Method for separating alpha-ketoglutaric acid and pyruvic acid

Abstract

The invention provides a method for separating alpha-ketoglutaric acid and pyruvic acid, which comprises the following steps: (1) carrying out multi-stage extraction on a raw material solution containing alpha-ketoglutaric acid and pyruvic acid to obtain extract liquor and raffinate; wherein an extracting agent for multi-stage extraction comprises a hydrophobic deep-eutectic solvent; (2) carrying out reverse extraction on the extract liquor, acidizing an extract phase obtained by reverse extraction, and crystallizing to obtain alpha-ketoglutaric acid; and (3) concentrating and drying the raffinate to obtain pyruvic acid. The method provided by the invention has the advantages of high selectivity and simple process, and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of chemical separation, and in particular to a method for separating alpha-ketoglutaric acid and pyruvic acid. Background Art

[0002] α-Ketoglutaric acid (AKG) is a white fine crystalline powder at room temperature. It participates in the tricarboxylic acid cycle and amino acid metabolism in microorganisms. It is an important dicarboxylic acid and plays a vital role in the intermediate metabolism process of regulating carbon-nitrogen balance. In the field of food health, the mixture of AKG and L-arginine is called arginine mixture, which is added to functional beverages as a nutritional enhancer; it is used in tissue engineering and drug delivery in biomedicine. Pyruvate (PYR), also known as 2-oxopropionic acid, α-hydroxypropionic acid, and acetyl formic acid, participates in energy metabolism in cells and has a wide range of applications in pharmaceuticals, daily chemicals, agriculture, and food. Calcium pyruvate can be used as a dietary supplement and has weight loss and health benefits; ethyl pyruvate can inhibit the synthesis of tyrosinase in the epidermis and has the effect of whitening skin; PYR also has the effect of treating depression and brain tissue trauma in clinical practice.

[0003] In the process of producing α-ketoglutaric acid, pyruvic acid is an important byproduct with a high content, and the two coexist in the raw material solution. AKG and PYR are both keto acids, containing carbonyl and carboxyl groups, and have similar molecular structures. The difference is that AKG has one more methyl group and one more carboxyl group than PYR, as shown in Formula 1 and Formula II. The extra methyl group weakens the polarity of AKG, while the extra carboxyl group increases its polarity and acidity. Under their combined influence, the polarity and acidity of AKG and PYR are close, and the pKa of AKG is 1 The pKa of AKG is 2.47 (25°C), and the pKa of PYR is 2.39 (25°C), so it is difficult to separate AKG from PYR.

[0004]

[0005] CN107739308B discloses a method for simultaneously extracting AKG and PYR from a microbial fermentation liquid or an enzyme conversion liquid, wherein the pretreated fermentation liquid is passed through a silica gel chromatography column, and a mixed solvent of different compositions is used for gradient elution, and the components enriched in AKG and PYR are respectively collected, and the AKG and PYR products are obtained by solvent evaporation, drying, and crushing. The process is cumbersome, and a large amount of organic waste liquid will be generated during the separation process, and the product yield and purity are both low. CN106496019A discloses a method for simultaneously extracting AKG and PYR from a microbial fermentation liquid or an enzyme conversion liquid containing α-ketoglutaric acid and pyruvic acid, wherein the pretreated raw material liquid is extracted three times with a water-insoluble organic solvent ethyl acetate or butyl acetate, and the crystallization method or the crystallization assisted by high vacuum decompression distillation method is selected according to the different ratios of AKG and PYR concentrations in the extract. The extractant ethyl acetate used in the process has a large mutual solubility with water, and the time cost and energy consumption required for the crystallization method are high, which is not conducive to amplification, and the industrial feasibility is low.

[0006] Therefore, there is an urgent need to develop a method for efficiently separating AKG and PYR from a raw material solution containing AKG and PYR. Summary of the invention

[0007] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a method for separating α-ketoglutaric acid and pyruvic acid. The present invention uses a hydrophobic deep eutectic solvent as an extractant, has higher separation selectivity, is simple in process, and is environmentally friendly. The multi-stage extraction process has a better effect of separating α-ketoglutaric acid than pyruvic acid, which is conducive to realizing industrial production.

[0008] The present invention provides a method for separating α-ketoglutarate and pyruvate, which comprises:

[0009] (1) subjecting a raw material liquid containing α-ketoglutaric acid and pyruvic acid to multi-stage extraction to obtain an extract and a raffinate; wherein the extractant of the multi-stage extraction comprises a hydrophobic low eutectic solvent;

[0010] (2) stripping the extract, acidifying and crystallizing the extract phase obtained by stripping to obtain α-ketoglutaric acid;

[0011] (3) Concentrating and drying the raffinate to obtain pyruvic acid.

[0012] In some embodiments, the hydrophobic deep eutectic solvent comprises a Class III deep eutectic solvent.

[0013] In some embodiments, the hydrophobic deep eutectic solvent comprises a Class V deep eutectic solvent.

[0014] In some embodiments, the hydrophobic deep eutectic solvent includes Class III and Class V deep eutectic solvents.

[0015] In some embodiments, the hydrophobic deep eutectic solvent comprises a hydrogen bond acceptor and a hydrogen bond donor, and the hydrogen bond acceptor and the hydrogen bond donor are of different types.

[0016] In some embodiments, the hydrophobic deep eutectic solvent consists of a hydrogen bond acceptor and a hydrogen bond donor.

[0017] According to the interaction mechanism between the extractant and the solute in the raw liquid, extraction is divided into physical extraction and chemical reaction extraction. Low eutectic solvents have the advantages of low toxicity, non-volatility, recyclability and recycling. Hydrogen bond acceptors containing atoms with large electronegativity such as N, O, Cl, etc. can form hydrogen bonds of different strengths with α-ketoglutaric acid and pyruvic acid, thereby achieving the separation of the two. The number and strength of the interaction sites of hydrophobic low eutectic solvents for α-ketoglutaric acid and pyruvic acid are different. The hydrogen bond effect formed by the low eutectic solvent and α-ketoglutaric acid is stronger. α-ketoglutaric acid is enriched in the extraction phase, and pyruvic acid is enriched in the residual phase. Using hydrophobic low eutectic solvents to separate α-ketoglutaric acid and pyruvic acid has a better separation effect.

[0018] α-ketoglutaric acid and pyruvic acid are similar in structure and have similar physical and chemical properties. Pyruvic acid is unstable and easily polymerized at higher temperatures and pH values, and exists in the form of dimers, so it is not feasible to use alkaline reagents in direct distillation and separation processes. However, since α-ketoglutaric acid has one more carboxyl group than pyruvic acid, this results in differences in the number and strength of hydrogen bonding sites between the separation medium and α-ketoglutaric acid and pyruvic acid molecules, so the present invention finds that extractants with different hydrogen bond acceptor abilities are used to separate α-ketoglutaric acid and pyruvic acid by forming different hydrogen bond forces between solute molecules and extractants. Since the deep eutectic solvent is composed of a hydrogen bond acceptor and a hydrogen bond donor, the oxygen-containing hydrogen bond acceptor can provide hydrogen bonding sites with different numbers and strengths formed with α-ketoglutaric acid and pyruvic acid, so in the present invention, a hydrophobic deep eutectic solvent is preferentially used as an extractant.

[0019] In some embodiments, the hydrogen bond acceptor is selected from one of amide compounds, alkylammonium chloride, alkylammonium halide, organic phosphine and terpene compounds.

[0020] In some embodiments, the hydrogen bond acceptor is selected from one of N,N-dibutylformamide, N,N-dibutylacetamide, N,N-di(1-methylheptyl)acetamide, N,N-di(2-ethylhexyl)acetamide, N,N-di(2-ethylhexyl)-3-butanoneacetamide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetraheptylammonium chloride, methyltrioctylammonium chloride, methyltrioctylammonium bromide, tetraoctylammonium chloride, tetraoctylammonium bromide, tributyl phosphate, trioctyl phosphate, tri-n-butylphosphine oxide, tri-n-octylphosphine oxide, tricyclohexylphosphine oxide, menthol, thymol, geraniol, linalool, linalool, pinoleol, 2-camphenol, myrtenol or citronellol.

[0021] In some embodiments, the hydrogen bond acceptor is selected from one of N,N-di-n-butylformamide, tri-n-octylphosphine oxide, linalool, tricyclohexylphosphine oxide, or methyltrioctylammonium chloride.

[0022] In some embodiments, the hydrogen bond donor is selected from one of natural terpenoid compounds, organic carboxylic acids and long-chain fatty alcohols. The hydrogen bond donor is derived from natural compounds with good biocompatibility, has a wide range of sources and is green and environmentally friendly, and reduces the impact on the environment and human body compared to conventional solvents.

[0023] In some embodiments, the hydrogen bond donor is selected from one of menthol, thymol, geraniol, linalool, linalool, terpineol, 2-camphenol, myrtenol, citronellol, camphor, 1,8-cineole, lidocaine, ibuprofen, caprylic acid, nonanoic acid, capric acid, lauric acid, decanol, nonanol, dodecanol or tetradecanol.

[0024] In some embodiments, the hydrogen bond donor is selected from one of menthol, geraniol, capric acid, n-dodecyl alcohol, lauric acid or thymol.

[0025] In some embodiments, the hydrogen bond acceptor is N,N-di-n-butylformamide, and the hydrogen bond donor is menthol.

[0026] In some embodiments, the hydrogen bond acceptor is N,N-di-n-butylformamide, and the hydrogen bond donor is geraniol.

[0027] In some embodiments, the hydrogen bond acceptor is N,N-di-n-butylformamide, and the hydrogen bond donor is tributyl phosphate.

[0028] In some embodiments, the hydrogen bond acceptor is N,N-di-n-butylformamide, and the hydrogen bond donor is decanoic acid.

[0029] In some embodiments, the hydrogen bond acceptor is N,N-di-n-butylformamide, and the hydrogen bond donor is n-dodecanol.

[0030] In some embodiments, the hydrogen bond acceptor is tri-n-octylphosphine oxide, and the hydrogen bond donor is linalool.

[0031] In some embodiments, the hydrogen bond acceptor is methyltrioctylammonium chloride, and the hydrogen bond donor is lauric acid.

[0032] In some embodiments, the hydrogen bond acceptor is tricyclohexylphosphine oxide, and the hydrogen bond donor is thymol.

[0033] In some embodiments, the molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 1:10-10:1, for example, 10:1, 7:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:7, 1:10 or any value therebetween.

[0034] In some embodiments, the molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 5:1-1:5.

[0035] In some embodiments, the extractant further comprises a diluent. The low eutectic solvent is used in the diluent, and the diluent can reduce the viscosity of the extraction system and adjust the surface tension, density and polarity of the extractant.

[0036] In some embodiments, the diluent is selected from one or more of alkane, halogenated hydrocarbon, alcohol, ether and ester organic solvents.

[0037] In some embodiments, the diluent is a polar oxygenated solvent.

[0038] Adding a hydrophobic deep eutectic solvent to a polar oxygen-containing solvent can make the extraction system have a more appropriate distribution coefficient and selectivity for α-ketoglutaric acid and pyruvic acid in the raw material solution.

[0039] In some embodiments, the diluent is one or more of alcohol, ether and ester organic solvents.

[0040] In some embodiments, the diluent is selected from at least one of n-butanol, n-hexanol, n-octanol, methyl isobutyl ketone, methyl tert-butyl ether, isopropyl ether, ethyl acetate, butyl acetate, amyl acetate, or tributyl phosphate.

[0041] In some embodiments, the diluent is selected from at least one of n-butanol, ethyl acetate, methyl tert-butyl ether, amyl acetate, or tributyl phosphate.

[0042] In some embodiments, the extractant includes a hydrophobic deep eutectic solvent and a diluent.

[0043] In some embodiments, the hydrogen bond acceptor of the hydrophobic deep eutectic solvent is N,N-di-n-butylformamide, the hydrogen bond donor is geraniol, and the diluent is tributyl phosphate.

[0044] In some embodiments, the hydrogen bond acceptor of the hydrophobic deep eutectic solvent is tri-n-octylphosphine oxide, the hydrogen bond donor is linalool, and the diluent is n-butanol.

[0045] In some embodiments, the hydrogen bond acceptor of the hydrophobic deep eutectic solvent is methyltrioctylammonium chloride, the hydrogen bond donor is lauric acid, and the diluent is ethyl acetate.

[0046] In some embodiments, the hydrogen bond acceptor of the hydrophobic deep eutectic solvent is methyl trioctyl ammonium chloride, the hydrogen bond donor is lauric acid, and the diluent is methyl tert-butyl ether.

[0047] In some embodiments, the hydrogen bond acceptor of the hydrophobic deep eutectic solvent is methyltrioctylammonium chloride, the hydrogen bond donor is lauric acid, and the diluent is amyl acetate.

[0048] In some embodiments, in the extractant, the mass fraction of the hydrophobic low eutectic solvent is 0.1%-100%, for example, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or any value therebetween.

[0049] In some embodiments, the mass fraction of the hydrophobic deep eutectic solvent in the extractant is 0.5%-50%.

[0050] In some embodiments, the mass fraction of the hydrophobic deep eutectic solvent in the extractant is 0.5%-40%.

[0051] In some embodiments, the total concentration of α-ketoglutarate and pyruvate in the raw material solution containing α-ketoglutarate and pyruvate is 0.5 g / L-500 g / L; for example, 0.5 g / L, 1 g / L, 2 g / L, 10 g / L, 50 g / L, 100 g / L, 150 g / L, 200 g / L, 250 g / L, 300 g / L, 350 g / L, 400 g / L, 450 g / L, 500 g / L or any value therebetween.

[0052] In some embodiments, the mass ratio of α-ketoglutarate to pyruvate in the raw material solution containing α-ketoglutarate and pyruvate is (0.5-20):1, for example, 0.5:1, 1:1, 1.5:1, 2:1, 5:1, 10:1, 20:1 or any value therebetween.

[0053] The mass ratio of α-ketoglutaric acid to pyruvic acid in the raw material liquid containing α-ketoglutaric acid and pyruvic acid is (0.5-10):1.

[0054] In some embodiments, the temperature of the multi-stage extraction is 15°C-60°C; for example, 20°C, 30°C, 40°C, 50°C, 60°C or any value therebetween. If the temperature is too low, the viscosity of the extractant increases, the mass transfer rate decreases, the processing volume decreases, and it is not conducive to production operation; if the temperature is too high, on the one hand, the volatilization rate of the diluent or solvent becomes faster, and on the other hand, due to the heat release during the extraction process, the high temperature will reduce the distribution coefficient and selectivity of α-ketoglutaric acid and pyruvic acid.

[0055] In some embodiments, the multi-stage extraction operation includes cross-current extraction, countercurrent extraction and fractional extraction. In order to obtain α-ketoglutaric acid and pyruvic acid with high purity and yield, fractional extraction is preferred.

[0056] In some embodiments, the fractional extraction includes an extraction section and a washing section. The extractant enters the system from the first stage of the extraction section, the raw material liquid enters the system from the last stage of the extraction section, the detergent enters the system from the first stage of the washing section, and the raw materials are combined at the last stage of the extraction section to enter the extraction section together. The extraction phase and the washing phase are subjected to multi-stage countercurrent contact, and the raffinate flows out from the first stage of the extraction section, and the extraction phase flows out from the first stage of the washing section, and the extraction phase and the raffinate phase are collected separately. After multi-stage fractional extraction and washing, α-ketoglutaric acid is enriched in the extraction phase, and pyruvic acid is enriched in the raffinate phase. The extraction phase is stripped with alkali solution, acidified and vacuum dried to obtain a high-purity α-ketoglutaric acid product, and the raffinate phase can be evaporated under reduced pressure and vacuum dried to obtain a high-purity pyruvic acid product.

[0057] In some embodiments, the multi-stage extraction device is selected from a multi-stage centrifugal extraction device or an extraction column.

[0058] In some embodiments, when the multi-stage extraction is fractional extraction, the multi-stage extraction further comprises a detergent.

[0059] In some embodiments, the detergent is selected from water.

[0060] In some embodiments, when performing multi-stage extraction, taking into account factors such as product quality and production cost, the volume flow ratio of the raw material liquid, the detergent and the extractant is 1:(0.5-20):(0.5-20), for example, 1:0.5:(0.5-20), 1:2:(0.5-20), 1:5:(0.5-20), 1:10:(0.5-20), 1:15:(0.5-20), 1:(0.5-20):0.5, 1:(0.5-20):2, 1:(0.5-20):5, 1:(0.5-20):10, 1:(0.5-20):15, 1:(0.5-20):20 or any value therebetween.

[0061] In some embodiments, the ratio of the volume flow rates of the feed solution, the washing agent, and the extractant is 1:(1-10):(1-10).

[0062] The volume flow ratio of the raw liquid, the detergent and the extractant is 1:(3-8):(3-10).

[0063] In some embodiments, the multi-stage extraction is 1-15 stages, preferably 5-10 stages.

[0064] In some embodiments, the stripping uses a stripping agent.

[0065] In some embodiments, the stripping agent is selected from an alkaline solution.

[0066] In some embodiments, the stripping agent is selected from aqueous sodium hydroxide solution.

[0067] In some embodiments, the concentration of the sodium hydroxide aqueous solution is 0.5-2 mol / L; for example, 0.5 mol / L, 1 mol / L, 1.5 mol / L, 2 mol / L or any value therebetween.

[0068] In some embodiments, the molar ratio of NaOH in the sodium hydroxide aqueous solution to α-ketoglutaric acid in the extract is 1:(0.5-2); for example, 1:0.5, 1:0.7, 1:0.9, 1:1.1, 1:1.3, 1:1.5, 1:1.7, 1:2 or any value therebetween.

[0069] In some embodiments, the stripping temperature is 20-40°C, for example, 20°C, 25°C, 30°C, 35°C, 40°C or any value therebetween.

[0070] In some embodiments, the acidification treatment uses a cation exchange resin.

[0071] In some embodiments, the crystallization temperature is 5-15°C, such as 5°C, 10°C, 15°C or any value therebetween.

[0072] In some embodiments, the crystallization time is 8-24 hours, for example, 8 hours, 12 hours, 24 hours or any value therebetween.

[0073] In some embodiments, the present invention uses a feed liquid containing α-ketoglutaric acid and pyruvic acid as a raw material liquid for multi-stage fractionation or countercurrent extraction. The fractionation extraction is divided into an extraction section and a washing section, and the extraction phase and the raffinate phase are collected respectively. According to the different number and strength of the interaction sites of the new hydrophobic low eutectic solvent for α-ketoglutaric acid and pyruvic acid, the hydrogen bond formed by the low eutectic solvent and α-ketoglutaric acid is stronger, α-ketoglutaric acid is enriched in the extraction phase, and pyruvic acid is enriched in the raffinate phase. The extract is stripped with a strong alkaline solution, treated with an ion exchange resin or acid solution, and crystallized to obtain a high-purity α-ketoglutaric acid product. The above-mentioned raffinate is concentrated by reduced pressure evaporation and vacuum drying to obtain a pyruvic acid product.

[0074] In some embodiments, the purity of the product α-ketoglutaric acid obtained by the separation method of the present invention reaches above 98 wt% (HPLC), and the recovery rate is greater than 95%, and the purity of pyruvic acid reaches above 93% wt% (HPLC), and the recovery rate is greater than 90%.

[0075] Compared with the prior art, the present invention has the following beneficial effects:

[0076] 1. The hydrophobic deep eutectic solvent used in the present invention belongs to a class of ionic liquids, and has the advantages of being liquid at room temperature, low vapor pressure, flexible design and adjustment of hydrogen bond acceptors and donors, environmental friendliness, and excellent circulation performance; the hydrophobic deep eutectic solvent has different numbers and strengths of interaction sites with α-ketoglutaric acid and pyruvic acid, and the hydrogen bond effect formed by the deep eutectic solvent and α-ketoglutaric acid is stronger, α-ketoglutaric acid is enriched in the extraction phase, and pyruvic acid is enriched in the raffinate phase. The use of the hydrophobic deep eutectic solvent for separating α-ketoglutaric acid and pyruvic acid has a better separation effect;

[0077] 2. The hydrogen bond donors of the hydrophobic deep eutectic solvent in the present invention are derived from natural compounds with good biocompatibility, which are widely available and environmentally friendly. Compared with conventional solvents, they reduce the impact on the environment and human body;

[0078] 3. The hydrophobic deep eutectic solvent used in the present invention can be used alone or mixed with a diluent. The synthesis method of the hydrophobic deep eutectic solvent is simple, the product does not need further purification, is easy to scale up, and can be recycled;

[0079] 4. The method of the present invention adopts optimized process conditions, uses a small amount of extractant but has a large processing volume, and has industrial application value. DETAILED DESCRIPTION

[0080] 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 embodiments. The specific embodiments described herein are only used to explain the present invention and are not intended to constitute any limitation to the present invention.

[0081] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0082] Unless otherwise defined, the technical terms used in the following examples have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. The reagents used in the following examples, unless otherwise specified, are all conventional biochemical reagents; the raw materials, instruments and equipment used in the following examples, etc., can all be purchased on the market or can be obtained by existing methods; the reagent amounts, unless otherwise specified, are the reagent amounts used in conventional experimental operations; the experimental methods, unless otherwise specified, are all conventional methods.

[0083] The deep eutectic solvent (DES) in the present invention is a low melting point liquid formed by eutectic interaction between two or more molecules at a specific ratio, and its melting point is significantly lower than the melting points of the constituent components.

[0084] The Class III deep eutectic solvent in the present invention refers to a deep eutectic solvent composed of a quaternary ammonium salt and an amide / carboxylic acid / polyol as a hydrogen bond donor, and its general formula is Cat + X – zRZ, where Cat + X – It is a quaternary ammonium salt, Z = CONH 2 ,COOH,OH.

[0085] The Class V deep eutectic solvent of the present invention is a novel nonionic deep eutectic solvent, which is composed of hydrogen bond donors and hydrogen bond acceptor molecules. The hydrogen bond acceptors include amides, organic phosphines, etc., and the hydrogen bond donors include alcohols, carboxylic acids, etc.

[0086] The "flow ratio" in the embodiment of the present invention refers to the volume flow ratio of the raw material liquid, the detergent and the extractant.

[0087] The purity in the examples of the present invention was obtained by HPLC testing and is expressed in percent by mass.

[0088] The following example is to separate α-ketoglutarate and pyruvic acid from a raw material liquid containing α-ketoglutarate and pyruvic acid. The separation of the two from a raw material liquid in which pyruvic acid is co-produced or by-produced in the process of producing α-ketoglutarate can be carried out according to the embodiments of the present invention. By implementing the method of the present invention, α-ketoglutarate and pyruvic acid products with higher purity can be obtained.

[0089] Example 1

[0090] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were both 1.2 g / L) for multi-stage fractional distillation extraction: N,N-di-n-butylformamide (DBM) was used as a hydrogen bond acceptor and menthol (Men) was used as a hydrogen bond donor with a molar ratio of 2:1. The mixture was stirred at 60°C for 24 hours. A hydrophobic low eutectic solvent [DBM][Men] was synthesized and used as an extractant. Water was used as a detergent. The flow ratio of the raw material liquid, detergent and extractant was 1:2:1. Fractional distillation extraction was carried out at 30°C. The fractionation extraction is divided into an extraction section and a washing section (the extraction section has 10 stages and the washing section has 5 stages). The extractant enters the fractionation extraction system from the first stage of the extraction section, the raw material liquid enters the fractionation extraction system from the last stage of the extraction section, the detergent enters the fractionation extraction system from the first stage of the washing section, and the extract enriched in α-ketoglutaric acid flows out from the first stage of the washing section, and the raffinate enriched in pyruvic acid flows out from the first stage of the extraction section, and the extract and the raffinate are collected separately.

[0091] The extract is added to a stirring tank, and a stripping agent (1 mol / L NaOH aqueous solution) is added dropwise while mechanically stirring until the stripping is complete. The molar ratio of NaOH in the stripping agent to α-ketoglutaric acid in the extract is 1:1, the operating temperature is 30°C, and the stripping agent is slowly added to the reactor with continuous mechanical stirring. After the stripping phase is acidified with a cation exchange resin, it is cooled to 5°C and crystallized for 10 hours. The resulting crystals are vacuum dried at 50°C to obtain the α-ketoglutaric acid product.

[0092] The raffinate was concentrated under reduced pressure by a rotary evaporator, cooled to 10°C for crystallization for 10 hours, and the obtained crystals were vacuum dried at 50°C to obtain a pyruvic acid product. Among them, the purity of α-ketoglutaric acid was 99.57%, and the yield was 95.08%; the purity of pyruvic acid was 93.30%, and the yield was 99.51%, as shown in Table 1.

[0093] Example 2

[0094] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material. The implementation method is the same as Example 1, except that the concentrations of α-ketoglutaric acid and pyruvic acid in the raw material liquid are different, both of which are 10.4 g / L. N,N-di-n-butylformamide (DBM) is used as a hydrogen bond acceptor, geraniol (Ger) is used as a hydrogen bond donor, and the molar ratio of the two is 2:1. Stirring is carried out at 60° C. for 24 hours. The synthesized hydrophobic low eutectic solvent [DBM][Ger] is used as an extractant, water is used as a detergent, and the raw material liquid The volume flow ratio of detergent and extractant is 1:6:8.3, and fractional distillation extraction is carried out at 30°C (10 stages in the extraction section and 8 stages in the washing section). The extractant enters the fractional distillation extraction system from the first stage of the extraction section, the raw material liquid enters the fractional distillation extraction system from the last stage of the extraction section, the detergent enters the fractional distillation extraction system from the first stage of the washing section, and the extract enriched in α-ketoglutaric acid flows out from the first stage of the washing section, and the raffinate enriched in pyruvic acid flows out from the first stage of the extraction section, and the extract and the raffinate are collected separately.

[0095] The post-treatment method of the extract and the raffinate is the same as that in Example 1.

[0096] The purity of α-ketoglutaric acid was 98.11%, and the yield was 95.85%. The purity of pyruvic acid was 95.78%, and the yield was 99.29%.

[0097] Example 3

[0098] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material. The implementation method is the same as that of Example 1, except that the concentrations of α-ketoglutaric acid and pyruvic acid in the raw material liquid are different, both of which are 50.8 g / L. A mixed solvent of [DBM][Ger] and tributyl phosphate (TBP) is used as the extractant, wherein the mass percentage of [DBM][Ger] in the mixed solvent is 10%, water is used as the detergent, and the volume flow ratio of the raw material liquid, the detergent, and the extractant is 1:8:5. Fractional extraction is performed at 30°C (8 extraction stages and 5 washing stages). The extractant enters the fractional extraction system from the first stage of the extraction stage, the raw material liquid enters the fractional extraction system from the last stage of the extraction stage, the detergent enters the fractional extraction system from the first stage of the washing stage, an extract enriched in α-ketoglutaric acid flows out from the first stage of the washing stage, and a raffinate enriched in pyruvic acid flows out from the first stage of the extraction stage, and the extract and the raffinate are collected respectively.

[0099] The post-treatment method of the extract and the raffinate is the same as that in Example 1.

[0100] The purity of the α-ketoglutaric acid product was 98.73%, and the yield was 96.27%. The purity of the pyruvic acid product was 95.52%, and the yield was 97.28%.

[0101] Example 4

[0102] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are both 50.8 g / L). The implementation method is the same as Example 1, except that N,N-di-n-butylformamide (DBM) is used as a hydrogen bond acceptor and decanoic acid (CA) is used as a hydrogen bond donor in a molar ratio of 1:2. The mixture is stirred at 70°C for 48 hours. A synthetic hydrophobic deep eutectic solvent [DBM][CA] is used as an extractant, water is used as a detergent, and the volume flow ratio of the raw material liquid, the detergent, and the extractant is 1:8:6. Fractional extraction is performed at 15°C (a total of 10 extraction stages and a total of 6 washing stages). The extractant enters the fractionation extraction system from the first stage of the extraction section, the raw liquid enters the fractionation extraction system from the last stage of the extraction section, the detergent enters the fractionation extraction system from the first stage of the washing section, an extract enriched in α-ketoglutaric acid flows out from the first stage of the washing section, and a raffinate enriched in pyruvic acid flows out from the first stage of the extraction section, and the extract and the raffinate are collected separately.

[0103] The post-treatment of the extract and the raffinate was the same as in Example 1, and the purity of the obtained α-ketoglutaric acid product was 98.80%, the yield was 97.29%, and the purity of the obtained pyruvic acid product was 98.37%, the yield was 98.69%.

[0104] Example 5

[0105] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were 100.3 g / L and 10.4 g / L, respectively), and multi-stage fractional distillation extraction was carried out at 25°C. N,N-di-n-butylformamide (DBM) was used as a hydrogen bond acceptor and n-dodecanol (Dode) was used as a hydrogen bond donor in a molar ratio of 1:1. The mixture was stirred at 70°C for 48 hours. The synthesized hydrophobic low eutectic solvent [DBM][Dode] was used as an extractant, water was used as a detergent, and the volume flow ratio of the raw material liquid, detergent and extractant was 1:2:3. Fractional distillation extraction was carried out at 40°C. The fractionation extraction is divided into an extraction section and a washing section (the extraction section has 10 stages and the washing section has 5 stages). The extractant enters the fractionation extraction system from the first stage of the extraction section, the raw material liquid enters the fractionation extraction system from the last stage of the extraction section, the detergent enters the fractionation extraction system from the first stage of the washing section, and the extract enriched in α-ketoglutaric acid flows out from the first stage of the washing section, and the raffinate enriched in pyruvic acid flows out from the first stage of the extraction section, and the extract and the raffinate are collected separately.

[0106] The post-treatment method of the extract and the raffinate is the same as that in Example 1.

[0107] The purity of α-ketoglutaric acid was 98.59%, and the yield was 99.07%; the purity of pyruvic acid was 98.28%, and the yield was 95.58%.

[0108] Example 6

[0109] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were 100.3 g / L and 50.8 g / L, respectively), tri-n-octylphosphine oxide (TOPO) was used as the hydrogen bond acceptor, linalool (Lin) was used as the hydrogen bond donor, and the molar ratio of the two was 1:3. The mixture was stirred at 70°C for 48 hours, and the synthesized hydrophobic low eutectic solvent [TOPO][Lin] was used as the extractant. Water was used as the detergent. Multi-stage fractional extraction was performed at 15°C. The volume flow ratio of the raw material liquid, the detergent, and the extractant was 1:9:7. There were 12 extraction stages and 5 washing stages. The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) were collected at the first stage of the extraction stage and the first stage of the washing stage, respectively.

[0110] The subsequent separation steps were the same as those in Example 1 to obtain α-ketoglutaric acid and pyruvic acid products. The α-ketoglutaric acid product had a purity of 98.33% and a yield of 99.27%, and the pyruvic acid product had a purity of 98.39% and a yield of 94.26%.

[0111] Example 7

[0112] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as an extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are 200.2 g / L and 100.3 g / L, respectively), [TOPO][Lin] is used as an extractant, and n-butanol is used as a diluent, wherein the mass percentage of [TOPO][Lin] is 0.64%, and the volume flow ratio of the raw material liquid, the detergent, and the extractant is 1:2.8:1.9, and fractional distillation extraction is performed at 15° C. (a total of 10 stages in the extraction section and a total of 5 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) are collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0113] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 98.64% and the yield was 99.36%, and the purity of the pyruvic acid product was 98.18% and the yield was 96.17%.

[0114] Example 8

[0115] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are 400.9 g / L and 100.6 g / L, respectively), the extractant is methyl trioctyl ammonium chloride (N1888Cl) as a hydrogen bond acceptor and lauric acid (Lau) as a hydrogen bond donor, the molar ratio of the two is 1:1, stirring at 70°C for 24 hours, the mixed solvent composed of the synthesized hydrophobic low eutectic solvent [N1888Cl][Lau] and the diluent ethyl acetate is used as the extractant, wherein the mass percentage of [N1888Cl][Lau] is 5.87%, the volume flow ratio of the raw material liquid, the detergent and the extractant is 1:5:2.8, and fractional distillation extraction is performed at 25°C (a total of 12 stages in the extraction section and a total of 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) are collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0116] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 98.07%, and the yield was 99.71%. The purity of the pyruvic acid product was 99.14%, and the yield was 94.47%.

[0117] Example 9

[0118] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are 400.9 g / L and 100.6 g / L, respectively). The implementation method is the same as that of Example 1, except that tricyclohexylphosphine oxide (TCHP) is used as a hydrogen bond acceptor and thymol (Thy) is used as a hydrogen bond donor, the molar ratio of the two is 1:3, stirring is performed at 70°C for 24 hours, the synthesized hydrophobic deep eutectic solvent [TCHP][Thy] is used as an extractant, the volume flow ratio of the raw material liquid, the detergent, and the extractant is 1:4.6:3.6, and fractional extraction is performed at 25°C (a total of 12 stages in the extraction section and a total of 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) are collected at the first stage of the extraction section and the first stage of the washing section, respectively.

[0119] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 98.35%, and the yield was 99.34%. The purity of the pyruvic acid product was 98.10%, and the yield was 95.31%.

[0120] Example 10

[0121] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were 400.9 g / L and 100.6 g / L, respectively), and the extractant was [N1888Cl][Lau]. Unlike Example 8, the extractant did not contain a diluent. The volume flow ratio of the raw material liquid, the detergent, and the extractant was 1:5:2.8, and fractional extraction was performed at 25°C (12 stages in the extraction section and 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) were collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0122] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 99.13%, and the yield was 98.57%. The purity of the pyruvic acid product was 99.35%, and the yield was 95.68%.

[0123] Embodiment 11

[0124] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were 400.9 g / L and 100.6 g / L, respectively), and the extractant was a mixed solvent consisting of [N1888Cl][Lau] and the diluent ethyl acetate. The difference from Example 8 was that the molar ratio of N1888Cl to Lau was 1:2. The volume flow ratio of the raw material liquid, the detergent, and the extractant was 1:5:2.8, and fractional distillation extraction was performed at 25°C (12 stages in the extraction section and 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) were collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0125] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 97.69%, and the yield was 97.56%. The purity of the pyruvic acid product was 98.97%, and the yield was 96.34%.

[0126] Example 12

[0127] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were 400.9 g / L and 100.6 g / L, respectively), and the extractant was a mixed solvent consisting of [N1888Cl][Lau] and the diluent ethyl acetate. The difference from Example 8 was that the molar ratio of N1888Cl to Lau was 2:1. The volume flow ratio of the raw material liquid, the detergent, and the extractant was 1:5:2.8, and fractional distillation extraction was performed at 25°C (12 stages in the extraction section and 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) were collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0128] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 97.46%, and the yield was 99.80%. The purity of the pyruvic acid product was 98.23%, and the yield was 97.62%.

[0129] Embodiment 13

[0130] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are 400.9 g / L and 100.6 g / L, respectively), and the extractant is a mixed solvent consisting of [N1888Cl][Lau] and a diluent. The difference from Example 8 is that the diluent is methyl tert-butyl ether. The volume flow ratio of the raw material liquid, the detergent, and the extractant is 1:5:2.8, and fractional distillation extraction is performed at 25°C (12 stages in the extraction section and 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) are collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0131] The subsequent separation steps were the same as those in Example 1, and the purity of the obtained α-ketoglutaric acid product was 97.88%, and the yield was 99.14%. The purity of the obtained pyruvic acid product was 99.02%, and the yield was 95.68%.

[0132] Embodiment 14

[0133] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were 400.9 g / L and 100.6 g / L, respectively), and the extractant was a mixed solvent consisting of [N1888Cl][Lau] and a diluent as the extractant. The difference from Example 8 was that the diluent was amyl acetate. The volume flow ratio of the raw material liquid, the detergent, and the extractant was 1:5:2.8, and fractional distillation extraction was performed at 25°C (12 stages in the extraction section and 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) were collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0134] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 99.01%, and the yield was 99.14%. The purity of the pyruvic acid product was 98.89%, and the yield was 96.28%.

[0135] Embodiment 15

[0136] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are 400.9 g / L and 100.6 g / L, respectively), and an extractant is a mixed solvent consisting of [N1888Cl][Lau] and a diluent ethyl acetate. The difference from Example 8 is that the mass percentage of [N1888Cl][Lau] is 30%. The volume flow ratio of the raw material liquid, the detergent, and the extractant is 1:5:2.8, and fractional distillation extraction is performed at 25°C (12 stages in the extraction section and 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) are collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0137] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 99.13%, and the yield was 99.20%. The purity of the pyruvic acid product was 99.25%, and the yield was 95.58%.

[0138] Example 16

[0139] The raw material liquid containing both α-ketoglutaric acid and pyruvic acid is used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are 400.9 g / L and 100.6 g / L, respectively), the extractant is a mixed solvent consisting of [N1888Cl][Lau] and diluent ethyl acetate as the extractant, and the difference from Example 8 is that the fractional extraction temperature is 60°C. The volume flow ratio of the raw material liquid, the detergent, and the extractant is 1:5:2.8, and the fractional extraction is carried out at 25°C (12 stages in the extraction section and 6 stages in the washing section). The effluents enriched with pyruvic acid (raffinate) and α-ketoglutaric acid (extract) are collected at the outlets of the first stage of the extraction section and the first stage of the washing section, respectively.

[0140] The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 97.34%, and the yield was 98.59%. The purity of the pyruvic acid product was 97.06%, and the yield was 93.26%.

[0141] Comparative Example 1

[0142] The raw material liquid containing α-ketoglutaric acid and pyruvic acid is used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid are 400.9 g / L and 100.6 g / L, respectively), [N1888Cl][Lau] is used as the extractant, and multi-stage countercurrent extraction is performed at 25°C, the number of extraction stages is 30, the volume flow ratio of the extractant to the raw material liquid is 2.8:1, the raw material liquid enters the countercurrent extraction system from the first stage of the extraction tower, and the extractant enters the countercurrent extraction system from the last stage of the extraction tower, and the two phases are fully contacted in countercurrent. α-ketoglutaric acid and pyruvic acid are enriched in the raffinate phase of the last stage of the extraction tower and the extraction phase of the first stage, respectively, and the extract and the raffinate are collected. The subsequent separation steps are the same as in Example 1, and the purity of the α-ketoglutaric acid product is 60.37%, the yield is 42.50%, and the purity of the pyruvic acid product is 15.25%, and the yield is 36.74%.

[0143] Comparative Example 2

[0144] A raw material liquid containing both α-ketoglutaric acid and pyruvic acid was used as the extraction raw material (the concentrations of α-ketoglutaric acid and pyruvic acid were 400.9 g / L and 100.6 g / L, respectively), and methyl tert-butyl ether was used as the extractant, and multi-stage fractional distillation extraction was performed at 25° C. The operating conditions were the same as those in Example 8. The subsequent separation steps were the same as those in Example 1, and the purity of the α-ketoglutaric acid product was 62.41%, and the yield was 50.24%, and the purity of the pyruvic acid product was 46.37%, and the yield was 43.23%.

[0145] Table 1

[0146]

[0147]

[0148] The mass percentage of the deep eutectic solvent in Table 1 refers to the percentage of the mass of the deep eutectic solvent to the total mass of the extractant. AKG refers to α-ketoglutarate, PYR refers to pyruvic acid. HBD:HBA refers to the molar ratio of hydrogen bond donor to hydrogen bond acceptor.

[0149] It can be seen from Table 1 that, compared with the commonly used extractants in the prior art, the present invention uses a hydrophobic organic solvent, which has a better separation effect, and the fractional extraction operation mode is conducive to improving the purity and yield of α-ketoglutaric acid.

[0150] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A method for separating α-ketoglutarate and pyruvate, comprising: (1) subjecting a raw material liquid containing α-ketoglutaric acid and pyruvic acid to multi-stage extraction to obtain an extract and a raffinate; wherein the extractant of the multi-stage extraction comprises a hydrophobic low eutectic solvent; (2) stripping the extract, acidifying and crystallizing the extract phase obtained by stripping to obtain α-ketoglutaric acid; (3) Concentrating and drying the raffinate to obtain pyruvic acid.

2. The method according to claim 1, characterized in that: The hydrophobic deep eutectic solvent includes a Class III and / or Class V deep eutectic solvent, and the hydrophobic deep eutectic solvent includes a hydrogen bond acceptor and a hydrogen bond donor, and the hydrogen bond acceptor and the hydrogen bond donor are of different types; Preferably, the hydrophobic deep eutectic solvent consists of a hydrogen bond acceptor and a hydrogen bond donor; Preferably, the hydrogen bond acceptor is selected from one of amide compounds, alkylammonium chlorides, alkylammonium halides, organic phosphine compounds and terpene compounds; and / or The hydrogen bond donor is selected from one of natural terpenoids, organic carboxylic acids and long-chain fatty alcohols; Preferably, the molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 10:1-1:10, preferably 5:1-1:

5.

3. The method according to claim 2, characterized in that The hydrogen bond acceptor is selected from one of N,N-dibutylformamide, N,N-dibutylacetamide, N,N-di(1-methylheptyl)acetamide, N,N-di(2-ethylhexyl)acetamide, N,N-di(2-ethylhexyl)-3-butanoneacetamide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetraheptylammonium chloride, methyltrioctylammonium chloride, methyltrioctylammonium bromide, tetraoctylammonium chloride, tetraoctylammonium bromide, tributyl phosphate, trioctyl phosphate, tri-n-butylphosphine oxide, tri-n-octylphosphine oxide, tricyclohexylphosphine oxide, menthol, thymol, geraniol, linalool, linalool, pinoleol, 2-camphenol, myrtenol or citronellol; Preferably, the hydrogen bond acceptor is selected from one of N,N-di-n-butylformamide, tri-n-octylphosphine oxide, linalool, tricyclohexylphosphine oxide or methyltrioctylammonium chloride; and / or The hydrogen bond donor is selected from one of menthol, thymol, geraniol, linalool, linalool, terpineol, 2-camphenol, myrtenol, citronellol, camphor, 1,8-cineole, lidocaine, ibuprofen, caprylic acid, nonanoic acid, capric acid, lauric acid, decanol, nonanol, dodecanol or tetradecanol; Preferably, the hydrogen bond donor is selected from one of menthol, geraniol, capric acid, n-dodecyl alcohol, lauric acid or thymol.

4. The method according to any one of claims 1 to 3, characterized in that The extractant also includes a diluent; Preferably, the diluent is selected from one or more of alkane, halogenated hydrocarbon, alcohol, ether and ester organic solvents; Preferably, the diluent is a polar oxygen-containing solvent; preferably one or more of alcohol, ether or ester organic solvents; Preferably, the diluent is selected from at least one of n-butanol, n-hexanol, n-octanol, methyl isobutyl ketone, methyl tert-butyl ether, isopropyl ether, ethyl acetate, butyl acetate, amyl acetate or tributyl phosphate; Preferably, the diluent is selected from at least one of n-butanol, ethyl acetate, methyl tert-butyl ether, amyl acetate or tributyl phosphate; Preferably, the extractant comprises a hydrophobic deep eutectic solvent and a diluent, Preferably, in the extractant, the mass fraction of the hydrophobic deep eutectic solvent is 0.1%-100%, preferably 0.5%-50%, more preferably 0.5%-40%.

5. The method according to any one of claims 1 to 4, characterized in that The total concentration of α-ketoglutarate and pyruvate in the raw material solution containing α-ketoglutarate and pyruvate is 0.5 g / L-500 g / L; The mass ratio of α-ketoglutaric acid to pyruvic acid in the raw material liquid containing α-ketoglutaric acid and pyruvic acid is (0.5-20):1, preferably (0.5-10):

1.

6. The method according to any one of claims 1 to 5, characterized in that The temperature of the multi-stage extraction is 15°C-60°C; and / or The operation mode of the multi-stage extraction is selected from cross-current extraction, countercurrent extraction and fractional extraction.

7. The method according to claim 6, characterized in that When the multi-stage extraction is fractional extraction, the multi-stage extraction further comprises a detergent; Preferably, the detergent is selected from water; Preferably, the volume flow ratio of the raw material liquid, the washing agent and the extracting agent is 1:(0.5-20):(0.5-20), preferably 1:(1-10):(1-10); Preferably, the multi-stage extraction is 1-15 stages, preferably 5-10 stages.

8. The method according to any one of claims 1 to 7, characterized in that The stripping adopts a stripping agent, Preferably, the stripping agent is selected from an alkaline solution, Preferably, the stripping agent is selected from aqueous sodium hydroxide solution, Preferably, the concentration of the sodium hydroxide aqueous solution is 0.5-2 mol / L; and / or The molar ratio of NaOH in the sodium hydroxide aqueous solution to α-ketoglutaric acid in the extract is 1:(0.5-2); and / or The stripping temperature is 20-40°C.

9. The method according to any one of claims 1 to 8, characterized in that The acidification treatment uses a cation exchange resin. The crystallization temperature is 5-15°C; and / or The crystallization time is 8-24h.

10. The method according to any one of claims 1 to 9, characterized in that The purity of the α-ketoglutaric acid is above 98 wt % and the yield is greater than 95%; and / or The purity of the pyruvic acid reaches above 93%wt%, and the yield is greater than 90%.

Images