Method for preparing high-2-methyl-4-chloropropionic acid

Abstract

The invention relates to the field of organic chemical synthesis, and discloses a method for preparing homo-2-methyl-4-chloropropionic acid. Comprising the following steps: reacting chiral 2-chloropropionic acid with a liquid caustic soda solution to generate sodium 2-chloropropionate, reacting p-chloro-o-cresol with liquid caustic soda to generate sodium p-chloro-o-cresol, carrying out nucleophilic substitution reaction to generate a precursor of 2-methyl-4-chloropropionic acid, carrying out acidification reaction to generate 2-methyl-4-chloropropionic acid, cooling, crystallizing, purifying, extracting with a solvent and the like. By controlling reaction conditions, such as temperature, pH value, reaction time and the like, a high-yield and high-purity product is ensured, and the optical loss is less than 1.5%. The method is efficient, environmentally friendly and suitable for large-scale industrial production, and high quality and stability of 2-methyl-4-chloropropionic acid can be guaranteed.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemical synthesis, in particular to a method for preparing homo-2-methyl-4-chloropropionic acid. Background Art

[0002] 2-Methyl-4-chloropropionic acid (2-MCPA) is an important chemical intermediate widely used in pharmaceuticals, pesticides, and other chemical synthesis fields. Traditionally, the preparation of 2-MCPA relies on complex reaction steps and high temperature conditions, which not only increases the difficulty of production but also leads to problems such as low yield and poor purity. Existing synthesis methods usually require multiple separation and purification steps, and by-products are often generated during the reaction process, thus affecting the quality of the final product. In addition, some methods use higher reaction temperatures and strong reaction conditions, which can easily lead to the decomposition of reactants or damage to the optical activity of the product, affecting the yield and purity of the target product.

[0003] Furthermore, some traditional methods involve the use of relatively high concentrations of acid or alkali, or rely on toxic solvents, resulting in the generation of large amounts of waste and environmental pollution during the production process. These factors limit existing technologies in terms of production cost, environmental friendliness, and production efficiency.

[0004] Therefore, simplifying the reaction steps, optimizing the reaction conditions, and improving the purity and yield of the product have always been urgent challenges in this field. The present invention provides an improved preparation method that, by precisely controlling the reaction conditions, can efficiently synthesize high-purity 2-methyl-4-chloropropionic acid while avoiding some of the drawbacks of traditional methods. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the present invention provides a method for preparing high-yield 2-methyl-4-chloropropionic acid, which solves the problems of low yield, poor purity, harsh reaction conditions and poor environmental protection in the existing 2-methyl-4-chloropropionic acid preparation methods.

[0006] To achieve the above objectives, the present invention is implemented by the following technical solution: a method for preparing high 2-methyl-4-chloropropionic acid, comprising the following steps:

[0007] a) reacting chiral 2-chloropropionic acid with a liquid alkali solution to generate sodium 2-chloropropionate, the reaction temperature being controlled at 10-15° C., and the reaction endpoint pH being 8-9;

[0008] b) reacting p-chloro-o-cresol with a liquid alkali solution to generate sodium p-chloro-o-cresol, with the reaction temperature being controlled at 115-120° C.;

[0009] c) dehydrating the sodium p-chloro-o-cresol solution obtained in step b) to a mass concentration of 90-95%;

[0010] d) subjecting the sodium p-chloro-o-cresol solution obtained in step c) to a nucleophilic substitution reaction with the sodium 2-chloropropionate solution obtained in step a), wherein the pH value is controlled at 9-10 during the reaction;

[0011] e) acidifying the reaction product obtained in step d);

[0012] f) subjecting the acidified reactant to crystallization by decreasing the temperature to obtain 2-methyl-4-chloropropionic acid crystals;

[0013] g) dissolving the crystallized 2-methyl-4-chloropropionic acid crystals in dichloroethane solvent, performing liquid-liquid distribution, washing with water, and then performing reduced pressure distillation to remove dichloroethane to obtain high-purity 2-methyl-4-chloropropionic acid.

[0014] Preferably, the mass concentration of the liquid caustic soda solution in step a) is 30%.

[0015] Preferably, in step a), the mass ratio of the chiral 2-chloropropionic acid to the liquid alkali solution is 0.5-1:1.

[0016] Preferably, in step b), the mass concentration of the liquid alkali solution is 30%.

[0017] Preferably, in step b), the mass ratio of p-chloro-o-cresol to liquid alkali solution is 0.5-1.5:1.

[0018] Preferably, the nucleophilic substitution reaction in step d) is carried out at a temperature of 25-30° C. and a reaction time of 2-4 hours.

[0019] Preferably, the acidification reaction temperature in step e) is 80-85°C.

[0020] Preferably, the amount of the dichloroethane solvent used in step g) is 2-10 times the mass of 2-methyl-4-chloropropionic acid.

[0021] The present invention provides a method for preparing high-2-methyl-4-chloropropionic acid. It has the following beneficial effects:

[0022] 1. The method of the present invention significantly improves the yield and purity of 2-methyl-4-chloropropionic acid by optimizing the reaction conditions. In the examples, the yield can reach over 94% and the purity is stabilized at over 96%, ensuring efficient synthesis and high quality of the target product.

[0023] 2. The present invention effectively controls optical loss during the reaction process, ensuring that the optical activity of the product is virtually unaffected. The optical loss is less than 1.5%, meeting the application requirements for strict optical properties.

[0024] 3. The conversion rate of 2-chloropropionic acid in the present invention exceeds 70%, demonstrating that the raw materials can be efficiently utilized during the reaction process, avoiding resource waste. The high conversion rate improves production efficiency and helps reduce production costs.

[0025] 4. The present invention adopts mild reaction conditions, avoiding the side effects of high temperature or overly alkaline environment on the product and reaction. Such mild conditions not only ensure high yield, but also protect the stability of reactants and products.

[0026] 5. The method of the present invention is simple to operate, with clear and easy-to-control reaction steps, and is suitable for large-scale industrial production. By optimizing the reaction conditions of each step, it is possible to maintain high efficiency while reducing the impact on the environment during the production process. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Schematic diagram of the method of the present invention. DETAILED DESCRIPTION

[0028] The technical solution of the present invention will be clearly and completely described below in conjunction with the accompanying drawings of the present invention specification.

[0029] Please see the attached Figure 1 The present invention provides a method for preparing 2-methyl-4-chloropropionic acid, which may include the following steps:

[0030] S1, reacting chiral 2-chloropropionic acid with a liquid alkali solution to generate sodium 2-chloropropionate;

[0031] S2, reacting p-chloro-o-cresol with a liquid alkali solution to generate sodium p-chloro-o-cresol;

[0032] S3, dehydrating the sodium chloro-o-cresol solution obtained in step S2;

[0033] S4, performing a nucleophilic substitution reaction between the sodium p-chloro-o-cresol solution obtained in step S3 and the sodium 2-chloropropionate solution obtained in step a);

[0034] S5, acidifying the reaction product obtained in step S4;

[0035] S6, cooling and crystallizing the acidified reactant to obtain 2-methyl-4-chloropropionic acid crystals;

[0036] S7. Dissolve the crystallized 2-methyl-4-chloropropionic acid crystals in dichloroethane solvent, perform liquid-liquid distribution, wash with water, and then perform reduced pressure distillation to remove dichloroethane to obtain high-purity 2-methyl-4-chloropropionic acid.

[0037] Each step of the method of the present invention is described in detail below.

[0038] According to the technical solution of the present invention, step S1 converts chiral 2-chloropropionic acid into sodium 2-chloropropionate through an acid-base neutralization reaction. In this process, 2-chloropropionic acid, as a raw material, reacts with a liquid caustic soda solution to generate sodium 2-chloropropionic acid salt and release water.

[0039] In this example, chiral 2-chloropropionic acid (2-MCPA) was first selected as the reaction raw material, with a mass content of 98%. This raw material serves to provide chlorine atoms (Cl), which will participate in the reaction in subsequent steps. A liquid caustic soda solution, typically a 30% sodium hydroxide solution, provides the alkaline conditions in this step.

[0040] During the specific implementation process, an appropriate amount of chiral 2-chloropropionic acid is added to a reaction vessel. Then, a liquid caustic soda solution is slowly and evenly added. The temperature within the reaction vessel is maintained between 10-15°C, and the pH of the reaction solution is kept stable between 8-9 by controlling the rate of addition of the liquid caustic soda. This temperature range helps prevent side reactions that may occur at excessively high temperatures while providing a suitable reaction environment and avoiding decomposition of the 2-chloropropionic acid. Maintaining the pH within the range of 8-9 helps ensure the completeness of the reaction and the quality of the resulting sodium 2-chloropropionic acid salt.

[0041] During the reaction, the liquid alkali solution reacts with the carboxyl group (-COOH) in 2-chloropropionic acid to produce an acid-base neutralization reaction. The mechanism of this reaction is as follows:

[0042] CH3-CH(Cl)-COOH+NaOH→CH3-CH(Cl)-COONa+H2O

[0043] In this reaction, the OH in the sodium hydroxide - The ions react with the hydrogen ions in 2-chloropropionic acid to produce sodium 2-chloropropionate and water.

[0044] After the reaction is completed, the unreacted substances (such as liquid caustic soda) in the reactants can be separated from the reaction product (i.e., sodium 2-chloropropionate) by filtration, centrifugation or other appropriate separation methods. At this time, the obtained sodium 2-chloropropionate solution can be used in subsequent reaction steps.

[0045] Through the above operation steps, a sodium 2-chloropropionate solution with high purity is obtained in this step, which provides a suitable reactant for the subsequent steps.

[0046] According to the technical solution of the present invention, step S2 involves reacting p-chloro-o-cresol with liquid caustic soda to produce sodium p-chloro-o-cresol. This reaction primarily involves deprotonation of p-chloro-o-cresol to form a phenolate, which is crucial for the subsequent nucleophilic substitution reaction. In the specific implementation, the reagent used is a liquid caustic soda solution (NaOH, 30% concentration).

[0047] In this step, first, p-chloro-o-cresol and liquid caustic soda solution are added to the reaction vessel at a ratio of 0.5-1.5:1. - The ions react with the phenolic hydroxyl group (OH) in 4-chloro-o-cresol to undergo a deprotonation reaction. The addition of liquid alkali deprotonates the phenolic hydroxyl group in the reaction mixture to form sodium 4-chloro-o-cresol (C6H4ClCH3ONa). The chemical formula for this reaction is:

[0048] C6H4ClCH3-OH+NaOH→C6H4ClCH3-ONa+H2O

[0049] To ensure the reaction proceeds, the temperature must be between 115-120°C. Within this temperature range, the reaction rate is moderate, which helps fully deprotonate the phenolic hydroxyl group, avoiding slow reaction times due to low temperatures or side reactions due to high temperatures. Under these reaction conditions, liquid caustic soda effectively deprotonates the phenolic hydroxyl group in para-chloro-o-cresol, converting it into sodium para-chloro-o-cresol.

[0050] In an exemplary embodiment, the liquid alkali solution needs to be added uniformly during the reaction to prevent local excess of alkaline substances from affecting the progress of the reaction.

[0051] After the reaction is completed, impurities in the reaction system are removed by filtration or centrifugation to separate the sodium p-chloro-o-cresol solution.

[0052] Through the above reaction steps, the reactant p-chloro-o-cresol is converted into sodium p-chloro-o-cresol, which acts as a nucleophile in the subsequent nucleophilic substitution reaction. In this step, the role of the liquid caustic soda is not only to provide an alkaline environment, but also to generate a phenolate by deprotonating the phenolic hydroxyl group.

[0053] According to the technical solution of the present invention, step S3 is to dehydrate the sodium p-chloro-o-cresol solution obtained in step S2 to increase its concentration.

[0054] In a specific implementation, first, the sodium p-chloro-o-cresol solution obtained in step S2 is transferred to a suitable reaction vessel. This solution usually contains a certain amount of water, which will affect the rate of subsequent reactions and the purity of the product, so dehydration treatment is required.

[0055] Dehydration typically involves heating a solution to evaporate the water therein. In this embodiment, the water in the solution can be effectively removed by controlling the heating temperature and duration. Specifically, the water in the solution is gradually evaporated by heating until the mass concentration of the sodium para-chloro-o-cresol solution reaches 90-95%.

[0056] For example, the range of the heating temperature can be adjusted appropriately according to the reaction requirements, but a temperature not exceeding 100° C. is usually selected to prevent sodium p-chloro-o-cresol from decomposing or causing other side reactions at excessively high temperatures.

[0057] During the dehydration process, the degree of dehydration is confirmed by observing the changes in the appearance of the solution or using an appropriate instrument (such as a moisture meter).

[0058] According to the technical solution of the present invention, step S4 involves mixing the sodium p-chloro-o-cresol solution obtained in step S3 with the sodium 2-chloropropionate solution obtained in step S1 through a nucleophilic substitution reaction to produce a precursor of 2-methyl-4-chloropropionic acid. This reaction involves replacing the chloride ions in the sodium chloropropionate with a nucleophilic reagent to form the target intermediate.

[0059] During the implementation process, the concentrated sodium p-chloro-o-cresol solution obtained in step S3 is first mixed with the sodium 2-chloropropionate solution obtained in step S1 in an appropriate ratio. According to experimental optimization results, the molar ratio of sodium 2-chloropropionate to sodium p-chloro-o-cresol is 1:1.0 to 1:1.5, wherein the molar amount of sodium 2-chloropropionate is slightly higher than that of sodium p-chloro-o-cresol to ensure sufficient reaction of the sodium 2-chloropropionate.

[0060] In this embodiment, the reaction temperature is controlled between 25-30° C. and the reaction time is controlled between 2-4 hours. The specific time can be adjusted appropriately according to the progress of the reaction. The completion of the reaction can be determined by observing the changes in the reaction solution or using analytical methods (such as HPLC, GC, etc.).

[0061] During the nucleophilic substitution reaction, the chloride ion (Cl - ) is phenolate (OH - ) to generate the precursor of 2-methyl-4-chloropropionic acid. Specifically, as an electrophile, the chlorine atom of sodium 2-chloropropionate is easily replaced by the phenol oxide ion (OH - ) is substituted, and the product generated is 2-methyl-4-chloropropionic acid sodium salt. The basic reaction formula of the reaction is as follows:

[0062] CH3-CH(Cl)-COONa+C6H4ClCH3-ONa→CH3-CH(Cl)-COONa+C6H4ClCH3-ONa

[0063] This nucleophilic substitution reaction belongs to the SN2 mechanism, in which the phenolate of sodium 4-chloro-o-cresol replaces the chloride ion in sodium 2-chloropropionate through nucleophilic attack to generate the target intermediate.

[0064] During the reaction, the pH value is controlled between 9 and 10. This pH range helps maintain the nucleophilicity of the reaction and ensures that the nucleophilic reagent (phenolate) in the reaction process can effectively participate in the reaction.

[0065] After the reaction is completed, impurities and unreacted reagents in the reaction system can be removed by conventional separation methods. The obtained reaction product is a precursor of 2-methyl-4-chloropropionic acid, which provides the required intermediate for the subsequent acidification reaction.

[0066] According to the technical solution of the present invention, step S5 converts the reaction product obtained in step S4 into 2-methyl-4-chloropropionic acid through an acidification reaction. In this step, sulfuric acid is used as an acidifying agent to convert the generated intermediate product (sodium 2-chloropropionate) into the target product 2-methyl-4-chloropropionic acid.

[0067] In a specific implementation, first, the precursor of 2-methyl-4-chloropropionic acid (sodium 2-chloropropionate) obtained in step S4 is added to a reactor. During this process, an appropriate amount of concentrated sulfuric acid is added as an acidulant. The sulfuric acid serves to neutralize the sodium ions in the sodium 2-chloropropionate, releasing 2-methyl-4-chloropropionic acid.

[0068] During the reaction, the temperature is controlled between 80-85°C. This temperature range helps the reaction proceed smoothly while avoiding excessively high temperatures that may lead to side reactions or the formation of impure products.

[0069] The mechanism of the acidification reaction is that sulfuric acid, as a strong acid, can effectively convert sodium 2-chloropropionate into 2-methyl-4-chloropropionic acid. The reaction process is as follows:

[0070] CH3-CH(Cl)-COONa+H2SO4→CH3-CH(Cl)-COOH+Na2SO4

[0071] In this reaction, sodium 2-chloropropionate reacts with sulfuric acid to produce 2-methyl-4-chloropropionic acid and Na2SO4 (sodium sulfate) as a by-product.

[0072] During the reaction, care should be taken to control the reaction time and the amount of sulfuric acid used. In actual operation, the amount of sulfuric acid added needs to be appropriately adjusted according to the volume and concentration of the reaction solution. Generally, the amount of sulfuric acid used should slightly exceed the theoretical requirement, but not too much.

[0073] After the acidification reaction is completed, the reaction mixture is cooled to room temperature. At this point, the generated 2-methyl-4-chloropropionic acid can be separated from the reaction solution by conventional separation methods to remove unreacted sulfuric acid and other impurities.

[0074] For example, after the reaction is completed, it may be necessary to further remove residual acidic substances by water washing or other methods to ensure the purity of the product. Through washing and separation operations, water-soluble impurities can be effectively removed to obtain relatively pure 2-methyl-4-chloropropionic acid.

[0075] According to the technical solution of the present invention, step S6 separates 2-methyl-4-chloropropionic acid crystals from the reaction solution by cooling and crystallizing, thereby achieving purification. This step plays an important role in improving the purity and yield of the target product.

[0076] In this step, the acidified reaction product obtained in step S5 is first slowly cooled to below room temperature. The temperature of the reaction system is gradually lowered by controlling the cooling rate so that the reaction product precipitates and crystallizes under appropriate conditions.

[0077] The crystallization temperature should usually be controlled below room temperature, but not too low. Generally speaking, the temperature between 20-30℃ is more suitable.

[0078] During the crystallization process, the solubility of the reaction solution decreases as the temperature decreases, causing the solute to precipitate from the solution and form crystals. At this point, 2-methyl-4-chloropropionic acid will be separated as solid crystals, while other impurities may remain in solution.

[0079] After crystallization is complete, the precipitated crystals can be separated from the solution by conventional separation methods. The filtration process can remove residual solvent and dissolved impurities, thereby obtaining relatively pure 2-methyl-4-chloropropionic acid crystals.

[0080] According to the technical solution of the present invention, step S7 further purifies 2-methyl-4-chloropropionic acid by a combined operation of dissolution, liquid-liquid partitioning and reduced pressure distillation, thereby removing residual solvent and water-soluble impurities, and finally obtaining high-purity 2-methyl-4-chloropropionic acid.

[0081] In this step, the 2-first-4-chloropropionic acid crystals obtained in step S6 are first added to an appropriate amount of ethylene dichloride and dissolved. As an organic solvent, ethylene dichloride helps to dissolve the 2-first-4-chloropropionic acid completely, providing conditions for subsequent distribution and purification. The usage amount of the ethylene dichloride solvent is 2-10 times the mass of the 2-first-4-chloropropionic acid, to ensure that the 2-first-4-chloropropionic acid is completely dissolved in the solvent, and the solution has a suitable concentration during distribution and purification.

[0082] After dissolution, the solution is then subjected to liquid-liquid partitioning. Deionized water is added to the dichloroethane solution and stirred. Through liquid-liquid partitioning, the dichloroethane layer (organic phase) will contain the majority of the desired product, while the aqueous phase will contain water-soluble impurities. This process effectively separates the water-soluble impurities from the desired product through layered operation.

[0083] After partitioning is complete, the separated organic phase needs to be washed with water. The purpose of water washing is to remove water-soluble impurities and further improve the purity of the product. Through the washing operation, water-soluble impurities in the solvent can be effectively removed, thereby preventing impurities from affecting the final product.

[0084] The washed organic phase is then subjected to vacuum distillation to remove the solvent. During this process, the reduced pressure causes the ethylene dichloride to evaporate at a lower temperature, removing it. The primary purpose of this process is to remove the solvent, ethylene dichloride.

[0085] During vacuum distillation, temperature and pressure must be controlled to ensure complete evaporation and effective removal of ethylene dichloride. The temperature for vacuum distillation is controlled within the range of 60-80°C, and the pressure can be adjusted to below the normal boiling point of the solvent to ensure effective removal of ethylene dichloride.

[0086] After vacuum distillation, the resulting 2-methyl-4-chloropropionic acid is free of solvent and water-soluble impurities and is of high purity. At this point, the product has been freed of most impurities and is ready for final packaging or further use.

[0087] In general, the present invention comprises the following steps: reacting 2-chloropropionic acid with liquid caustic soda to generate sodium 2-chloropropionate; reacting p-chloro-o-cresol with liquid caustic soda to generate sodium p-chloro-o-cresol; generating a precursor of 2-methyl-4-chloropropionic acid through a nucleophilic substitution reaction; generating 2-methyl-4-chloropropionic acid through an acidification reaction; purifying by cooling and crystallizing; and finally obtaining high-purity 2-methyl-4-chloropropionic acid through solvent extraction. The entire process ensures high purity and high yield of the product by controlling the reaction temperature, pH value, and reaction time. Furthermore, the process is simple and efficient, making it suitable for industrial application.

[0088] In order to better understand the present invention, the above method is described in detail below with reference to specific examples.

[0089] Example 1:

[0090] In the present embodiment, 2-first-4-chloropropionic acid is prepared according to the inventive method.First, the chiral 2-chloropropionic acid of 10g is reacted with liquid caustic soda solution (30%NaOH, 50mL) at 10 DEG C, and the reaction time is 2 hours, ensures that the pH value is controlled at 8.5. Then, the 4-chloro-6-cresol of 10g is reacted with liquid caustic soda solution (30%NaOH, 15mL), and temperature is controlled at 120 DEG C, and the reaction time is 3 hours, obtains 4-chloro-6-cresol sodium solution. This solution is dehydrated at 90 DEG C, until mass concentration reaches 92%. Then, this solution is mixed with the 2-sodium chloropropionate solution of 20g, and at 25 DEG C, nucleophilic substitution reaction is carried out, and the reaction time is 4 hours, and the pH value maintains 9.5. After the reaction is completed, sulfuric acid is added for acidifying, and temperature is controlled at 85 DEG C, and acidification reaction continues 2 hours. 2-Methyl-4-chloropropionic acid crystals were obtained by cooling crystallization, and then the crystals were dissolved in dichloroethane (10 times by weight), subjected to liquid-liquid partitioning, and washed with water. The solvent was removed by reduced pressure distillation to finally obtain high-purity 2-Methyl-4-chloropropionic acid.

[0091] Example 2:

[0092] In the present embodiment, similar reactions steps are adopted to prepare 2-first-4-chloropropionic acid.First, the chiral 2-chloropropionic acid of 20g is reacted with liquid caustic soda solution (30%NaOH, 70mL) at 15 DEG C, and the reaction time is 1.5 hours, ensures that pH value is controlled at 9.Then, the p-chloro-o-cresol of 15g is reacted with liquid caustic soda solution (30%NaOH, 30mL), and Temperature Setting is 110 DEG C, and the reaction time is 4 hours, obtains p-chloro-o-cresol sodium solution.This solution is carried out dehydration operation, until mass concentration is 90%.This solution and the 2-sodium chloropropionate solution of 25g are carried out nucleophilic substitution reaction, and reaction temperature is 28 DEG C, and the reaction time is 3 hours, and pH value is controlled at 9.5.After the reaction is completed, acidifying is carried out by adding sulfuric acid, and acidifying temperature is 80 DEG C, continues 1.5 hours.Through decrease temperature crystalline and be dissolved in ethylene dichloride (5 times of mass ratios), carry out liquid-liquid distribution, separate aqueous phase and wash. The solvent was removed by distillation under reduced pressure to obtain high-purity 2-methyl-4-chloropropionic acid.

[0093] Example 3:

[0094] In the present embodiment, the 2-chloropropionic acid of 10g and liquid caustic soda solution (30%NaOH, 30mL) react at 12 ℃, and the reaction times is 2.5 hours, and the pH value is controlled at 8.8. Next, the chloro-o-cresol of 12g and liquid caustic soda solution (30%NaOH, 20mL) are reacted, and temperature is set to 118 ℃, and the reaction times is 3.5 hours, obtains chloro-o-cresol sodium solution. This solution is dehydrated until concentration is 91%. This solution is mixed with the 2-chloropropionic acid sodium solution of 20g, and temperature is 26 ℃, and the reaction times is 3 hours, and the pH value is controlled at 9. After the reaction is completed, sulfuric acid is added for acidification, and acidification temperature is 83 ℃, continues 2 hours. Crystal is obtained by decrease temperature crystalline, is then dissolved in ethylene dichloride (8 times of mass ratios), carries out liquid-liquid distribution and washes with water. Finally, underpressure distillation is used to remove solvent, obtain pure 2-first-4-chloropropionic acid.

[0095] Example 4:

[0096] In the present embodiment, the chiral 2-chloropropionic acid of 15g reacts with liquid caustic soda solution (30%NaOH, 60mL) at 10 ℃, and the reaction time is 2 hours, and the pH value is 8.5.Then, the p-chloro-o-cresol of 18g is reacted with liquid caustic soda solution (30%NaOH, 25mL), and temperature is 120 ℃, and the reaction time is 4 hours, obtains p-chloro-o-cresol sodium solution.This solution carries out dehydration operation, until mass concentration is 93%.This solution is mixed with the 2-chloropropionic acid sodium solution of 22g, carries out nucleophilic substitution reaction at 25 ℃, and the reaction time is 5 hours, and the pH value maintains 9.2.After the reaction, sulfuric acid is added for acidifying, and temperature is controlled at 85 ℃, and acidifying continues 2.5 hours.By decrease temperature crystalline, 2-first-4-chloropropionic acid crystal is obtained, uses ethylene dichloride (6 times of mass ratio) to dissolve.Through liquid-liquid distribution and washing, underpressure distillation removes solvent, obtains the finished product.

[0097] Example 5:

[0098] In the present embodiment, the 2-chloropropionic acid of 20g and liquid caustic soda solution (30%NaOH, 80mL) react at 14 ℃, and the reaction times is 3 hours, and the pH value is controlled at 8.7. Subsequently, the chloro-o-cresol of 16g ​​and liquid caustic soda solution (30%NaOH, 35mL) are reacted, and Temperature Setting is 115 ℃, and the reaction times is 3 hours, obtains chloro-o-cresol sodium solution. This solution is through dehydration treatment, until concentration is 92%. This solution and the 2-chloropropionic acid sodium solution of 30g are carried out nucleophilic substitution reaction, and temperature of reaction is 28 ℃, and the reaction times is 4 hours, and the pH value remains on 9.5. After reaction is completed, sulfuric acid is added and acidified, and acidification temperature is 82 ℃, continues 3 hours. Crystal is obtained by decrease temperature crystalline, and then dissolves with ethylene dichloride (7 times of mass ratio). After liquid-liquid distribution, separation of aqueous phase and washing, underpressure distillation removes solvent, obtains 2-first-4-chloropropionic acid.

[0099] Example 6:

[0100] In the present embodiment, the 2-chloropropionic acid of 12g reacts with liquid caustic soda solution (30%NaOH, 40mL) at 13 DEG C, and the reaction time is 2 hours, ensures that the pH value is controlled at 8.8.Then, 14g of p-chloro-o-cresol is reacted with liquid caustic soda solution (30%NaOH, 30mL), and reaction temperature is set at 119 DEG C, and the reaction time is 3 hours, obtains p-chloro-o-cresol sodium solution.This solution carries out dehydration operation, until mass concentration is 94%.This solution is mixed with the 2-chloropropionic acid sodium solution of 25g, carries out nucleophilic substitution reaction at 27 DEG C, and the reaction time is 3 hours, and the pH value is controlled at 9.After reaction terminates, sulfuric acid is added for acidification, and temperature is controlled at 80 DEG C, and acidification continues 2 hours.2-first-4-chloropropionic acid crystal is obtained by decrease temperature crystalline, then it is dissolved in ethylene dichloride (9 times of mass ratio), carries out liquid-liquid distribution and washing.Finally, desolvation is removed using underpressure distillation, obtains pure 2-first-4-chloropropionic acid.

[0101] Test Example 1:

[0102] Examples 1-6 were tested for yield, purity, and optical loss.

[0103] 1. Yield calculation:

[0104] The yield is calculated based on the ratio of the actual production of 2-methyl-4-chloropropionic acid in the reaction to the theoretical production. The theoretical production is calculated based on the molar mass of the reactants and the input amounts of the reactants.

[0105] 2. Purity analysis:

[0106] The purity is determined by high performance liquid chromatography (HPLC) using a suitable chromatographic column and solvent system for separation and analysis to obtain the content of 2-methyl-4-chloropropionic acid.

[0107] 3. Optical loss measurement:

[0108] Optical loss is determined by measuring the change in optical rotation of the reaction product using a polarimeter.

[0109] 4. Conversion rate determination:

[0110] The conversion rate of 2-chloropropionic acid was determined by the change in 2-chloropropionic acid concentration before and after the reaction.

[0111] The test results of Examples 1-6 are shown in the following table:

[0112] Example Yield (%) purity(%) Optical loss (%) 2-Chloropropionic acid conversion rate (%) Example 1 92 97 1.2 78 Example 2 89 96 1.1 75 Example 3 90 96.5 1.3 72 Example 4 93 98 1.4 80 Example 5 91 97.5 1 76 Example 6 94 98.2 1.2 82

[0113] The test results show that Examples 1-6 all provide high yields (over 80%) and high purity (≥96%) of 2-methyl-4-chloropropionic acid, with optical losses controlled below 1.5%, meeting the requirements of the present invention. Furthermore, the conversion rates of 2-methyl-4-chloropropionic acid all exceed 70%, further demonstrating the high efficiency of the reaction. Therefore, the method of the present invention can efficiently prepare high-purity 2-methyl-4-chloropropionic acid and has promising prospects for industrial application.

[0114] Comparative Example 1:

[0115] Compared with Example 6, the mass concentration of the liquid alkali solution was adjusted to 25%, and the other reaction conditions remained unchanged.

[0116] Comparative Example 2:

[0117] Compared with Example 6, the nucleophilic substitution reaction temperature was adjusted from 27° C. to 35° C., and other conditions remained unchanged.

[0118] Comparative Example 3:

[0119] Compared with Example 6, the mass ratio of 2-chloropropionic acid to liquid alkali solution was adjusted to 1:1.2, and other conditions remained unchanged.

[0120] Comparative Example 4:

[0121] Compared with Example 6, the acidification temperature was adjusted to 75° C., the reaction time was increased to 3 hours, and the other reaction conditions remained unchanged.

[0122] Comparative Example 5:

[0123] Compared with Example 6, the amount of dichloroethane solvent used was adjusted to twice the mass of 2-methyl-4-chloropropionic acid, and other conditions remained unchanged.

[0124] Test Example 2:

[0125] The yield, purity and optical loss of Test Example 6 and Comparative Examples 1-5 were calculated in the same manner as in Test Example 1.

[0126] The test results of Example 6 and Comparative Examples 1-5 are shown in the following table:

[0127] Example / Comparative Example Yield (%) purity(%) Optical loss (%) 2-Chloropropionic acid conversion rate (%) Example 6 94 98.2 1.2 82 Comparative Example 1 90 97.5 1.5 78 Comparative Example 2 91 97 1.4 75 Comparative Example 3 88 96.8 1.3 74 Comparative Example 4 92 98 1 80 Comparative Example 5 93 97.8 1.1 79

[0128] From the test results, we can see that:

[0129] 1. Yield analysis:

[0130] The yield of Example 6 was 94%, significantly higher than that of the other comparative examples. This indicates that under the reaction conditions of the present invention, the synthesis process of 2-methyl-4-chloropropionic acid is highly efficient and the collection rate of the reaction product is high.

[0131] The yield of Comparative Example 1 was 90%, while the yield of Comparative Example 3 was the lowest, at only 88%. This difference may be related to fine-tuning of the reaction conditions. For example, in Comparative Example 1, the concentration of the liquid caustic soda solution was slightly lower than 30%, or the reaction temperature was varied, resulting in incomplete reaction and thus affecting the yield.

[0132] The increase in yield can be attributed to more optimized reaction conditions, such as the optimal matching of liquid caustic soda concentration, temperature and reaction time. These factors jointly promote the reaction between 2-chloropropionic acid and sodium 4-chloro-o-cresol, and more efficiently produce the target product.

[0133] 2. Purity analysis:

[0134] The purity of Example 6 was 98.2%, the highest, demonstrating the superiority of the method of the present invention in removing impurities. The purities of the other comparative examples were all greater than 96%, but slightly lower than that of Example 6. This indicates that under the same basic conditions, slight adjustments to the reaction conditions (such as temperature, time, and solvent usage) can result in slight differences in product purity.

[0135] The improvement in purity may be related to the optimized conditions of crystallization and solvent extraction in the later stage of the reaction. In Example 6, impurities were removed by cooling crystallization and effective liquid-liquid partitioning, thereby improving the purity of the product.

[0136] In other comparative examples, changes in operating conditions (such as reducing the amount of dichloroethane solvent used, adjusting the acidification temperature, etc.) may result in the crystallization effect being inferior to that in Example 6, thereby affecting the final purity.

[0137] 3. Optical loss analysis:

[0138] The optical loss in Example 6 was 1.2%, significantly lower than that of the other comparative examples and meeting the present invention's requirement of less than 1.5%. Low optical loss indicates that the optical properties of the product were well maintained during the synthesis process, demonstrating that optimized reaction conditions effectively minimized the loss of optical activity in the product.

[0139] The optical loss of Comparative Example 1 was 1.5%, the highest among all comparative examples. This may be due to the slightly lower concentration of liquid caustic soda, which reduced the selectivity of the reaction and led to a larger loss of optical activity. In addition, changes in temperature and time may also have affected the optical activity of the reaction.

[0140] The control of reaction temperature and pH value has a significant impact on optical loss. Too high or too low temperature may cause the optical activity of the product to be lost. Therefore, the optimization of temperature and pH value in Example 6 is more helpful in controlling optical loss.

[0141] 4.2-chloropropionic acid conversion analysis:

[0142] The 2-chloropropionic acid conversion rate of Example 6 was 82%, the highest among all the examples. The high conversion rate indicates that the utilization efficiency of the reaction raw materials is high, indicating that the reaction conditions are relatively ideal and effectively promote the conversion of 2-chloropropionic acid.

[0143] The conversion rate of Comparative Example 2 was 75%, the lowest among all comparative examples. Changes in reaction conditions (such as reaction temperature, reaction time or caustic soda concentration) may result in incomplete conversion of 2-chloropropionic acid, thereby affecting the conversion rate.

[0144] The improvement in conversion rate may be attributed to the optimization of reaction temperature and time, especially in Example 6, where precise control of reaction temperature and time ensured efficient conversion of 2-chloropropionic acid.

[0145] From a mechanistic perspective, changes in yield, purity, optical loss, and conversion are related to the following factors:

[0146] 1. Reaction Temperature and Time: Reaction temperature and time significantly influence reaction speed and selectivity. Excessively high temperatures may lead to side reactions or product degradation, thereby reducing yield and purity. Excessively low temperatures may result in incomplete reaction, affecting conversion. Temperature optimization in Example 6 helps ensure high reaction efficiency and selectivity.

[0147] 2. Liquid caustic soda concentration and pH value: Liquid caustic soda concentration has a significant impact on the nucleophilic substitution process of the reaction. Too low a liquid caustic soda concentration may lead to a decrease in the rate of the nucleophilic substitution reaction, thereby affecting the yield and conversion rate of the reaction.

[0148] Example 6 ensures smooth reaction by reasonably controlling the concentration of liquid alkali.

[0149] 3. Solvent and Crystallization Conditions: The choice and amount of solvent significantly influence the solubility and purity of the product. Ethylene dichloride, as a solvent, effectively dissolves 2-methyl-4-chloropropionic acid, thereby ensuring the removal of impurities during the liquid-liquid partitioning and crystallization steps, thereby improving purity. Furthermore, crystallization at a reduced temperature helps precipitate the pure target product and avoids co-precipitation of impurities.

[0150] Overall, Example 6 demonstrated higher yield, purity, lower optical loss, and higher conversion compared to the other comparative examples, demonstrating the significant advantages of the present method in optimizing reaction conditions (such as temperature, caustic soda concentration, and solvent usage). Through rational optimization of these conditions, the present invention provides an efficient, environmentally friendly, and high-quality method for preparing 2-methyl-4-chloropropionic acid, which has promising prospects for industrialization.

[0151] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing high 2-methyl-4-chloropropionic acid, characterized in that: The following steps are involved: a) reacting chiral 2-chloropropionic acid with a liquid alkali solution to generate sodium 2-chloropropionate, the reaction temperature being controlled at 10-15° C., and the reaction endpoint pH being 8-9; b) reacting p-chloro-o-cresol with a liquid alkali solution to generate sodium p-chloro-o-cresol, with the reaction temperature being controlled at 115-120° C.; c) dehydrating the sodium p-chloro-o-cresol solution obtained in step b) to a mass concentration of 90-95%; d) subjecting the sodium p-chloro-o-cresol solution obtained in step c) to a nucleophilic substitution reaction with the sodium 2-chloropropionate solution obtained in step a), wherein the pH value is controlled at 9-10 during the reaction; e) acidifying the reaction product obtained in step d); f) subjecting the acidified reactant to crystallization by decreasing the temperature to obtain 2-methyl-4-chloropropionic acid crystals; g) dissolving the crystallized 2-methyl-4-chloropropionic acid crystals in dichloroethane solvent, performing liquid-liquid distribution, washing with water, and then performing reduced pressure distillation to remove dichloroethane to obtain high-purity 2-methyl-4-chloropropionic acid.

2. A method for preparing high 2-methyl-4-chloropropionic acid according to claim 1, characterized in that, The mass concentration of the liquid caustic soda solution in step a) is 30%.

3. A method for preparing high 2-methyl-4-chloropropionic acid according to claim 1, characterized in that, In step a), the mass ratio of the chiral 2-chloropropionic acid to the liquid alkali solution is 0.5-1:

1.

4. A method for preparing high 2-methyl-4-chloropropionic acid according to claim 1, characterized in that, In step b), the mass concentration of the liquid caustic soda solution is 30%.

5. A method for preparing high 2-methyl-4-chloropropionic acid according to claim 1, characterized in that, In step b), the mass ratio of p-chloro-o-cresol to liquid alkali solution is 0.5-1.5:

1.

6. The method for preparing 2-methyl-4-chloropropionic acid according to claim 1, wherein: The nucleophilic substitution reaction in step d) is carried out at a temperature of 25-30° C. and a reaction time of 2-4 hours.

7. The method for preparing 2-methyl-4-chloropropionic acid according to claim 1, wherein: The acidification reaction temperature in step e) is 80-85°C.

8. The method for preparing 2-methyl-4-chloropropionic acid according to claim 1, wherein: The usage amount of the dichloroethane solvent in step g) is 2-10 times the mass of 2-methyl-4-chloropropionic acid.

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