Preparation method of tetrasodium glutamate diacetate

Abstract

The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of tetrasodium glutamate diacetate. The preparation method comprises the following steps: (1) dissolving sodium glutamate with deionized water, and then adding a sodium hydroxide solution for neutralization to obtain a disodium glutamate solution; (2) dissolving chloroacetic acid with deionized water, and adding a sodium hydroxide solution for neutralization to obtain a sodium chloroacetate solution; and (3) mixing the disodium glutamate solution obtained in the step (1) with the sodium chloroacetate solution obtained in the step (2), carrying out a condensation reaction under gradient temperature and alkaline conditions, after the condensation reaction is completed, continuing heating to carry out a hydrolysis reaction, and after the reaction is completed, carrying out vacuum concentration, filtering and desalting to obtain the tetrasodium glutamate diacetate solution. Through gradient control of temperature and alkaline reaction conditions, the synthesis efficiency of the tetrasodium glutamate diacetate can be remarkably improved, and the product quality can be improved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of fine chemical industry, and particularly relates to a preparation method of tetrasodium glutamate diacetate. BACKGROUND

[0002] Tetrasodium glutamate diacetate (GLDA-4Na) is a green chelating agent prepared from L-glutamic acid. GLDA-4Na can stabilize trace metal ions in a formula, improve the storage stability of an emulsion, has a mild pH buffering capacity, is suitable for sensitive skin, cooperates with a moisturizing agent to improve the skin water content and prolong the moisturizing time, belongs to a green low-sensitivity system, and meets the sustainable cosmetic trend. Compared with other commonly used chelating additives such as disodium ethylenediaminetetraacetate (EDTA-2Na), trisodium amino triacetate (NTA-3Na) and sodium tripolyphosphate (STPP), GLDA-4Na has the advantages of environmental friendliness and use safety, and thus has a growing application demand. Therefore, the development of an efficient and low-cost preparation method of tetrasodium glutamate diacetate has a good industrial application prospect.

[0003] At present, the synthesis process routes of tetrasodium glutamate diacetate mainly include a hydrocyanic acid route, a hydroxyacetonitrile route, an ethylene oxide route and a chloroacetic acid route. The hydrocyanic acid route uses a toxic raw material hydrocyanic acid, the obtained product has a high impurity content, is easy to generate NTA byproducts, and a large amount of cyanide-containing wastewater is generated in the reaction process, which corrodes the production equipment. The hydroxyacetonitrile route (as recorded in the patent document with the publication number CN105924365A) avoids the generation of NTA byproducts in the hydrocyanic acid route, but still has toxicity and generates ammonia gas, which affects the product odor. The ethylene oxide route (as recorded in the patent document with the publication number WO2014090943A1) has a very low GLDA yield, and ethylene oxide has a high explosion risk. The chloroacetic acid route gradually attracts attention because of avoiding the use of toxic cyanide, having a short reaction period, a high conversion rate, relatively mild conditions and easy industrial production.

[0004] The chloroacetic acid route uses sodium glutamate and chloroacetic acid as raw materials to generate tetrasodium glutamate diacetate under alkaline conditions. However, under high-temperature alkaline conditions, chloroacetic acid is easy to hydrolyze to generate sodium hydroxyacetate, which reduces the product yield and increases the impurity content. SUMMARY

[0005] In view of the defects and deficiencies of the prior art, the purpose of the present application is to provide a preparation method of tetrasodium glutamate diacetate.

[0006] The purpose of the present application is achieved by the following technical scheme. A preparation method of tetrasodium glutamate diacetate comprises the following preparation steps: (1) Dissolve sodium glutamate in deionized water and then add sodium hydroxide solution to neutralize it to obtain a sodium glutamate solution; (2) Dissolve chloroacetic acid in deionized water and then add sodium hydroxide solution to neutralize it to obtain a sodium chloroacetate solution; wherein the molar ratio of chloroacetic acid to sodium glutamate is greater than 2; (3) Mix the sodium glutamate solution of step (1) with the sodium chloroacetate solution of step (2) and perform condensation reaction under gradient temperature and alkaline conditions; the gradient temperature conditions are: first, raise the temperature to a first temperature for 1-3 h, then raise the temperature to a second temperature for 8-16 h, after the completion of the condensation reaction, continue to raise the temperature to a third temperature for 1-3 h of hydrolysis reaction, after the reaction is completed, reduce the pressure to concentrate, filter to remove salt, and obtain a sodium glutamate bis-acetate solution; wherein the first temperature is higher than 30℃ and lower than the second temperature, the second temperature is lower than the third temperature, and the third temperature is lower than 100℃.

[0007] Further preferably, the first temperature is 30-50℃; the second temperature is 55-75℃; and the third temperature is 85-100℃.

[0008] Further, when the temperature is raised to the first temperature for 1-3 h, the pH is 8.2-9.2; When the temperature is raised to the second temperature for 8-16 h, the pH is 9-10.5; When the temperature is raised to the third temperature for 1-3 h of hydrolysis reaction, the pH is 11-12.

[0009] Further, the molar ratio of chloroacetic acid to sodium glutamate is 2.05-2.19.

[0010] The theoretical molar ratio of chloroacetic acid to sodium glutamate for the reaction is 2:1. By using a slight excess of chloroacetic acid, the conversion rate of the target product can be improved and the salt content of the target product can be reduced. Moreover, the excess chloroacetic acid can be converted into sodium hydroxyacetate with high safety under the subsequent high-temperature and high-pH value conditions, which meets the requirements of cosmetic raw materials.

[0011] Further, the amount of deionized water used in step (1) is 0.5-2 times the mass of sodium glutamate; and the amount of deionized water used in step (2) is 0.5-2 times the mass of chloroacetic acid. The use of an appropriate amount of deionized water as a reaction solvent can ensure good mass and heat transfer efficiency.

[0012] Further, the mass concentration of the sodium hydroxide solution in steps (1) and (2) is 30-50%.

[0013] Further, the neutralization in step (1) and (2) is to neutralize to pH = 7 ± 0.2. By neutralizing to neutral, the reactants are converted into the form of glutamic acid disodium and sodium chloroacetate, which can improve the reaction efficiency and reduce the generation of by-products.

[0014] Further, the neutralization in step (1) and (2) is carried out under stirring conditions, and the neutralization temperature is controlled at 15-25℃, and the stirring time is 5-30 min. By neutralizing at low temperature, the hydrolysis of chloroacetic acid to generate sodium hydroxyacetate can be avoided.

[0015] Further, the basic condition in step (3) can be maintained by continuously adding alkali during the reaction.

[0016] Further, the reduced pressure concentration in step (3) refers to reduced pressure concentration at a temperature of 85-90℃ to a solid content > 70%.

[0017] Further, the salt removal by filtration in step (3) refers to first hot filtration to remove salt, and then cooling to room temperature and pressure filtration to remove salt for the second time.

[0018] The principle of the present application is that by pre-neutralizing chloroacetic acid with sodium hydroxide solution at low temperature (preferably 15-25℃), the hydrolysis of chloroacetic acid to generate sodium hydroxyacetate at high reaction temperature and high alkaline conditions can be avoided, thereby improving the reaction efficiency of the subsequent condensation reaction with glutamic acid disodium. By pre-neutralizing sodium glutamate with sodium hydroxide solution, the reaction activity of the activated glutamic acid disodium and sodium chloroacetate is higher, which can also improve the reaction efficiency. Combined with further gradient temperature and alkaline conditions for condensation reaction, first, a preliminary reaction is carried out at relatively low temperature (preferably 30-50℃) and relatively low pH value of alkaline conditions (preferably pH value 8.2-9.2), which can reduce the hydrolysis of sodium chloroacetate and inhibit the generation of by-products, improve the conversion rate of target product and product quality; then, a main reaction is carried out at relatively high temperature (preferably 55-75℃) and relatively high pH value of alkaline conditions (preferably pH value 9-10.5), which can improve the reaction efficiency. Finally, the excess unreacted sodium chloroacetate is hydrolyzed to convert into safe sodium hydroxyacetate under high temperature (preferably 85-100℃) and high pH value (preferably pH value 11-12) conditions, thereby obtaining glutamic acid tetrasodium diacetate that meets the use of cosmetic raw materials.

[0019] Compared with the prior art, the present application has the following beneficial effects: (1) The method of the present application can activate the reaction raw materials and reduce the hydrolysis of sodium chloroacetate by pre-neutralizing sodium glutamate and chloroacetic acid with sodium hydroxide solution, thereby improving the reaction efficiency and the yield of target product.

[0020] (2) The method of the present application can reduce the hydrolysis of sodium chloroacetate and inhibit the generation of by-products, improve the conversion rate of the target product and the quality of the product by adopting gradient temperature and / or gradient pH value conditions for the condensation reaction, preliminarily reacting at relatively low temperature and relatively low pH value alkaline conditions, then reacting at relatively high temperature and relatively high pH value alkaline conditions for the main reaction, improving the reaction efficiency, and through the above-mentioned step-by-step reaction, the product conversion rate can be improved to more than 90%, and the product quality meets the use of cosmetic raw materials. DETAILED DESCRIPTION

[0021] The present application will be further described in detail below in combination with examples, but the embodiments of the present application are not limited thereto.

[0022] Example 1 A preparation method of tetrasodium glutamate diacetate, comprising the following preparation steps: (1) Put sodium glutamate (C5H9NO4Na.H2O) 47 kg and deionized water 50 kg into a reaction kettle, and after completely dissolving, add 32% liquid alkali 31 kg, neutralize to neutral (pH=7±0.2) after stirring at 20°C for 20 min, and obtain a disodium glutamate solution.

[0023] (2) Put chloroacetic acid 50 kg into a preparation tank, dissolve by adding 50 kg of deionized water, and after completely dissolving, add 32% liquid alkali 65 kg, neutralize to neutral after stirring at 20°C for 10 min, and obtain a sodium chloroacetate solution. The content of hydrolysis product sodium hydroxyacetate in the solution is 0.55% measured by HPLC.

[0024] (3) Add the sodium chloroacetate solution in the preparation tank to the reaction kettle of step (1), then heat to 45°C, and add 32% liquid alkali to control the pH value to 8.5 and react for 2 h; then heat to 65°C, add 32% liquid alkali to control the pH value to 9.5 and react for 12 h. Then heat to 85°C, add 32% liquid alkali to control the pH value to 11 and hydrolyze for 2 h. Concentrate to solid content >70% at 85-90°C under reduced pressure, filter preliminarily to remove salt while hot, and filter twice to remove salt after cooling to room temperature, and obtain tetrasodium glutamate diacetate.

[0025] The obtained product is detected by TLC to calculate the yield of tetrasodium glutamate diacetate (the actual mass of tetrasodium glutamate diacetate generated / theoretical mass of tetrasodium glutamate diacetate generated) as 95.3%, and the content of sodium chloride (salt) is 1.20%.

[0026] Example 2 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the difference lies in that in step (3), the pH value is controlled to 9.2 during the heating to 45°C reaction process, the pH value is controlled to 10.5 during the heating to 65°C reaction process, and the pH value is controlled to 12 during the heating to 85°C hydrolysis process, and the rest of the steps and parameter conditions are the same.

[0027] The product obtained was detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 95.1%, and the sodium chloride content as 1.18%.

[0028] Example 3 A method for preparing tetrasodium glutamate diacetate, compared with Example 1, the difference is that in step (3), the temperature is raised to 45℃, the pH value is controlled to 8.2 during the reaction process, the temperature is raised to 65℃, the pH value is controlled to 9 during the reaction process, and the pH value is controlled to 11 during the hydrolysis process, and the rest of the steps and parameter conditions are the same.

[0029] The product obtained was detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 95.5%, and the sodium chloride content as 1.22%.

[0030] Example 4 A method for preparing tetrasodium glutamate diacetate, comprising the following preparation steps: (1) Put 47 kg of sodium glutamate and 50 kg of deionized water into a reaction kettle, and after complete dissolution, add 31 kg of 32% liquid alkali, and stir at 20℃ for 20 min to neutralize to neutral (pH=7±0.2), to obtain a disodium glutamate solution.

[0031] (2) Put 48.6 kg of chloroacetic acid into a preparation tank, add 50 kg of deionized water to dissolve, and after complete dissolution, add 64 kg of 32% liquid alkali, and stir at 20℃ for 10 min to neutralize to neutral, to obtain a sodium chloroacetate solution. HPLC determination of the content of hydrolysis product sodium hydroxyacetate in the solution is 0.62%.

[0032] Step (3) is the same as Example 1.

[0033] The product obtained was detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 94.9%, and the sodium chloride content as 1.21%.

[0034] Example 5 A method for preparing tetrasodium glutamate diacetate, comprising the following preparation steps: (1) Put 47 kg of sodium glutamate and 50 kg of deionized water into a reaction kettle, and after complete dissolution, add 31 kg of 32% liquid alkali, and stir at 20℃ for 20 min to neutralize to neutral (pH=7±0.2), to obtain a disodium glutamate solution.

[0035] (2) Put 51 kg of chloroacetic acid into a preparation tank, add 50 kg of deionized water to dissolve, and after complete dissolution, add 66 kg of 32% liquid alkali, and stir at 20℃ for 10 min to neutralize to neutral, to obtain a sodium chloroacetate solution. HPLC determination of the content of hydrolysis product sodium hydroxyacetate in the solution is 0.60%.

[0036] Step (3) is the same as Example 1.

[0037] The obtained product was detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 95.6%, and the sodium chloride content as 1.19%.

[0038] Example 6 A method for preparing tetrasodium glutamate diacetate comprises the following preparation steps: (1) Put 47 kg of sodium glutamate and 50 kg of deionized water into a reaction kettle, and after completely dissolving, add 31 kg of 32% liquid alkali, and stir at 20°C for 20 min to neutralize to neutral (pH=7±0.2) to obtain a disodium glutamate solution.

[0039] (2) Put 52 kg of chloroacetic acid into a preparation tank, add 50 kg of deionized water to dissolve, and after completely dissolving, add 68 kg of 32% liquid alkali, and stir at 20°C for 10 min to neutralize to neutral to obtain a sodium chloroacetate solution. The HPLC determination of the hydrolysis product sodium hydroxyacetate content in the solution is 0.68%.

[0040] Step (3) is the same as Example 1.

[0041] The obtained product was detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 95.6%, and the sodium chloride content as 1.19%.

[0042] Example 7 (1) Put 47 kg of sodium glutamate and 50 kg of deionized water into a reaction kettle, and after completely dissolving, add 31 kg of 32% liquid alkali, and stir at 20°C for 20 min to neutralize to neutral (pH=7±0.2) to obtain a disodium glutamate solution.

[0043] (2) Put 48.6 kg of chloroacetic acid into a preparation tank, add 50 kg of deionized water to dissolve, and after completely dissolving, add 64 kg of 32% liquid alkali, and stir at 20°C for 10 min to neutralize to neutral to obtain a sodium chloroacetate solution.

[0044] (3) Add the sodium chloroacetate solution in the preparation tank to the reaction kettle of step (1), then heat to 40°C, and add 32% liquid alkali to control the pH to 9.0 for 2 h; then heat to 60°C, and add 32% liquid alkali to control the pH to 10 for 10 h. Further heat to 90°C, and add 32% liquid alkali to control the pH to 11.5 for 2 h. Concentrate under reduced pressure at 85-90°C to solid content >70%, filter while hot to preliminarily remove salt, and after cooling to room temperature, filter twice to remove salt to obtain tetrasodium glutamate diacetate.

[0045] The obtained product was detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 95.6%, and the sodium chloride content as 1.19%.

[0046] Example 8 (1) Put sodium glutamate 47 kg, deionized water 50 kg into the reactor, after completely dissolved, add 32% liquid alkali 31 kg, 20 ℃ stirring 20 min to neutralization (pH = 7 ± 0.2), get the sodium glutamate solution.

[0047] (2) Put chloroacetic acid 51 kg into the configuration tank, add 50 kg deionized water to dissolve, after completely dissolved, add 32% liquid alkali 66 kg, 20 ℃ stirring 10 min to neutralization, get the sodium chloroacetate solution.

[0048] (3) Put the sodium chloroacetate solution in the configuration tank into the reactor of step (1), then warm up to 35 ℃, and add 32% liquid alkali to control pH 8.5 reaction 3 h; then warm up to 65 ℃, add 32% liquid alkali to control pH 9 reaction 12 h. Again warm up to 85 ℃, add 32% liquid alkali to control pH 12 hydrolysis 1 h. 85-90 ℃ reduced pressure concentration to solid content > 70%, hot filtration to preliminary desalination, cool to room temperature, then pressure filtration to secondary desalination, get tetrasodium glutamate diacetate.

[0049] The product is detected by TLC, the yield of tetrasodium glutamate diacetate is 95.9%, and the sodium chloride (salt) content is 1.60%.

[0050] Example 9 (1) Put sodium glutamate 47 kg, deionized water 50 kg into the reactor, after completely dissolved, add 32% liquid alkali 31 kg, 20 ℃ stirring 20 min to neutralization (pH = 7 ± 0.2), get the sodium glutamate solution.

[0051] (2) Put chloroacetic acid 52 kg into the configuration tank, add 50 kg deionized water to dissolve, after completely dissolved, add 32% liquid alkali 68 kg, 20 ℃ stirring 10 min to neutralization, get the sodium chloroacetate solution.

[0052] (3) Put the sodium chloroacetate solution in the configuration tank into the reactor of step (1), then warm up to 30 ℃, and add 32% liquid alkali to control pH 8.2 reaction 3 h; then warm up to 55 ℃, add 32% liquid alkali to control pH 9.5 reaction 16 h. Again warm up to 100 ℃, add 32% liquid alkali to control pH 11 hydrolysis 1 h. 85-90 ℃ reduced pressure concentration to solid content > 70%, hot filtration to preliminary desalination, cool to room temperature, then pressure filtration to secondary desalination, get tetrasodium glutamate diacetate.

[0053] The product is detected by TLC, the yield of tetrasodium glutamate diacetate is 96.2%, and the sodium chloride (salt) content is 1.81%.

[0054] Example 10 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization time of step (2) is adjusted to 5 min, and the rest is the same.

[0055] The content of hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) is 0.50%.

[0056] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 95.1%, and the content of sodium chloride (salt) is 1.21%.

[0057] Example 11 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization time of step (2) is adjusted to 30 min, and the rest is the same.

[0058] The content of hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) is 0.64%.

[0059] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 95.4%, and the content of sodium chloride (salt) is 1.20%.

[0060] Example 12 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization temperature of step (2) is adjusted to 15℃, and the rest is the same.

[0061] The content of hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) is 0.47%.

[0062] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 95.2%, and the content of sodium chloride (salt) is 1.22%.

[0063] Example 13 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization temperature of step (2) is adjusted to 25℃, and the rest is the same.

[0064] The content of hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) is 0.72%.

[0065] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 95.5%, and the content of sodium chloride (salt) is 1.18%.

[0066] Example 14 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization temperature of step (2) is adjusted to 10℃, and the rest is the same.

[0067] The hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) has a content of 0.38%.

[0068] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 95.0%, and the sodium chloride content is 1.22%.

[0069] Example 15 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization temperature in step (2) is adjusted to 10℃, and the stirring neutralization time is adjusted to 30 min, and the rest is the same.

[0070] The hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) has a content of 0.45%.

[0071] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 95.4%, and the sodium chloride content is 1.19%.

[0072] Example 16 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization temperature in step (2) is adjusted to 30℃, and the rest is the same.

[0073] The hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) has a content of 0.91%.

[0074] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 94.1%, and the sodium chloride content is 1.19%.

[0075] Comparative example 1 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the stirring neutralization process in step (2) is free of heat, and the temperature fluctuation is not controlled additionally, and the rest is the same.

[0076] The hydrolysis product sodium hydroxyacetate in the sodium chloroacetate solution obtained in step (2) has a content of 2.56%.

[0077] The product obtained in step (3) is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 91.6%, and the sodium chloride content is 1.22%.

[0078] Comparative example 2 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the chloroacetic acid is not pre-neutralized under low temperature conditions, and the specific steps are as follows: Step (1) is the same as example 1.

[0079] (2) Put 50 kg of chloroacetic acid into the configuration tank, add 50 kg of deionized water to dissolve, and obtain a chloroacetic acid solution.

[0080] (3) The chloroacetic acid solution in the configuration tank is added to the reaction kettle of step (1), then warmed to 45℃, and 32% liquid alkali is added to control the pH to 8.5, and reacted for 2h; then warmed to 65℃, and 32% liquid alkali is added to control the pH to 9.5, and reacted for 12h. Then warmed to 85℃, and 32% liquid alkali is added to control the pH to 11, and hydrolyzed for 2h. Concentrated to solid content >70% at 85-90℃ under reduced pressure, filtered while hot for primary desalination, and then filtered under pressure for secondary desalination after cooling to room temperature, to obtain tetrasodium glutamate diacetate.

[0081] The obtained product is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 89.7%, and the sodium chloride (salt) content is 1.2%.

[0082] It can be seen from the comparison results of Comparative Examples 1-2 and Example 1 that, by pre-neutralizing chloroacetic acid under low temperature conditions, and then performing condensation reaction, the present application can reduce the early hydrolysis of chloroacetic acid and the hydrolysis side reaction in the reaction process, thereby improving the conversion rate of the target product.

[0083] Comparative Example 3 A preparation method of tetrasodium glutamate diacetate, compared with Example 1, the condensation reaction adopts one-step reaction, and the specific steps are as follows: Steps (1) and (2) are the same as Example 1.

[0084] (3) The sodium chloroacetate solution in the configuration tank is added to the reaction kettle of step (1), then warmed to 65℃, and 32% liquid alkali is added to control the pH to 9.5, and reacted for 12h. Then warmed to 85℃, and 32% liquid alkali is added to control the pH to 11, and hydrolyzed for 2h. Concentrated to solid content >70% at 85-90℃ under reduced pressure, filtered while hot for primary desalination, and then filtered under pressure for secondary desalination after cooling to room temperature, to obtain tetrasodium glutamate diacetate.

[0085] The obtained product is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 88.5%, and the sodium chloride (salt) content is 1.20%.

[0086] It can be seen from the comparison results of Example 1 that, by performing condensation reaction under gradient temperature and gradient pH conditions, and performing preliminary reaction under relatively low temperature and relatively low pH alkali conditions, the present application can reduce the hydrolysis side reaction of sodium chloroacetate, thereby improving the conversion rate of the target product.

[0087] Comparative Example 4 A preparation method of tetrasodium glutamate diacetate, compared with Example 1, does not perform hydrolysis reaction, and the specific steps are as follows: Steps (1) and (2) are the same as Example 1.

[0088] (3) The sodium chloroacetate solution in the configuration tank is added to the reaction kettle of step (1), then the temperature is raised to 45℃, and 32% liquid alkali is added to control the pH to 8.5, and reacted for 2h; then the temperature is raised to 65℃, 32% liquid alkali is added to control the pH to 9.5, and reacted for 12h. Concentration under reduced pressure at 85-90℃ to solid content >70%, hot filtration for primary desalination, and cooling to room temperature for pressure filtration for secondary desalination to obtain tetrasodium glutamate diacetate.

[0089] The obtained product is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 95.1%, and the sodium chloride (salt) content is 1.2%.

[0090] It can be seen from the comparison results of Example 1 that the step of removing sodium chloroacetate by hydrolysis reaction under high temperature and high pH value conditions after the completion of the condensation reaction does not affect the conversion rate of the target product and the salt content of the final product.

[0091] Comparative Example 5 A preparation method of tetrasodium glutamate diacetate comprises the following preparation steps: (1) 47kg of sodium glutamate and 50kg of deionized water are put into a reaction kettle, and after complete dissolution, 31kg of 32% liquid alkali is added, and stirred at 20℃ for 20min to neutralize to neutral, to obtain a disodium glutamate solution.

[0092] (2) 50kg of chloroacetic acid is dissolved in 50kg of deionized water to obtain a chloroacetic acid aqueous solution; the obtained chloroacetic acid aqueous solution and 65kg of 32% liquid alkali are respectively loaded into a dropping device for standby.

[0093] (3) The temperature of the reaction kettle system is raised to 85℃, and the chloroacetic acid aqueous solution and liquid alkali in step (2) are added dropwise, the dropping speed is controlled, the temperature of the reaction system is kept at 85±2℃, and the pH value is kept in the range of 10.0-10.5, 3h dropwise addition is completed, then the temperature is kept for 1h, vacuum dehydration to solid content >70%, hot filtration for primary desalination, cooling to room temperature for pressure filtration for secondary desalination to obtain tetrasodium glutamate diacetate.

[0094] The obtained product is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 83.2%, and the sodium chloride (salt) content is 1.20%.

[0095] It can be seen from the comparison results of Example 1 that the target product conversion rate can be significantly improved by pre-neutralizing chloroacetic acid under low temperature conditions, and then performing condensation reaction under gradient temperature and gradient pH value conditions.

[0096] Comparative Example 6 A preparation method of tetrasodium glutamate diacetate comprises the following preparation steps: Steps (1) and (2) are the same as those of Example 1.

[0097] (3) Add the sodium chloroacetate solution in the configuration tank to the reaction kettle of step (1), then warm to 65°C, and add 32% liquid alkali to control the pH to 8.5 and react for 2 h; then cool to 45°C, add 32% liquid alkali to control the pH to 9.5 and react for 12 h. Then warm to 85°C, add 32% liquid alkali to control the pH to 11 and hydrolyze for 2 h. Concentrate under reduced pressure to a solid content > 70% at 85-90°C, filter while hot to remove salt preliminarily, and then filter under pressure to remove salt again after cooling to room temperature, to obtain tetrasodium glutamate diacetate.

[0098] The obtained product is detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 84.5%, and the sodium chloride (salt) content as 1.25%.

[0099] Comparative Example 7 A method for preparing tetrasodium glutamate diacetate, comprising the following preparation steps: Steps (1) and (2) are the same as in Example 1.

[0100] Add the sodium chloroacetate solution in the configuration tank to the reaction kettle of step (1), then warm to 85°C, and add 32% liquid alkali to control the pH to 8.5 and react for 2 h; then add 32% liquid alkali to control the pH to 9.5 and continue to react for 12 h. Then add 32% liquid alkali to control the pH to 11 and continue to hydrolyze for 2 h. Concentrate under reduced pressure to a solid content > 70% at 85-90°C, filter while hot to remove salt preliminarily, and then filter under pressure to remove salt again after cooling to room temperature, to obtain tetrasodium glutamate diacetate.

[0101] The obtained product is detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 83.8%, and the sodium chloride (salt) content as 1.22%.

[0102] Comparative Example 8 A method for preparing tetrasodium glutamate diacetate, comprising the following preparation steps: Steps (1) and (2) are the same as in Example 1.

[0103] Add the sodium chloroacetate solution in the configuration tank to the reaction kettle of step (1), then warm to 65°C, and add 32% liquid alkali to control the pH to 8.5 and react for 2 h; then add 32% liquid alkali to control the pH to 9.5 and continue to react for 12 h. Then add 32% liquid alkali to control the pH to 11 and continue to hydrolyze for 2 h. Concentrate under reduced pressure to a solid content > 70% at 85-90°C, filter while hot to remove salt preliminarily, and then filter under pressure to remove salt again after cooling to room temperature, to obtain tetrasodium glutamate diacetate.

[0104] The obtained product is detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 85.1%, and the sodium chloride (salt) content as 1.28%.

[0105] Comparative Example 9 A preparation method of tetrasodium glutamate diacetate, comprising the following preparation steps: Steps (1) and (2) are the same as those in Example 1.

[0106] The sodium chloroacetate solution in the configuration tank is added to the reaction kettle of step (1), then the temperature is raised to 45°C, and 32% liquid alkali is added to control the pH to 8.5 for 2h of reaction; then 32% liquid alkali is added to control the pH to 9.5 for 12h of continuous reaction. Then 32% liquid alkali is added to control the pH to 11 for 2h of continuous hydrolysis. Concentration is carried out at 85-90°C under reduced pressure until the solid content is >70%, and then hot filtration is carried out for primary desalting. After cooling to room temperature, pressure filtration is carried out for secondary desalting to obtain tetrasodium glutamate diacetate.

[0107] The obtained product is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 84.0%, and the sodium chloride (salt) content is 1.26%.

[0108] Comparative Example 10 A preparation method of tetrasodium glutamate diacetate, compared with Example 1, the molar ratio of sodium chloroacetate to glutamate disodium is 2.00, and the specific steps are as follows: (1) Sodium glutamate (C5H9NO4Na·H2O) 47 kg and deionized water 50 kg are put into a reaction kettle, and after complete dissolution, 32% liquid alkali 31 kg is added, and stirring is carried out at 20°C for 20 min to neutralize to neutral (pH=7±0.2) to obtain a glutamate disodium solution.

[0109] (2) Chloroacetic acid 47.5 kg is put into a configuration tank, and 50 kg of deionized water is added for dissolution. After complete dissolution, 32% liquid alkali 63 kg is added, and stirring is carried out at 20°C for 10 min to neutralize to neutral to obtain a sodium chloroacetate solution. HPLC determination shows that the content of hydrolysis product sodium hydroxyacetate in the solution is 0.57%.

[0110] (3) The sodium chloroacetate solution in the configuration tank is added to the reaction kettle of step (1), then the temperature is raised to 50°C, and 32% liquid alkali is added to control the pH to 9.2 for 1h of reaction; then the temperature is raised to 75°C, and 32% liquid alkali is added to control the pH to 10.5 for 8h of reaction. Then the temperature is raised to 95°C, and 32% liquid alkali is added to control the pH to 12 for 2h of hydrolysis. Concentration is carried out at 85-90°C under reduced pressure until the solid content is >70%, and then hot filtration is carried out for primary desalting. After cooling to room temperature, pressure filtration is carried out for secondary desalting to obtain tetrasodium glutamate diacetate.

[0111] The obtained product is detected by TLC to calculate that the yield of tetrasodium glutamate diacetate is 78.5%, and the sodium chloride (salt) content is 3.50%.

[0112] Comparative Example 11 A preparation method of tetrasodium glutamate diacetate, compared with example 1, the molar ratio of sodium chloroacetate and glutamate disodium is 2.00, and the specific steps are as follows: (1) Put 47 kg of sodium glutamate and 50 kg of deionized water into a reaction kettle, and after completely dissolving, add 31 kg of 32% liquid alkali, stir at 20°C for 20 min, and neutralize to neutral (pH=7±0.2) to obtain a glutamate disodium solution.

[0113] (2) Put 47.5 kg of chloroacetic acid into a configuration tank, add 50 kg of deionized water to dissolve, and after completely dissolving, add 63 kg of 32% liquid alkali, stir at 20°C for 10 min, and neutralize to neutral to obtain a sodium chloroacetate solution. The HPLC determination of the hydrolysis product sodium hydroxyacetate content in the solution is 0.58%.

[0114] Step (3) is the same as example 1.

[0115] The obtained product is detected by TLC to calculate the yield of tetrasodium glutamate diacetate as 66.80%, and the sodium chloride (salt) content is 3.80%.

[0116] From the comparison results of comparative examples 10-11 and example 1, it can be seen that by using a little excess of chloroacetic acid, the conversion rate of the target product can be improved, and the salt content in the product can be significantly reduced, and the product quality is improved.

[0117] The above examples are preferred embodiments of the present application, but the embodiments of the present application are not limited by the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application are equivalent replacement methods, and are all included in the protection scope of the present application.

Claims

1. A process for the preparation of tetrasodium glutamate diacetate, characterized in that: The preparation process comprises the following steps: (1) dissolving sodium glutamate in deionized water and adding sodium hydroxide solution to neutralize, obtaining a disodium glutamate solution; (2) dissolving chloroacetic acid in deionized water and adding sodium hydroxide solution to neutralize, obtaining a sodium chloroacetate solution; wherein the molar ratio of chloroacetic acid to sodium glutamate is greater than 2; (3) mixing the disodium glutamate solution of step (1) with the sodium chloroacetate solution of step (2) and performing condensation reaction under gradient temperature and alkaline conditions; the gradient temperature conditions are: first heating to a first temperature for 1-3 h, then heating to a second temperature for 8-16 h, after the completion of the condensation reaction, continuing to heat to a third temperature for 1-3 h of hydrolysis reaction, after the completion of the reaction, reducing pressure concentration, filtering to remove salt, obtaining a tetrasodium glutamate bisacetate solution; wherein the first temperature is higher than 30℃ and lower than the second temperature, the second temperature is lower than the third temperature, and the third temperature is lower than 100℃.

2. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized in that: The first temperature is 30-50℃; The second temperature is 55-75℃; The third temperature is 85-100℃.

3. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized by: When heating to the first temperature for 1-3 h, the pH is 8.2-9.2; When heating to the second temperature for 8-16 h, the pH is 9-10.5; When heating to the third temperature for 1-3 h of hydrolysis reaction, the pH is 11-12.

4. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized by: The molar ratio of chloroacetic acid to sodium glutamate is 2.05-2.

19.

5. The process for the preparation of tetrasodium glutamate diacetate as claimed in claim 1, wherein: In step (1), the amount of deionized water is 0.5-2 times the mass of sodium glutamate; in step (2), the amount of deionized water is 0.5-2 times the mass of chloroacetic acid.

6. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized by: In steps (1) and (2), the mass concentration of the sodium hydroxide solution is 30-50%.

7. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized by: In steps (1) and (2), the neutralization refers to neutralization to pH=7±0.

2.

8. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized by: In steps (1) and (2), the neutralization is performed under stirring, the temperature is controlled to be 15-25℃, and the stirring time is 5-30 min.

9. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized by: In step (3), the reducing pressure concentration refers to reducing pressure concentration at a temperature of 85-90℃ to a solid content of >70%.

10. A process for the preparation of tetrasodium glutamate diacetate according to claim 1, characterized by: In step (3), the filtering to remove salt refers to first hot filtering to remove salt, and then cooling to room temperature and pressure filtering to remove salt again.