A method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine

Abstract

The present invention discloses a method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine, wherein the process for recovering p-hydroxyphenylglycine comprises the following process steps: (1) performing deoiling and concentration operations on the synthetic mother liquor, then adding an extractant for treatment, and then filtering to obtain a DLH double salt and recover the mother liquor; (2) decomposing the DLH double salt obtained in step (1) to obtain a DLH product. The inventive process has a DLH recovery rate of up to 80% for the mother liquor, and after recycling, the neutralization yield can be increased by 6.8 percentage points, and the total yield can be increased by 4.4 percentage points. At the same time, the recovery of o-hydroxyphenylglycine in the recovered mother liquor is also disclosed, and the recovery rate of o-PG in the mother liquor is as high as 90%, realizing the recovery of about 50% of the total organic matter in the mother liquor.

Description

Technical Field

[0001] The invention relates to the field of synthesis of pharmaceutical intermediates, in particular to a recovery and treatment process of synthetic mother liquor of antibiotic drug intermediates, and belongs to the field of pharmaceutical chemical industry. Background Art

[0002] L-4-hydroxyphenylglycine is an essential intermediate for the synthesis of β-lactam antibiotics such as amoxicillin and cephalosporin, and is mainly prepared by the resolution of DL-4-hydroxyphenylglycine.

[0003] DL-p-hydroxyphenylglycine (abbreviated as DLH), as shown in formula (I), is mainly synthesized by first reacting phenol, glyoxylic acid and aminosulfonic acid to obtain DLH sulfate, and then undergoing alkali neutralization, filtration, washing and other operations to obtain DLH.

[0004]

[0005] In the US5336805 patent, a synthesis method of DLH is reported: aminosulfonic acid, phenol, and glyoxylic acid are added at room temperature, the temperature is raised to 50-70°C and the reaction is carried out for about 4 hours, ammonia water is added under stirring to neutralize to pH = 4-5, the temperature is lowered by 20-40°C, and DLH is obtained after filtration, washing, and drying. The yield is 60-65%, the HPLC purity is 95-98%, and the pure yield is 57-63%. It can be seen that there are about 35-40% by-products or other unknown impurities in the mother liquor; at the same time, a large amount of ammonium sulfate is generated. Theoretical analysis: if 1 mol of aminosulfonic acid is added, 1 mol of ammonium sulfate will be generated in the mother liquor. The preliminary estimate of the ammonium sulfate concentration in the mother liquor is about 20%. However, there is no information on the treatment of the mother liquor in the patent.

[0006] The DLH synthesis process was studied in detail in the literature by Zhang Jing et al. ([J], Applied Chemistry, 2003, 32(5):46-48). This process also uses phenol, glyoxylic acid and aminosulfonic acid as the main raw materials. The raw material ratio, reaction temperature, solvent selection, catalyst and other aspects were studied, and the optimal process conditions were obtained: water as solvent, sulfuric acid as catalyst, phenol: aminosulfonic acid: glyoxylic acid = 1:1.2:1 (molar ratio), 40-60°C for 5-6h, and finally neutralized with ammonia water to obtain DLH with a yield of 66.7%. The literature also recovers the mother liquor: after the mother liquor is concentrated, it is used as the reaction solvent for the next batch, and the yield can be increased to 83.8%. However, the mother liquor may have the following problems: the large amount of organic by-products (about 33% of the theoretical amount) and inorganic salts (saturated ammonium sulfate) in the mother liquor have an unpredictable effect on the reaction after use. At the same time, the presence of a large amount of organic impurities has a certain impact on the product quality, but the product purity is not reported in the literature. Moreover, after application, a large amount of organic impurities and inorganic salts will accumulate, so the mother liquor recovery and treatment process is not suitable for industrial production.

[0007] Patent CN109354261B introduces a synthetic mother liquor treatment process: under acidic conditions, an extractant is added for extraction, and an organic phase and an aqueous phase are separated. The aqueous phase is concentrated to recover inorganic salts, and the organic phase is treated with a series of extractants for recovery and reuse, and the residual organic matter is incinerated. The process is simple to operate, has a good separation effect between organic and inorganic matter, and is suitable for industrial production. However, a large amount of products or by-products contained in the mother liquor are not recovered and treated, and are disposed of as waste, which increases the amount of subsequent organic matter incineration treatment and waste gas emissions, which is unfavorable to economic benefits and the environment.

[0008] The inventors studied the synthesis process of DLH according to the document US5336805 and found that the yield of DLH was 60-63%, which was consistent with the literature. The product HPLC purity was above 98%, and there was a major impurity accounting for about 1-2%, which was determined to be o-hydroxyphenylglycine (abbreviated as: o-PG) after analysis, as shown in formula (II):

[0009]

[0010] The main reason for the production of o-PG is due to the ortho-para positioning effect of phenol. Experimental studies have found that the conversion of DLH in the reaction is about 66%, and the selectivity of DLH to o-PG is about 4:1, that is, the conversion of o-PG is about 16.5%. Except for a small amount of o-PG removed with the product (about 1.0-1.5%), the rest of the o-PG remains in the mother liquor. The o-PG concentration is about 3.0-3.5% after detection. At the same time, the solubility of DLH product in the mother liquor is about 1%, and the loss of product accounts for about 4-5% of the total amount of DLH generated. The organic components such as products, by-products, impurities, etc. in the mother liquor account for about 7-8% of the total amount of the mother liquor, of which DLH and o-PG account for about 60% of the total organic matter. In the existing public process data, there is no report on its recovery and treatment.

[0011] The present invention provides a method for extracting DLH and o-PG from synthetic mother liquor, breaking through the current situation that the products or by-products in the process mother liquor cannot be recovered, creating a precedent for recycling and turning waste into treasure; at the same time, reducing organic matter emissions, and being environmentally friendly. The process operation is simple, the recovery rate is high, the quality of the recovered products is good, and it is suitable for industrial production. Summary of the invention

[0012] In view of the defects of the existing process, the present invention provides a method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine from a synthetic mother liquor. The method has simple process operation, high recovery rate, good quality of the recovered product, and is suitable for industrial production.

[0013] The technical solution of the present invention is as follows:

[0014] A method for recovering p-hydroxyphenylglycine comprises the following steps:

[0015] (1) deoiling and concentrating the synthetic mother liquor, then adding an extractant to form a double salt, and then filtering to obtain a DLH double salt and recovering the mother liquor;

[0016] (2) decomposing the DLH double salt obtained in step (1) to obtain a DLH product;

[0017] The extractant is diphenylacetic acid or one of its substitutes, and the structure of the diphenylacetic acid or its substitute is shown in formula (III):

[0018]

[0019] In formula (III), R is selected from one of -H, F, Br, Cl, -OH, -NO2, C1~C4 alkyl (e.g., -CH3, -CH2CH3), C1~C4 alkoxy (e.g., -OCH3), etc.

[0020] In the present invention, the synthetic mother liquor is the remaining crystallization mother liquor after the synthetic DLH reaction liquid is neutralized and crystallized to obtain DLH. The method for obtaining the mother liquor is prior art, and reference may be made to US5336805 and other documents.

[0021] The mass percentage concentration of DLH in the synthetic mother solution is 0.5-1.5%.

[0022] Specifically, the DLH synthesis reaction liquid is neutralized to pH 4-5 by adding ammonia water under stirring, and the temperature is reduced by 20-40° C., and DLH is obtained after filtering, washing and drying, and the remainder is the synthesis mother liquor.

[0023] Preferably, R is -OH, and the structure of the extractant is shown in (IV):

[0024]

[0025] This compound is an impurity produced by the synthesis reaction itself and has a certain content in the mother liquor. Using it as an extractant will not change the composition of the solution system.

[0026] In the present invention, the oil removal operation is one of extraction, activated carbon adsorption, bubbling and the like.

[0027] In the extraction and oil removal method, the extractant is one of ketones and alcohols. Ketones include butanone, pentanone and its isomers, hexanone and its isomers, etc.; alcohols include butanol and its isomers, pentanol and its isomers, octanol and its isomers, cyclohexanol, etc.; the amount of the extractant is not strictly limited, and the amount used is 10% to 100% of the mother liquor, preferably 30 to 50%; at this time, a better extraction efficiency can be obtained, and the amount of the extractant used is the least.

[0028] The activated carbon adsorption degreasing method has no strict restrictions on the type and model of activated carbon, and generally large-pore activated carbon is preferred, which is easy to adsorb oily substances and has a small adsorption amount on the product. The amount of activated carbon used is 0.1-10% of the mother liquor, preferably 1-5%, at which time a better degreasing effect can be obtained.

[0029] The bubbling degreasing method is a physical degreasing method, that is, a certain number of air pipes are introduced into the lower part of the mother liquid, and air is pumped in at a certain speed to generate bubbles. During the floating process of the bubbles, due to the effect of surface tension, the oil is taken out of the mother liquid. After the bubbles are broken, the oil is enriched on the surface of the mother liquid, thereby achieving the purpose of degreasing. There is no strict restriction on the number of air pipes and air speed; more air pipes and faster air speed means less degreasing time and better degreasing effect.

[0030] Among the three oil removal methods, the bubbling oil removal method is preferred because it is simple to operate, does not generate solid waste, has low cost, and has a good oil removal effect.

[0031] In the present invention, the factors affecting the effect of the concentration operation include the concentration method and the degree of concentration. There is no strict restriction on the concentration method, and all existing industrial concentration methods can be used for the concentration of this method, such as atmospheric pressure concentration, reduced pressure concentration, multi-effect concentration, etc.; the degree of concentration is measured by the specific gravity of the feed liquid; the lower the concentration, the smaller the specific gravity, and the greater the solubility of the subsequent recovery of the double salt, resulting in a low recovery rate; on the contrary, the higher the concentration, the smaller the solubility of the product, the higher the recovery rate, which is beneficial to the recovery of the product. However, after excessive concentration, inorganic salts will precipitate, which is not conducive to subsequent recovery. The specific gravity is preferably 1.15 to 1.30, and more preferably: 1.20 to 1.25; at this time, the concentrated solution obtained has a small solubility for the product, a high recovery rate, and no organic salt precipitation, which is most beneficial for subsequent recovery.

[0032] In step (1), the amount of the extractant used has a great influence on the recovery rate of the DLH double salt. A small amount leads to a low recovery rate; a large amount leads to increased costs, which is unfavorable to the economy. The molar ratio of the extractant to DLH is preferably: 1.0-4.0:1, and more preferably: 2.0-3.0:1, at which the DLH content in the solution is the smallest and the recovery rate of the obtained DLH double salt is the highest.

[0033] In step (1), the pH value during treatment has a great influence on the quality and recovery rate of the recovered DLH double salt. When the pH value is low, o-PG double salt may precipitate, resulting in poor quality of the recovered DLH double salt; when the pH value is too high, DLH and the extractant cannot form double salt, and the purpose of recovery cannot be achieved. The pH value is preferably 5.0 to 8.0, and more preferably 6.0 to 7.0, at which time the recovered DLH double salt has the best quality and the highest recovery rate.

[0034] In step (1), the treatment temperature has a great influence on the crystal form and solubility of the recovered DLH double salt. When the temperature is low, the recovered double salt has a small crystal form, resulting in a slow double salt filtration speed; when the temperature is high, the recovered double salt has a good crystal form and is easy to filter, but too high a temperature will increase the solubility of the double salt and the recovery rate is low. The temperature is preferably 20 to 70°C, and more preferably 30 to 50°C, at which time the recovered double salt has a good crystal form, is easy to filter, and has the highest recovery rate.

[0035] In step (1), the treatment time has a great influence on the recovery rate of DLH double salt. Due to the complex components of the mother liquor, the crystallization speed is slow, the reaction time is short, the crystallization is incomplete, and the recovery rate is low. Prolonging the time is conducive to the precipitation of double salt, but the increase in time is not conducive to production capacity and cost. The reaction time is preferably: 3 to 50 hours, and more preferably: 15 to 25 hours, at which time the crystallization is complete and the recovery rate is high.

[0036] The present invention also provides a method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine, comprising the following steps:

[0037] (A) obtaining a recovered mother liquor and a p-hydroxyphenylglycine product according to the method described above;

[0038] (B) adding the extractant to the recovered mother liquor obtained in step (A) for treatment, and then filtering to obtain o-PG double salt;

[0039] (C) The o-PG double salt obtained in step (B) is decomposed to obtain the o-hydroxyphenylglycine product.

[0040] In step (B), the amount of the extractant used has a great influence on the recovery of o-PG double salt. A small amount leads to a low recovery rate; a large amount leads to increased costs, which is unfavorable to the economy. Since the solution contains a certain amount of extractant, it needs to be taken into account when calculating the ratio. The molar ratio of the extractant to o-PG is preferably: 0.8-2.0:1, and more preferably: 1.0-1.5:1. At this time, the o-PG content in the solution is the smallest, and the recovery rate of the obtained o-PG double salt is the highest.

[0041] In step (B), the pH value of the treatment has a great influence on the recovery of o-PG double salt. When the pH value is too low or too high, o-PG and the extractant cannot form double salts, and the purpose of recovery cannot be achieved. The pH value is preferably: 2.0-5.0, and more preferably: 3.0-4.0, at which time the recovered o-PG double salt has the best quality and the highest recovery rate.

[0042] In step (B), the treatment temperature also has a great influence on the crystal form and solubility of the recovered o-PG double salt. When the temperature is low, the recovered double salt has a small crystal form, resulting in a slow double salt filtration speed and the possibility of oily matter precipitation; when the temperature is high, the recovered double salt has a good crystal form, which is easy to filter, and the oily matter will not precipitate, but too high a temperature will increase the solubility of the double salt and the recovery rate is low. The temperature is preferably 20 to 70°C, and more preferably 30 to 50°C, at which time the recovered double salt has a good crystal form, is easy to filter, and has the highest recovery rate and the best recovery quality.

[0043] In step (B), the treatment time has a great influence on the recovery rate of o-PG double salt. Due to the slow crystallization speed, the required equilibrium time is long; if the reaction time is short, the crystallization is incomplete and the recovery rate is low. Prolonging the time is conducive to the precipitation of double salt, but the increase in time is not conducive to production capacity and cost. The reaction time is preferably: 3 to 50 hours, and more preferably: 10 to 25 hours, at which time the crystallization is complete and the recovery rate is high.

[0044] In step (C), factors affecting the decomposition operation of recovering the o-PG double salt include: decomposition solvent, solvent ratio, decomposition temperature and time.

[0045] The decomposition solvent has a great influence on the quality and yield of the recovered o-PG; the selection of the solvent must be good in solubility to the extractant, insoluble or low in solubility to the product, and at the same time conducive to the product crystal form. The decomposition solvent is preferably at least one of water, methanol, ethanol, isopropanol, butanol, acetonitrile, acetone, ethyl acetate, butyl acetate, etc., more preferably methanol and ethanol, and most preferably methanol. At this time, the solvent is cheap, the obtained o-PG recovery is easy to filter and wash, has good quality, and high yield.

[0046] The solvent ratio has a great influence on the quality and yield of the recovered o-PG; when the solvent ratio is small, the extractant is not completely dissolved, resulting in residual double salt in the recovered product and low quality. When the solvent ratio is large, the double salt is completely decomposed and the quality is good, but the increase in solvent will increase the dissolution amount of the recovered product, resulting in a low recovery rate. The weight ratio of the decomposition solvent to the double salt is preferably: 1 to 5: 1, and more preferably: 1 to 3: 1. At this time, the recovered product is of good quality, high yield, and cost-effective.

[0047] The decomposition temperature has a great influence on the quality of the recovered o-PG; if the decomposition temperature is low, the double salt is not completely decomposed, and the resulting product has a poor crystal form, which is not conducive to filtering and washing, resulting in poor product quality. The decomposition temperature is preferably 20-70°C, and more preferably 30-50°C, at which time the resulting product has a good crystal form, is easy to filter and wash, and has good product quality.

[0048] The decomposition time has a great influence on the quality of the recovered o-PG; if the decomposition time is short, the double salt is not completely decomposed, it is easy to produce encapsulation, and the product crystal form is not good. Prolonging the time is conducive to complete decomposition, and it is also conducive to increasing the product crystal form, which is convenient for filtering and washing. The decomposition time is preferably: 1 to 5 hours, and more preferably: 2 to 3 hours. At this time, the obtained product has less encapsulation, good crystal form, easy to filter and wash, and good product quality.

[0049] In the present invention, the decomposition method of the o-PG double salt is also applicable to the decomposition of the DLH double salt, but the corresponding operation steps will be increased, resulting in yield loss and increased cost. Preferably, the recovered DLH double salt does not need to be treated in any way, but is directly dissolved in the DLH synthesis reaction solution, and DLH is obtained after subsequent neutralization, filtration, washing and other operations. The quality of the obtained product is consistent with the original process, has no effect on the product quality, and can greatly improve the product yield.

[0050] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0051] A method for extracting DLH and o-PG from synthetic mother liquor is provided, which makes up for the deficiency of existing processes that there is no recycling, creates a precedent for recycling, turns waste into treasure, reduces organic matter emissions, and is environmentally friendly. At the same time, the inventive process can be combined with existing processes to further treat subsequent residual liquids, making the process more green and environmentally friendly. The process of the invention is simple to operate, has a high recovery rate, and has good quality of the recovered product, and is suitable for industrial production. DETAILED DESCRIPTION

[0052] The present invention is further described below in conjunction with specific embodiments. The following specific embodiments are for a better understanding of the technical solutions of the present invention, but those skilled in the art should recognize that the present invention is not limited to these embodiments. Those skilled in the art can make various modifications to the present invention without departing from the spirit and scope of the present invention, and these equivalent forms of modifications also fall within the protection scope of the present invention.

[0053] The reaction solution or mother solution in the present invention and the examples were prepared by the method in US Pat. No. 5,336,805, and the products, by-products, major impurities and other components were identified by HPLC and compared with standard samples.

[0054] Example 1: DLH double salt recovery experiment

[0055] Into a suitable reaction bottle equipped with stirring, a mother liquor (22.4 kg, wherein the external standard concentration of DLH is 0.96%, and the total amount of DLH contained is 215 g, 1.29 mol; the external standard concentration of the extractant is 1.66%, and the total amount of the extractant diphenolyl acetic acid (structure as shown in the compound shown in IV) contained is 372 g, 1.52 mol), and a bubbling deoiling operation is performed at room temperature. After 24 hours, the obtained filtrate is concentrated under reduced pressure, and the concentration is completed by controlling the solution specific gravity to 1.22-1.24; the obtained concentrated solution is stirred at 40° C., and an extractant (265 g, external standard content: 98%, 1.06 mol) is added, stirred to dissolve, and the pH of the system is adjusted to between 6 and 7, and a double salt seed formed by the compound shown in IV and DLH is added, and crystallization is performed for 24 hours, and filtration is performed to recover the wet product of the DLH double salt and the recovered mother liquor. The wet product was dried to obtain a dry product (675 g, DLH external standard content: 26.1%, 1.05 mol, the dry product exists in the form of a double salt), and the calculated recovery rate was 81.9%.

[0056] The remaining solution was recovered for the o-PG double salt recovery experiment.

[0057] Example 2: DLH double salt recovery experiment

[0058] Into a suitable reaction bottle equipped with stirring, put mother liquor (21.5 kg, wherein DLH external standard concentration: 0.97%, total DLH contained: 209 g, 1.25 mol; extractant external standard concentration: 1.72%, total extractant diphenol acetic acid (structure as shown in compound IV) contained: 370 g, 1.51 mol), add 2% activated carbon at room temperature to perform oil removal operation for 2 hours, and the filtrate obtained by filtration is concentrated under reduced pressure, and the concentration is completed by controlling the solution specific gravity to 1.22-1.24; the obtained concentrated solution is stirred at 50° C., and an extractant (390 g, external standard content: 98%, 1.60 mol) is added, stirred to dissolve, and the pH of the system is adjusted to between 6 and 7, and a double salt seed formed by the compound shown in IV and DLH is added, and crystallization is carried out for 24 hours, and DLH double salt is recovered by filtration. Wet product and mother liquor are recovered. The wet product was dried to obtain a dry product (692 g, DLH external standard content: 24.5%, 1.01 mol, the dry product exists in the form of a double salt), and the calculated recovery rate was 80.8%.

[0059] The remaining mother liquor was recovered for the o-PG double salt recovery experiment.

[0060] Example 3: Recycling o-PG double salt experiment

[0061] Into a suitable reaction flask equipped with stirring, the remaining mother liquor in Example 1 (11.8 kg, wherein the external standard concentration of o-PG is 4.66%, and the total amount of o-PG contained is 550 g, 3.29 mol; the external standard concentration of the extractant is 2.28%, and the total amount of the extractant contained is 269 g, 1.10 mol) is added, and the extractant diphenolyl acetic acid (structure as shown in the compound shown in IV) (630 g, content 98%, 2.53 mol) is added, stirred and dissolved at 40°C, and the pH of the system is adjusted to 3-4 with sulfuric acid, and a double salt seed crystal formed by the compound shown in IV and o-PG is added, stirred and crystallized for 24 hours, and the o-PG double salt is filtered to recover the wet product. After drying the wet product, a dry product (1385 g, o-PG external standard content: 34.0%, 2.82 mol, the dry product exists in the form of a double salt) is obtained, and the calculated recovery rate is: 85.6%.

[0062] Example 4: Experiment on recovery of o-PG double salt

[0063] Into a suitable reaction flask equipped with stirring, the remaining mother liquor in Example 2 (12.0 kg, wherein the external standard concentration of o-PG is 4.88%, and the total amount of o-PG contained is 586 g, 3.50 mol; the external standard concentration of the extractant is 3.67%, and the total amount of the extractant contained is 440 g, 1.80 mol), and the extractant diphenolacetic acid (structure as shown in the compound shown in IV) is added in total (527 g, content 95%, 2.05 mol), stirred and dissolved at 50°C, and the pH of the system is adjusted to 3-4 with sulfuric acid, and double salt seed crystals formed by the compound shown in IV and o-PG are added, stirred and crystallized for 24 hours, and the o-PG double salt is filtered to recover the wet product. After drying the wet product, a dry product (1501 g, o-PG external standard content: 34.9%, 3.13 mol, the dry product exists in the form of double salt) is obtained, and the calculated recovery rate is: 89.4%.

[0064] Example 5: DLH recovery and double salt application experiment

[0065] Into a suitable reaction bottle equipped with mechanical stirring, DLH reaction solution (15.0 kg, DLH external standard content: 20.2%, total DLH contained: 3.03 kg, 18.1 mol) was added, the temperature was controlled between 50 and 70°C, the full batch of DLH recovery double salt in Example 1 was added, stirred to dissolve, and then neutralized with industrial ammonia water to a pH value of 4 to 6, cooled to below 30°C, filtered and washed to obtain a DLH wet product, and dried to obtain a finished product (3.00 kg, external standard content: 99.1%, 17.9 mol). The calculated neutralization yield was: 98.9%, and the total molar yield was: 65.3% (calculated as phenol).

[0066] Example 6: o-PG recovery and double salt decomposition experiment

[0067] In a suitable reaction bottle equipped with a mechanical stirrer, 100 g of methanol was added, the temperature was raised to between 40 and 60° C., and the o-PG recovery double salt (100 g, o-PG external standard content: 34.9%, 0.21 mol) in Example 4 was slowly added. The reaction was carried out at a constant temperature for more than 1 hour, and then the temperature was slowly lowered to below 30° C., and the o-PG wet product was filtered and washed. After drying, the finished product (33.3 g, chromatographic purity 99.2%, external standard content: 90.3%, 0.18 mol) was obtained. The calculated yield was 85.7%.

[0068] Comparative Example 1 (US5336805)

[0069] The DLH reaction solution was prepared according to the method in US Pat. No. 5,336,805: phenol: aminosulfonic acid: glyoxylic acid = 1:1.2:1 (molar ratio) was added, and the reaction temperature was controlled at 40-70°C for about 4 hours to obtain the DLH reaction solution. The DLH external standard concentration was 20.2% and the conversion rate was 66%. This reaction solution is used in Example 5.

[0070] Into a suitable reaction bottle equipped with mechanical stirring, add DLH reaction solution (15.0 kg, DLH external standard content: 20.2%, total DLH contained: 3.03 kg, 18.1 mol), control the temperature between 50 and 70°C, neutralize with industrial ammonia water to a pH value of 4 to 6, cool to below 30°C, filter and wash to obtain a DLH wet product, and dry to obtain a finished product (2.82 kg, external standard content: 99.0%, 16.7 mol). The calculated neutralization yield is: 92.2%, and the total molar yield is: 60.9% (calculated as phenol).

[0071] The results of comparative example 1 show that the recovery rate of DLH in the mother liquor by the process of the present invention is as high as more than 80%. After application, the yield of DLH can be greatly improved: the neutralization yield is 6.8 percentage points higher than that of the patented process, and the total molar yield is 4.4 percentage points higher, which is close to the reaction conversion rate and reaches the limit yield. At the same time, the present invention can recover the by-product o-PG, and the recovery rate in the mother liquor can reach 90%. Since most of the DLH and o-PG are recovered, the organic content in the mother liquor is greatly reduced, with a reduction of up to 50%.

Claims

1. A method for recovering p-hydroxyphenylglycine, It is characterized in that The following steps are involved: (1) deoiling and concentrating the synthetic mother liquor, then adding an extractant for treatment, and then filtering to obtain DL-p-hydroxyphenylglycine double salt and recovering the mother liquor; (2) decomposing the DL-p-hydroxyphenylglycine double salt obtained in step (1) to obtain a p-hydroxyphenylglycine product; The extractant is a diphenylacetic acid substituted product, and its structure is shown in formula (III): (III) In formula (III), R is selected from -OH; The synthesis mother liquor is the remaining crystallization mother liquor after the reaction liquid of synthesizing DL-p-hydroxyphenylglycine is neutralized and crystallized to obtain DL-p-hydroxyphenylglycine; The mass percentage concentration of DL-p-hydroxyphenylglycine in the synthetic mother solution is 0.5-1.5%; In step (1), the oil removal operation is one of extraction, activated carbon adsorption, and bubbling; In step (1), the molar ratio of the extractant to the DL-p-hydroxyphenylglycine contained in the synthetic mother liquor is 1.0-4.0:1; In step (1), the treatment process after adding the extractant is as follows: stirring to dissolve, adjusting the pH value of the system to 5.0-8.0, and then crystallizing; The crystallization temperature is: 20~70℃.

2. The method for recovering p-hydroxyphenylglycine according to claim 1, It is characterized in that In step (1), the concentration operation is performed until the solution has a specific gravity of 1.15 to 1.

30.

3. The method for recovering p-hydroxyphenylglycine according to claim 1, It is characterized in that In step (1), the temperature of adding the extractant is 20 to 70°C; The crystallization time is: 3 to 50 hours.

4. The method for recovering p-hydroxyphenylglycine according to claim 1, It is characterized in that In step (2), the process of decomposing DL-p-hydroxyphenylglycine double salt is as follows: Under heating conditions, the DL-p-hydroxyphenylglycine complex salt is dissolved in the DL-p-hydroxyphenylglycine reaction solution, stirred to dissolve, neutralized to a pH value of 4 to 6, cooled to below 30° C., filtered, washed and dried to obtain a DL-p-hydroxyphenylglycine finished product.

5. A method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine, It is characterized in that The following steps are involved: (A) obtaining a recovered mother liquor and a p-hydroxyphenylglycine product according to the method described in any one of claims 1 to 4; (B) adding the extractant to the recovered mother liquor obtained in step (1) for treatment, and then filtering to obtain o-hydroxyphenylglycine double salt; (C) The o-hydroxyphenylglycine double salt obtained in step (B) is decomposed to obtain the o-hydroxyphenylglycine finished product.

6. The method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine according to claim 5, It is characterized in that In step (B), the molar ratio of the extractant to o-hydroxyphenylglycine is 0.8 to 2:

1.

7. The method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine according to claim 5, It is characterized in that In step (B), the treatment process is as follows: stirring to dissolve, adjusting the pH value of the system to 2.0-5.0, and then performing crystallization; The temperature for adding the extractant and crystallizing is: 20-70°C; The crystallization time is: 3 to 50 hours.

8. The method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine according to claim 5, It is characterized in that In step (C), the process of decomposing o-hydroxyphenylglycine double salt is as follows: A decomposition solvent is added to the o-hydroxyphenylglycine double salt, heated for decomposition, then cooled to below 30° C., filtered, washed and dried to obtain the o-hydroxyphenylglycine finished product.

9. The method for recovering p-hydroxyphenylglycine and o-hydroxyphenylglycine according to claim 8, It is characterized in that The decomposition solvent is at least one of water, methanol, ethanol, isopropanol, butanol, acetonitrile, acetone, ethyl acetate, and butyl acetate; The weight ratio of the decomposition solvent to the o-hydroxyphenylglycine double salt is 1 to 5:1; The decomposition temperature is: 20-70°C; The decomposition time is 1 to 5 hours.

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