Preparation method of ethylene glycol bis (2-aminoethyl ether) tetraacetic acid

Abstract

The invention relates to a preparation method of ethylene glycol bis (2-aminoethyl ether) tetraacetic acid, and belongs to the technical field of organic synthesis. According to the method, iminodiacetic acid and dichlorotriethyl ether are taken as raw materials, water and ethanol are taken as solvents, and ethylene glycol bis (2-aminoethyl ether) tetraacetic acid is obtained through reaction at 75-85 DEG C under the catalysis of sodium hydroxide. Compared with an existing preparation method, the method has the advantages that the reaction temperature is reduced and does not need to be strictly controlled in a relatively small range. The content of the finally prepared crude product can meet the index requirement only after being washed and pulped. The method is a green and efficient preparation method of ethylene glycol bis (2-aminoethyl ether) tetraacetic acid, and can be industrially popularized.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a preparation method of ethylene glycol bis(2-aminoethylether) tetraacetic acid. BACKGROUND

[0002] EGTA, full name Ethylene Glycol Tetraacetic Acid, Chinese name ethylene glycol bis(2-aminoethylether) tetraacetic acid, is one of important chemical components in many buffers. EGTA is a metal ion chelator, and has a function similar to EDTA, but EGTA has higher calcium ion chelation selectivity, and is suitable for calcium ion concentration determination in a magnesium ion existing environment. It can also be used to chelate calcium ions in blood to play an anticoagulation role (1g EGTA / 100ml blood), and the application rate of EDTA is higher for this use. However, the EGTA products produced by the existing technologies at home and abroad have low purity, and repeated refining consumes a large amount of time and energy.

[0003] Patent CN101898974A discloses a production method of ethylene glycol-bis-(2-aminoethylether) tetraacetic acid, which discloses that iminodiacetic acid disodium and dichloro triethyl ether are used as raw materials, glycerol is used as a solvent, and ethylene glycol bis(2-aminoethylether) tetraacetic acid is prepared under the catalysis of sodium carbonate. However, the reaction temperature of the above method needs to be strictly controlled at 100℃, and the glycerol solution of iminodiacetic acid disodium needs to be heated to 60-65℃ before dichloro triethyl ether is added. Otherwise, it is difficult to obtain a product with a purity of more than 99%. In addition, glycerol is used as a solvent in the above process, and the viscosity of glycerol is high at a relatively low temperature, so the raw materials cannot be fully mixed at the initial stage of feeding, and agglomeration occurs. At the same time, iminodiacetic acid disodium and sodium carbonate do not completely dissolve in the reaction system, which leads to a non-homogeneous system and slows down the reaction process. It can be seen that the reaction conditions of the above process are relatively harsh, and therefore a simpler preparation process needs to be developed. SUMMARY

[0004] In view of the problems such as harsh reaction conditions in the preparation of ethylene glycol bis(2-aminoethylether) tetraacetic acid, the present application provides a preparation method of ethylene glycol bis(2-aminoethylether) tetraacetic acid to solve the above problems.

[0005] The technical scheme of the present application is as follows: In a first aspect, the present application provides a preparation method of ethylene glycol bis(2-aminoethylether) tetraacetic acid, and the reaction formula is as follows: ; The method comprises the following steps: (1) adding iminodiacetic acid, dichloro triethyl ether and sodium hydroxide aqueous solution into a reactor, then adding ethanol, stirring to warm up to 60~70℃, detecting the pH of the reaction solution to be 6~7, then continuously adding sodium hydroxide solution, then warming the reaction solution to 75~85℃ to react; (2) after the reaction is completed, cooling to 20~30℃, adding hydrochloric acid to adjust the pH of the reaction solution to 1~2, and keeping warm to crystallize; filtering to obtain a crude product of ethylene glycol bis(2-aminoethyl ether) tetraacetic acid; (3) using water to pulp the crude product to obtain ethylene glycol bis(2-aminoethyl ether) tetraacetic acid.

[0006] Further, in step (1), the molar ratio of iminodiacetic acid to dichloro triethyl ether is 2:1.

[0007] Further, in step (1), the total amount of sodium hydroxide is 3.0~3.2 mol / mol based on the amount of iminodiacetic acid.

[0008] Further, in step (1), the amount of ethanol is 2~6 g / g based on the amount of iminodiacetic acid.

[0009] Further, in step (1), the reaction time is 3~6 hours.

[0010] Further, in step (1), the concentration of sodium hydroxide aqueous solution is 30%~36%.

[0011] Further, in step (2), before the reaction solution is cooled, it further includes a hot filtration process, which can remove insoluble impurities and avoid the residual of insoluble impurities in the product.

[0012] Further, in step (2), the crystallization time is 1~2 hours.

[0013] Further, in step (3), the amount of water used for pulping is 2~5 g / g based on the mass of the crude product.

[0014] The beneficial effects of the present application are: The application provides a preparation method of ethylene glycol bis(2-aminoethylether) tetraacetic acid, which is easy to obtain raw materials, simple to operate, high in process yield and stable, and excellent in product quality. The application uses iminodiacetic acid and dichloro triethyl ether as raw materials, ethanol and water as solvents, and sodium hydroxide as a catalyst to prepare ethylene glycol bis(2-aminoethylether) tetraacetic acid. The reaction system of the application is homogeneous, which ensures that the reaction can be quickly carried out. The application reduces the reaction temperature and does not need to be strictly controlled in a small range. The content of the finally prepared crude product can meet the index requirements after water washing and beating. Meanwhile, the alcohol solvent used in the application can be recovered and reused after distillation, reducing the discharge of waste water and waste liquid, and the comprehensive utilization efficiency of the solvent is greater than 90%. The application is a green and efficient preparation method of ethylene glycol bis(2-aminoethylether) tetraacetic acid and can be popularized and applied in industry. DETAILED DESCRIPTION

[0015] In order to make the personnel in the technical field better understand the technical solutions in the application, the technical solutions in the embodiments of the application will be clearly and completely described below. Obviously, the described embodiments are only some of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor should belong to the protection scope of the application.

[0016] Embodiment 1 A preparation method of ethylene glycol bis(2-aminoethylether) tetraacetic acid is as follows: (1) 300.7 g (2.25 mol) of iminodiacetic acid, 200.6 g (1.07 mol) of dichloro triethyl ether and 550 g (4.4 mol) of 32% sodium hydroxide aqueous solution are added into a reaction bottle, then 400 g of ethanol is added, the system is clear, stirring is performed to heat the system to 60 DEG C, the pH of the reaction solution is detected to be 7, then 280 g (2.1 mol) of 32% sodium hydroxide aqueous solution is slowly added into the reaction bottle, the temperature of the system is controlled to be 60 DEG C~70 DEG C during the adding process, after the adding process is completed, the system is heated to reflux, at this time, the internal temperature is 81 DEG C, and the reflux reaction is maintained for 6 h.

[0017] (2) After the heat preservation is completed, the insoluble impurities are removed by filtration, the filtrate is cooled to 20 DEG C~30 DEG C, then 500 g (4.9 mol) of concentrated hydrochloric acid (concentration: 36%) is added dropwise to adjust the pH of the reaction system to 1, and the crystal is precipitated at 20 DEG C~30 DEG C for 2 h.

[0018] (3) After the heat preservation is completed, the crystal is precipitated, filtration is performed, the filter cake is rinsed with 50 g of ethanol, and 392 g of the crude product is obtained.

[0019] (4) The product crude obtained in step (3) is added to 784 g of water, and the slurry is prepared at 60°C for 1 h, and then hot filtration is performed, and the filter cake is dried to obtain ethylene glycol bis(2-aminoethylether)tetraacetic acid 304 g, content 99.32% (external standard method), yield 74.87%.

[0020] Example 2 A preparation method of ethylene glycol bis(2-aminoethylether)tetraacetic acid is as follows: (1) In a reaction bottle, iminodiacetic acid 562.6 g (4.23 mol), dichloro triethyl ether 377.7 g (2.02 mol) and 32% sodium hydroxide aqueous solution 1087.5 g (8.7 mol) are added, then 1200 g of ethanol is added, the system is clear, after stirring and heating to 65°C, the pH of the reaction solution is detected to be 7, 32% sodium hydroxide aqueous solution 537.5 g (4.3 mol) is slowly added to the reaction bottle, and the system temperature is controlled at 60°C-70°C during the addition process, after the addition is completed, the temperature is increased to reflux reaction, at this time the internal temperature is 82°C, and the reflux reaction is maintained for 6 h.

[0021] (2) After the heat preservation is completed, the insoluble impurities are removed by hot filtration, and then the filtrate is cooled to 20°C-30°C, and then 985.8 g (9.72 mol) of concentrated hydrochloric acid (concentration 36%) is added dropwise to adjust the pH of the reaction system to 1, and the crystal is precipitated at 20°C-30°C for 2 h.

[0022] (3) After the crystal precipitation heat preservation is completed, filtration is performed, and the filter cake is rinsed with 112 g of ethanol to obtain the product crude 765 g.

[0023] (4) The product crude obtained in step (3) is added to 2000 g of water, and the slurry is prepared at 60°C for 1 h, and then hot filtration is performed, and the filter cake is dried to obtain ethylene glycol bis(2-aminoethylether)tetraacetic acid 602 g, content 99.64% (external standard method), yield 78.48%.

[0024] Example 3 A preparation method of ethylene glycol bis(2-aminoethylether)tetraacetic acid is as follows: (1) In a reaction bottle, iminodiacetic acid 562.6 g (4.23 mol), dichloro triethyl ether 377.7 g (2.02 mol) and 32% sodium hydroxide aqueous solution 1087.5 g (8.7 mol) are added, then 1200 g of ethanol is added, the system is clear, after stirring and heating to 65°C, the pH of the reaction solution is detected to be 7, 32% sodium hydroxide aqueous solution 537.5 g (4.3 mol) is slowly added to the reaction bottle, and the system temperature is controlled at 60°C-70°C during the addition process, after the addition is completed, the temperature is increased to reflux reaction, at this time the internal temperature is 82°C, and the reflux reaction is maintained for 6 h.

[0025] (2) After the end of the heat preservation, remove the insoluble impurities by hot filtration, and then cool the filtrate to 20-30°C, and then add 736.3 g (7.26 mol) of concentrated hydrochloric acid (concentration 36%) dropwise to adjust the pH of the reaction system to 2, and crystallize for 2 h at 20-30°C.

[0026] (3) After the end of the crystallization heat preservation, filtration is performed, and the filter cake is rinsed with 80 g of ethanol to obtain 765 g of the crude product.

[0027] (4) The crude product obtained in step (3) is added to 784 g of water, and the slurry is heated to 60°C for 1 h, and then hot filtration is performed, and the filter cake is dried to obtain 449.5 g of ethylene glycol bis(2-aminoethylether)tetraacetic acid with a content of 99.72% (external standard method) and a yield of 76.33%.

[0028] Comparative Example According to the method disclosed in patent CN101898974A, ethylene glycol-bis-(2-aminoethylether)tetraacetic acid is prepared, and the specific steps are as follows: Glycerol is added to a reaction bottle, Glycerol 2120 g is added to the reaction bottle, and then disodium iminodiacetate 559.54 g (3.16 mol) and sodium carbonate 333.9 g (3.15 mol) are added. The reaction system is viscous, and the raw materials are suspended in the glycerol and partially agglomerated. Then, the temperature is slowly increased to 65°C, and dichloro triethyl ether 289.8 g (1.55 mol) is slowly added dropwise. After the dropwise addition is completed, the temperature is slowly increased to 100°C, and the flowability of the reaction system is improved. Part of the raw materials is not dissolved. After the reaction is completed, part of the solid is still not dissolved. Then, the temperature is slowly cooled to 60°C, and hydrochloric acid is slowly added dropwise until the pH of the reaction system is 7. The temperature of the reaction liquid is increased to 95°C, and then the filtrate is hot filtered. Then, hydrochloric acid is added dropwise to the filtrate until the pH is 1. After standing for 10 h, 2200 g of water is added, and stirring is performed for 1 h. Filtration is performed, and the filter cake is rinsed with 80 g of ethanol to obtain 685 g of the crude product. The crude product is added to 3500 g of water, and heated to reflux. After 2 h of dissolution, the temperature is cooled to room temperature, and then filtration is performed. The filter cake is rinsed with water, and dried to obtain 386.4 g of ethylene glycol-bis-(2-aminoethylether)tetraacetic acid with a yield of 65.61% and a content of 99.3% (external standard method).

[0029] Although the present application has been described in detail by preferred embodiments, the present application is not limited thereto. Various equivalent modifications or replacements can be made to the embodiments of the present application by those skilled in the art without departing from the spirit and essence of the present application, and these modifications or replacements shall be within the scope of the present application. Any person skilled in the art can easily think of changes or replacements within the technical range disclosed in the present application, and these changes or replacements shall be within the protection scope of the present application.

Claims

1. A process for the preparation of ethylene glycol bis(2-aminoethylether) tetraacetic acid, characterized in that, The reaction formula is as follows: ； The method comprises the following steps: (1) adding iminodiacetic acid, dichloro triethyl ether and sodium hydroxide aqueous solution into a reactor, then adding ethanol, stirring and heating to 60-70 DEG C, detecting the pH value of the reaction solution, and then adding sodium hydroxide solution, and then heating the reaction solution to 75-85 DEG C for reaction; (2) cooling the reaction solution to 20-30 DEG C after the reaction is completed, adding hydrochloric acid to adjust the pH value of the reaction solution to 1-2, and then crystallizing under insulation; filtering to obtain the crude ethylene glycol bis (2-aminoethyl ether) tetraacetic acid; (3) using water to pulp the crude product to obtain ethylene glycol bis (2-aminoethyl ether) tetraacetic acid.

2. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (1), the molar ratio of iminodiacetic acid to dichloro triethyl ether is 2:

1.

3. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (1), the total amount of sodium hydroxide is 3.0-3.2 mol / mol based on the amount of iminodiacetic acid.

4. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (1), the amount of ethanol is 2-6 g / g based on the amount of iminodiacetic acid.

5. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (1), the reaction time is 3-6 hours.

6. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (1), the concentration of sodium hydroxide aqueous solution is 30%-36%.

7. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (2), before the reaction solution is cooled, the process of hot filtration is further included, which can remove insoluble impurities and avoid the residual of insoluble impurities in the product.

8. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (2), the crystallization time is 1-2 hours.

9. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (3), the amount of water used for pulping is 2-5 g / g based on the mass of the crude product.

10. A process for the preparation of ethylene glycol bis (2-aminoethylether) tetraacetic acid as claimed in claim 1, wherein, In step (3), the pulping temperature is 60 DEG C, and the pulping time is 1 hour.

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