CN116003246A - Synthesis method of alpha-ketoglutaric acid - Google Patents
Synthesis method of alpha-ketoglutaric acid Download PDFInfo
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- CN116003246A CN116003246A CN202310015064.8A CN202310015064A CN116003246A CN 116003246 A CN116003246 A CN 116003246A CN 202310015064 A CN202310015064 A CN 202310015064A CN 116003246 A CN116003246 A CN 116003246A
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Abstract
The invention relates to the technical field of organic synthesis, and provides a synthesis method of alpha-ketoglutaric acid, which comprises the following steps: s1, reacting methyl dichloroacetate with methyl acrylate in the presence of sodium methoxide to obtain 2, 2-dimethyl dichloroglutarate; s2, reacting 2, 2-dimethyl dichloroglutarate with 10-20% alkali solution and 25-35% alkali solution in sequence to obtain a crude product of alpha-ketoglutarate aqueous solution; s3, refining the mixture to obtain the alpha-ketoglutaric acid. By the technical scheme, the problems of low yield and low purity of the alpha-ketoglutaric acid in the synthesis method of the alpha-ketoglutaric acid in the prior art are solved.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a synthesis method of alpha-ketoglutaric acid.
Background
Alpha-ketoglutaric acid (alpha-Ketoglutaric acid) is one of two keto-group-bearing derivatives of glutaric acid, white finely crystalline powder. The anion α -ketoglutarate of α -ketoglutarate is an important biological compound, which is a keto acid product of glutamic acid deamination, and is an important metabolic intermediate in the tricarboxylic acid cycle of microorganisms, and is a key node for linking intracellular carbon-nitrogen metabolism. The alpha-ketoglutarate can be combined with nitrogen formed in cells, and can prevent excessive accumulation of nitrogen in cells. Alpha-ketoglutarate is also useful as a dietary supplement, reducing many of the problems associated with ammonia poisoning, and has been used in patients undergoing hemodialysis, and is therefore very well used. However, the existing synthesis method of the alpha-ketoglutaric acid has low yield and purity, and affects the wide application of the alpha-ketoglutaric acid.
Disclosure of Invention
The invention provides a synthesis method of alpha-ketoglutaric acid, which solves the problems of low yield and low purity of the alpha-ketoglutaric acid in the synthesis method of the alpha-ketoglutaric acid in the related technology.
The technical scheme of the invention is as follows:
the synthesis method of the alpha-ketoglutaric acid comprises the following steps:
s1, reacting methyl dichloroacetate with methyl acrylate in the presence of sodium methoxide to obtain 2, 2-dimethyl dichloroglutarate;
s2, reacting 2, 2-dimethyl dichloroglutarate with 10-20% alkali solution and 25-35% alkali solution in sequence to obtain a crude product of alpha-ketoglutarate aqueous solution;
s3, refining the crude product of the alpha-ketoglutaric acid aqueous solution to obtain the alpha-ketoglutaric acid.
As a further technical scheme, 2-dimethyl dichloroglutarate in S2 reacts with 15% alkali solution and 30% alkali solution in sequence to obtain crude alpha-ketoglutarate aqueous solution.
As a further technical scheme, the step S2 includes the following steps:
a1, adding water and 2, 2-dimethyl dichloroglutarate into a reactor A, and controlling the temperature to be 8-10 ℃;
a2, dropwise adding 15% sodium hydroxide into the reactor A, and dropwise adding the sodium hydroxide into the reactor A until the pH is 6.5-7.0;
a3, adding 30% sodium hydroxide to continue the reaction until the pH value is 8-8.5;
a4, adding inorganic salt, controlling the temperature to be 70-80 ℃, and stirring for 2-3h;
a5, cooling to 20-25 ℃ after stirring, and centrifuging to obtain a mixture;
a6, adding water and the mixture into the reactor B, and controlling the temperature to be less than or equal to 10 ℃;
a7, dropwise adding an acid solution into the reactor B, regulating the pH value to be 1.3-1.4, controlling the temperature to be 22-27 ℃ and reacting for 1.5-2.5 hours;
a8, filtering, washing and collecting filtrate to obtain a crude product of the alpha-ketoglutaric acid aqueous solution.
As a further technical scheme, when 15% sodium hydroxide is added into the A2 in a dropwise manner, the temperature is controlled to be less than or equal to 25 ℃, and the dropwise addition time is 1.5-2.5h.
As a further technical scheme, 30% sodium hydroxide is added into the A3, the temperature is controlled to be 95-100 ℃, and the reflux is carried out for 3-4 hours.
As a further technical scheme, the mass ratio of the 2, 2-dichloro dimethyl glutarate to the water in the A1 is 1:2; the mass ratio of the mixture to water in the A6 is 1:2-3.
As a further technical scheme, the mass ratio of the 2, 2-dimethyl dichloroglutarate to the inorganic salt in the A2 is 1:0.5-1.
As a further technical scheme, the step S3 includes the following steps:
b1, adding the crude product of the alpha-ketoglutaric acid aqueous solution and active carbon into a reactor for reaction, and then carrying out decompression dehydration;
adding acetone into the reactor, stirring, cooling to 23-27 ℃, filtering, washing, and evaporating to remove the acetone;
b3, adding ethyl acetate into the reactor, controlling the temperature to be-5-10 ℃, and stirring for 1.2-2.5h;
and B4, centrifuging and drying to obtain the alpha-ketoglutaric acid.
As a further technical scheme, the reaction temperature in the B1 is 55-65 ℃ and the reaction time is 35-45min.
As a further technical scheme, the temperature is controlled to be less than or equal to 45 ℃ after the acetone is added into the B2, and the mixture is stirred for 25 to 35 minutes.
The working principle and the beneficial effects of the invention are as follows:
1. in the synthesis process, 15% sodium hydroxide is used firstly to finish dechlorination, olefin is not polymerized, and 30% sodium hydroxide is used later, so that the yield and purity of alpha-ketoglutaric acid can be improved.
2. The invention refines the crude product of the alpha-ketoglutaric acid aqueous solution by sequentially using active carbon, acetone and ethyl acetate, thereby improving the purity of the product.
Detailed Description
The technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by one of ordinary skill in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The following examples and comparative examples were each prepared by synthesizing dimethyl 2, 2-dichloroglutarate by the following steps:
(1) 144.18kg of methyl acrylate and 220kg of methyl dichloroacetate are added into an enamel kettle A for stirring, and the temperature is reduced to 10 ℃ after the reaction
(2) Dropwise adding 24.28kg of 30% sodium methoxide solution into the enamel kettle A for 2.5h at 15-20 ℃;
(3) After the dripping is finished, controlling the temperature to be 24-26 ℃, and stirring for 2.5 hours to generate a reaction product;
(4) After the reaction is qualified, adding 100L of water, stirring for 30min, standing, layering, and collecting an organic phase; carrying out twice liquid separation;
(5) Transferring the organic phase into a distillation kettle, adding 30L of pure water twice, and distilling under reduced pressure of-0.09 MPa at 55 ℃ until the content of 2, 2-dimethyl dichloroglutarate in the gas phase detection product is more than or equal to 93%, thereby obtaining the 2, 2-dimethyl dichloroglutarate.
Example 1
The synthesis method of the alpha-ketoglutaric acid comprises the following steps:
(1) 200kg of water and 100kg of 2, 2-dimethyl dichloroglutarate are added into an enamel kettle B, and the temperature is controlled to be 8-10 ℃;
(2) Dropwise adding 15% sodium hydroxide into the enamel kettle B, dropwise adding the sodium hydroxide into the enamel kettle B until the pH is 6.5, controlling the temperature to be 20-25 ℃ and dropwise adding the sodium hydroxide for 2 hours;
(3) Adding 30% sodium hydroxide into an enamel kettle B, controlling the temperature to be 95-100 ℃, refluxing for 3 hours, and reacting until the pH value is 8;
(4) Adding 75kg of anhydrous calcium chloride into the enamel kettle B, controlling the temperature to be 70-75 ℃, and stirring for 2h;
(5) Cooling to 20 ℃ after stirring, and centrifuging to obtain a mixture;
(6) Adding 240kg of water and 80kg of mixture into a reaction kettle, stirring, and controlling the temperature to be 0-5 ℃;
(7) Dropwise adding 30% sulfuric acid aqueous solution into a reaction kettle, regulating the pH to 1.3, controlling the temperature to 22-25 ℃ and reacting for 2h; the pH is kept at 1.3-1.4 during the reaction;
(8) Spin-drying by a plastic-lined centrifuge, eluting the filtrate by pure water, and collecting the filtrate after spin-drying again to obtain a crude alpha-ketoglutaric acid aqueous solution;
(9) Mixing and heating the crude alpha-ketoglutaric acid aqueous solution and 8kg of activated carbon in an enamel kettle C to 60 ℃, and carrying out reduced pressure dehydration after the reaction time is 40 min;
(10) Adding 130kg of acetone into the enamel kettle C, controlling the temperature to be 35-40 ℃, stirring for 30min, cooling to 25 ℃, filtering by using a plastic filter, washing by using acetone, and evaporating to remove the acetone;
(11) Cooling to 10deg.C, adding 16kg ethyl acetate into enamel kettle C, controlling temperature to-2-2deg.C, and stirring for 2 hr;
(12) After centrifugation, the filter cake was dried in a double cone dryer to give 192.1kg of α -ketoglutaric acid with a yield of 85.44% and a purity of 99.22%.
Example 2
The synthesis method of the alpha-ketoglutaric acid comprises the following steps:
(1) 200kg of water and 100kg of 2, 2-dimethyl dichloroglutarate are added into an enamel kettle B, and the temperature is controlled to be 8-10 ℃;
(2) Dropwise adding 15% sodium hydroxide into the enamel kettle B, dropwise adding the sodium hydroxide into the enamel kettle B until the pH is 7.0, controlling the temperature to be 15-20 ℃ and dropwise adding the sodium hydroxide for 1.5h;
(3) Adding 30% sodium hydroxide into an enamel kettle B, controlling the temperature to be 95-100 ℃, refluxing for 3.5 hours, and keeping the pH value to be 8.3;
(4) Adding 50kg of anhydrous calcium chloride into the enamel kettle B, controlling the temperature to be 75-80 ℃, and stirring for 2.5h;
(5) Cooling to 23 ℃ after stirring, and centrifuging to obtain a mixture;
(6) 160kg of water and 80kg of mixture are added into a reaction kettle to be stirred, and the temperature is controlled to be 6-10 ℃;
(7) Dropwise adding 30% sulfuric acid aqueous solution into a reaction kettle, regulating the pH to 1.4, controlling the temperature to 25-27 ℃ and reacting for 1.5h; the pH is kept to be 1.3-1.4 in the reaction process;
(8) Spin-drying by a plastic-lined centrifuge, eluting the filtrate by pure water, and collecting the filtrate after spin-drying again to obtain a crude alpha-ketoglutaric acid aqueous solution;
(9) Mixing the crude alpha-ketoglutaric acid aqueous solution and 8kg of activated carbon in an enamel kettle C, heating to 55 ℃, and carrying out decompression dehydration after the reaction time is 35 min;
(10) Adding 124kg of acetone into the enamel kettle C, controlling the temperature to be 30-35 ℃, stirring for 25min, cooling to 23 ℃, filtering by using a plastic filter, washing by using acetone, and evaporating to remove the acetone;
(11) Cooling to 10deg.C, adding 12kg of ethyl acetate into enamel kettle C, controlling temperature to 3-7deg.C, and stirring for 2 hr;
(12) After centrifugation, the filter cake is dried in a biconical dryer to obtain 191.4kg of alpha-ketoglutaric acid with a yield of 85.13% and a purity of 98.95%
Example 3
The synthesis method of the alpha-ketoglutaric acid comprises the following steps:
(1) 200kg of water and 100kg of 2, 2-dimethyl dichloroglutarate are added into an enamel kettle B, and the temperature is controlled to be 8-10 ℃;
(2) Dropwise adding 15% sodium hydroxide into the enamel kettle B, dropwise adding the sodium hydroxide into the enamel kettle B until the pH is 7.0, controlling the temperature to be 10-15 ℃ and dropwise adding the sodium hydroxide for 2.5h;
(3) Adding 30% sodium hydroxide into an enamel kettle B, controlling the temperature to be 95-100 ℃, refluxing for 4 hours, and keeping the pH value to be 8.5;
(4) Adding 100kg of anhydrous calcium chloride into the enamel kettle B, controlling the temperature to be 70-75 ℃, and stirring for 3 hours;
(5) Cooling to 25 ℃ after stirring, and centrifuging to obtain a mixture;
(6) Adding 200kg of water and 80kg of mixture into a reaction kettle, stirring, and controlling the temperature to be 2-6 ℃;
(7) Dropwise adding 30% sulfuric acid aqueous solution into a reaction kettle, regulating the pH to 1.3, controlling the temperature to 25-27 ℃ and reacting for 2.5h; the pH is kept to be 1.3-1.4 in the reaction process;
(8) Spin-drying by a plastic-lined centrifuge, eluting the filtrate by pure water, and collecting the filtrate after spin-drying again to obtain a crude alpha-ketoglutaric acid aqueous solution;
(9) Adding the crude product of alpha-ketoglutaric acid aqueous solution and 8kg of activated carbon into an enamel kettle, mixing in the enamel kettle C, heating to 65 ℃, and carrying out decompression dehydration after the reaction time is 45 min;
(10) Adding 132kg of acetone into the enamel kettle C, controlling the temperature to be 25-30 ℃, stirring for 35min, cooling to 27 ℃, filtering by using a plastic filter, washing by using acetone, and evaporating to remove the acetone;
(11) Cooling to 10deg.C, adding 18kg of ethyl acetate into enamel kettle C, controlling temperature to-5-0deg.C, and stirring for 2 hr;
(12) After centrifugation, the filter cake was dried in a double cone dryer to give 191.8kg of α -ketoglutaric acid with a yield of 85.35% and a purity of 99.15%.
Example 4
The synthesis method of the alpha-ketoglutaric acid comprises the following steps:
(1) 200kg of water and 100kg of 2, 2-dimethyl dichloroglutarate are added into an enamel kettle B, and the temperature is controlled to be 8 ℃;
(2) Dropwise adding 15% sodium hydroxide into the enamel kettle B, dropwise adding the sodium hydroxide into the enamel kettle B until the pH is 7, controlling the temperature to be 20-25 ℃ and dropwise adding the sodium hydroxide for 2 hours;
(3) Adding 30% sodium hydroxide into an enamel kettle B, controlling the temperature to be 95-100 ℃, refluxing for 3 hours, and keeping the pH value to be 8.2;
(4) Adding 75kg of anhydrous calcium chloride into the enamel kettle B, controlling the temperature to be 72-76 ℃, and stirring for 2h;
(5) Cooling to 25 ℃ after stirring, and centrifuging to obtain a mixture;
(6) Adding 200kg of water and 80kg of mixture into a reaction kettle, stirring, and controlling the temperature to be 5-10 ℃;
(7) Dropwise adding 30% sulfuric acid aqueous solution into a reaction kettle, regulating the pH to 1.3, controlling the temperature to 24-26 ℃ and reacting for 2h; the pH is kept at 1.3-1.4 during the reaction;
(8) Spin-drying by a plastic-lined centrifuge, eluting the filtrate by pure water, and collecting the filtrate after spin-drying again to obtain a crude alpha-ketoglutaric acid aqueous solution;
(9) Mixing the crude alpha-ketoglutaric acid aqueous solution and 8kg of activated carbon in an enamel kettle C, heating to 60 ℃, and carrying out decompression dehydration after the reaction time is 40 min;
(10) Adding 130kg of acetone into the enamel kettle C, controlling the temperature to be 35-40 ℃, stirring for 30min, cooling to 25 ℃, filtering by using a plastic filter, washing by using acetone, and evaporating to remove the acetone;
(11) Cooling to 10deg.C, adding 16kg ethyl acetate into enamel kettle C, controlling temperature to-2-2deg.C, and stirring for 2 hr;
(12) After centrifugation, the filter cake was dried in a double cone dryer to give 191.1kg of α -ketoglutaric acid with a yield of 84.99% and a purity of 98.92%.
Comparative example 1
Comparative example 1 was performed in the same manner as example 1 except that 15% sodium hydroxide was replaced with 30% sodium hydroxide as in example 1. 182.9kg of alpha-ketoglutaric acid was obtained in a yield of 81.35% and a purity of 98.97%.
Comparative example 2
Comparative example 2 was performed in the same manner as example 1 except that 30% sodium hydroxide was replaced with 15% sodium hydroxide as in example 1. 183.8kg of alpha-ketoglutaric acid were obtained in a yield of 81.75% and a purity of 99.03%.
Comparative example 3
Comparative example 3 was conducted by adding 30% sodium hydroxide at a temperature of 70 to 75℃as compared with example 1, and the other steps were conducted in the same manner as in example 1. 185.4kg of alpha-ketoglutaric acid were obtained in a yield of 82.46% and a purity of 99.13%.
Comparative example 4
The synthesis method of the alpha-ketoglutaric acid comprises the following steps:
(1) 200kg of water and 100kg of 2, 2-dimethyl dichloroglutarate are added into an enamel kettle B, and the temperature is controlled to be 8-10 ℃;
(2) Dropwise adding 30% sodium hydroxide into the enamel kettle B, dropwise adding the sodium hydroxide into the enamel kettle B until the pH is 6.5, controlling the temperature to be 20-25 ℃ and dropwise adding the sodium hydroxide for 2 hours;
(3) 15% sodium hydroxide is added into an enamel kettle B, the temperature is controlled to be 95-100 ℃, reflux is carried out for 3 hours, and the pH value is kept to be 8;
(4) Adding 75kg of anhydrous calcium chloride into the enamel kettle B, controlling the temperature to be 70-75 ℃, and stirring for 2h;
(5) Cooling to 20 ℃ after stirring, and centrifuging to obtain a mixture;
(6) Adding 240kg of water and 80kg of mixture into a reaction kettle, stirring, and controlling the temperature to be 0-5 ℃;
(7) Dropwise adding 30% sulfuric acid aqueous solution into a reaction kettle, regulating the pH to 1.3, controlling the temperature to 22-25 ℃ and reacting for 2h; the pH is kept at 1.3-1.4 during the reaction;
(8) Spin-drying by a plastic-lined centrifuge, eluting the filtrate by pure water, and collecting the filtrate after spin-drying again to obtain a crude alpha-ketoglutaric acid aqueous solution;
(9) Mixing the crude alpha-ketoglutaric acid aqueous solution and 8kg of activated carbon in an enamel kettle C, heating to 60 ℃, and carrying out decompression dehydration after the reaction time is 40 min;
(10) Adding 130kg of acetone into the enamel kettle C, controlling the temperature to be 35-40 ℃, stirring for 30min, cooling to 25 ℃, filtering by using a plastic filter, washing by using acetone, and evaporating to remove the acetone;
(11) Cooling to 10deg.C, adding 16kg ethyl acetate into enamel kettle C, controlling temperature to-2-2deg.C, and stirring for 2 hr;
(12) After centrifugation, the filter cake was dried in a double cone dryer to give 182.2kg of α -ketoglutaric acid with a yield of 81.04% and a purity of 99.01%.
Comparative example 5
The synthesis method of the alpha-ketoglutaric acid comprises the following steps:
(1) 200kg of water and 100kg of 2, 2-dimethyl dichloroglutarate are added into an enamel kettle B, and the temperature is controlled to be 8-10 ℃;
(2) Dropwise adding 15% sodium hydroxide into the enamel kettle B, dropwise adding the sodium hydroxide into the enamel kettle B until the pH is 6.5, controlling the temperature to be 20-25 ℃ and dropwise adding the sodium hydroxide for 2 hours;
(3) Adding 30% sodium hydroxide into an enamel kettle B, controlling the temperature to be 95-100 ℃, refluxing for 3 hours, and keeping the pH value to be 8;
(4) Adding 75kg of anhydrous calcium chloride into the enamel kettle B, controlling the temperature to be 70-75 ℃, and stirring for 2h;
(5) Cooling to 20 ℃ after stirring, and centrifuging to obtain a mixture;
(6) Adding 240kg of water and 80kg of mixture into a reaction kettle, stirring, and controlling the temperature to be 0-5 ℃;
(7) Dropwise adding 30% sulfuric acid aqueous solution into a reaction kettle, regulating the pH to 1.3, controlling the temperature to 22-25 ℃ and reacting for 2h; the pH is kept at 1.3-1.4 during the reaction;
(8) Spin-drying by a plastic-lined centrifuge, eluting the filtrate by pure water, and collecting the filtrate after spin-drying again to obtain a crude alpha-ketoglutaric acid aqueous solution;
(10) Mixing alpha-ketoglutaric acid aqueous solution crude product and 30kg acetone in enamel kettle C, heating to 35-40deg.C, stirring for 30min, cooling to 25deg.C, filtering with plastic filter, washing with acetone, and evaporating to remove acetone;
(11) Cooling to 10deg.C, adding 16kg ethyl acetate into enamel kettle C, controlling temperature to-2-2deg.C, and stirring for 2 hr;
(12) After centrifugation, the filter cake was dried in a double cone dryer to give 191.5kg of α -ketoglutaric acid with a yield of 85.17% and a purity of 99.01%.
As can be seen from the yields and purities of examples 1 to 4 and comparative examples 1 to 5, example 1 is the most preferred example of the present invention, and the yield is 85.44% and the purity is 99.22%.
In comparison with example 1, comparative example 1 replaced 15% sodium hydroxide with 30% sodium hydroxide, comparative example 2 replaced 30% sodium hydroxide with 15% sodium hydroxide, comparative example 3 lowered the temperature of the 30% sodium hydroxide reaction, and comparative example 4 changed the order of addition of 15% sodium hydroxide and 30% sodium hydroxide, resulting in lower yields of α -ketoglutaric acid in comparative examples 1-4 than in example 1. Comparative example 5 the purity of alpha-ketoglutaric acid was lower than in example 1 without the addition of acetone.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.
Claims (10)
1. The synthesis method of the alpha-ketoglutaric acid is characterized by comprising the following steps of:
s1, reacting methyl dichloroacetate with methyl acrylate in the presence of sodium methoxide to obtain 2, 2-dimethyl dichloroglutarate;
s2, reacting 2, 2-dimethyl dichloroglutarate with 10-20% alkali solution and 25-35% alkali solution in sequence to obtain a crude product of alpha-ketoglutarate aqueous solution;
s3, refining the crude product of the alpha-ketoglutaric acid aqueous solution to obtain the alpha-ketoglutaric acid.
2. The method for synthesizing alpha-ketoglutaric acid according to claim 1, wherein the dimethyl 2, 2-dichloroglutarate in S2 is reacted with 15% alkali solution and 30% alkali solution in sequence to obtain crude alpha-ketoglutaric acid aqueous solution.
3. The method for synthesizing alpha-ketoglutaric acid according to claim 2, wherein the step S2 comprises the steps of:
a1, adding water and 2, 2-dimethyl dichloroglutarate into a reactor A, and controlling the temperature to be 8-10 ℃;
a2, dropwise adding 15% sodium hydroxide into the reactor A, and dropwise adding the sodium hydroxide into the reactor A until the pH is 6.5-7.0;
a3, adding 30% sodium hydroxide to continue the reaction until the pH value is 8-8.5;
a4, adding inorganic salt, controlling the temperature to be 70-80 ℃, and stirring for 2-3h;
a5, cooling to 20-25 ℃ after stirring, and centrifuging to obtain a mixture;
a6, adding water and the mixture into the reactor B, and controlling the temperature to be less than or equal to 10 ℃;
a7, dropwise adding an acid solution into the reactor B, regulating the pH value to be 1.3-1.4, controlling the temperature to be 22-27 ℃ and reacting for 1.5-2.5 hours;
a8, filtering, washing and collecting filtrate to obtain a crude product of the alpha-ketoglutaric acid aqueous solution.
4. The method for synthesizing alpha-ketoglutaric acid according to claim 3, wherein the temperature is controlled to be less than or equal to 25 ℃ and the dripping time is 1.5-2.5h when 15% sodium hydroxide is dripped into the A2.
5. The method for synthesizing alpha-ketoglutaric acid according to claim 3, wherein the temperature of the solution A3 added with 30% sodium hydroxide is controlled at 95-100 ℃, and the solution A is refluxed for 3-4 hours.
6. A method for synthesizing alpha-ketoglutaric acid according to claim 3, wherein the mass ratio of dimethyl 2, 2-dichloroglutarate to water in A1 is 1:2; the mass ratio of the mixture to water in the A6 is 1:2-3.
7. A method for synthesizing alpha-ketoglutaric acid according to claim 3, wherein the mass ratio of 2, 2-dichloro-dimethyl glutarate to inorganic salt in A2 is 1:0.5-1.
8. The method for synthesizing alpha-ketoglutaric acid according to claim 1, wherein the step S3 comprises the steps of:
b1, adding the crude product of the alpha-ketoglutaric acid aqueous solution and active carbon into a reactor for reaction, and then carrying out decompression dehydration;
adding acetone into the reactor, stirring, cooling to 23-27 ℃, filtering, washing, and evaporating to remove the acetone;
b3, adding ethyl acetate into the reactor, controlling the temperature to be-5-10 ℃, and stirring for 1.2-2.5h;
and B4, centrifuging and drying to obtain the alpha-ketoglutaric acid.
9. The method for synthesizing alpha-ketoglutaric acid according to claim 8, wherein the reaction temperature in B1 is 55-65 ℃ and the reaction time is 35-45min.
10. The method for synthesizing alpha-ketoglutaric acid according to claim 8, wherein the temperature is controlled to be less than or equal to 45 ℃ after the acetone is added into the B2, and the mixture is stirred for 25-35min.
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