A method for recovering materials from metronidazole crude product mother liquor

Abstract

The present invention relates to the technical field of metronidazole, and specifically discloses a method for recovering materials from a crude metronidazole mother liquor. The present invention first adjusts acid for neutralization, then concentrates and distills water, and adds low-carbon alcohol to remove salt (sodium sulfate), thereby avoiding the "first concentration and then neutralization" treatment mode in which acid adjustment generates salt in the subsequent process, which is mixed into the recovered material, affecting the recovery rate and purity of the material; low-carbon alcohol is added to dissolve organic matter, so as to achieve effective separation of organic matter and sodium sulfate, and the obtained sodium sulfate is of high quality, meets the quality standard of industrial-grade sodium sulfate, can be sold as a by-product or directly used, and reduces the cost of solid waste treatment; carbon disulfide is used to extract the first filtrate for removing low-carbon alcohol, so as to achieve effective separation of 2-methyl-5-nitroimidazole and metronidazole, improve the recovery rate of materials 2-methyl-5-nitroimidazole and metronidazole, solve the use problem of recovered materials, significantly improve economic benefits and environmental benefits, and is suitable for large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of metronidazole, and specifically discloses a method for recovering materials from a crude metronidazole mother liquor. Background Art

[0002] Metronidazole is a nitroimidazole antiprotozoal and anaerobic drug. Its Chinese name is 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, its molecular formula is C6H9N3O3, and its CAS number is 443-48-1. In 1978, metronidazole was selected by the World Health Organization as a basic drug for anti-anaerobic infection. Metronidazole has a strong killing effect on Trichomonas in the urogenital system, amebas in the intestines and tissues, and Giardia, and can be used to treat diseases caused by protozoa such as trichomoniasis, amoebic dysentery, and amoebic liver abscess; Metronidazole also has a killing effect on anaerobic microorganisms, and can be used to treat and prevent various diseases caused by anaerobic bacteria. When metronidazole is used in the growth period of protozoa or anaerobic bacteria, it can cause the death of protozoa and anaerobic bacteria by destroying DNA chains or inhibiting DNA synthesis.

[0003] At present, the production process of metronidazole is generally to carry out a hydroxyalkylation reaction of 2-methyl-5-nitroimidazole and ethylene oxide in a formic acid and sulfuric acid environment; after the reaction, methanol is added to convert the formic acid ester into methyl formate and distill it for separation; after the methyl formate is distilled, the feed liquid is neutralized once with liquid alkali to separate the unreacted 2-methyl-5-nitroimidazole; the obtained filtrate is neutralized twice to separate the crude metronidazole and the crude metronidazole mother liquor; the crude product is refined to obtain the metronidazole product.

[0004] The crude metronidazole mother liquor contains a certain amount of 2-methyl-5-nitroimidazole and metronidazole, which need to be recycled. According to the solubility properties of the material, the industry generally cools down and crystallizes sodium sulfate, then distills and removes water, and finally cools down and precipitates 2-methyl-5-nitroimidazole and metronidazole to recycle sodium sulfate, 2-methyl-5-nitroimidazole and metronidazole. However, during the cooling crystallization, some materials will also precipitate together with sodium sulfate, resulting in poor quality of the recovered sodium sulfate, which cannot be sold or used as a by-product, and can only be treated as hazardous waste, which not only increases the processing cost, but also reduces the recovery rate of the material. In addition, the material 2-methyl-5-nitroimidazole and metronidazole and salt obtained by cooling and crystallization are mixed together, which causes certain difficulties in the utilization of the recycled material. Therefore, it is urgent to optimize the material recovery process of the crude metronidazole mother liquor to solve the problems of poor quality of by-product sodium sulfate and low material recovery rate. Summary of the invention

[0005] In view of the above problems, the present invention provides a method for recovering materials from a crude metronidazole mother liquor, wherein the main product metronidazole recovered has a high recovery rate and the content of the byproduct sodium sulfate is high.

[0006] In order to solve the above technical problems, the technical solution provided by the present invention is:

[0007] A method for recovering material from a crude metronidazole mother liquor comprises the following steps:

[0008] S1, adjusting the pH value of the crude metronidazole mother liquor to neutral with sulfuric acid, and concentrating; adding low-carbon alcohol to the concentrate, beating, and separating the solid and liquid to obtain sodium sulfate and a first filtrate;

[0009] S2, distilling the first filtrate to remove low-carbon alcohols; adding carbon disulfide and water to the distillation residue, beating the residue, and separating the solid and the liquid to obtain 2-methyl-5-nitroimidazole and the second filtrate;

[0010] S3, separating the second filtrate, taking the carbon disulfide phase for distillation, adding water to the residue, evaporating under vacuum to remove the carbon disulfide; cooling the residue, crystallizing, and separating the solid from the liquid to obtain metronidazole.

[0011] Compared with the prior art, the method for recovering materials from a crude metronidazole mother liquor provided by the present invention comprises the following steps: firstly adjusting the acid for neutralization, then concentrating and distilling the water, and adding a low-carbon alcohol for removing salt (sodium sulfate), thereby avoiding the problem that in a treatment mode of "first concentrating and then neutralizing", salt is generated again during acid adjustment in a subsequent process, and the salt is mixed into the recovered materials, thereby affecting the recovery rate and purity of the product (i.e., the material); adding a low-carbon alcohol to dissolve organic matter, thereby achieving effective separation of the organic matter and sodium sulfate, and the obtained sodium sulfate is of high quality and meets the quality standard of industrial-grade sodium sulfate, and can be sold as a by-product or used directly, thereby reducing the cost of solid waste treatment; and using carbon disulfide to extract the first filtrate from which the low-carbon alcohol is removed, thereby achieving effective separation of 2-methyl-5-nitroimidazole and metronidazole, thereby improving the recovery rates of the materials 2-methyl-5-nitroimidazole and metronidazole, and solving the problem of using the recovered materials.

[0012] The results of the embodiments show that the content of sodium sulfate obtained by the present invention is above 99%, and the whiteness is above 82%; the recovery rate of 2-methyl-5-nitroimidazole is as high as above 90%, and the purity is above 97%; the recovery rate of metronidazole is as high as above 90%, and the purity is above 99%; the problems of low material recovery rate of crude metronidazole mother liquor and poor quality of recovered materials in the prior art are solved, and the economic benefits and environmental benefits are significantly improved, and the present invention is suitable for large-scale production.

[0013] Preferably, in step S1, the crude metronidazole mother liquor is obtained by the following preparation method:

[0014] Step a, hydroxylating 2-methyl-5-nitroimidazole with ethylene oxide under the action of formic acid and sulfuric acid; adding methanol, carrying out esterification reaction, and distilling to obtain a first liquid system;

[0015] Step b, adding water to the first liquid system, neutralizing once with liquid alkali to a pH of 2 to 3, and separating the solid and the liquid to obtain 2-methyl-5-nitroimidazole and a second liquid system;

[0016] Step c, the second feed liquid system is neutralized twice with alkali solution to a pH of 9-11, and the solid-liquid is separated to obtain a crude metronidazole product and the crude metronidazole mother liquor.

[0017] More preferably, the temperature of the hydroxylation reaction is 85-95°C, the temperature of the esterification reaction is 40-45°C, the temperature of the primary neutralization is 15-20°C, and the temperature of the secondary neutralization is 20-25°C.

[0018] Preferably, in step S1, in the crude metronidazole mother liquor, the concentration of 2-methyl-5-nitroimidazole is 1 to 10 g / L, and the concentration of metronidazole is 1 to 10 g / L.

[0019] The present invention does not impose too many requirements on the production method of metronidazole, as long as the above conditions are met.

[0020] Preferably, in step S1, the mass concentration of sulfuric acid is 30% to 60%.

[0021] Preferably, in step S1, the neutrality is pH=6-7.

[0022] Preferably, in step S1, the concentration is SDR concentration.

[0023] Further preferably, the temperature of the SDR concentration is 70-80° C., and the vacuum degree is lower than -0.08 MPa.

[0024] The present invention adopts advanced SDR concentration technology to distill and remove water, which has higher process safety and lower energy consumption. Compared with double-effect multi-effect evaporation, SDR concentration uses electric energy, which has advantages in energy cost; compared with MVR concentration, SDR concentration does not compress the secondary steam, but uses the heat energy of the secondary steam to heat the heat transfer medium, avoiding safety risks when treating wastewater containing organic solvents (a certain amount of organic solvent methanol remains in the mother liquor of crude metronidazole). In the present invention, the water evaporated by SDR concentration is discharged for environmentally friendly biochemical treatment.

[0025] Preferably, in step S1, the low-carbon alcohol is at least one of methanol, ethanol or isopropanol, more preferably methanol or ethanol.

[0026] Preferably, in step S1, the volume ratio of the low-carbon alcohol to the crude metronidazole mother liquor is (0.15-0.60):1, and more preferably (0.25-0.45):1.

[0027] Preferably, in step S1, the beating temperature is 30-60°C, and the time is 0.5-3h, and more preferably the temperature is 45-50°C, and the time is 1-2h.

[0028] The preferred amount of low-carbon alcohol added and the beating conditions of the present invention can further improve the solubility of organic matter contained in the crude metronidazole mother liquor in the low-carbon alcohol, so as to improve the quality of the subsequent product (material) sodium sulfate.

[0029] Preferably, in step S2, the distillation includes atmospheric distillation and reduced pressure distillation.

[0030] Further preferably, in step S2, the distillation temperature is 75-90°C, and the vacuum degree of the reduced pressure distillation is lower than -0.090 MPa.

[0031] In step S2 of the present invention, the atmospheric distillation and then the reduced pressure distillation can more fully distill out the low-carbon alcohol to ensure the recovery rate and purity of the subsequent products (materials) 2-methyl-5-nitroimidazole and metronidazole. In the present invention, the low-carbon alcohol obtained by distillation can be used again in step S1 for recycling.

[0032] Preferably, in step S2, the volume ratio of the carbon disulfide, the water and the crude metronidazole mother liquor is (0.2-0.5):(0.02-0.1):1, and more preferably (0.25-0.3):(0.03-0.08):1.

[0033] Preferably, in step S2, the beating temperature is 5 to 30°C and the time is 1 to 5 hours, and more preferably the temperature is 10 to 20°C and the time is 1.5 to 3.5 hours.

[0034] The preferred amount of carbon disulfide added, the amount of water added and the pulping conditions of the present invention can further improve the effect of pulping extraction, so as to improve the quality of the subsequent product (material) 2-methyl-5-nitroimidazole.

[0035] For example, in step S3, the liquid separation method may be static liquid separation.

[0036] It should be noted that the aqueous phase obtained by liquid separation in step S3 of the present invention is collected and the ethylene glycol is removed before being recycled.

[0037] Preferably, in step S3, the distillation is atmospheric distillation at a temperature of 50-55°C.

[0038] Preferably, in step S3, the volume ratio of the water to the crude metronidazole mother liquor is (0.02-0.1):1, and more preferably (0.04-0.07):1.

[0039] Preferably, in step S3, the temperature of the vacuum evaporation is 50-55° C., and the vacuum degree is lower than -0.090 MPa.

[0040] In step S3 of the present invention, the carbon disulfide can be more fully evaporated by distilling at normal pressure and then distilling at reduced pressure with water addition to ensure the recovery rate and purity of the subsequent product (material) metronidazole. In the present invention, the carbon disulfide obtained by distillation and vacuum evaporation can be used again in step S2 for recycling.

[0041] Preferably, in step S3, the crystallization temperature is 5 to 25° C., and the time is 0.5 to 2 h. More preferably, the temperature is 10 to 15° C., and the time is 1 to 1.5 h.

[0042] The preferred crystallization conditions of the present invention can further improve the quality of the product (material) metronidazole.

[0043] It should be noted that, in the present invention, the filtrate obtained after the solid-liquid separation in step S3 is used for recycling treatment in the mother liquor of the crude metronidazole. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 The present invention is a schematic flow diagram of a method for recovering materials from a crude metronidazole mother liquor. DETAILED DESCRIPTION

[0045] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0046] The crude metronidazole mother liquor in the examples and comparative examples of the present invention is obtained by the following preparation method:

[0047] Step a, add 1500 kg of 85 wt% formic acid solution into the reaction kettle, control the temperature to 38°C, and dropwise add 850 g of concentrated sulfuric acid to obtain a mixed acid.

[0048] Step b, add 1850g of 2-methyl-5-nitroimidazole to the above mixed acid, raise the temperature to 90°C, and introduce 1400kg of ethylene oxide at a rate of 200kg / h (when 250kg, 600kg and 900kg of ethylene oxide are introduced, 80kg, 75kg and 35kg of concentrated sulfuric acid are added respectively). After the introduction of ethylene oxide is completed, continue to keep warm and carry out hydroxylation reaction for 1h to obtain a feed liquid system.

[0049] Step c, cooling the above feed liquid system to 42° C., adding 900 kg of methanol, carrying out esterification reaction for 2 hours, and distilling out the generated methyl formate at 65° C. until no fraction is produced, thereby obtaining a first feed liquid system.

[0050] Step d, transfer the above-mentioned first liquid feed system into a primary neutralization kettle, add 2000 kg of process water, control the temperature to 18°C, neutralize with liquid alkali to pH = 2.5, centrifuge out the incompletely reacted 2-methyl-5-nitroimidazole, and obtain the second liquid feed system.

[0051] Step e, transferring the second liquid system into a secondary neutralization kettle, controlling the temperature at 22° C., continuously adding liquid alkali until the pH value is 10, centrifuging, obtaining a crude metronidazole product and a crude metronidazole mother liquor, and storing the crude metronidazole mother liquor in a crude mother liquor tank for further treatment.

[0052] After multiple batches of metronidazole were produced, the metronidazole crude mother liquor in the crude mother liquor tank accumulated to a certain amount. The mother liquor in the crude mother liquor tank was sampled and tested. The content of 2-methyl-5-nitroimidazole in the crude mother liquor of metronidazole was 5.38 g / L, and the content of metronidazole was 8.51 g / L.

[0053] In order to better illustrate the present invention, further examples are given below.

[0054] Example 1

[0055] This embodiment provides a method for recovering material from a crude metronidazole mother liquor, comprising the following steps:

[0056] S1, using sulfuric acid with a mass concentration of 60% to adjust 10m 3 The pH of the crude metronidazole mother liquor is 7. After the pH value is adjusted, the crude metronidazole mother liquor is continuously pumped to the SDR high-efficiency energy-saving concentrator for concentration (the SDR concentration temperature is 80°C and the vacuum degree is -0.080MPa). The volume of the concentrated crude metronidazole mother liquor is 2.24m 3 , transferred to the reactor, added 6m 3 Ethanol, after beating at 60℃ for 1h, the material was discharged and centrifuged to dry, and 1089.28kg of sodium sulfate wet product and the first filtrate were obtained. The sodium sulfate wet product was dried to obtain 1003.32kg of sodium sulfate. After testing, the content of sodium sulfate was 99.07% and the whiteness was 83.49%.

[0057] S2, the first filtrate is transferred to a concentration kettle, and ethanol is first distilled out at 90°C under normal pressure until no fraction is produced, and then concentrated under reduced pressure (vacuum degree is -0.090MPa) until no fraction is produced. Cool to room temperature, add 5m 3 Carbon disulfide and 0.8m 3 Water, controlled at 30°C, slurried for 1.5 hours, discharged, centrifuged and dried to obtain solid and the second filtrate. After the solid was dried, 49.69 kg of 2-methyl-5-nitroimidazole was obtained, with a recovery rate of 90.84% ​​and a HPLC purity of 98.36%.

[0058] S3, the second filtrate is transferred to a reactor and allowed to stand for 1 hour for separation, the lower carbon disulfide phase is taken and transferred to a concentration kettle, distilled at 50°C under normal pressure until the feed liquid becomes viscous, 700L of water is added to the residue and distilled (vacuum degree is -0.090MPa) until no carbon disulfide is produced. The residue is cooled to 5°C, crystallized for 1 hour, discharged and centrifuged to dry, and 78.82kg of metronidazole is obtained after the solid is dried, with a recovery rate of 92.03% and an HPLC purity of 99.36%.

[0059] Example 2

[0060] This embodiment provides a method for recovering material from a crude metronidazole mother liquor, comprising the following steps:

[0061] S1, using sulfuric acid with a mass concentration of 45% to adjust 10m 3 The pH of the crude metronidazole mother liquor is 6.5. After the pH value is adjusted, the crude metronidazole mother liquor is continuously pumped to the SDR high-efficiency energy-saving concentrator for concentration (the SDR concentration temperature is 75°C and the vacuum degree is -0.085MPa). The volume of the concentrated crude metronidazole mother liquor is 2.30m 3 , transferred to the reactor, added 4.5m 3 Ethanol, after beating at 50℃ for 2h, the material was centrifuged and dried to obtain 1059.83kg of sodium sulfate wet product and the first filtrate. The sodium sulfate wet product was dried to obtain 984.51kg of sodium sulfate. After testing, the content of sodium sulfate was 99.13% and the whiteness was 83.42%.

[0062] S2, transfer the first filtrate into a concentration kettle, distill the ethanol at 90°C under normal pressure until no fraction is produced, and then concentrate under reduced pressure (vacuum degree is -0.090MPa) until no fraction is produced. Cool to room temperature, add 3m 3 Carbon disulfide and 1m 3 Water, controlled at 20°C, slurried for 3.5 hours, discharged, centrifuged and dried to obtain solid and the second filtrate. After the solid was dried, 49.57 kg of 2-methyl-5-nitroimidazole was obtained, with a recovery rate of 90.88% and a HPLC purity of 98.64%.

[0063] S3, the second filtrate is transferred to a reactor and allowed to stand for 1.2 hours for separation, the lower carbon disulfide phase is taken and transferred to a concentration kettle, distilled at 55°C under normal pressure until the feed liquid becomes viscous, 1000L of water is added to the distillation residue and distillation is continued (vacuum degree is -0.090MPa) until no carbon disulfide is produced. The distillation residue is cooled to 25°C, crystallized for 2 hours, discharged and centrifuged to dry, and 77.64kg of metronidazole is obtained after solid drying, with a recovery rate of 90.43% and an HPLC purity of 99.12%.

[0064] Example 3

[0065] This embodiment provides a method for recovering material from a crude metronidazole mother liquor, comprising the following steps:

[0066] S1, using 35% sulfuric acid to adjust 10m 3 The pH of the crude metronidazole mother liquor is 6. After the pH value is adjusted, the crude metronidazole mother liquor is continuously pumped to the SDR high-efficiency energy-saving concentrator for concentration (the SDR concentration temperature is 70°C and the vacuum degree is -0.090MPa). The volume of the concentrated crude metronidazole mother liquor is 2.35m 3 , transferred to the reactor, added 2.5m 3 Methanol, after beating at 30℃ for 3h, the material was discharged and centrifuged to dry, and 1075.67kg of sodium sulfate wet product and the first filtrate were obtained. The sodium sulfate wet product was dried to obtain 990.42kg of sodium sulfate. After testing, the content of sodium sulfate was 99.05% and the whiteness was 82.91%.

[0067] S2, transfer the first filtrate into a concentration kettle, distill the methanol at 75°C under normal pressure until no fraction is produced, and then concentrate under reduced pressure (vacuum degree is -0.090MPa) until no fraction is produced. Cool to room temperature, add 2m 3 Carbon disulfide and 0.3m 3 Water, controlled at 5°C for 5 hours, centrifuged to dry, and obtained solid and the second filtrate. After the solid was dried, 49.88 kg of 2-methyl-5-nitroimidazole was obtained, with a recovery rate of 91.27% and a HPLC purity of 98.44%.

[0068] S3, the second filtrate is transferred to a reactor and allowed to stand for 1 hour for separation, the lower carbon disulfide phase is taken and transferred to a concentration kettle, distilled at 50°C under normal pressure until the feed liquid becomes viscous, 200L of water is added to the distillation residue and distillation is continued (vacuum degree is -0.085MPa) until no carbon disulfide is produced. The distillation residue is cooled to 15°C, crystallized for 1.5 hours, discharged and centrifuged to dry, and 78.47kg of metronidazole is obtained after solid drying, with a recovery rate of 91.66% and an HPLC purity of 99.40%.

[0069] Example 4

[0070] This embodiment provides a method for recovering material from a crude metronidazole mother liquor, comprising the following steps:

[0071] S1, using 30% sulfuric acid to adjust 10m 3 The pH of the crude metronidazole mother liquor is 6.5. After the pH value is adjusted, the crude metronidazole mother liquor is continuously pumped to a double-effect multi-effect evaporator for concentration (the concentration temperature is 75°C and the vacuum degree is -0.085MPa). The volume of the concentrated crude metronidazole mother liquor is 2.28m 3, transferred to the reactor, added 1.5m 3 Methanol, after beating at 45℃ for 0.5h, the material was discharged and centrifuged to dry, and 1098.08kg of sodium sulfate wet product and the first filtrate were obtained. The sodium sulfate wet product was dried to obtain 1012.85kg of sodium sulfate. After testing, the content of sodium sulfate was 99.12% and the whiteness was 82.76%.

[0072] S2, transfer the first filtrate into a concentration kettle, distill the methanol at 75°C under normal pressure until no fraction is produced, and then concentrate under reduced pressure (vacuum degree is -0.090MPa) until no fraction is produced. Cool to room temperature, add 2.5m 3 Carbon disulfide and 0.2m 3 Water, controlled at 10°C for 1 hour, centrifuged to dry, and obtained solid and the second filtrate. After the solid was dried, 50.14 kg of 2-methyl-5-nitroimidazole was obtained, with a recovery rate of 91.56% and a HPLC purity of 98.25%.

[0073] S3, the second filtrate is transferred to a reactor and allowed to stand for 1.2 hours for separation, the lower carbon disulfide phase is taken and transferred to a concentration kettle, distilled at 55°C under normal pressure until the feed liquid becomes viscous, 400L of water is added to the distillation residue and distilled (vacuum degree is -0.090MPa) until no carbon disulfide is produced. The distillation residue is cooled to 10°C, crystallized for 0.5 hours, discharged and centrifuged to dry, and 78.12kg of metronidazole is obtained after the solid is dried, with a recovery rate of 91.19% and a HPLC purity of 99.34%.

[0074] Example 5

[0075] This embodiment provides a method for recovering materials from a crude metronidazole mother liquor, which is similar to that of Embodiment 2, except that methanol is replaced with isopropanol in step S1, and the distillation in step S2 only includes atmospheric distillation. Specifically, the following steps are included:

[0076] S1, using sulfuric acid with a mass concentration of 45% to adjust 10m 3 The pH of the crude metronidazole mother liquor is 6.5. After the pH value is adjusted, the crude metronidazole mother liquor is continuously pumped to the SDR high-efficiency energy-saving concentrator for concentration (the SDR concentration temperature is 75°C and the vacuum degree is -0.085MPa). The volume of the concentrated crude metronidazole mother liquor is 2.31m 3 , transferred to the reactor, added 4.5m 3 Isopropanol, after beating at 50℃ for 2h, the material was centrifuged and dried to obtain 1109.57kg sodium sulfate wet product and the first filtrate. The sodium sulfate wet product was dried to obtain 1054.90kg sodium sulfate. After testing, the sodium sulfate content was 95.61% and the whiteness was 82.13%.

[0077] S2, the first filtrate is transferred to a concentration kettle, and isopropanol is distilled out at 90°C under normal pressure until no fraction is produced. Cool to room temperature, and add 3m 3 Carbon disulfide and 1m 3 Water, controlled at 20°C, slurried for 3.5 hours, discharged, centrifuged and dried to obtain solid and second filtrate. After the solid was dried, 48.47 kg of 2-methyl-5-nitroimidazole was obtained, with a recovery rate of 87.46% and a HPLC purity of 97.07%.

[0078] S3, the second filtrate is transferred to a reactor and allowed to stand for 1.2 hours for separation, the lower carbon disulfide phase is taken and transferred to a concentration kettle, distilled at 55°C under normal pressure until the feed liquid becomes viscous, 1000L of water is added to the distillation residue and distillation is continued (vacuum degree is -0.090MPa) until no carbon disulfide is produced. The distillation residue is cooled to 25°C, crystallized for 2 hours, discharged and centrifuged to dry, and 75.84kg of metronidazole is obtained after solid drying, with a recovery rate of 88.35% and a HPLC purity of 99.14%.

[0079] Comparative Example 1

[0080] This comparative example provides a method for recovering materials from the mother liquor of crude metronidazole, which is similar to Example 2, except that: in step S1, the SDR high-efficiency energy-saving concentrator is replaced by an MVR concentrator; in step S3, the atmospheric distillation is replaced by reduced pressure distillation, and vacuum evaporation is performed without adding water. Specifically, the following steps are included:

[0081] S1, using sulfuric acid with a mass concentration of 45% to adjust 10m 3 The pH of the crude metronidazole mother liquor is 6.5. After the pH value is adjusted, the crude metronidazole mother liquor is continuously pumped to the MVR concentrator for concentration (the concentration temperature is 75°C and the vacuum degree is -0.085MPa). The volume of the concentrated crude metronidazole mother liquor is 2.43m 3 , transferred to the reactor, added 4.5m 3 Ethanol, after beating at 50℃ for 2h, the material was centrifuged and dried to obtain 1033.84kg of sodium sulfate wet product and the first filtrate. The sodium sulfate wet product was dried to obtain 962.88kg of sodium sulfate. After testing, the content of sodium sulfate was 99.04% and the whiteness was 82.63%.

[0082] S2 is the same as Example 2 and will not be described again. 48.63 kg of 2-methyl-5-nitroimidazole was obtained with a recovery rate of 88.35% and a HPLC purity of 97.75%.

[0083] S3, the second filtrate is transferred to a reactor and allowed to stand for 1.2 hours for separation, the lower carbon disulfide phase is taken and transferred to a concentration kettle, and vacuum distilled at 55°C and a vacuum degree of -0.090MPa until no carbon disulfide is produced. The residue is cooled to 25°C, crystallized for 2 hours, discharged and centrifuged to dry, and 75.95 kg of metronidazole is obtained after the solid is dried, with a recovery rate of 85.17% and a HPLC purity of 95.43%.

[0084] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for recovering material from a crude metronidazole mother liquor, characterized in that: The following steps are involved: S1, adjusting the pH value of the crude metronidazole mother liquor to neutral with sulfuric acid, and concentrating; adding low-carbon alcohol to the concentrate, beating, and separating the solid and liquid to obtain sodium sulfate and a first filtrate; The metronidazole crude product mother liquor is obtained by the following preparation method: Step a, hydroxylating 2-methyl-5-nitroimidazole with ethylene oxide under the action of formic acid and sulfuric acid; adding methanol, carrying out esterification reaction, and distilling to obtain a first liquid system; Step b, adding water to the first liquid system, neutralizing once with liquid alkali to a pH of 2-3, and separating the solid and the liquid to obtain 2-methyl-5-nitroimidazole and a second liquid system; Step c, the second feed liquid system is neutralized twice with alkali solution to a pH of 9-11, and solid-liquid separation is performed to obtain a crude metronidazole product and the crude metronidazole mother liquor; S2, distilling the first filtrate to remove low-carbon alcohols; Add carbon disulfide and water to the distillation residue, slurry, and separate the solid and liquid to obtain 2-methyl-5-nitroimidazole and the second filtrate; S3, separating the second filtrate, taking the carbon disulfide phase for distillation, adding water to the residue, evaporating under vacuum to remove the carbon disulfide; cooling the residue, crystallizing, and separating the solid from the liquid to obtain metronidazole.

2. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1, characterized in that: In step S1, the temperature of the hydroxylation reaction is 85-95°C, the temperature of the esterification reaction is 40-45°C, the temperature of the primary neutralization is 15-20°C, and the temperature of the secondary neutralization is 20-25°C.

3. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1 or 2, characterized in that: In the crude metronidazole mother liquor, the concentration of 2-methyl-5-nitroimidazole is 1-10 g / L, and the concentration of metronidazole is 1-10 g / L.

4. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1, characterized in that: In step S1, the concentration is SDR concentration; the temperature of the SDR concentration is 70-80° C., and the vacuum degree is lower than -0.08 MPa.

5. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1, characterized in that: In step S1, the volume ratio of the low-carbon alcohol to the metronidazole crude product mother liquor is (0.15-0.60):1; and / or In step S2, the volume ratio of the carbon disulfide, the water and the metronidazole crude product mother liquor is (0.2-0.5):(0.02-0.1):1; and / or In step S3, the volume ratio of the water to the metronidazole crude product mother liquor is (0.02-0.1):

1.

6. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1, characterized in that: In step S1, the mass concentration of the sulfuric acid is 30% to 60%; and / or In step S1, the low-carbon alcohol is at least one of methanol, ethanol or isopropanol.

7. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1, characterized in that: In step S1, the beating temperature is 30-60°C and the time is 0.5-3h; and / or In step S2, the beating temperature is 5-30°C and the time is 1-5h; and / or In step S3, the crystallization temperature is 5-25° C. and the time is 0.5-2 h.

8. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1, characterized in that: In step S2, the distillation includes atmospheric distillation and reduced pressure distillation; The distillation temperature is 75-90° C., and the vacuum degree of the reduced pressure distillation is lower than -0.090 MPa.

9. The method for recovering material from a crude metronidazole mother liquor as claimed in claim 1, characterized in that: In step S3, the distillation is atmospheric distillation at a temperature of 50-55° C.; and / or In step S3, the temperature of the vacuum evaporation is 50-55° C., and the vacuum degree is lower than -0.090 MPa.

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