Preparation method of high-yield 4-chlorophthalic acid monosodium salt

Abstract

The invention relates to the technical field of organic synthesis, and provides a high-yield preparation method of 4-chlorophthalic acid monosodium salt, which comprises the following steps: mixing phthalic anhydride, sodium hydroxide, a solvent and a catalyst to obtain a reaction liquid; introducing chlorine gas into the reaction liquid to perform chlorination reaction, performing reduced pressure distillation and cooling, performing solid-liquid separation after the product is fully crystallized and separated out to obtain a 4-chlorophthalic acid monosodium salt crude product, and then performing refining treatment to obtain the 4-chlorophthalic acid monosodium salt; wherein the solvent comprises sulfolane, tetrahydrofuran and water. According to the technical scheme, the problem of low yield of the 4-chlorophthalic acid monosodium salt in the prior art is solved.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for preparing a high-yield monosodium 4-chlorophthalic acid salt. Background Technology

[0002] Sodium 4-chlorophthalate, as an important fine chemical intermediate and key raw material, has a wide range of applications and significant implications in the fields of pharmaceuticals, pesticides, dyes, and polymer materials. In particular, it serves as an indispensable core framework in the synthesis of broad-spectrum antibiotics such as chloramphenicol and chlorzoxazone, directly affecting the purity and production efficiency of the final product. At the same time, in the preparation of functional dyes, its unique halobenzene ring structure can effectively regulate the photoelectric properties of the molecule, giving the dyes superior color and fastness.

[0003] However, in existing technologies, the yield of monosodium 4-chlorophthalate is generally low, which not only wastes raw materials but also directly increases production costs in downstream high-end applications. Therefore, in order to meet the growing market demand for high-quality, low-cost intermediates, it is urgent to develop a method for preparing monosodium 4-chlorophthalate with a high yield. Summary of the Invention

[0004] This invention proposes a method for preparing monosodium 4-chlorophthalic acid with high yield, which solves the problem of low yield of monosodium 4-chlorophthalic acid in related technologies.

[0005] The technical solution of the present invention is as follows: This invention proposes a method for preparing high-yield monosodium 4-chlorophthalic acid, comprising the following steps: S1. Phthalic anhydride, sodium hydroxide, solvent and catalyst are mixed to obtain a reaction solution; S2. After chlorination reaction by introducing chlorine gas into the reaction solution, the solution is distilled under reduced pressure and cooled. After the product has fully crystallized out, solid-liquid separation is performed to obtain crude monosodium 4-chlorophthalic acid salt. S3. The crude product of 4-chlorophthalic acid monosodium salt is purified to obtain 4-chlorophthalic acid monosodium salt. The solvents include sulfolane, tetrahydrofuran, and water.

[0006] As a further technical solution, the vacuum distillation is carried out at a vacuum level of 0.08~0.09MPa, a temperature of 40~60℃, and a time of 1~2h.

[0007] As a further technical solution, the volume ratio of sulfolane, tetrahydrofuran and water in the solvent is 2~4:7:9.

[0008] In the high-yield preparation method of monosodium 4-chlorophthalate of this invention, the yield of monosodium 4-chlorophthalate can be effectively improved by limiting the volume ratio of sulfolane, tetrahydrofuran, and water in the solvent to 2~4:7:9. If the volume ratio of sulfolane, tetrahydrofuran, and water in the solvent is less than 2~4:7:9, the solubilizing effect of sulfolane is insufficient, leading to premature crystallization and precipitation of monosodium 4-chlorophthalate during the reaction, which encapsulates the raw materials and reduces the yield. If the volume ratio of sulfolane, tetrahydrofuran, and water in the solvent is greater than 2~4:7:9, the system viscosity is too high, which inhibits the mass transfer efficiency. When the volume ratio of sulfolane, tetrahydrofuran, and water in the solvent is 2~4:7:9, the three components work synergistically to ensure the efficient and complete chlorination reaction, thereby further improving the yield of monosodium 4-chlorophthalate.

[0009] As a further technical solution, in step S3, the purification process involves mixing crude 4-chlorophthalic acid monosodium salt with ethanol until completely dissolved, adding isopropanol, cooling and crystallizing, and then performing solid-liquid separation to obtain 4-chlorophthalic acid monosodium salt.

[0010] In the high-yield preparation method of monosodium 4-chlorophthalate of this invention, a purification process combining ethanol and isopropanol is employed. By constructing a solvent-antisolvent system, the purity and yield of the product are synergistically improved. Ethanol, as a good solvent, effectively dissolves monosodium 4-chlorophthalate in the crude product, while retaining residual polyethylene glycol catalyst, sulfolane, and other organic impurities in the solution. The subsequently added isopropanol, as an antisolvent, significantly reduces the solubility of monosodium 4-chlorophthalate by lowering the system polarity, promoting the selective precipitation of high-purity crystals. This process effectively separates organic impurities from the product through solubility differences and reduces the residual loss of the target product in the mother liquor through controlled crystallization, thus ensuring the final yield of monosodium 4-chlorophthalate while achieving efficient purification.

[0011] As a further technical solution, the volume ratio of isopropanol to ethanol is 3~5:1.

[0012] As a further technical solution, the mixing temperature is 50-60°C.

[0013] As a further technical solution, the total amount of ethanol and isopropanol added is 1200-1500 parts by weight.

[0014] As a further technical solution, the catalyst is polyethylene glycol.

[0015] In the high-yield preparation method of monosodium 4-chlorophthalic acid salt of this invention, polyethylene glycol (PEG) is selected as a phase transfer catalyst. Its mechanism of action lies in the fact that the ether oxygen atoms in the PEG molecular chain can chelate with sodium ions to form a stable complex structure, thereby transferring the monosodium phthalic acid anion from the aqueous phase into the organic phase. This significantly increases the contact probability and reaction efficiency with hydrophobic chlorine molecules. This process effectively solves the mass transfer limitation problem caused by phase separation in traditional aqueous chlorination reactions, achieving highly efficient chlorination in a homogeneous reaction environment. Compared with traditional quaternary ammonium salt phase transfer catalysts, PEG has significant advantages such as low cost, stable chemical properties, and environmental friendliness, thus ensuring high yield while also possessing good industrial application prospects.

[0016] As a further technical solution, the number average molecular weight of the polyethylene glycol is 400-800, preferably 600.

[0017] As a further technical solution, by weight, the phthalic anhydride is 95-105 parts, the sodium hydroxide is 40-50 parts, the solvent is 400-450 parts, and the catalyst is 8-10 parts.

[0018] As a further technical solution, in step S2, the flow rate of the chlorine gas is 0.15 to 0.25 L / min.

[0019] As a further technical solution, in step S2, the chlorination reaction is carried out at a temperature of 35~45℃, a pH value of 4~6, and a time of 3~6h.

[0020] The working principle and beneficial effects of this invention are as follows: In this invention, the ternary composite solvent system of sulfolane, tetrahydrofuran, and water effectively overcomes the technical bottlenecks of low mass transfer efficiency and easy product precipitation encapsulation of raw materials in traditional aqueous chlorination reactions through the synergistic effect of each component. Tetrahydrofuran, as an excellent co-solvent, significantly improves the solubility and dispersibility of chlorine gas in the reaction system and the uniformity of the reaction. Sulfolane, with its ability to dissolve organic salts, effectively maintains the solubility of 4-chlorophthalic acid monosodium salt in the reaction solution, avoiding reaction equilibrium inhibition caused by premature crystallization of the product. This solvent combination ensures that the chlorination reaction can proceed continuously and efficiently, thereby significantly improving the final yield of 4-chlorophthalic acid monosodium salt. Detailed Implementation

[0021] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0022] Example 1 A method for preparing a high-yield monosodium 4-chlorophthalic acid salt includes the following steps: S1. Mix 95g phthalic anhydride, 40g sodium hydroxide, 400g solvent and 8g polyethylene glycol (PEG600) to obtain a reaction solution; wherein the solvent is composed of sulfolane, tetrahydrofuran and water in a volume ratio of 2:7:9. S2. Chlorine gas was added to the reaction solution at a rate of 0.2 L / min, and the temperature was maintained at 40 °C. During the reaction, the pH value was adjusted to 5 using a 35 wt% NaOH aqueous solution. After 5 h of chlorination reaction, the solution was distilled under reduced pressure at 0.09 MPa and 50 °C for 1.5 h to remove water and tetrahydrofuran. After cooling, the product was allowed to crystallize and precipitate. The solid and liquid were then separated by centrifugation to obtain crude monosodium 4-chlorophthalic acid salt. S3. Crude monosodium 4-chlorophthalate was added to ethanol and mixed at 55°C until completely dissolved. Isopropanol was then added, and after cooling and crystallization, solid-liquid separation was performed to obtain monosodium 4-chlorophthalate. The total amount of ethanol and isopropanol added was 1200g, and the volume ratio of isopropanol to ethanol was 3:1. In this example, 138.04g of monosodium 4-chlorophthalate was obtained, with a yield of 96.7% and a purity of 84.1%.

[0023] Example 2 A method for preparing a high-yield monosodium 4-chlorophthalic acid salt includes the following steps: S1. Mix 100g phthalic anhydride, 45g sodium hydroxide, 420g solvent and 9g polyethylene glycol (PEG600) to obtain a reaction solution; wherein the solvent is composed of sulfolane, tetrahydrofuran and water in a volume ratio of 2:7:9. S2. Chlorine gas was added to the reaction solution at a rate of 0.2 L / min, and the temperature was maintained at 40 °C. During the reaction, the pH value was adjusted to 5 using a 35 wt% NaOH aqueous solution. After 5 h of chlorination reaction, the solution was distilled under reduced pressure at 0.09 MPa and 50 °C for 1.5 h to remove water and tetrahydrofuran. After cooling, the product was allowed to crystallize and precipitate. The solid and liquid were then separated by centrifugation to obtain crude monosodium 4-chlorophthalic acid salt. S3. Crude monosodium 4-chlorophthalic acid was added to ethanol and mixed at 55°C until completely dissolved. Isopropanol was then added, and after cooling and crystallization, solid-liquid separation was performed to obtain monosodium 4-chlorophthalic acid. The total amount of ethanol and isopropanol added was 1400g, and the volume ratio of isopropanol to ethanol was 3:1. In this example, 147.40g of monosodium 4-chlorophthalic acid was obtained, with a yield of 98.1% and a purity of 84.8%.

[0024] Example 3 A method for preparing a high-yield monosodium 4-chlorophthalic acid salt includes the following steps: S1. Mix 105g phthalic anhydride, 50g sodium hydroxide, 450g solvent and 10g polyethylene glycol (PEG600) to obtain a reaction solution; wherein the solvent is composed of sulfolane, tetrahydrofuran and water in a volume ratio of 2:7:9. S2. Chlorine gas was added to the reaction solution at a rate of 0.2 L / min, and the temperature was maintained at 40 °C. During the reaction, the pH value was adjusted to 5 using a 35 wt% NaOH aqueous solution. After 5 h of chlorination reaction, the solution was distilled under reduced pressure at 0.09 MPa and 50 °C for 1.5 h to remove water and tetrahydrofuran. After cooling, the product was allowed to crystallize and precipitate. The solid and liquid were then separated by centrifugation to obtain crude monosodium 4-chlorophthalic acid salt. S3. Crude monosodium 4-chlorophthalate was added to ethanol and mixed at 55°C until completely dissolved. Isopropanol was then added, and after cooling and crystallization, solid-liquid separation was performed to obtain monosodium 4-chlorophthalate. The total amount of ethanol and isopropanol added was 1500g, and the volume ratio of isopropanol to ethanol was 3:1. In this example, 153.67g of monosodium 4-chlorophthalate was obtained, with a yield of 97.4% and a purity of 84.4%.

[0025] Example 4 Compared with Example 2, the only difference in Example 4 is that in step S1 of this example, the solvent is composed of sulfolane, tetrahydrofuran and water in a volume ratio of 3:7:9. In this example, 148.31g of monosodium 4-chlorophthalic acid was obtained, with a yield of 98.7% and a purity of 85.1%.

[0026] Example 5 Compared with Example 2, the only difference in Example 5 is that in step S1 of this example, the solvent is composed of sulfolane, tetrahydrofuran and water in a volume ratio of 4:7:9. In this example, 146.95g of monosodium 4-chlorophthalic acid was obtained, with a yield of 97.8% and a purity of 84.6%.

[0027] Example 6 Compared with Example 2, the only difference in Example 6 is that in step S3 of this example, the volume ratio of isopropanol to ethanol is 4:1. In this example, 148.00g of 4-chlorophthalic acid monosodium salt was obtained, with a yield of 98.5% and a purity of 87.0%.

[0028] Example 7 Compared with Example 2, the only difference in Example 7 is that in step S3 of this example, the volume ratio of isopropanol to ethanol is 5:1. In this example, 147.55g of 4-chlorophthalic acid monosodium salt was obtained, with a yield of 98.2% and a purity of 85.4%.

[0029] Comparative Example 1 Compared with Example 2, the only difference in Comparative Example 1 is that in step S1 of this Comparative Example, the solvent is composed of sulfolane and water in a volume ratio of 4:9. In this Comparative Example, 141.84 g of monosodium 4-chlorophthalic acid was obtained, with a yield of 94.4% and a purity of 83.7%.

[0030] Comparative Example 2 Compared with Example 2, the only difference in Comparative Example 2 is that in step S1 of this Comparative Example, the solvent is composed of tetrahydrofuran and water in a volume ratio of 7:9. In this Comparative Example, 140.94 g of monosodium 4-chlorophthalic acid was obtained, with a yield of 93.8% and a purity of 83.5%.

[0031] Comparative Example 3 Compared with Example 2, the only difference in Comparative Example 3 is that in step S1 of this Comparative Example, the solvent is only water. In this Comparative Example, 139.14 g of 4-chlorophthalic acid monosodium salt was obtained, with a yield of 92.6% and a purity of 81.2%.

[0032] The comparison between Examples 1-7 and Comparative Examples 1-3 shows that in the preparation method of the high-yield monosodium 4-chlorophthalic acid salt of the present invention, when the solvent is composed of sulfolane, tetrahydrofuran and water, the yield of monosodium 4-chlorophthalic acid salt can be significantly improved.

[0033] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A process for the preparation of high yield 4-chlorophthalic acid monosodium salt, characterized by, The method comprises the following steps: S1, mixing phthalic anhydride, sodium hydroxide, a solvent and a catalyst to obtain a reaction solution; S2, after chlorine is introduced into the reaction solution to perform a chlorination reaction, the reaction solution is distilled under reduced pressure and cooled, and after the product is fully crystallized and separated out, solid-liquid separation is performed to obtain 4-chlorophthalic acid monosodium salt crude product; S3, the 4-chlorophthalic acid monosodium salt crude product is refined to obtain 4-chlorophthalic acid monosodium salt; The solvent comprises sulfolane, tetrahydrofuran and water.

2. The method for preparing high yield 4-chlorophthalic acid monosodium salt according to claim 1, characterized in that, The volume ratio of sulfolane, tetrahydrofuran and water in the solvent is 2-4:7:

9.

3. The method for preparing a high-yield monosodium 4-chlorophthalic acid salt according to claim 1, characterized in that, In step S3, the refining treatment is that the 4-chlorophthalic acid monosodium salt crude product and ethanol are mixed until completely dissolved, then isopropyl alcohol is added, and after cooling and crystallization, solid-liquid separation is performed to obtain 4-chlorophthalic acid monosodium salt.

4. The method for preparing a high-yield monosodium 4-chlorophthalic acid salt according to claim 3, characterized in that, The volume ratio of isopropyl alcohol and ethanol is 3-5:

1.

5. The method for preparing a high-yield monosodium 4-chlorophthalic acid salt according to claim 3, characterized in that, The temperature of the mixing is 50-60℃.

6. The method for preparing a high-yield monosodium 4-chlorophthalic acid salt according to claim 1, characterized in that, The catalyst is polyethylene glycol.

7. The process for preparing high yield 4-chlorophthalic acid monosodium salt according to claim 6, characterized by, The number average molecular weight of the polyethylene glycol is 400-800.

8. The process for preparing high yield 4-chlorophthalic acid monosodium salt according to claim 1, characterized in that, In terms of weight parts, the phthalic anhydride is 95-105 parts, the sodium hydroxide is 40-50 parts, the solvent is 400-450 parts, and the catalyst is 8-10 parts.

9. The method for preparing a high-yield monosodium 4-chlorophthalic acid salt according to claim 1, characterized in that, In step S2, the flow rate of the chlorine introduced is 0.15-0.25 L / min.

10. The process for preparing high yield 4-chlorophthalic acid monosodium salt according to claim 1, characterized in that, In step S2, the temperature of the chlorination reaction is 35-45℃, the pH value is 4-6, and the time is 3-6 h.