Synthesis method of high-quality phenylacetyl chloride

Abstract

The invention discloses a synthesis method of high-quality phenylacetyl chloride, and belongs to the technical field of synthesis of phenylacetyl chloride. According to the method, the crude phenylacetyl chloride is purified by combining the strong-polarity aprotic solvent dimethyl sulfoxide and the disubstituted ionic liquid, the solvent is strong in polarity, can remove high-polarity colored group impurities, does not contain reactive hydrogen and does not react with phenylacetyl chloride, and the phenylacetyl chloride and the solvent are separated by standing and layering after mixing at normal temperature. A double bond and a benzene ring in the disubstituted ionic liquid can form a pi-pi accumulation effect with macromolecular impurities containing conjugated systems such as oligomers in the impurities, ester groups can form stable hydrogen bonds with strong hydrogen bond donors such as aldehyde groups in the impurities, ether bonds can adsorb thioether impurities, and the adsorption capacity is further enhanced through SbF6 anions. The purity of the phenylacetyl chloride synthesized through the method reaches 99.0% or above through liquid phase analysis, and the phenylacetyl chloride does not change color through high-temperature tests and completely meets the standard of high-quality phenylacetyl chloride.

Description

Technical Field

[0001] This invention belongs to the field of phenylacetyl chloride synthesis technology, and particularly relates to a method for synthesizing high-quality phenylacetyl chloride. Background Technology

[0002] Phenylacetyl chloride is an important organic synthesis intermediate widely used in pharmaceuticals, pesticides, fragrances, and polymer materials. Currently, the industrial production of phenylacetyl chloride mainly utilizes the acyl chloride reaction of phenylacetic acid and thionyl chloride. However, traditional production processes suffer from several common and challenging problems:

[0003] Insufficient product purity and poor color: During the reaction process, especially at higher temperatures, side reactions are prone to occur, generating colored impurities (usually tar-like substances or polymers with large molecular weights). This causes the crude product to be yellow or even darker in color. Although the purity may be high according to gas chromatography analysis, the purity of liquid chromatography, which better reflects the total amount of impurities, is often lower.

[0004] Poor thermal stability and easy discoloration: Phenylacetyl chloride containing the aforementioned colored impurities is highly unstable when heated and easily reacts to deepen its color. The industry typically uses temperature testing to verify its thermal stability. Traditional products readily discolor in this test, failing to meet the demands of high-end applications.

[0005] Therefore, developing a synthesis method that can effectively remove colored impurities and improve product purity and thermal stability has become a pressing technical challenge in this field. Summary of the Invention

[0006] In view of the above situation and to overcome the defects of the prior art, the present invention uses a combination of a strongly polar aprotic solvent, dimethyl sulfoxide, and a disubstituted ionic liquid to purify crude phenylacetyl chloride, thereby obtaining high-purity, high-stability, high-quality phenylacetyl chloride.

[0007] To achieve the above objectives, the following technical solution is adopted: This invention provides a method for synthesizing high-quality phenylacetyl chloride, comprising the following steps:

[0008] (1) Preparation of crude product: Add phenylacetic acid to the reaction vessel, slowly add thionyl chloride at a stirring rate of 200-300 rpm, control the adding temperature at 40-45℃, and after the addition is completed, raise the temperature to 50-55℃ and keep the reaction for 2-4 hours to generate crude phenylacetyl chloride; the waste gas generated by the reaction is introduced into a 5-10wt% sodium hydroxide solution through a conduit for absorption.

[0009] (2) Removal of impurities: Crude phenylacetyl chloride is added to a mixed solvent, which is composed of dimethyl sulfoxide and disubstituted ionic liquid in a volume ratio of 1:1-1.5:1. The mixture is reacted at a temperature of 40-60℃ and a stirring rate of 300-400rpm for 1-2 hours. After standing for 30-60 minutes, the mixture is separated into two phases: the upper phase is the phenylacetyl chloride phase and the lower phase is the mixed solvent phase. The mixture is then separated by liquid separation. The mixed solvent phase is purified and recycled.

[0010] (3) Distillation purification: Add the phenylacetyl chloride phase into a vacuum distillation apparatus, control the vacuum degree to 0.090-0.095MPa, raise the temperature to 100-120℃, collect the fraction, and obtain colorless and transparent phenylacetyl chloride;

[0011] (4) Testing before leaving the factory: The phenylacetyl chloride from step (3) is tested, and the product is packaged and shipped after the indicators meet the standards.

[0012] Furthermore, the disubstituted ionic liquid is prepared by the following steps:

[0013] S1. Preparation of imidazole monosubstituted intermediate: Imidazole and methyl 4-bromomethylcinnamate were added to a reaction vessel, then to an acetonitrile-DMF solution with a volume ratio of 3:1 (acetonitrile to DMF), and potassium carbonate was added. The reaction was carried out at 65-85℃ for 5-7 h. After the reaction was completed, the insoluble matter was removed by filtration, the solvent was removed by rotary evaporation of the filtrate, and the residue was recrystallized with a mixed solvent of ethyl acetate and n-hexane with a volume ratio of 1:2 to obtain the imidazole monosubstituted intermediate.

[0014] S2. Preparation of disubstituted cationic intermediate: The imidazole monosubstituted intermediate obtained in step S1 and methyl 2-bromo-3-methoxypropionate were added to a reaction vessel, DMF was added, potassium carbonate was added, and the reaction was carried out at 65-85℃ for 8-10 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was washed three times with ethyl acetate to obtain the disubstituted cationic intermediate.

[0015] S3. Preparation of disubstituted ionic liquid: The disubstituted cation intermediate obtained in step S2 and the anion exchanger are added to a reaction vessel, and 75% (v / v) acetone solution is added. The mixture is stirred at room temperature for 3-5 hours. After the reaction is completed, the mixture is allowed to stand and separate into layers. The lower layer is collected, washed three times with deionized water, and dried under vacuum to obtain the disubstituted ionic liquid.

[0016] Further, in step S1, the molar ratio of imidazole to methyl 4-bromomethylcinnamate is 1:1.05-1.2, and the amount of acetonitrile-DMF solution used is 5-8 times the mass of imidazole; the amount of potassium carbonate added in step S1 is 1.1-1.3 times the molar amount of imidazole.

[0017] Further, in step S2, the molar ratio of the imidazole monosubstituted intermediate to methyl 2-bromo-3-methoxypropionate is 1:1.2-1.6; the amount of DMF used is 6-9 times the mass of the monosubstituted intermediate; and the amount of potassium carbonate added in step S2 is 1.2-1.4 times the molar amount of the monosubstituted intermediate.

[0018] Furthermore, in step S3, the molar ratio of the disubstituted cationic intermediate to the anionic displacing agent is 1:1.05-1.2; and the amount of acetone solution used is 8-12 times the mass of the disubstituted cationic intermediate.

[0019] Furthermore, the anion exchanger is any one or more of sodium hexafluoroantimonate and potassium hexafluoroantimonate.

[0020] Furthermore, in step (1), the molar ratio of phenylacetic acid to thionyl chloride is 1:1.1-1.3.

[0021] Furthermore, in step (2), the mass ratio of crude phenylacetyl chloride to the mixed solvent is 1:0.5-1.5.

[0022] Furthermore, in step (1), the temperature of the sodium hydroxide solution is controlled at 20-30℃, and the gas-liquid contact time is ≥30s.

[0023] The beneficial effects of this invention are:

[0024] The phenylacetyl chloride synthesized by the legal method of this invention has a purity of over 99.0% as determined by liquid chromatography, and does not change color after high-temperature tests at 100°C and 120°C, fully meeting the high-quality phenylacetyl chloride standard.

[0025] This invention purifies crude phenylacetyl chloride by combining a highly polar aprotic solvent, dimethyl sulfoxide, with a disubstituted ionic liquid. This solvent is highly polar and can remove highly polar colored group impurities. It does not contain active hydrogen and does not react with phenylacetyl chloride. After mixing at room temperature and allowing it to stand for layering, the phenylacetyl chloride and the solvent are separated with a clear interface.

[0026] Methyl methyl cinnamate in disubstituted ionic liquids contains double bonds and a benzene ring, which can form π-π stacking interactions with macromolecular impurities containing conjugated systems, such as oligomers in the impurities. Furthermore, the cinnamic group has weak polarity and low polarity matching with phenylacetyl chloride, so it does not affect the layering. In disubstituted ionic liquids, ester groups and ether bonds are introduced through methyl 2-bromo-3-methoxypropionate. The oxygen atom in the ester group is a strong hydrogen bond acceptor, which can form stable hydrogen bonds with strong hydrogen bond donors such as aldehyde groups in the impurities. The oxygen atom in the ether bond has lone pair electrons, which can form coordination interactions with the empty orbitals of sulfur atoms and the lone pair electrons of chlorine atoms in the impurities, enhancing the adsorption of thioether impurities. In addition, the strong polarity of the SbF6⁻ anion can help stabilize the coordination structure, further enhancing the adsorption capacity.

[0027] Furthermore, mixing the disubstituted ionic liquid with dimethyl sulfoxide increases the density of the mixed solvent, making it denser than phenylacetyl chloride. This facilitates separation by causing the disubstituted ionic liquid to separate from the phenylacetyl chloride. This method is simple to operate, allows for solvent recycling, and is suitable for industrial production, significantly improving the quality and stability of phenylacetyl chloride. Attached Figure Description

[0028] Figure 1 This is a process flow diagram of a method for synthesizing high-quality phenylacetyl chloride according to the present invention.

[0029] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation

[0030] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0032] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the experimental materials used in the following examples are all purchased from commercial channels.

[0033] Example 1:

[0034] Reference Figure 1 A method for synthesizing high-quality phenylacetyl chloride includes the following steps:

[0035] (1) Preparation of crude product: Phenylacetic acid was added to the reaction vessel, and thionyl chloride was slowly added dropwise at a stirring rate of 200 rpm. The dropwise temperature was controlled at 40°C. After the dropwise addition was completed, the temperature was raised to 50°C and kept at the temperature for 2 hours to generate crude phenylacetyl chloride. The waste gas generated by the reaction was introduced into a 5 wt% sodium hydroxide solution through a conduit for absorption.

[0036] (2) Impurity removal: Crude phenylacetyl chloride was added to a mixed solvent, which was composed of dimethyl sulfoxide and disubstituted ionic liquid in a volume ratio of 1:1. The mixture was reacted at 40°C and 300 rpm for 1 h, and then allowed to stand for 30 min to separate into two phases. The upper phase was the phenylacetyl chloride phase and the lower phase was the mixed solvent phase. The mixture was then separated and the mixed solvent phase was purified and recycled.

[0037] (3) Distillation purification: Add phenylacetyl chloride phase to a vacuum distillation apparatus, control the vacuum degree to 0.090 MPa, heat to 100℃, collect the fraction, and obtain colorless and transparent phenylacetyl chloride;

[0038] (4) Testing before leaving the factory: The phenylacetyl chloride from step (3) is tested, and the product is packaged and shipped after the indicators meet the standards.

[0039] The disubstituted ionic liquid is prepared by the following steps:

[0040] S1. Preparation of imidazole monosubstituted intermediate: Imidazole and methyl 4-bromomethylcinnamate were added to a reaction vessel, then to an acetonitrile-DMF solution with a volume ratio of 3:1 (acetonitrile and DMF), and potassium carbonate was added. The reaction was carried out at 65°C for 5 h. After the reaction was completed, the insoluble matter was removed by filtration, the solvent was removed by rotary evaporation of the filtrate, and the residue was recrystallized with a mixed solvent of ethyl acetate and n-hexane with a volume ratio of 1:2 to obtain the imidazole monosubstituted intermediate.

[0041] S2. Preparation of the disubstituted cationic intermediate: The imidazole monosubstituted intermediate obtained in step S1 and methyl 2-bromo-3-methoxypropionate were added to a reaction vessel, DMF was added, potassium carbonate was added, and the reaction was carried out at 65°C for 8 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was washed three times with ethyl acetate to obtain the disubstituted cationic intermediate.

[0042] S3. Preparation of disubstituted ionic liquid: The disubstituted cation intermediate obtained in step S2 and the anion exchanger were added to a reaction vessel, and 75% (v / v) acetone solution was added. The mixture was stirred at room temperature for 3 hours. After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer was collected, washed three times with deionized water, and dried under vacuum to obtain the disubstituted ionic liquid.

[0043] In step S1, the molar ratio of imidazole to methyl 4-bromomethylcinnamate is 1:1.05, and the amount of acetonitrile-DMF solution used is 5 times the mass of imidazole; the amount of potassium carbonate added in step S1 is 1.1 times the molar amount of imidazole; in step S2, the molar ratio of the imidazole monosubstituted intermediate to methyl 2-bromo-3-methoxypropionate is 1:1.2; the amount of DMF used is 6 times the mass of the monosubstituted intermediate; and the amount of potassium carbonate added in step S2 is 1 / 3 the molar amount of the monosubstituted intermediate. 2 times; the molar ratio of the disubstituted cationic intermediate to the anionic displacing agent in step S3 is 1:1.05; the amount of acetone solution used is 8 times the mass of the disubstituted cationic intermediate; the anionic displacing agent is potassium hexafluoroantimonate; the molar ratio of phenylacetic acid to thionyl chloride in step (1) is 1:1.1; the mass ratio of crude phenylacetyl chloride to mixed solvent in step (2) is 1:0.5; the temperature of sodium hydroxide solution in step (1) is controlled at 20℃, and the gas-liquid contact time is ≥30s.

[0044] Example 2:

[0045] Reference Figure 1 A method for synthesizing high-quality phenylacetyl chloride includes the following steps:

[0046] (1) Preparation of crude product: Phenylacetic acid was added to the reaction vessel, and thionyl chloride was slowly added dropwise at a stirring rate of 300 rpm. The dropwise temperature was controlled at 45°C. After the dropwise addition was completed, the temperature was raised to 55°C and kept at the temperature for 4 hours to generate crude phenylacetyl chloride. The waste gas generated in the reaction was introduced into a 10 wt% sodium hydroxide solution for absorption through a conduit.

[0047] (2) Removal of impurities: Crude phenylacetyl chloride was added to a mixed solvent, which was composed of dimethyl sulfoxide and disubstituted ionic liquid in a volume ratio of 1.5:1. The mixture was reacted at 60°C and 400 rpm for 2 hours, and then allowed to stand for 60 minutes to separate into two phases. The upper phase was the phenylacetyl chloride phase and the lower phase was the mixed solvent phase. The mixture was then separated and the mixed solvent phase was purified and recycled.

[0048] (3) Distillation purification: Add the phenylacetyl chloride phase to a vacuum distillation apparatus, control the vacuum degree to 0.095 MPa, raise the temperature to 120°C, collect the fraction, and obtain colorless and transparent phenylacetyl chloride;

[0049] (4) Testing before leaving the factory: The phenylacetyl chloride from step (3) is tested, and the product is packaged and shipped after the indicators meet the standards.

[0050] The disubstituted ionic liquid is prepared by the following steps:

[0051] S1. Preparation of imidazole monosubstituted intermediate: Imidazole and methyl 4-bromomethylcinnamate were added to a reaction vessel, then to an acetonitrile-DMF solution with a volume ratio of 3:1 (acetonitrile and DMF), and potassium carbonate was added. The reaction was carried out at 85°C for 7 h. After the reaction was completed, the insoluble matter was removed by filtration, the solvent was removed by rotary evaporation of the filtrate, and the residue was recrystallized with a mixed solvent of ethyl acetate and n-hexane with a volume ratio of 1:2 to obtain the imidazole monosubstituted intermediate.

[0052] S2. Preparation of the disubstituted cationic intermediate: The imidazole monosubstituted intermediate obtained in step S1 and methyl 2-bromo-3-methoxypropionate were added to a reaction vessel, DMF was added, potassium carbonate was added, and the reaction was carried out at 85°C for 10 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was washed three times with ethyl acetate to obtain the disubstituted cationic intermediate.

[0053] S3. Preparation of disubstituted ionic liquid: The disubstituted cation intermediate obtained in step S2 and the anion exchanger were added to a reaction vessel, and 75% (v / v) acetone solution was added. The mixture was stirred at room temperature for 5 h. After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer was collected, washed three times with deionized water, and dried under vacuum to obtain the disubstituted ionic liquid.

[0054] In step S1, the molar ratio of imidazole to methyl 4-bromomethylcinnamate is 1:1.2, and the amount of acetonitrile-DMF solution used is 8 times the mass of imidazole; the amount of potassium carbonate added in step S1 is 1.3 times the molar amount of imidazole; in step S2, the molar ratio of the imidazole monosubstituted intermediate to methyl 2-bromo-3-methoxypropionate is 1:1.6; the amount of DMF used is 9 times the mass of the monosubstituted intermediate; and the amount of potassium carbonate added in step S2 is 1.4 times the molar amount of the monosubstituted intermediate. The molar ratio of the disubstituted cationic intermediate to the anionic displacing agent in step S3 is 1:1.2; the amount of acetone solution used is 12 times the mass of the disubstituted cationic intermediate; the anionic displacing agent is sodium hexafluoroantimonate; the molar ratio of phenylacetic acid to thionyl chloride in step (1) is 1:1.3; the mass ratio of crude phenylacetyl chloride to mixed solvent in step (2) is 1:1.5; the temperature of sodium hydroxide solution in step (1) is controlled at 30℃, and the gas-liquid contact time is ≥30s.

[0055] Example 3:

[0056] Reference Figure 1 A method for synthesizing high-quality phenylacetyl chloride includes the following steps:

[0057] (1) Preparation of crude product: Phenylacetic acid was added to the reaction vessel, and thionyl chloride was slowly added dropwise at a stirring rate of 250 rpm. The dropwise temperature was controlled at 42.5℃. After the dropwise addition was completed, the temperature was raised to 52.5℃ and kept at the temperature for 3 hours to generate crude phenylacetyl chloride. The waste gas generated by the reaction was introduced into a 7.5 wt% sodium hydroxide solution through a conduit for absorption.

[0058] (2) Removal of impurities: Crude phenylacetyl chloride was added to a mixed solvent, which consisted of dimethyl sulfoxide and a disubstituted ionic liquid in a volume ratio of 1.25:1. The mixture was reacted at 50°C and 350 rpm for 1.5 h. After standing for 45 min to separate the phases, the upper layer was the phenylacetyl chloride phase and the lower layer was the mixed solvent phase. The mixture was then separated by liquid separation. The mixed solvent phase was purified and recycled.

[0059] (3) Distillation purification: Add phenylacetyl chloride phase to a vacuum distillation apparatus, control the vacuum degree to 0.0925 MPa, heat to 110℃, collect the fraction, and obtain colorless and transparent phenylacetyl chloride;

[0060] (4) Testing before leaving the factory: The phenylacetyl chloride from step (3) is tested, and the product is packaged and shipped after the indicators meet the standards.

[0061] The disubstituted ionic liquid is prepared by the following steps:

[0062] S1. Preparation of imidazole monosubstituted intermediate: Imidazole and methyl 4-bromomethylcinnamate were added to a reaction vessel, then to an acetonitrile-DMF solution with a volume ratio of 3:1 (acetonitrile and DMF), and potassium carbonate was added. The reaction was carried out at 75°C for 6 hours. After the reaction was completed, the insoluble matter was removed by filtration, the solvent was removed by rotary evaporation of the filtrate, and the residue was recrystallized from the ethyl acetate-n-hexane mixed solvent with a volume ratio of 1:2 to obtain the imidazole monosubstituted intermediate.

[0063] S2. Preparation of the disubstituted cationic intermediate: The imidazole monosubstituted intermediate obtained in step S1 and methyl 2-bromo-3-methoxypropionate were added to a reaction vessel, DMF was added, potassium carbonate was added, and the reaction was carried out at 75°C for 9 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was washed three times with ethyl acetate to obtain the disubstituted cationic intermediate.

[0064] S3. Preparation of disubstituted ionic liquid: The disubstituted cation intermediate obtained in step S2 and the anion exchanger were added to a reaction vessel, and 75% (v / v) acetone solution was added. The mixture was stirred at room temperature for 4 hours. After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer was collected, washed three times with deionized water, and dried under vacuum to obtain the disubstituted ionic liquid.

[0065] In step S1, the molar ratio of imidazole to methyl 4-bromomethylcinnamate is 1:1.125, and the amount of acetonitrile-DMF solution used is 6.5 times the mass of imidazole; the amount of potassium carbonate added in step S1 is 1.2 times the molar amount of imidazole; in step S2, the molar ratio of the imidazole monosubstituted intermediate to methyl 2-bromo-3-methoxypropionate is 1:1.4; the amount of DMF used is 7.5 times the mass of the monosubstituted intermediate; the amount of potassium carbonate added in step S2 is 1.3 times the molar amount of the monosubstituted intermediate; the steps In S3, the molar ratio of the disubstituted cationic intermediate to the anionic displacing agent is 1:1.125; the amount of acetone solution used is 10 times the mass of the disubstituted cationic intermediate; the anionic displacing agent is obtained by combining sodium hexafluoroantimonate and potassium hexafluoroantimonate in a molar ratio of 1:1; in step (1), the molar ratio of phenylacetic acid to thionyl chloride is 1:1.2; in step (2), the mass ratio of crude phenylacetyl chloride to the mixed solvent is 1:1; in step (1), the temperature of the sodium hydroxide solution is controlled at 25℃, and the gas-liquid contact time is ≥30s.

[0066] Comparative Example 1:

[0067] A method for synthesizing phenylacetyl chloride, which differs from Example 3 in that only pure dimethyl sulfoxide is used for impurity removal in this comparative example compared to Example 1, while the rest is the same as in Example 3.

[0068] Results Analysis

[0069] The phenylacetyl chloride prepared in each embodiment and comparative example of the present invention was subjected to visual inspection, gas chromatography purity test, liquid chromatography purity test and thermal stability test. The results are shown in Table 1.

[0070] The gas chromatography purity test conditions are as follows:

[0071] Chromatographic column: HP-5 (30m×0.25mm×0.25μm).

[0072] Carrier gas: high-purity nitrogen, flow rate 1.0 mL / min.

[0073] Inlet temperature: 210℃.

[0074] Detector temperature: 230℃.

[0075] Column oven program: 160℃ for 15 minutes.

[0076] Injection method: split injection, split ratio 50:1.

[0077] Injection volume: 0.2 μL.

[0078] The steps for gas chromatography purity testing are as follows:

[0079] Add 2.0g of this product to a 25mL test tube. Weigh 2g of anhydrous methanol and slowly add it dropwise to the test tube over a time of 2-2.5 minutes. After the addition is complete, incubate the tube in an oil bath for 30 minutes. Add 2g of toluene and 2g of distilled water to the test tube, shake for 30 seconds, allow it to settle for 5 minutes, and accurately pipette 0.2μL of the supernatant for analysis. Record the chromatogram. The chromatographic time is 15 minutes. Calculate the percentage content of phenylacetyl chloride using the area normalization method.

[0080] phenylacetyl chloride %= ×100%;

[0081] Ai – the chromatographic peak area of ​​phenylacetyl chloride;

[0082] ΣA 总 —The sum of the areas of all chromatographic peaks.

[0083] The conditions for liquid chromatography purity testing are as follows:

[0084] Reversed-phase C18 column (150 mm × 4.6 mm, 5 μm).

[0085] Mobile phase: Phase A consisted of 9.09 g of phosphoric acid dissolved in 1 L of ultrapure water, and Phase B consisted of acetonitrile. An isocratic elution program was used, with a mixture of 40% Phase A and 60% Phase B, running for 15 min.

[0086] Flow rate: 1.0 mL / min.

[0087] Detection wavelength: 214nm.

[0088] Injection volume: 20 μL.

[0089] Sample preparation: Accurately weigh 50 mg of sample into a 100 mL volumetric flask, dilute with 5 mL of methanol for esterification for 5 min, then dilute to the mark with the mobile phase to obtain the test solution. Filter the solution using a 0.22 μm organic microporous membrane before injection.

[0090] Thermal stability testing was conducted using a constant-temperature heating device. The specific steps are as follows: A constant-temperature heating device with a temperature control accuracy of ±1℃ was used. Approximately 5 mL of each comparative example and embodiment sample was placed in a clean, dry test tube, and the stopper was tightened. The test tubes were placed in the constant-temperature device preheated to 100℃ and maintained for 1 hour. After removal, the samples were allowed to cool naturally at room temperature. The color changes were then visually compared to the unheated sample against a white background. A new sample was then taken and the above process was repeated at 120℃. The color changes of the samples after heating were recorded.

[0091] Table 1 Comparison of Test Results for Phenylacetyl Chloride Samples

[0092] project Comparative Example 1 Example 1 Example 2 Example 3 Appearance (at room temperature) light yellow transparent liquid Colorless and transparent liquid Colorless and transparent liquid Colorless and transparent liquid Gas chromatography purity % 99.1% 99.6% 99.6% 99.7% Liquid chromatography purity % 97.8% 99.2% 99.3% 99.3% Thermal stability test (100℃, 1h) Noticeably turned yellow Colorless, unchanging Colorless, unchanging Colorless, unchanging Thermal stability test (120℃, 1h) Turns reddish-brown Colorless, unchanging Colorless, unchanging Colorless, unchanging

[0093] As shown in Table 1, while the comparative product exhibited high purity under gas chromatography, its purity under liquid chromatography was significantly lower. This indicates the presence of a considerable amount of high molecular weight or high-boiling-point impurities, which may not have been completely vaporized or detected under gas chromatography but can be effectively detected under liquid chromatography. In contrast, the liquid chromatography purity of all embodiments of this invention reached over 99%, significantly superior to the comparative example, demonstrating that the synthesis method of this invention can efficiently remove these colored and high molecular weight impurities. The comparative product was initially yellow and rapidly darkened upon heating, exhibiting poor thermal stability. In contrast, the product of this invention was initially colorless and demonstrated excellent stability in temperature tests at 110°C and 120°C.

[0094] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0095] The present invention and its embodiments have been described above. This description is not restrictive, and the embodiments shown are only one of the embodiments of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A method for synthesizing high-quality phenylacetyl chloride, characterized in that: Includes the following steps: (1) Preparation of crude product: Add phenylacetic acid to the reaction vessel, slowly add thionyl chloride at a stirring rate of 200-300 rpm, control the adding temperature at 40-45℃, and after the addition is completed, raise the temperature to 50-55℃ and keep the reaction for 2-4 hours to generate crude phenylacetyl chloride; the waste gas generated by the reaction is introduced into a 5-10wt% sodium hydroxide solution through a conduit for absorption. (2) Removal of impurities: Crude phenylacetyl chloride is added to a mixed solvent, which is composed of dimethyl sulfoxide and disubstituted ionic liquid in a volume ratio of 1:1-1.5:

1. The mixture is reacted at a temperature of 40-60℃ and a stirring rate of 300-400rpm for 1-2 hours. After standing for 30-60 minutes, the mixture is separated into two phases: the upper phase is the phenylacetyl chloride phase and the lower phase is the mixed solvent phase. The mixture is then separated by liquid separation. The mixed solvent phase is purified and recycled. (3) Distillation purification: Add the phenylacetyl chloride phase into a vacuum distillation apparatus, control the vacuum degree to 0.090-0.095MPa, raise the temperature to 100-120℃, collect the fraction, and obtain colorless and transparent phenylacetyl chloride; (4) Testing before leaving the factory: The phenylacetyl chloride from step (3) is tested, and the product is packaged and shipped after the indicators meet the standards.

2. The method for synthesizing high-quality phenylacetyl chloride according to claim 1, characterized in that: The disubstituted ionic liquid is prepared by the following steps: S1. Preparation of imidazole monosubstituted intermediate: Imidazole and methyl 4-bromomethylcinnamate were added to a reaction vessel, then to an acetonitrile-DMF solution with a volume ratio of 3:1 (acetonitrile to DMF), and potassium carbonate was added. The reaction was carried out at 65-85℃ for 5-7 h. After the reaction was completed, the insoluble matter was removed by filtration, the solvent was removed by rotary evaporation of the filtrate, and the residue was recrystallized with a mixed solvent of ethyl acetate and n-hexane with a volume ratio of 1:2 to obtain the imidazole monosubstituted intermediate. S2. Preparation of disubstituted cationic intermediate: The imidazole monosubstituted intermediate obtained in step S1 and methyl 2-bromo-3-methoxypropionate were added to a reaction vessel, DMF was added, potassium carbonate was added, and the reaction was carried out at 65-85℃ for 8-10 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was washed three times with ethyl acetate to obtain the disubstituted cationic intermediate. S3. Preparation of disubstituted ionic liquid: The disubstituted cation intermediate obtained in step S2 and the anion exchanger are added to a reaction vessel, and 75% (v / v) acetone solution is added. The mixture is stirred at room temperature for 3-5 hours. After the reaction is completed, the mixture is allowed to stand and separate into layers. The lower layer is collected, washed three times with deionized water, and dried under vacuum to obtain the disubstituted ionic liquid.

3. The method for synthesizing high-quality phenylacetyl chloride according to claim 2, characterized in that: In step S1, the molar ratio of imidazole to methyl 4-bromomethylcinnamate is 1:1.05-1.2, and the amount of acetonitrile-DMF solution used is 5-8 times the mass of imidazole; the amount of potassium carbonate added in step S1 is 1.1-1.3 times the molar amount of imidazole.

4. The method for synthesizing high-quality phenylacetyl chloride according to claim 3, characterized in that: In step S2, the molar ratio of the imidazole monosubstituted intermediate to methyl 2-bromo-3-methoxypropionate is 1:1.2-1.6; the amount of DMF used is 6-9 times the mass of the monosubstituted intermediate; and the amount of potassium carbonate added in step S2 is 1.2-1.4 times the molar amount of the monosubstituted intermediate.

5. The method for synthesizing high-quality phenylacetyl chloride according to claim 4, characterized in that: In step S3, the molar ratio of the disubstituted cationic intermediate to the anionic displacing agent is 1:1.05-1.2; the amount of acetone solution used is 8-12 times the mass of the disubstituted cationic intermediate.

6. The method for synthesizing high-quality phenylacetyl chloride according to claim 5, characterized in that: The anion exchanger is any one or more of sodium hexafluoroantimonate and potassium hexafluoroantimonate.

7. The method for synthesizing high-quality phenylacetyl chloride according to claim 6, characterized in that: In step (1), the molar ratio of phenylacetic acid to thionyl chloride is 1:1.1-1.

3.

8. The method for synthesizing high-quality phenylacetyl chloride according to claim 7, characterized in that: In step (2), the mass ratio of crude phenylacetyl chloride to the mixed solvent is 1:0.5-1.

5.

9. The method for synthesizing high-quality phenylacetyl chloride according to claim 8, characterized in that: In step (1), the temperature of the sodium hydroxide solution is controlled at 20-30℃, and the gas-liquid contact time is ≥30s.

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