CN117342960A - Preparation method and application of pentetic acid - Google Patents

Abstract

The invention provides a preparation method of pentetic acid, which takes chloroacetic acid and diethylenetriamine as raw materials, obtains the pentetic acid by optimizing a process method, has high product purity of more than 99.8%, good uniformity, no caking and difficult impurity removal, has the content of aminotriacetic acid lower than 0.1%, meets the requirements of accurate chemical product use and medicinal use, and has more economic benefit and is suitable for industrial production of the pentetic acid.

Description

Preparation method and application of pentetic acid

Technical Field

The invention relates to the technical field of chelating agent products, in particular to a preparation method and application of pentetic acid.

Background

Pentetic Acid (DTPA) with CAS number 67-43-6 is a chelating agent with extremely strong complexing ability to metal ions, and has the characteristics of white crystalline powder, and the structural formula is shown as follows:

pentetic acid has wide application in paper, textile, cosmetic and pharmaceutical industries. For example, in the papermaking process, pentetic acid may be used as a stabilizer in H ₂ O ₂ In bleaching, various metal ion pairs H are prevented ₂ O ₂ Is decomposed; when the textile is processed, the pentetic acid can be used as a water softener to remove metal ions such as calcium, magnesium and the like in water, so that the generation of scale is reduced. Meanwhile, the pentetic acid can also be used as an auxiliary material for radiopharmaceutical preparations, such as lutetium 177 injection

At present, the synthesis method of pentetic acid by domestic enterprises is mainly divided into two types: the first chloroacetic acid method is synthesized by using chloroacetic acid, diethylenetriamine, sodium hydroxide and other raw materials; the second is synthesized by using formaldehyde, sodium cyanide and diethylenetriamine as raw materials. The chloroacetic acid method is widely adopted for preparation due to the reasons of simpler process, lower equipment requirement and the like. However, when the chloroacetic acid is prepared by the chloroacetic acid method in the prior art, side reactions are easy to occur on chloroacetic acid under the condition of sodium hydroxide, so that impurities such as glycolic acid are generated, and mixed salts such as sodium chloride are generated in the reaction, so that repeated desalting and purification are required for the crude product of the pentetic acid, and the final yield is not high. In particular, purification by a conventional crystallization method, although removing most of impurities, requires sacrificing the yield for some difficult impurities (such as aminotriacetic acid) and refining at least 2 times to be controlled to 0.1% or less, which is disadvantageous for industrial production.

In order to solve the problem that the industrial production of pentetic acid requires multiple purification and desalination and impurity control, chinese patent CN101607921A discloses a synthesis method of pentetic acid, which takes chloroacetic acid and diethylenetriamine as raw materials and prepares the pentetic acid through the steps of salification, condensation, acidification and purification. In the route, the alkali is regulated by sodium hydroxide in the condensation reaction, and the operation steps of each step are complicated, so that the method is not beneficial to industrialized production.

Chinese patent CN115650870a discloses a method for preparing high-purity pentetic acid, which uses sodium chloroacetate and ethylene triamine as raw materials, and obtains pentetic acid with purity up to 99.9% by adding antioxidant, controlling dropping temperature in the reaction process and controlling related substances in the refining process. However, this post-treatment still requires two recrystallization refinements.

In recent years, solid supported alkali catalysts have been used in deacidification, desulfurization, cracking, and other reactions. The use of Na is disclosed, for example, in Chinese patent CN116120168A ₂ O/SiO ₂ As a solid base catalyst for synthesis, the synthesis of 2, 4-dichlorophenols and chloroacetic acid into 2, 4-dichlorophenoxyacetic acid is promoted.

When pentetic acid is used as an intermediate to prepare fine chemical products or to prepare bulk drugs or pharmaceutical preparations, accurate weighing is often required, and the quality is particularly important. For example, in the preparation of a developer gadopentetate meglumine bulk drug, the feeding mole ratio of the gadopentetate to the gadolinium oxide needs to be strictly controlled to be 2:1, even to the nearest thousandth (see description of chinese patent CN103664672 a). When the pentetic acid with poor quality is used as a raw material in the subsequent application, the pentetic acid needs to be crushed or ground before treatment, so that the reliability and the accuracy of the subsequent experiment can be ensured, and the production requirement is difficult to meet.

In summary, it is necessary to find a preparation method of pentetic acid, which meets the mild process conditions, is simple to operate, can effectively control the content of impurities in the large-scale production of pentetic acid, has higher property quality, is easy to realize accurate metering, and meets the requirements of accurate chemical product use and medicine.

Disclosure of Invention

In view of the above requirements, the invention aims to provide a preparation method of pentetic acid, which takes chloroacetic acid and diethylenetriamine as raw materials, and obtains the pentetic acid by optimizing a process method, wherein the product has high yield and purity, good uniformity, no caking and difficult impurity removal content of less than 0.1%, meets the requirements of accurate chemical product use and medicinal use, and has more economic benefit and is suitable for industrialized production of the pentetic acid.

The above object of the present invention is achieved by the following means:

a process for the preparation of pentetic acid, said process comprising the steps of:

s1, dissolving chloroacetic acid in a proper amount of water, controlling the temperature to be 10-25 ℃, adding sodium hydroxide aqueous solution, and reacting for 0.3-0.8 h to prepare sodium chloroacetate solution;

s2, dissolving diethylenetriamine in a proper amount of water to obtain a diethylenetriamine aqueous solution; adding a solid carrier base catalyst, adding sodium chloroacetate solution, controlling the temperature to be 55-85 ℃ and reacting for 1-6 h;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 20-35 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.2-2.5, cooling to the crystallization temperature to be 0-20 ℃, and stirring for 8-18 h to precipitate crystals; filtering, washing with cold water, and drying to obtain pentetic acid.

Specifically, in order to ensure the reaction is complete, in the preparation method of the pentetic acid, the molar ratio of chloroacetic acid to diethylenetriamine is 1:0.16 to 0.22; preferably 1:0.18 to 0.20.

The condensation reaction has the following reaction formula:

in the step S1, chloroacetic acid and sodium hydroxide are reacted to generate sodium chloroacetate for neutralization exothermic reaction, and condensing equipment is conventionally required in the prior art, so that the reaction system is maintained at less than or equal to 10 ℃. In the method, chloroacetic acid hydrolysis caused by overhigh temperature can be avoided by optimizing the feeding ratio and the feeding sequence, so that the reaction can be carried out under milder conditions, and the optimal reaction conversion rate can be ensured. Specifically, chloroacetic acid and sodium hydroxide are first dissolved in proper amount of water, and after partial dilution heat is released, sodium hydroxide aqua is added for mixing reaction. The concentration of the sodium hydroxide aqueous solution is 25-40%, more preferably 30-35% by integrating factors such as process equipment and efficiency. In the subsequent condensation reaction, when the alkalinity in the system is stronger, chloroacetic acid is hydrolyzed to generate glycolic acid, and then the glycolic acid salt is formed subsequently. In order to ensure the reaction is complete, in the step S1, the molar ratio of chloroacetic acid to sodium hydroxide is 1:1.0 to 1.8; the preferred molar ratio of chloroacetic acid to sodium hydroxide is 1:1.2 to 1.6; more preferably 1:1.3 to 1.5.

In the step S1, the chloroacetic acid decomposition is promoted by an excessively high temperature, and the reaction conversion rate is low by an excessively low temperature, so that the temperature is preferably controlled to 15 to 20 ℃.

In the step S1, the reaction time is preferably 0.4 to 0.6h in order to ensure a better reaction effect.

In the step S2, adding a solid supported base catalyst to the aqueous diethylenetriamine solution is one of the keys for achieving the technical effects. Chloroacetic acid and diethylenetriamine need to be catalyzed in alkaline systems, with the addition of a homogeneous base, such as sodium hydroxide, being common in the art. However, the technical personnel find that sodium hydroxide is used for catalyzing the reaction in the step, and sodium hydroxide is added later to neutralize the generated hydrochloric acid, namely, sodium hydroxide is added to serve as a reaction catalyst and a reaction acid binding agent, so that the sodium salt serving as a byproduct in the product is more, the subsequent acidification degree of the sodium salt of pentetate can be influenced, the purity of the obtained pentetate is low, the properties are poor, the phenomenon of sticky/jelly exists, and repeated purification treatment is needed. The skilled artisan has occasionally found that the addition of a solid supported base catalyst promotes the condensation reaction of chloroacetic acid and diethylenetriamine with a better conversion of the reaction. The reason is presumed that the solid carrier base catalyst is added into the diethylenetriamine, so that the nitrogen atom in the diethylenetriamine can be activated, and nucleophilic substitution of carbon atoms adjacent to chlorine atoms in chloroacetic acid/sodium chloroacetate is facilitated, thereby completing condensation.

Specifically, in the aforementioned step S2, the volume-to-mass ratio of the water addition amount (volume) to the diethylenetriamine (mass) is 1:18 to 22ml/g, preferably 1: 19-21 ml/g.

Specifically, in the aforementioned step S2, the solid supported base catalyst is added in an amount of 3 to 10% by mass, preferably 5 to 8% by mass, of the aqueous diethylenetriamine solution.

Further, in the step S2, the solid supported alkali catalyst is Na ₂ O/SiO ₂ Or MgO/SiO ₂ Catalysts, preferably Na ₂ O/SiO ₂ A catalyst. In this application, the skilled artisan has found that the solid supported base catalyst can be used as an important catalyst support in addition to its use as a catalyst. For example, chloroacetic acid and diethylenetriamine in Na ₂ The hydrogen chloride (hydrochloric acid) by-product of small molecule generated by condensation under the catalysis of O can be adsorbed on Na ₂ O, presumably due to the fact that hydrogen chloride can react with Na on the surface ₂ O reacts with sodium chloride and is deposited on the surface of the catalyst, thereby being beneficial to separating the secondary salt from the product.

Further, in the step S2, the reaction temperature is preferably 65 to 75 ℃.

Further, in the step S2, the reaction time is preferably 2 to 5 hours, more preferably 3 to 4 hours.

In the step S3, the acidification temperature and the acid-base environment are one of the keys for achieving the technical effects of the invention. In actual production of pentetic acid, the reaction solution before acidification contains pentetic acid sodium salt which is a liquid easy to dissolve in water, and if the acidification effect is poor, the crude product of the pentetic acid can be sticky, the color is yellow, and the product is seriously agglomerated after drying. Meanwhile, in the crystallization process, the unsuitable reaction condition can also lead to poor spray acidity, such as thinner precipitated products, unfavorable filtration, white powder of products which are easy to embed impurities, poor fluidity and agglomeration phenomenon after drying. The production of impurities can be effectively controlled at proper temperature, and the product precipitation amount can be effectively improved in proper acid-base environment. The temperature is too high, part of the product dissolved in the reaction cannot be fully precipitated, the temperature is too low, and related impurities (such as aminotriacetic acid, edetic acid and the like) and sodium salt are also precipitated together when the pentetic acid is precipitated; meanwhile, too high or too low pH value affects the precipitation of the product, and the pentetic acid can be promoted to be sufficiently precipitated only when the pH value is in a proper range.

Specifically, in the step S3, the acidification temperature is preferably controlled to 25 to 30 ℃.

Specifically, in the step S3, concentrated hydrochloric acid is preferably added to adjust ph=1.5 to 2.0.

Specifically, in the step S3, the crystallization temperature is preferably 5 to 15 ℃.

Specifically, in the step S3, the stirring time is preferably 10 to 16 hours, more preferably 13 to 15 hours.

In the step S3, the post-treatment of the crude product after acidification and crystallization is simple, and the pentetic acid with good quality and properties can be obtained only by washing with cold water, wherein the washing times are 1-2 times, preferably 1 time.

According to a preferred technical scheme, the preparation method of the pentetic acid comprises the following steps:

s1, dissolving chloroacetic acid in a proper amount of water, controlling the temperature at 15-20 ℃, adding sodium hydroxide aqueous solution, and reacting for 0.4-0.6 h to prepare sodium chloroacetate solution;

s2, dissolving diethylenetriamine in water to obtain a diethylenetriamine aqueous solution; adding Na 3-10% relative to the mass of the diethylenetriamine aqueous solution ₂ O/SiO ₂ Adding sodium chloroacetate solution into the catalyst, controlling the temperature to be 65-75 ℃ and reacting for 2-5 hours;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 25-30 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.5-2.0, cooling to the crystallization temperature to be 5-15 ℃, and stirring for 10-16 h to precipitate crystals; filtering, washing with cold water, and drying to obtain pentetic acid;

wherein the molar ratio of the chloroacetic acid to the diethylenetriamine is 1:0.18 to 0.20; in the step S1, the molar ratio of the chloroacetic acid to the sodium hydroxide is 1:1.2 to 1.6; in the step S2, the volume-mass ratio of the water addition amount (volume) to the diethylenetriamine (mass) is 1: 18-22 ml/g.

According to a preferred technical scheme, the preparation method of the pentetic acid comprises the following steps:

s1, dissolving chloroacetic acid in a proper amount of water, controlling the temperature at 18 ℃, adding 30-35% sodium hydroxide aqueous solution, and reacting for 0.5h to prepare sodium chloroacetate solution, wherein the molar ratio of chloroacetic acid to sodium hydroxide is 1:1.4;

s2, dissolving diethylenetriamine in water to obtain a diethylenetriamine aqueous solution; adding Na 5-8% relative to the mass of the diethylenetriamine aqueous solution ₂ O/SiO ₂ Adding sodium chloroacetate solution into the catalyst, controlling the temperature to be 70 ℃ and reacting for 3.5 hours; wherein the volume-mass ratio of the water adding amount (volume) to the diethylenetriamine (mass) is 1: 19-21 ml/g;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 28 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.8, cooling to the crystallization temperature of 10 ℃, and stirring for 14 hours to precipitate crystals; filtering, washing with cold water for one time, and drying to obtain pentetic acid;

wherein the molar ratio of chloroacetic acid to diethylenetriamine is 1:0.19.

the second purpose of the invention is to provide an application of the pentetic acid, which is used for purifying water quality and preparing cosmetics or medicines, wherein the preparation method of the pentetic acid is defined by the invention, and the pentetic acid has high purity, good uniformity and good property and is easy to realize the requirement of accurate weighing.

Compared with the prior art, the invention has the following advantages and beneficial effects:

1. in the invention, the solid carrier base catalyst is added in the preparation of the pentetic acid through condensation reaction, so that the stability of a reaction system is good, the conversion rate is high, the steps of repeated desalting crystallization and purification are reduced, and the optimization of the product properties is facilitated.

2. According to the invention, through optimizing the acidification and crystallization conditions, the content of the difficult-to-remove impurity aminotriacetic acid is controlled to be below 0.1%, the yield and the purity are high, the HPLC detection purity is higher than 99.8%, and the use and medicinal requirements of accurate chemical products are met.

3. The product obtained by the invention has good uniformity, no caking, good character, qualified color and easy realization of industrialization.

4. The method has the advantages of reasonable overall design in the process, simple and convenient operation, no need of high-pressure and high-temperature conditions, readily available raw materials, low cost and high economical efficiency.

Drawings

FIG. 1 is a HPLC analysis chart of the pentetic acid product prepared in example 1.

Detailed Description

Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention. The chloroacetic acid and diethylenetriamine used in the examples are all commercial raw materials, and the purity is more than or equal to 99.0%.

Example 1 preparation of pentetic acid

S1, dissolving 500mol of chloroacetic acid with a proper amount of water, controlling the temperature at 18 ℃, adding 30-35% sodium hydroxide aqueous solution (700 mol), and reacting for 0.5h to prepare sodium chloroacetate solution;

s2, dissolving 95mol of diethylenetriamine in 200L of water to obtain a diethylenetriamine aqueous solution; 12.6Kg Na was added ₂ O/SiO ₂ Adding sodium chloroacetate solution into the catalyst, controlling the temperature to be 70 ℃ and reacting for 3.5 hours;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 28 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.8, cooling to the crystallization temperature of 10 ℃, and stirring for 14 hours to precipitate crystals; filtering, washing with cold water (once), and drying to obtain pentetic acid.

Example 2 preparation of pentetic acid

S1, dissolving 0.05mol of chloroacetic acid with a proper amount of water, controlling the temperature at 20 ℃, adding 30-35% sodium hydroxide aqueous solution (0.07 mol) and reacting for 0.5h to prepare sodium chloroacetate solution;

s2, dissolving 0.0095mol of diethylenetriamine in 20ml of water to obtain a diethylenetriamine aqueous solution; 1.26g Na was added ₂ O/SiO ₂ A catalyst, a catalyst and a catalyst preparation method,adding sodium chloroacetate solution, controlling the temperature at 70 ℃ and reacting for 3.5 hours;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 28 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.8, cooling to the crystallization temperature of 10 ℃, and stirring for 14 hours to precipitate crystals; filtering, washing with cold water (once), and drying to obtain pentetic acid.

Example 3 preparation of pentetic acid

S1, dissolving 0.05mol of chloroacetic acid with a proper amount of water, controlling the temperature at 20 ℃, adding 30-35% sodium hydroxide aqueous solution (0.07 mol) and reacting for 0.5h to prepare sodium chloroacetate solution;

s2, dissolving 0.0095mol of diethylenetriamine in 20ml of water to obtain a diethylenetriamine aqueous solution; 1.36g MgO/SiO was added ₂ Adding sodium chloroacetate solution into the catalyst, controlling the temperature to be 70 ℃ and reacting for 3 hours;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 30 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.8, cooling to the crystallization temperature of 10 ℃, and stirring for 14 hours to precipitate crystals; filtering, washing with cold water (once), and drying to obtain pentetic acid.

Comparative example 1 preparation of pentetic acid (without addition of solid base catalyst)

S1, dissolving 0.05mol of chloroacetic acid with a proper amount of water, controlling the temperature at 20 ℃, adding 30-35% sodium hydroxide aqueous solution (0.07 mol) and reacting for 0.5h to prepare sodium chloroacetate solution;

s2, dissolving 0.0095mol of diethylenetriamine in 20ml of water to obtain a diethylenetriamine aqueous solution; adjusting the pH value to be 10-11 by using 30-35% sodium hydroxide solution, then adding sodium chloroacetate solution, controlling the temperature to be 70 ℃, reacting for 6 hours, and monitoring the reaction solution to be close to neutral by using pH test paper;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 28 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.8, cooling to the crystallization temperature of 10 ℃, and stirring for 14 hours to precipitate crystals; filtering, washing with cold water (once), and drying to obtain pentetic acid.

Comparative example 2 preparation of pentetic acid (solid base catalyst not according to the invention)

The procedure is as in example 1Preparation of pentetic acid, except that 1.26g ZnO/SiO was added in step S2 ₂ A type catalyst.

Comparative example 3 preparation of pentetic acid (refer to patent CN101607921 example 1)

Dissolving 0.01mol of chloroacetic acid and 0.022mol of sodium hydroxide respectively with a proper amount of water, controlling the temperature at 20-25 ℃, dropwise adding a sodium hydroxide aqueous solution into the chloroacetic acid solution for 2.5h, and stirring for 1h under heat preservation; adding 0.0095mol of diethylenetriamine, dripping for 3 hours, stirring for 0.5 hour, heating to 40 ℃, continuously preserving heat and stirring for 12 hours, and monitoring the reaction liquid to be close to neutral by using pH test paper; after the reaction, filtering, controlling the temperature to be 5 ℃, adding concentrated hydrochloric acid, adjusting the pH to be 2, carrying out heat preservation, stirring and crystallization for 12 hours, filtering, recrystallizing with water (twice), and drying to obtain the pentetic acid.

Examples 4-10 and comparative examples 4-13 preparation of pentetic acid

The feed ratio of chloroacetic acid (4.73 g) and diethylenetriamine (0.98 g) was calculated at 0.05mol:0.0095 mol=1: 0.19, with reference to the procedure of example 2, the pentetic acid product was prepared according to the reaction condition parameters in table 1, other parameters being the same as in example 2, unless otherwise specified:

table 1: examples/comparative examples reaction conditions table

Test 1 results of the analysis for the quality of pentetic acid

Table 2 results of mass analysis of pentetic acid obtained in examples and comparative examples

Note that: a: the limit of the aminotriacetic acid content refers to the quality standard for pentetic acid products in the united states pharmacopeia USP43-NF 38: the content of aminotriacetic acid is less than 0.1%. b: chloride detection limit requirements: it should not be more concentrated (0.01%) than the control solution prepared with 3.0ml of standard sodium chloride solution. c: the total impurity limit was set to <0.3%.

Analysis of the data in Table 2 shows that the reaction conditions in each step of the reaction have an effect on the quality and yield of the product. Specifically, in examples 1-10, the molar ratio of chloroacetic acid to sodium hydroxide in step S1 was 1:1.4 (0.05 mol:0.07 mol), adding a solid supported base catalyst in step S2; in the step S3, the acidification temperature is controlled to be 70 or 75 ℃, the acidification pH is controlled to be 1.8-2.0, the crystallization temperature is controlled to be 10 ℃, the stirring time is 14 hours, the content of the amino triacetic acid which is difficult to remove can be effectively controlled, the total content of impurities is less than limit, the product yield is ideal and has good uniformity, and the phenomenon of caking does not exist.

In particular, example 1 is a scheme of the invention for pilot scale-up, and the result shows that the technical effect can be achieved in industrial scale-up reaction, wherein the HPLC analysis spectrum of the product obtained in example 1 is shown in figure 1, the purity is as high as 99.8 or more, and the impurity aminotriacetic acid and the impurity edetic acid can be controlled in an extremely low range, namely, only 0.01% and 0.02%.

Further analysis of the quality results of the products of comparative examples 1 to 11 revealed that one condition exists in the reaction process and the post-treatment, and the quality or the yield of the obtained product is inferior to that of the product obtained by the method of the present invention. Specific:

according to the preparation method of the comparative example 1, a solid base catalyst is not used in the condensation reaction, sodium hydroxide is used for maintaining the alkaline condition of the system, the detection of the chloride does not meet the standard, meanwhile, excessive byproduct sodium chloride is doped in the product, after acidification and crystallization, the impurity removal effect cannot be achieved only by washing with cold water, the content of the aminotriacetic acid and the total impurity content do not meet the quality control standard, and the dried product has poor properties, is hard and caked and has yellow color.

The preparation method described in comparative example 2, zn was used for the condensation reactionO/SiO ₂ The solid base catalyst has low product yield, and it is presumed that ZnO/SiO is known ₂ The catalytic effect of the reaction is poor, the reaction degree is low, the properties of the obtained product are not improved, and the impurity aminotriacetic acid and the total impurity content do not meet the quality control standard.

Comparative example 3 is the preparation method of example 1 of reference patent CN101607921, and the yield is slightly inferior to the scheme of the present invention, though the quality of the obtained product can meet the requirements through the process control of each step and recrystallization purification. In addition, the content of the aminotriacetic acid impurity is 0.09%, approaching the limit of 0.1%, and the possibility of amplifying the impurity exists in the large-scale production, so that the purification times are required to be increased to reduce the impurity.

In the preparation method described in comparative example 4, too much sodium hydroxide is added in the step S1, and the chloride (side salt) content is too high.

In the preparation method of comparative example 5, the reaction temperature in the step S1 is too low, the salification of chloroacetic acid is incomplete, the subsequent reaction conversion rate is low, and the yield is obviously reduced.

From the results of comparative examples 6 to 8, it was found that the addition of the catalyst gave a product with significantly reduced control of chloride compared to comparative example 1 without the catalyst, but the amount of water added/catalyst in step S2, the reaction temperature and the reaction time parameters had an important effect on the quality and yield of the product. In comparative example 6, the amount of water added was too large, and the reaction degree was slightly lowered, resulting in a decrease in yield. In comparative example 7, the reaction temperature was too low, the reaction was incomplete, and unreacted raw materials were doped in the product, resulting in yellowish appearance with caking and impurity content not meeting the quality control requirement. In comparative example 8, the reaction time was too long, and the yield was not improved although the product quality was satisfactory.

From the results of comparative examples 9 to 13, it is understood that the acidification temperature, pH and crystallization temperature and time in the step S3 have a significant influence on the quality and yield of the product. Comparative example 9 has a lower acidification temperature, incomplete acidification, excessive pentetate or other auxiliary salts remained, comparative example 10 has a higher acidification temperature, and products or impurities are decomposed, which leads to higher impurity content of the obtained products, yellow appearance and serious caking after drying. In comparative example 11, the crystallization temperature was low and the impurity content was increased. In comparative example 12, the crystallization stirring time was short, crystallization was insufficient, the obtained product was yellowish in color, and the dried product had a lump. In comparative example 13, the pH during acidification was low and pentetic acid was dissolved, resulting in poor yields.

In summary, the invention synthesizes and prepares the pentetic acid through optimizing the process route, and can effectively control the impurity content by regulating and controlling the reaction conditions of the substrate content, the solvent and the like of each step, and the purity is up to more than 99.8 percent, thus being applicable to various fine chemical products and preparing raw materials or preparations of medicines.

The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.

Claims (10)

1. A process for the preparation of pentetic acid, said process comprising the steps of:

s1, dissolving chloroacetic acid in a proper amount of water, controlling the temperature to be 10-25 ℃, adding sodium hydroxide aqueous solution, and reacting for 0.3-0.8 h to prepare sodium chloroacetate solution;

s2, dissolving diethylenetriamine in water to obtain a diethylenetriamine aqueous solution; adding a solid carrier base catalyst, adding sodium chloroacetate solution, controlling the temperature to be 55-85 ℃ and reacting for 1-6 h;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 20-35 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.2-2.5, cooling to the crystallization temperature to be 0-20 ℃, and stirring for 8-18 h to precipitate crystals; filtering, washing with cold water, and drying to obtain pentetic acid;

wherein, the mol ratio of chloroacetic acid to diethylenetriamine is 1:0.16 to 0.22.

2. The method according to claim 1, wherein in the step S2, the volume/mass ratio of the amount of water (volume) to the diethylenetriamine (mass) is 1: 18-22 ml/g.

3. The process according to claim 1, wherein in step S2, the solid supported base catalyst is selected from Na ₂ O/SiO ₂ Or MgO/SiO ₂ A type catalyst.

4. The process according to claim 3, wherein the solid supported alkali catalyst is Na ₂ O/SiO ₂ A catalyst.

5. The preparation method according to claim 3, wherein the solid supported base catalyst is added in an amount of 3 to 10% by mass based on the mass of the aqueous diethylenetriamine solution.

6. The method according to claim 1, wherein in step S1, the molar ratio of chloroacetic acid to sodium hydroxide is 1:1.0 to 1.8.

7. The process according to claim 1, wherein in step S3, the acidification temperature is comprised between 25 and 30 ℃.

8. The method according to claim 1, wherein in step S3, the crystallization temperature is 5 to 15 ℃.

9. A process for the preparation of pentetic acid according to any one of claims 1-8, said process comprising:

s1, dissolving chloroacetic acid in a proper amount of water, controlling the temperature at 15-20 ℃, adding sodium hydroxide aqueous solution, and reacting for 0.4-0.6 h to prepare sodium chloroacetate solution;

s2, dissolving diethylenetriamine in water to obtain a diethylenetriamine aqueous solution; adding Na 3-10% relative to the mass of the diethylenetriamine aqueous solution ₂ O/SiO ₂ Adding sodium chloroacetate solution into the catalyst, controlling the temperature to be 65-75 ℃ and reacting for 2-5 hours;

s3, after the reaction is finished, filtering, controlling the acidification temperature to be 25-30 ℃, adding concentrated hydrochloric acid, adjusting the pH value to be 1.5-2.0, cooling to the crystallization temperature to be 5-15 ℃, and stirring for 10-16 h to precipitate crystals; filtering, washing with cold water, and drying to obtain pentetic acid;

wherein the molar ratio of the chloroacetic acid to the diethylenetriamine is 1:0.18 to 0.20; in the step S1, the molar ratio of the chloroacetic acid to the sodium hydroxide is 1:1.2 to 1.6; in the step S2, the volume-mass ratio of the water addition amount (volume) to the diethylenetriamine (mass) is 1: 18-22 ml/g.

10. Use of pentetic acid for purifying water, for preparing cosmetics or pharmaceuticals, characterized in that the process for preparing pentetic acid is as claimed in any of the preceding claims 1 to 9.