3,5-trichloro-2-(trichloromethyl)benzene can be obtained in high purity and high yield at a relatively fast rate. If the temperature is too low, the toluene conversion is incomplete; if the temperature is too high, the amount of byproducts increases. Therefore, the present invention controls the chlorination reaction temperature to 50-70°C.

[0041] After the chlorination reaction is completed, the pH of the chlorination reaction system is adjusted to 8-9, and then washed with water and distilled to obtain 1,3,5-trichloro-2-(trichloromethyl)benzene; the distillation pressure is 3-8 MPa and the temperature is 90-100℃.

[0042] The above process is a post-treatment process for the chlorination reaction system.

[0043] By adjusting the pH of the chlorination reaction system to 8-9, acidic substances produced during the chlorination reaction, such as hydrogen chloride, can be neutralized. This invention does not limit the reagent used to adjust the pH; for example, it can be sodium carbonate. The acidic substances are present in the aqueous phase by water washing, and then the aqueous phase and organic phase are separated by static separation. During the static separation process, the acidic substances and chlorination catalyst are removed, resulting in an organic phase including 1,3,5-trichloro-2-(trichloromethyl)benzene.

[0044] To obtain high-purity 1,3,5-trichloro-2-(trichloromethyl)benzene, this invention further involves distilling the organic phase at a pressure of 3-8 MPa and a temperature of 90-100°C to remove impurities and byproducts. Under these pressure conditions, excessively high or low distillation temperatures will result in incomplete removal of impurities and byproducts, leading to a decrease in the yield and purity of 1,3,5-trichloro-2-(trichloromethyl)benzene. It is understood that the distillation temperature will change accordingly with pressure variations, and the inventors can adjust the pressure and temperature as needed.

[0045] Step 2) of the present invention includes: adding an oxidant to water, and then adding 1,3,5-trichloro-2-(trichloromethyl)benzene to undergo an oxidation reaction to obtain 2,4,6-trichlorobenzoic acid;

[0046] The oxidizing agent includes at least one of concentrated sulfuric acid and concentrated nitric acid; the mass ratio of the oxidizing agent to water is (6-9):1.

[0047] Because the commercially available concentrated sulfuric acid (98% sulfuric acid aqueous solution) and concentrated nitric acid (68% nitric acid aqueous solution) used in this invention have excessively high concentrations, their direct reaction with 1,3,5-trichloro-2-(trichloromethyl)benzene would lead to carbonization of 1,3,5-trichloro-2-(trichloromethyl)benzene, which is not conducive to obtaining high-purity and high-yield 2,4,6-trichlorobenzoic acid. Therefore, the inventors mixed concentrated sulfuric acid with water and found that when the mass ratio of oxidant to water is controlled at (6-9):1, the carbonization caused by concentrated sulfuric acid and concentrated nitric acid can be avoided while ensuring efficient oxidation reaction, resulting in high-purity and high-yield 2,4,6-trichlorobenzoic acid. Furthermore, the preferred mass ratio of oxidant to water is 7:1.

[0048] For ease of calculation, the present invention determines the amount of oxidant by controlling the mass ratio of toluene to oxidant. Studies have shown that when the mass ratio of toluene to oxidant is 1:(6-10), the oxidation reaction can be guaranteed while avoiding waste of oxidant and carbonization of 1,3,5-trichloro-2-(trichloromethyl)benzene caused by excessive oxidant. The preferred ratio is 1:8.

[0049] It is understood that the oxidant of the present invention is in excess relative to 1,3,5-trichloro-2-(trichloromethyl)benzene. Therefore, the content of 1,3,5-trichloro-2-(trichloromethyl)benzene can be detected by HPLC to track the oxidation reaction. When the content of 1,3,5-trichloro-2-(trichloromethyl)benzene is less than 0.2%, it indicates that the oxidation reaction is complete.

[0050] Furthermore, the addition rate of 1,3,5-trichloro-2-(trichloromethyl)benzene is 3-6 g / min.

[0051] When the addition rate of 1,3,5-trichloro-2-(trichloromethyl)benzene is too fast, the reaction is too vigorous and impurities are easily generated. When the addition rate is too slow, the reaction rate is low. Therefore, the present invention controls the addition rate of 1,3,5-trichloro-2-(trichloromethyl)benzene to be 3-6 g / min, preferably 4.5 g / min.

[0052] In the actual implementation process, the oxidation reaction temperature is 110-120℃.

[0053] Excessively high temperatures will also cause the carbonization of 1,3,5-trichloro-2-(trichloromethyl)benzene; excessively low temperatures make the oxidation reaction difficult and result in a lower conversion rate. Therefore, both excessively high and excessively low temperatures are detrimental to improving the yield and purity of 2,4,6-trichlorobenzoic acid. Thus, this invention controls the oxidation reaction temperature to 110-120°C.

[0054] In this invention, after the oxidation reaction is completed, the oxidation reaction system is cooled to 20-30°C, sodium hydroxide aqueous solution is added to the crude product, and then an organic solvent is added for washing to obtain an aqueous phase. After filtering the aqueous phase, the pH of the aqueous phase is adjusted to 1.0 to obtain the 1,3,5-trichloro-2-(trichloromethyl)benzene.

[0055] The above process is a post-treatment process for the oxidation reaction system.

[0056] The process of adding sodium hydroxide aqueous solution to the crude product is to convert 1,3,5-trichloro-2-(trichloromethyl)benzene in the crude product into sodium salt, which then dissolves. Adding organic solvent is to separate the aqueous phase and organic phase in the solution. Sodium salt of 1,3,5-trichloro-2-(trichloromethyl)benzene exists in the aqueous phase. Filtering the aqueous phase can remove insoluble impurities, thereby improving the purity of sodium salt of 1,3,5-trichloro-2-(trichloromethyl)benzene. By adjusting the pH of the aqueous phase to 1.0, the sodium salt can be converted back into 1,3,5-trichloro-2-(trichloromethyl)benzene, which then crystallizes out to obtain 1,3,5-trichloro-2-(trichloromethyl)benzene with higher purity. In practice, dried 1,3,5-trichloro-2-(trichloromethyl)benzene can be obtained through filtration and drying.

[0057] This invention does not limit the concentration and amount of sodium hydroxide aqueous solution, as long as 1,3,5-trichloro-2-(trichloromethyl)benzene is fully dissolved. For example, the molar ratio of sodium hydroxide to 1,3,5-trichloro-2-(trichloromethyl)benzene can be controlled to be (1.2-2):1, and the concentration of sodium hydroxide aqueous solution can be 10%. This invention also does not specifically limit the specific type of organic solvent, the amount of organic solvent, or the number of organic solvent washing treatments, as long as the aqueous phase and organic phase can be fully separated. The inventors can choose according to actual needs, such as ether, dichloromethane, dichloroethane, ethyl acetate, etc., wherein the ether can be methyl tert-butyl ether, diethyl ether, etc., the number of extractions can be 2, and the amount can be 237 mL.

[0058] The present invention will now be described in more detail through specific embodiments.

[0059] Example 1

[0060] The 2,4,6-trichlorobenzoic acid in this embodiment was prepared by the following method:

[0061] 1) Mix 184.28g of toluene with 1.84g of MoCl5, control the temperature at 60℃, and pass Cl2 below the liquid surface to cause a chlorination reaction; wherein the mass ratio of toluene to MoCl5 is 1:0.01;

[0062] After the chlorination reaction was completed (HPLC detection showed that the toluene reaction was complete), the pH of the chlorination reaction system was adjusted to 8 using 5 wt% NaHCO3 solution. After washing with 185 mL of water, the system was distilled at 90 °C under a pressure of 5 MPa to obtain 548.6 g of the first product.

[0063] The first product was 1,3,5-trichloro-2-(trichloromethyl)benzene; the HPLC purity of 1,3,5-trichloro-2-(trichloromethyl)benzene was 98.9%, and the molar yield was 91.8%.

[0064] 2) Slowly add 1474g of concentrated nitric acid to 185g of water, heat to 115℃, and then add 548.6g of 1,3,5-trichloro-2-(trichloromethyl)benzene at a rate of 4.57g / min to induce an oxidation reaction, controlling the temperature at 115℃; wherein, the mass ratio of concentrated nitric acid to water is 8:1; and the mass ratio of toluene to concentrated nitric acid is 1:8;

[0065] After the oxidation reaction was completed (HPLC detection showed that the reaction of 1,3,5-trichloro-2-(trichloromethyl)benzene was complete), the temperature of the oxidation reaction system was lowered to 20-30℃, and 430g of crude product was obtained by filtration.

[0066] 1200g of 10% sodium hydroxide aqueous solution was added to the crude product, followed by two washings with methyl tert-butyl ether to obtain an aqueous phase. 237mL of methyl tert-butyl ether was used each time. The pH of the aqueous phase was adjusted to 1.0 with hydrochloric acid to precipitate crystals. After filtration and drying, 382.4g of the second product was obtained.

[0067] Figure 1 The 1H NMR spectrum of the second product confirms that the second product is 2,4,6-trichlorobenzoic acid; the HPLC purity of 2,4,6-trichlorobenzoic acid is 99.3%, and the total molar yield of the two-step reaction is 84.8%.

[0068] Example 2

[0069] The difference between this embodiment and Embodiment 1 is that 1.84g of MoCl5 in step 1 is replaced with 5.52g of MoCl5, so that the mass ratio of toluene to MoCl5 is 1:0.03; the other conditions are the same as in Embodiment 1.

[0070] In this example, 395.0 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.4%, and the total molar yield was 87.6%.

[0071] Example 3

[0072] The difference between this embodiment and Embodiment 1 is that the 1.84g MoCl5 in step 1 is replaced with 9.2g MoCl5, that is, the mass ratio of toluene to MoCl5 is 1:0.05; the other conditions are the same as in Embodiment 1.

[0073] In this example, 407.6 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.6%, and the total molar yield was 90.4%.

[0074] Example 4

[0075] The difference between this embodiment and Embodiment 1 is that 1.84g MoCl5 in step 1 is replaced with 1.84g MoO2, that is, the mass ratio of toluene to MoO2 is 1:0.01; the other conditions are the same as in Embodiment 1.

[0076] In this example, 365.8g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.3%, and the total molar yield was 81.1%.

[0077] Example 5

[0078] The difference between this embodiment and Embodiment 1 is that 1.84g MoCl5 in step 1 is replaced with 1.84g MoO3, that is, the mass ratio of toluene to MoO3 is 1:0.01; the other conditions are the same as in Embodiment 1.

[0079] In this example, 367.5g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.3%, and the total molar yield was 81.5%.

[0080] Example 6

[0081] The difference between this embodiment and Embodiment 1 is that the 185g water and 1474g concentrated nitric acid in step 2 are replaced with 221g water and 1566g concentrated nitric acid, that is, the mass ratio of concentrated nitric acid to water is 7.09:1; the other conditions are the same as in Embodiment 1.

[0082] In this example, 392.3g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.4%, and the total molar yield was 87.0%.

[0083] Example 7

[0084] The difference between this embodiment and Embodiment 1 is that concentrated nitric acid is replaced with concentrated sulfuric acid in step 2; the other conditions are the same as in Embodiment 1.

[0085] In this example, 368.9 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.3%, and the total molar yield was 81.8%.

[0086] Example 8

[0087] The difference between this embodiment and Embodiment 1 is that 1.84g of MoCl5 in step 1 is replaced with 9.2g of MoCl5; that is, the mass ratio of toluene to MoCl5 is 1:0.05; and 185g of water and 1474g of concentrated nitric acid in step 2 are replaced with 221g of water and 1566g of concentrated nitric acid, that is, the mass ratio of concentrated nitric acid to water is 7.09:1; the other conditions are the same as in Embodiment 1.

[0088] In this example, 418.0 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.6%, and the total molar yield was 92.7%.

[0089] Example 9

[0090] The difference between this embodiment and Embodiment 1 is that the concentrated nitric acid in step 2 is recovered and reused; the other conditions are the same as in Embodiment 1.

[0091] In this example, 370.2 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.3%, and the total molar yield was 82.1%.

[0092] Example 10

[0093] The difference between this embodiment and Example 1 is that the chlorine gas introduction rate in step 1 is adjusted to 5 g / min, the chlorination reaction temperature is adjusted to 68°C, the distillation pressure is 3 MPa, and the temperature is 100°C; the amount of concentrated nitric acid in step 2) is replaced with 1850 g, so that the mass ratio of toluene to concentrated nitric acid is 1:10, the reaction temperature is controlled at 110°C, the addition rate of 1,3,5-trichloro-2-(trichloromethyl)benzene is adjusted to 3 g / min, and the dissolved crude product is washed with diethyl ether; the remaining conditions are the same as in Example 1.

[0094] In this example, 388.7g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.4%, and the total molar yield was 86.2%.

[0095] Example 11

[0096] The difference between this embodiment and Embodiment 1 is that the chlorine gas introduction rate in step 1 is adjusted to 15 g / min; the other conditions are the same as in Embodiment 1.

[0097] In this example, 367.5g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.0%, and the total molar yield was 81.5%.

[0098] Example 12

[0099] The difference between this embodiment and Example 1 is that the amount of chlorination catalyst in step 1 is adjusted to 18.4g, that is, the mass ratio of toluene to chlorination catalyst is 1:0.1; the other conditions are the same as in Example 1.

[0100] In this example, 372.5g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.0%, and the total molar yield was 82.6%.

[0101] Example 13

[0102] The difference between this embodiment and Embodiment 1 is that the temperature of the chlorination reaction in step 1 is adjusted to 40°C; the other conditions are the same as in Embodiment 1.

[0103] In this example, 365.7g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.2%, and the total molar yield was 81.1%.

[0104] Example 14

[0105] The difference between this embodiment and Embodiment 1 is that the temperature of the chlorination reaction in step 1 is adjusted to 80°C; the other conditions are the same as in Embodiment 1.

[0106] In this example, 368.4 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.0%, and the total molar yield was 81.7%.

[0107] Example 15

[0108] The difference between this embodiment and Embodiment 1 is that the temperature of the distillation process in step 1 is adjusted to 80°C; the other conditions are the same as in Embodiment 1.

[0109] In this example, 377.42 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.3%, and the total molar yield was 83.7%.

[0110] Example 16

[0111] The difference between this embodiment and Embodiment 1 is that the amount of water in step 2 is adjusted to 295g and concentrated nitric acid to 1474g, that is, the mass ratio of oxidant to water is 5:1; the other conditions are the same as in Embodiment 1.

[0112] In this example, 363.4 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.0%, and the total molar yield was 80.6%.

[0113] Example 17

[0114] The difference between this embodiment and Embodiment 1 is that the amount of concentrated nitric acid used in step 2 is adjusted to 2220g, that is, the mass ratio of toluene to concentrated nitric acid is 1:12; the other conditions are the same as in Embodiment 1.

[0115] In this example, 367.0 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.0%, and the total molar yield was 81.4%.

[0116] Example 18

[0117] The difference between this embodiment and Embodiment 1 is that the temperature of the oxidation reaction in step 2 is controlled at 130°C; the other conditions are the same as in Embodiment 1.

[0118] In this example, 370.7g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.2%, and the total molar yield was 82.2%.

[0119] Example 19

[0120] The difference between this embodiment and Example 1 is that the addition rate of 1,3,5-trichloro-2-(trichloromethyl)benzene in step 2 is adjusted to 8 g / min; the other conditions are the same as in Example 1.

[0121] In this example, 368.9 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.1%, and the total molar yield was 81.8%.

[0122] Example 20

[0123] The difference between this embodiment and Example 1 lies in the purification method of the crude product after the oxidation reaction. Specifically, the crude product is mixed with water at a mass ratio of 1:2, the pH is adjusted to 10 with 40% sodium hydroxide, activated carbon is added at a mass ratio of crude product to activated carbon of 1:0.01, the temperature is raised to 70°C and maintained for 2 hours, and the activated carbon is removed by hot filtration; the temperature is lowered to 50°C, and the pH is acidified to 1 with concentrated industrial hydrochloric acid, followed by cooling, filtration, and drying.

[0124] Glacial acetic acid, water, and activated carbon were added to the dried product, the temperature was raised to 90°C and maintained for 1 hour, and the product was obtained by hot filtration and cooling crystallization. The mass ratio of crude product, glacial acetic acid, water, and activated carbon was 1:1:1:0.1, and the other conditions were the same as in Example 1.

[0125] In this example, 290.0 g of the second product was obtained. The ¹H NMR spectrum of the second product was basically consistent with the peak position and intensity of the second product in Example 1, which proved that the second product was 2,4,6-trichlorobenzoic acid. The HPLC purity of 2,4,6-trichlorobenzoic acid was 99.6%, and the total molar yield was 64.3%.

[0126] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention have been clearly and completely described above in conjunction with specific embodiments. The described embodiments are only a part of the embodiments of this invention, not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

Claims

1. A method for preparing 2,4,6-trichlorobenzoic acid, characterized in that, include: 1) Chlorine gas is introduced into a system comprising toluene and a chlorination catalyst to produce chlorination reaction, yielding 1,3,5-trichloro-2-(trichloromethyl)benzene; the chlorination catalyst comprises at least one of MoO2, MoO3, and MoCl5; the chlorine gas introduction rate is 5-10 g / min; the chlorination reaction temperature is 50-70℃; 2) Add an oxidant to water, then add the 1,3,5-trichloro-2-(trichloromethyl)benzene to undergo an oxidation reaction to obtain 2,4,6-trichlorobenzoic acid; the oxidant includes at least one of concentrated sulfuric acid and concentrated nitric acid; the mass ratio of the oxidant to the water is (6-9):1; the temperature of the oxidation reaction is 110-120℃; After the oxidation reaction is completed, the oxidation reaction system is cooled to 20-30℃, and then the oxidation reaction system is filtered to obtain the crude product. An aqueous solution of sodium hydroxide was added to the crude product, followed by washing with an organic solvent to obtain an aqueous phase. The aqueous phase was then filtered, and the pH of the aqueous phase was adjusted to 1.0 to obtain the 1,3,5-trichloro-2-(trichloromethyl)benzene.

2. The preparation method according to claim 1, characterized in that, The mass ratio of toluene to the chlorination catalyst is 1:(0.01-0.08).

3. The preparation method according to claim 1 or 2, characterized in that, After the chlorination reaction is completed, the pH of the chlorination reaction system is adjusted to 8-9, and then the system is washed with water and distilled to obtain the 1,3,5-trichloro-2-(trichloromethyl)benzene. The distillation process is carried out at a pressure of 3-8 MPa and a temperature of 90-100℃.

4. The preparation method according to claim 1, characterized in that, The mass ratio of toluene to the oxidant is 1:(6-10).

5. The preparation method according to claim 1 or 4, characterized in that, The addition rate of the 1,3,5-trichloro-2-(trichloromethyl)benzene is 3-6 g / min.

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