Process for the preparation of 2-oxoglutaric acid

Abstract

The present application relates to a kind of 2-oxopentanedioic acid preparation method.The invention method is as follows: 2-methylene pentanedioic acid is dissolved in a certain amount of dimethyl carbonate, a certain amount of V2O5 / K2O / zeolite composite catalyst is added, air (or oxygen) is introduced at reflux temperature for a certain time.Oxidation is carried out.After reaction, the catalyst is removed by filtration, dimethyl carbonate is removed by vacuum distillation, 2-oxopentanedioic acid crude product is obtained, the yield is 98.5%, and refined 2-oxopentanedioic acid is obtained by recrystallization with water, the purity is 99.2%.The synthesis process of the present application is simple, the yield and product purity are high, the process cost is low, and it is an environment-friendly 2-oxopentanedioic acid synthesis method.

Description

TECHNICAL FIELD

[0001] The application relates to a preparation method of 2-oxoglutaric acid and belongs to the technical field of organic chemical industry. BACKGROUND

[0002] 2-oxoglutaric acid is an important biological compound. It is the keto acid product of glutamic acid deamination and is an intermediate product of the tricarboxylic acid cycle, thus having important physiological functions. At present, 2-oxoglutaric acid is mainly used for the production of sports nutrition beverages and has the functions of supplementing nutrition and relieving fatigue. Studies have shown that 2-oxoglutaric acid is a longevity molecule and can delay the life span of fruit flies, mice and other organisms. 2-oxoglutaric acid has wide applications in biochemical reagents for liver function tests, inflammation inhibition and organic synthesis intermediates.

[0003] At present, there are two methods for synthesizing 2-oxoglutaric acid, namely a biological method and a chemical method. The biological method uses glutamic acid as raw material, uses a strain capable of producing glutamic acid deaminase as a production strain, and obtains 2-oxoglutaric acid through steps such as activation, seed culture and fermentation culture. The yield of 2-oxoglutaric acid is about 70% based on glutamic acid. The method has the advantages of easy availability of raw materials, no use of chemicals and less pollution in the production process. However, the method has the disadvantages of a long production cycle, large energy consumption and high production cost.

[0004] The chemical synthesis method mainly has two kinds. One is that oxalic acid diethyl ester is condensed with succinic acid diethyl ester to obtain oxalyl succinic acid triethyl ester, and then the product is obtained through acid (or alkali) hydrolysis. The other is that ethyl dichloroacetate is condensed with ethyl acrylate to obtain 2,2-dichloropentanedioic acid diethyl ester, and then the product is obtained through hydrolysis and dechlorination. The two methods have the advantages of simple reaction process and high product yield. However, the methods have the disadvantages that strong acid or strong base is involved in the reaction, the equipment is severely corroded, the atomic utilization rate is low, a large amount of by-products are produced and the by-products are difficult to recover.

[0005] The application provides a new synthesis method of 2-oxoglutaric acid, that is, 2-methylene glutaric acid is used as raw material, and high-purity 2-oxoglutaric acid is obtained through air oxidation under the catalysis of a V2O5 / KOH / zeolite composite catalyst. The 2-methylene glutaric acid is obtained through dimerization of malonic acid under the catalysis of a nitrogen-containing heterocyclic ring, is abundant in source and low in price. The method has the advantages of good atomic economy, simple reaction process, few by-products, high product yield, low process cost and good product economy. SUMMARY

[0006] The application aims to solve the problems of severe corrosion of equipment, low atomic utilization rate, production of a large amount of by-products and difficulty in recovery in the preparation process of 2-oxoglutaric acid by the existing chemical method, and provides a preparation method with the advantages of good atomic economy, simple reaction process, few by-products, high product yield, low process cost and good product economy.

[0007] The application is a preparation method of 2-oxoglutaric acid, and the preparation method is specifically as follows:

[0008] 2-methylene glutaric acid is dissolved in a certain amount of dimethyl carbonate, a certain amount of V2O5 / KOH / zeolite composite catalyst is added, and air is introduced for oxidation at a reflux temperature for a certain time. After the reaction is completed, the catalyst is removed by filtration, and dimethyl carbonate is removed by distillation to obtain a crude 2-oxoglutaric acid product with a yield of 98.5%, and refined 2-oxoglutaric acid with a purity of 99.2% is obtained by recrystallization with water.

[0009] The reaction equation of the application is as follows:

[0010]

[0011] The reaction is carried out at a reflux temperature of dimethyl carbonate, and the oxidant is air or oxygen. Under the action of the V2O5 / KOH / zeolite composite catalyst, the reaction is almost quantitative, and the conversion rate of the raw material can reach 100% in 8 hours. Except CO2, no other by-products are generated, and the product purity is very good, and the product purity can reach about 98.5% after simple hot water recrystallization.

[0012] After the catalyst is separated by filtration, the activity loss is very small, and the catalyst can be reused. Experimental results show that the activity of the catalyst does not decrease obviously after being reused for 10 times.

[0013] The reaction raw material can be obtained by simple dimerization and hydrolysis reaction of acrylic acid with the assistance of a nitrogen-containing heterocyclic ring, and the nitrogen-containing heterocyclic ring can be reused, so that the cost of the raw material is greatly reduced. The reaction principle is as follows:

[0014]

[0015] Without calculating the yield and other reaction reagents, the total atomic utilization rate of the preparation method of the application is 90.3%, which is better than 89.0% of the biological method and 45.0% of the chemical method (oxalic acid diethyl ester plus succinic acid diethyl ester). In terms of product yield, the yield of the biological method is lower than 80%, and the yield of the chemical method is only about 90%, which is lower than 98.5% of the application. Whether the biological method or the chemical method, a large amount of reaction reagents (or culture medium) needs to be added, and a large amount of by-products is generated. The application only needs to introduce air, the catalyst can be recovered, no by-products are generated except carbon dioxide, and the atomic utilization rate is good, which is an environmentally friendly synthesis process.

[0016] The beneficial effects of the application are as follows:

[0017] 1. The application uses acrylic acid as the raw material for preparing 2-oxoglutaric acid, which has the advantages of easy availability and low price.

[0018] 2、The present application uses air as oxidant to prepare 2-oxoglutaric acid, and the oxidant itself has no by-product, so that the product has high purity and the purification process is simple.

[0019] 3、The V2O5 / KOH / zeolite composite catalyst has high reactivity and can be recycled and reused, thereby greatly reducing the process cost.

[0020] 4、The method for preparing 2-oxoglutaric acid has high atomic utilization rate, less by-product and low production cost, and is an environment-friendly production process. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 HNMR of 1-N-pyrazolyl-1-(2'-N-pyrazolylethyl) ethylene prepared in Example 24 1 HNMR;

[0022] Figure 2 HNMR of 1-N-pyrazolyl-1-(2'-N-pyrazolylethyl) ethylene prepared in Example 24 DETAILED DESCRIPTION

[0023] The embodiments of the present application are used to further illustrate the technical solutions of the present application, but are not limited to the following specific embodiments, and any combination of the specific embodiments is also included.

[0024] Example 1

[0025] This embodiment is a method for preparing 2-oxoglutaric acid, and the specific operation of the preparation method is as follows:

[0026] 30g 2-methylene glutaric acid is dissolved in 200ml dimethyl carbonate, 0.15g V2O5 / KOH / zeolite composite catalyst is added, and air is introduced for oxidation at reflux temperature for 8h. After the reaction is completed, the catalyst is removed by filtration, and dimethyl carbonate is removed by distillation to obtain 30.0g of crude 2-oxoglutaric acid product with a yield of 98.5%. After recrystallization with water, 29.1g of refined 2-oxoglutaric acid product is obtained with a purity of 99.2%.

[0027] Example 2

[0028] The operation in Example 1 is repeated, except that the amount of dimethyl carbonate is changed to 150ml. 28.9g of crude 2-oxoglutaric acid product is obtained with a yield of 95.0%, and 27.8g of refined product is obtained after recrystallization with a purity of 99.1%.

[0029] Example 3

[0030] The procedure of Example 1 was repeated except that the amount of dimethyl carbonate was changed to 250 ml. The crude 2-oxoglutaric acid product was 29.9 g with a yield of 98.3% and the purified product was 29.1 g with a purity of 99.1% after recrystallization.

[0031] Example Four

[0032] The procedure of Example 1 was repeated except that the amount of dimethyl carbonate was changed to 300 ml. The crude 2-oxoglutaric acid product was 30.1 g with a yield of 98.9% and the purified product was 29.1 g with a purity of 99.3% after recrystallization.

[0033] Example Five

[0034] The procedure of Example 1 was repeated except that the amount of V2O5 / KOH / zeolite composite catalyst was changed to 0.03 g. The crude 2-oxoglutaric acid product was 23.7 g with a yield of 77.9% and the purified product was 23.1 g with a purity of 99.0% after recrystallization.

[0035] Example Six

[0036] The procedure of Example 1 was repeated except that the amount of V2O5 / KOH / zeolite composite catalyst was changed to 0.1 g. The crude 2-oxoglutaric acid product was 26.3 g with a yield of 86.5% and the purified product was 25.2 g with a purity of 99.1% after recrystallization.

[0037] Example Seven

[0038] The procedure of Example 1 was repeated except that the amount of V2O5 / KOH / zeolite composite catalyst was changed to 0.2 g. The crude 2-oxoglutaric acid product was 29.8 g with a yield of 98.0% and the purified product was 28.9 g with a purity of 99.2% after recrystallization.

[0039] Example Eight

[0040] The procedure of Example 1 was repeated except that the amount of V2O5 / KOH / zeolite composite catalyst was changed to 0.3 g. The crude 2-oxoglutaric acid product was 29.9 g with a yield of 98.3% and the purified product was 29.0 g with a purity of 99.1% after recrystallization.

[0041] Example Nine

[0042] The procedure of Example 1 was repeated except that the reaction time was changed to 6 h. The crude 2-oxoglutaric acid product was 28.5 g with a yield of 93.7% and the purified product was 27.4 g with a purity of 99.0% after recrystallization.

[0043] Example Ten

[0044] The procedure of Example 1 was repeated except that the reaction time was changed to 10 hours. The crude 2-oxoglutaric acid product was 29.9 g with a yield of 98.3% and the purified product was 29.1 g with a purity of 99.2% after recrystallization.

[0045] Example Eleven

[0046] The procedure of Example 1 was repeated except that the reaction time was changed to 12 hours. The crude 2-oxoglutaric acid product was 28.7 g with a yield of 94.3% and the purified product was 27.9 g with a purity of 99.1% after recrystallization.

[0047] Example Twelve

[0048] The procedure of Example 1 was repeated except that the air was changed to oxygen and the reaction time was changed to 6 hours. The crude 2-oxoglutaric acid product was 29.9 g with a yield of 98.3% and the purified product was 29.1 g with a purity of 99.4% after recrystallization.

[0049] Example Thirteen

[0050] 1 g of ammonium metavanadate, 0.1 g of KOH, and 10 ml of distilled water were placed in a 100 ml beaker and heated to a slight boil with stirring. The water was evaporated until dryness. The solid product was ground to 100 mesh and heated to 300°C for 2 hours and then to 500°C for 2 hours in a tube furnace. The product was cooled and ground to 100 mesh to obtain the V2O5 / KOH / zeolite composite catalyst.

[0051] Example Fourteen

[0052] 1 g of ammonium metavanadate, 0.1 g of LiOH, and 10 ml of distilled water were placed in a 100 ml beaker and heated to a slight boil with stirring. The water was evaporated until dryness. The solid product was ground to 100 mesh and heated to 300°C for 2 hours and then to 500°C for 2 hours in a tube furnace. The product was cooled and ground to 100 mesh to obtain the V2O5 / LiOH / zeolite composite catalyst.

[0053] Example Fifteen

[0054] 1 g of ammonium metavanadate, 0.1 g of NaOH, and 10 ml of distilled water were placed in a 100 ml beaker and heated to a slight boil with stirring. The water was evaporated until dryness. The solid product was ground to 100 mesh and heated to 300°C for 2 hours and then to 500°C for 2 hours in a tube furnace. The product was cooled and ground to 100 mesh to obtain the V2O5 / NaOH / zeolite composite catalyst.

[0055] Example Sixteen

[0056] 1 g ammonium metavanadate, 0.1 g LiCO3, 10 ml distilled water into a 100 ml beaker, heated to a slight boil under stirring, evaporate water to complete dryness. The solid product obtained is ground to 100 mesh, heated to 300°C in a tube furnace for 2 hours, then heated to 500°C for 2 hours. After cooling, ground again to 100 mesh, the V2O5 / LiCO3 / zeolite composite catalyst is obtained.

[0057] Example Seventeen

[0058] 1 g ammonium metavanadate, 0.1 g NaCO3, 10 ml distilled water into a 100 ml beaker, heated to a slight boil under stirring, evaporate water to complete dryness. The solid product obtained is ground to 100 mesh, heated to 300°C in a tube furnace for 2 hours, then heated to 500°C for 2 hours. After cooling, ground again to 100 mesh, the V2O5 / NaCO3 / zeolite composite catalyst is obtained.

[0059] Example Eighteen

[0060] 1 g ammonium metavanadate, 0.1 g KCO3, 10 ml distilled water into a 100 ml beaker, heated to a slight boil under stirring, evaporate water to complete dryness. The solid product obtained is ground to 100 mesh, heated to 300°C in a tube furnace for 2 hours, then heated to 500°C for 2 hours. After cooling, ground again to 100 mesh, the V2O5 / KCO3 / zeolite composite catalyst is obtained.

[0061] Example Nineteen

[0062] Repeat the operation in Example One, except that the catalyst is replaced by V2O5 / LiOH / zeolite composite catalyst. The crude 2-oxoglutaric acid product is obtained 28.7 g, yield 94.3%, after recrystallization, the refined product is obtained 27.8 g, purity 99.0%.

[0063] Example Twenty

[0064] Repeat the operation in Example One, except that the catalyst is replaced by V2O5 / NaOH / zeolite composite catalyst. The crude 2-oxoglutaric acid product is obtained 29.1 g, yield 95.7%, after recrystallization, the refined product is obtained 28.1 g, purity 99.1%.

[0065] Example Twenty-one

[0066] Repeat the operation in Example One, except that the catalyst is replaced by V2O5 / LiCO3 / zeolite composite catalyst. The crude 2-oxoglutaric acid product is obtained 26.7 g, yield 87.8%, after recrystallization, the refined product is obtained 25.7 g, purity 99.2%.

[0067] Example Twenty-two

[0068] The operation in Example 1 was repeated except that the catalyst was changed to V2O5 / NaCO3 / zeolite composite catalyst. 2-oxoglutaric acid crude product 27.9 g was obtained with a yield of 91.7%, and refined product 26.8 g was obtained after recrystallization with a purity of 99.3%.

[0069] Example Twenty-three

[0070] The operation in Example 1 was repeated except that the catalyst was changed to V2O5 / NaCO3 / zeolite composite catalyst. 2-oxoglutaric acid crude product 27.9 g was obtained with a yield of 91.7%, and refined product 26.8 g was obtained after recrystallization with a purity of 99.3%.

[0071] Example Twenty-four

[0072] 7.2 g of acrylic acid was placed in a 100 ml reaction flask, and 12 g of thionyl chloride was added dropwise at 60°C for 4 h. Pyridine 10 ml, 7 g of pyrazole was added in the reaction flask, and reacted for another 4 h. DMAP 3 g was added, and reacted for 2 h. 1-N-pyrazolyl-1-(2'-N-pyrazolylethyl) ethylene 14.4 g was obtained by extraction separation with a yield of 80%. m.p. 26.6-28.0°C; 1 H NMR (300 MHz, CDC13, unit: ppm) δ 8.27 (m, 2H), 7.61 (d, 2H), 6.46 (m, 2H), 6.23 (s, 1H), 6.00 (s, 1H), 3.44 (t, J = 9 Hz, 2H), 3.04 (t, J = 6 Hz, 2H); HRMS: M+Na = 267.0860 (M = 244.2540).

[0073] 1-N-pyrazolyl-1-(2'-N-pyrazolylethyl) ethylene 14.4 g was suspended in 60 ml of water, and 10 ml of concentrated hydrochloric acid was added. It was heated to reflux for 6 h, and after cooling, it was neutralized to pH = 3. 2-methylene glutaric acid was extracted with ethyl acetate, and after removing the solvent, product 10.4 g was obtained with a yield of 90%.

[0074] The water phase was continuously neutralized to pH = 10, and pyrazole was recovered for reuse.

[0075] It should be noted that the above description and preferred embodiments are not to be construed as limiting the design idea of the present application. Those skilled in the art with the same knowledge as the present application can modify and change the technical idea of the present application in various forms, and such modifications and changes should be understood as falling within the scope of protection of the present application.

Claims

1. A process for the preparation of 2-oxoglutaric acid, characterized in that The specific method is as follows: 2-Methyleneglutarate is dissolved in a certain amount of dimethyl carbonate, and a certain amount of V2O5 / KOH / zeolite composite catalyst is added. The mixture is oxidized by passing air through it at reflux temperature for a certain period of time. After the reaction is completed, the catalyst is removed by filtration, and the dimethyl carbonate is removed by vacuum distillation to obtain crude 2-oxoglutarate product with a yield of 98.5%. The purified 2-oxoglutarate is obtained by recrystallization with water with a purity of 99.2%. The V2O5 / KOH / zeolite composite catalyst described in the specific method is prepared as follows: 1g ammonium metavanadate, 0.1g KOH, and 10ml distilled water are placed in a 100ml beaker, heated to a gentle boil with stirring, and the water is evaporated until completely dry; the obtained solid product is ground to 100 mesh, placed in a tube furnace and heated to 300℃ and held for 2 hours, then heated to 500℃ and held for 2 hours; after cooling, it is ground to 100 mesh again to obtain the V2O5 / KOH / zeolite composite catalyst.

2. The method for preparing 2-oxoglutaric acid according to claim 1, characterized in that... The amount of V2O5 / KOH / zeolite composite catalyst used in the specific method is 0.1-1% of the amount of 2-methyleneglutarate.

3. The method for preparing 2-oxoglutaric acid according to claim 1, characterized in that... The specific method describes an air oxidation time of 6-12 hours.

4. The method for preparing 2-oxoglutaric acid according to claim 1, characterized in that... The air used for oxidation, as described in the specific method, is replaced with oxygen.

5. The method for preparing 2-oxoglutaric acid according to claim 1, characterized in that... In the specific method, KOH in the V2O5 / KOH / zeolite composite catalyst is replaced with LiOH, NaOH, LiCO3, NaCO3, or KCO3.

Images