Method for recovering organic solvent from waste liquid of potassium clavulanate production

Abstract

The present invention relates to a method for recovering an organic solvent from potassium clavulanate production wastewater. The method comprises a desalting process, a rough distillation process, an alkali extraction process and a dehydration process. The present invention adopts a scheme combining distillation with pervaporation membrane dehydration technology, and combines the alkali extraction process to effectively remove salt and water in the recovered solvent, significantly reducing process energy consumption, and the recovered solvent can be reused in the preparation of potassium clavulanate.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceuticals and relates to a method for recovering an organic solvent from waste liquid produced by potassium clavulanate production. Background Art

[0002] Potassium clavulanate is a β-lactamase inhibitor. It is ineffective when used alone. It is often used in combination with penicillins to overcome the drug resistance caused by microbial β-lactamase production and improve the efficacy. Potassium clavulanate is produced by reacting and crystallizing with tert-butylamine clavulanate as a raw material and a salt-forming agent, potassium isooctanoate. The reaction equation is as follows:

[0003]

[0004] The paper "Research on Reaction Crystallization of Potassium Clavulanate" published by Liu Baoshu et al. reported the process scheme of reaction and crystallization of potassium clavulanate. At present, the crystallization solvents of potassium clavulanate are mainly ethanol, isopropanol or a mixture of the two. According to the analysis of the production process of potassium clavulanate, the components of the production waste liquid mainly include: organic solvent as the main component, that is, organic solvent ethanol, isopropanol or a mixture of the two; uncrystallized potassium clavulanate; potassium isooctanoate and tert-butylamine salt of isooctanoic acid generated by the reaction. As an example, the pH of the production waste liquid is generally 8 to 10, wherein the organic solvent is ethanol, isopropanol or a mixture of the two, wherein the ratio of ethanol and isopropanol in the mixture system of ethanol and isopropanol is a mixture of any ratio of the two; the concentration range of uncrystallized potassium clavulanate is 0.1wt% to 1wt%; the concentration range of unreacted potassium isooctanoate is 0.5wt% to 2.5wt%; the concentration range of tert-butylamine salt of isooctanoic acid generated by the reaction is 2wt% to 5wt%; and the water content is 1wt% to 5wt%.

[0005] Since potassium clavulanate is highly soluble in water, the reuse standard of the recovered solvent has strict requirements not only in terms of impurity control, but also in terms of the moisture content of the recovered solvent. According to the traditional tower bottom distillation recovery theory, the recovery of the above-mentioned component waste liquid needs to be subjected to desalination, isooctanoic acid removal, and impurity removal, and also needs to be strictly dehydrated. In order to achieve the above purpose, it is necessary to go through multiple distillation and extractive distillation methods to reach the reuse standard. There are problems such as complicated process, introduction of extraction solvent, and huge energy consumption during the operation process.

[0006] In recent years, with the development of inorganic pervaporation membrane technology, inorganic pervaporation membrane technology has made great progress in the dehydration of organic solvents and achieved industrial production. However, in the process of recovering organic solvents from waste liquid of potassium clavulanate production, if the waste liquid is not fully pretreated, the membrane pores will be seriously blocked, which affects the application of the technology. Summary of the invention

[0007] In view of the above problems existing in the prior art, the present invention is completed. The purpose of the present invention is to provide an effective method for recovering an organic solvent from waste liquid produced by potassium clavulanate, which is simple to operate, effectively removes salt and water in the recovered solvent, can be reused in the preparation of potassium clavulanate, and significantly reduces process energy consumption.

[0008] According to the present invention, the method for recovering an organic solvent from potassium clavulanate production waste liquid provided by the present invention comprises:

[0009] (1) Desalination process

[0010] Adding concentrated sulfuric acid to the waste liquid from potassium clavulanate production to convert the tert-butylamine isooctanoate salt therein into tert-butylamine sulfate salt for precipitation, and filtering to obtain a feed liquid from which the tert-butylamine sulfate salt has been removed;

[0011] (2) Rough Steaming Process

[0012] The feed liquid from which the tert-butylamine sulfate salt has been removed is transferred into a distillation tower for distillation, and an organic solvent fraction with improved purity is collected at the top of the tower;

[0013] (3) Alkali extraction process

[0014] Adding an alkaline salt water extractant to the organic solvent fraction collected from the top of the tower, stirring and standing at 50°C to 80°C to obtain an organic solvent layer with improved purity;

[0015] (4) Dehydration process

[0016] The organic solvent layer with improved purity obtained above is heated and vaporized, and the vaporized steam is passed through a pervaporation membrane separation unit to separate the organic solvent and water to obtain a purified organic solvent.

[0017] Figure 1 The process flow chart of the method for recovering organic solvent from potassium clavulanate production waste liquid of the present invention is as follows. Figure 1 , more specifically describing the method of the present invention for recovering organic solvent from potassium clavulanate production waste liquid.

[0018] As described above, the pH value of the potassium clavulanate production waste liquid is generally 8-10, wherein the organic solvent is ethanol, isopropanol or a mixture of the two; the concentration range of uncrystallized potassium clavulanate is 0.1wt%-1wt%; the concentration range of unreacted potassium isooctanoate is 0.5wt%-2.5wt%; the concentration range of tert-butylamine isooctanoate salt generated by the reaction is 2wt%-5wt%; and the water content is 1wt%-5wt%.

[0019] In the desalination process of step (1), concentrated sulfuric acid is added to the waste liquid of potassium clavulanate production to convert tert-butylamine isooctanoate therein into tert-butylamine sulfate, which is then precipitated and filtered to obtain a feed liquid from which tert-butylamine sulfate is removed.

[0020] Specifically, concentrated sulfuric acid (e.g., about 98% concentrated sulfuric acid (mass percentage)) is added to the waste liquid of potassium clavulanate production to make its pH value 1 to 5.5, and preferably 2 to 4.5; at this time, the tert-butylamine salt of isooctanoic acid in the waste liquid is converted into isooctanoic acid and tert-butylamine sulfate, the isooctanoic acid is dissolved in the waste liquid, and the tert-butylamine sulfate is precipitated in the form of a solid. The tert-butylamine sulfate is filtered out by filtration, so that most of the tert-butylamine ions can be removed as "tert-butylamine sulfate" through this step.

[0021] In the rough distillation process of step (2), the feed liquid from which the tert-butylamine sulfate salt has been removed is transferred into a distillation tower for distillation, and an organic solvent fraction with improved purity is collected at the top of the tower.

[0022] Specifically, the feed liquid from which the tert-butylamine sulfate salt is removed is transferred to a distillation tower for distillation, and the distillation tower is a continuous distillation tower or an intermittent distillation tower, preferably a continuous distillation tower. The distillation is not limited and can be carried out according to conventional processes in the art.

[0023] The feed liquid from which the tert-butylamine sulfate salt has been removed is transferred to a distillation tower for distillation, and an organic solvent fraction with improved purity, i.e., ethanol, isopropanol, or a mixture of the two with improved purity, is collected at the top of the tower; and the waste liquid remaining at the bottom of the tower contains residual tert-butylamine sulfate salt, isooctanoic acid, and other high-boiling point substances, which can be further processed as needed. This step is distilled under acidic conditions, and the acidic compounds introduced from the clavulanic acid tert-butylamine in the system, such as formic acid, acetic acid, propionic acid, etc., will react with ethanol and isopropanol to generate ester compounds under the action of sulfuric acid, and a small amount of clavulanic acid and its degradation products are also distilled out with the bottom of the tower.

[0024] In the alkali extraction process of step (3), an alkali salt water extractant is added to the organic solvent fraction collected from the top of the tower, stirred at 50°C to 80°C for 2 to 3 hours, and allowed to stand to separate layers to obtain an organic solvent layer with improved purity.

[0025] Specifically, an alkaline salt water extractant is added to the organic solvent fraction collected from the top of the tower, wherein the alkaline salt water extractant is an aqueous solution of potassium hydroxide and an inorganic potassium salt, wherein the inorganic potassium salt is potassium carbonate, potassium chloride or potassium nitrate, preferably potassium carbonate; the alkaline salt water extractant is prepared according to the following weight ratio: the weight ratio of water: potassium hydroxide: inorganic potassium salt is 1: 0.1-0.6: 0.2-0.6; the amount of the alkaline salt water extractant added is 10%-20% of the volume of the organic solvent fraction collected from the top of the tower.

[0026] The alkali extraction process can hydrolyze the ester compounds in the organic solvent fraction into salts, destroy clavulanic acid and its degradation products into salts, and extract the relevant impurities into the water phase by liquid separation operation at 50° C. to 80° C., and a small amount of water in the water phase will enter the organic solvent layer. Therefore, the obtained organic solvent layer with improved purity has a water content of 5wt% to 20wt% and a pH of 8 to 10.

[0027] In the dehydration process of step (4), the organic solvent layer with improved purity obtained above is heated and vaporized, and the vaporized steam is passed through a pervaporation membrane separation unit to separate the organic solvent and water to obtain a dehydrated and purified organic solvent.

[0028] The heating and vaporization of the organic solvent layer with improved purity can be carried out by using a vaporization tower. The vaporization tower can be an intermittent pressurized distillation tower, which is used to preheat the organic solvent in the organic solvent layer to 90°C to 150°C and then enter the pervaporation membrane separation unit in the form of steam with a steam pressure of 0.1MPa to 0.3MPa.

[0029] The pervaporation membrane separation unit is composed of 10-50 membrane separators connected in parallel or in series to achieve different processing requirements and production capacities. The membrane used in the membrane separator is a water-permeable membrane, preferably a chitosan membrane, a PVA membrane, a PVDF membrane, a sodium alginate membrane or a molecular sieve membrane.

[0030] In the dehydration process, the pervaporation membrane separation unit uses the pervaporation membrane as the dividing line, which can be briefly described as a high-pressure side and a low-pressure side. The high-pressure side is the high-pressure solvent vapor input through the vaporization tower, and the low-pressure side is connected to the vacuum system, and the pressure is maintained at 200Pa-5000Pa by vacuum pump suction; water molecules pass through the pervaporation membrane under the pressure difference between the high-pressure side and the low-pressure side, and enter the low-pressure side from the high-pressure side, thereby realizing the separation of water molecules and organic solvents. The two phases after separation are condensed to obtain recovered solvent and water respectively.

[0031] The obtained dehydrated and purified organic solvent has a water content of 0.1wt%-0.3wt%.

[0032] Beneficial Effects

[0033] Compared with the existing distillation technology, the present invention adopts a scheme combining distillation with pervaporation membrane dehydration technology. The present invention has the advantage of not introducing an organic extraction solvent, avoiding the operation of extraction distillation and reducing the influence of the organic extraction solvent on product quality. The cancellation of extraction distillation also saves a large amount of organic solvent and energy consumption, saving recovery costs.

[0034] The alkali extraction process of the alkali salt water extractant proposed in the present invention is different from the traditional alkali dehydration operation. After the alkali extraction process of the present invention, the water content of the feed liquid is increased, but the quality of the liquid to be recovered is significantly improved, and the ester impurities and macromolecular organic compounds in the recovery solvent are completely degraded. These degradation products are extracted into the alkali salt water phase, which not only improves the quality of the recovery solvent, but also solves the problem of pervaporation blockage.

[0035] The dehydration process proposed in the present invention adopts an intermittent pressurized distillation tower to replace the existing traditional heat exchanger vaporization mode, thereby achieving the purpose of vaporizing the feed and separating the salt compounds in the organic solvent, reducing the pressure of salt discharge and clogging when the pervaporation membrane separation unit is working, and improving the working efficiency.

[0036] The purity of the organic solvent product recovered by the method of the present invention can be controlled to be above 99%, and the moisture content can be controlled to be below 0.3%, so the product has the conditions for being recycled and reused in the production of potassium clavulanate. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 The present invention is a process flow chart of a method for recovering an organic solvent from waste liquid produced by potassium clavulanate. DETAILED DESCRIPTION

[0038] The method for recovering an organic solvent from potassium clavulanate production waste liquid of the present invention is further described in detail below by way of examples, and the protection scope of the present invention is not limited to the following examples, which are listed only for illustrative purposes and do not limit the present invention in any way.

[0039] Example 1

[0040] 9500L of potassium clavulanate ethanol production waste liquid (waste liquid components: solvent is ethanol, water content is 5%, pH is 8.3, potassium clavulanate concentration is 0.5%, potassium isooctanoate concentration is 0.8%, isooctanoic acid tert-butylamine salt concentration is 3%, by weight percentage) is taken, stirring is started, concentrated sulfuric acid is added to adjust pH=4, and tert-butylamine sulfate solid is precipitated in the process. The feed liquid is filtered through a centrifuge, the filter residue can be used to recover tert-butylamine, and the filtrate is collected to obtain a feed liquid from which tert-butylamine sulfate is removed.

[0041] The continuous distillation tower is opened, and the above-mentioned feed liquid is input into the continuous distillation tower for distillation. About 8600L of ethanol fraction with improved purity at 73°C-80°C (based on local atmospheric pressure) is collected at the top of the tower, and waste liquid containing isooctanoic acid, etc. is collected at the bottom of the tower (which can be further processed as needed).

[0042] 360 kg of potassium hydroxide and 180 kg of potassium chloride were added to 700 kg of water and mixed and dissolved to obtain an alkaline salt water extractant of potassium chloride and potassium hydroxide aqueous solution. The extractant was mixed with the above fraction and stirred and heated to 70°C, and kept stirring for 2 hours, then allowed to stand for 1 hour and separated while hot to obtain about 8900 L of extract, the water content of which was 7.8 wt%, and pH 8.9.

[0043] The extract is transferred to a pressurized distillation tower and the temperature is raised to distill. When the steam pressure in the kettle reaches 0.15 MPa, the high-temperature gas at the top of the tower enters a pervaporation membrane separation unit. The pervaporation membrane separation unit is composed of a membrane separator composed of a PVDF membrane for alcohol-water separation. The high-pressure pressure is 0.15 MPa, and the low-pressure side pressure is controlled at 3000 Pa. After dehydration, about 8000 L of recovered ethanol is obtained, with a water content of 0.15 wt% and a purity of 99.3%.

[0044] Example 2

[0045] Take 11000L of isopropanol waste liquid produced by potassium clavulanate (waste liquid components: solvent isopropanol, water 2%, pH 9.1, potassium clavulanate concentration 0.3%, potassium isooctanoate concentration 0.9%, isooctanoic acid tert-butylamine salt concentration 2.6%, by weight percentage), start stirring, add concentrated sulfuric acid to adjust pH=3, tert-butylamine sulfate solid precipitates in the process. The feed liquid is filtered through a centrifuge, the filter residue can be used to recover tert-butylamine, and the filtrate is collected to obtain a feed liquid from which tert-butylamine sulfate is removed.

[0046] The continuous distillation tower is opened, and the feed liquid is input into the continuous distillation tower for distillation. About 10,000 L of the propanol fraction with improved purity at 75° C.-85° C. is collected at the top of the tower, and the waste liquid containing isooctanoic acid, etc. is collected at the bottom of the tower (which can be further processed as needed).

[0047] 500 kg of potassium hydroxide and 300 kg of potassium carbonate were added to 1000 kg of water and mixed and dissolved to obtain an alkaline salt water extractant of potassium carbonate and potassium hydroxide aqueous solution. The extractant was mixed with the above fraction and stirred and heated to 65°C, and kept stirring for 3 hours, then allowed to stand for 1 hour and separated while hot to obtain about 10500 L of extract, the water content of the extract was 8.2 wt%, and the pH was 9.6.

[0048] The extract is transferred to a pressure distillation tower and the temperature is raised to distill. When the steam pressure in the kettle reaches 0.2 MPa, the high-temperature gas at the top of the tower enters the pervaporation membrane separation unit. The pervaporation membrane separation unit composed of a membrane separator composed of NaA membrane is used to separate alcohol from water. The high-pressure pressure is 0.2 MPa, and the low-pressure side pressure is controlled at 1000 Pa. After dehydration, about 9500L of recovered isopropyl alcohol is obtained, with a water content of 0.11wt% and a purity of 99.5%.

[0049] Example 3

[0050] Take 12500L of mixed waste liquid of ethanol and isopropanol produced by potassium clavulanate (waste liquid components: solvent is ethanol: isopropanol = 1:1 V / V, water content is 4.3%, pH is 8.5, potassium clavulanate concentration is 0.5%, potassium isooctanoate concentration is 1.1%, isooctanoic acid tert-butylamine salt concentration is 2.2%, by weight percentage), start stirring, add concentrated sulfuric acid to adjust pH=3.5, and tert-butylamine sulfate solid is precipitated in the process. The feed liquid is filtered through a centrifuge, the filter residue can be used to recover tert-butylamine, and the filtrate is collected to obtain a feed liquid from which tert-butylamine sulfate salt is removed.

[0051] The continuous distillation tower is opened, and the feed liquid is input into the continuous distillation tower for distillation. About 11000L of ethanol isopropanol fraction with improved purity at 70°C-85°C is collected at the top of the tower, and the waste liquid containing isooctanoic acid, etc. is collected at the bottom of the tower (which can be further processed as needed).

[0052] 300 kg of potassium hydroxide and 300 kg of potassium nitrate were added to 1500 kg of water and mixed and dissolved to obtain an alkaline salt water extractant of potassium nitrate and potassium hydroxide aqueous solution. The extractant was mixed with the above fraction and stirred and heated to 80°C, and kept stirred for 2 hours, then allowed to stand for 1 hour and separated while hot to obtain about 11900 L of extract, the water content of which was 14 wt%, and pH 9.9.

[0053] The extract is transferred to a pressure distillation tower and the temperature is raised to distill. When the steam pressure in the kettle reaches 0.23 MPa, the high-temperature gas at the top of the tower enters a pervaporation membrane separation unit. The pervaporation membrane separation unit is composed of a membrane separator composed of NaA membranes for alcohol-water separation. The high-pressure pressure is 0.23 MPa, and the low-pressure side pressure is controlled at 5000 Pa. After dehydration, about 10,000 L of the recovered ethanol-isopropanol mixed liquid is obtained, with a water content of 0.25 wt% and a purity of 99.2%.

Claims

1. A method for recovering an organic solvent from waste liquid produced by potassium clavulanate, comprising: (1) Desalination process Adding concentrated sulfuric acid to the waste liquid from potassium clavulanate production to convert the tert-butylamine isooctanoate salt therein into tert-butylamine sulfate salt for precipitation, and filtering to obtain a feed liquid from which the tert-butylamine sulfate salt has been removed; (2) Rough Steaming Process The feed liquid from which the tert-butylamine sulfate salt has been removed is transferred into a distillation tower for distillation, and an organic solvent fraction with improved purity is collected at the top of the tower; (3) Alkali extraction process Adding an alkaline salt water extractant to the organic solvent fraction collected from the top of the tower, stirring and standing at 50°C to 80°C to obtain an organic solvent layer with improved purity; (4) Dehydration process The organic solvent layer with improved purity obtained above is heated and vaporized, and the vaporized steam is separated from the organic solvent and water by a pervaporation membrane separation unit to obtain a purified organic solvent. The pH value of the potassium clavulanate production waste liquid is 8-10, the organic solvent in the waste liquid is ethanol, isopropanol or a mixture of the two, the concentration of potassium clavulanate is in the range of 0.1wt%-1wt%, the concentration of potassium isooctanoate is in the range of 0.5wt%-2.5wt%, the concentration of tert-butylamine isooctanoate is in the range of 2wt%-5wt%, and the water content is in the range of 1wt%-5wt%; In the alkali extraction process of step (3), the alkaline salt water extractant is an aqueous solution of potassium hydroxide and an inorganic potassium salt, and the inorganic potassium salt is potassium carbonate, potassium chloride or potassium nitrate; the alkaline salt water extractant is prepared according to the following weight ratio: the weight ratio of water: potassium hydroxide: inorganic potassium salt is 1: 0.1-0.6: 0.2-0.6; the amount of the alkaline salt water extractant added is 10%-20% of the volume of the organic solvent fraction.

2. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 1, wherein In the desalination process of step (1), 98% by mass of concentrated sulfuric acid is added to the potassium clavulanate production wastewater to make its pH value 1 to 5.

5.

3. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 1, wherein: In the rough distillation process of step (2), the distillation tower is a continuous distillation tower or a batch distillation tower.

4. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 1, wherein In the alkali extraction process of step (3), an alkali salt water extractant is added to the organic solvent fraction collected from the top of the tower, stirred at 50° C. to 80° C. for 2 to 3 hours, and allowed to stand to separate into layers, thereby obtaining an organic solvent layer with improved purity.

5. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 1, characterized in that: In the alkaline extraction process of step (3), the inorganic potassium salt is potassium carbonate.

6. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 1, wherein In the dehydration process of step (4), a vaporization tower is used to heat and vaporize the organic solvent layer with improved purity.

7. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 6, wherein: The vaporization tower is an intermittent pressurized distillation tower, and the steam enters the pervaporation membrane separation unit in the form of steam at the top of the tower, and the steam pressure is 0.1MPa to 0.3MPa.

8. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 1, wherein In the dehydration process of step (4), the pervaporation membrane of the pervaporation membrane separation unit is a chitosan membrane, a PVA membrane, a PVDF membrane, a sodium alginate membrane or a molecular sieve membrane.

9. The method for recovering an organic solvent from waste liquid produced by potassium clavulanate according to claim 1, wherein: The purified organic solvent is recovered, wherein the water content is 0.1 wt % to 0.3 wt %.

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