CN112028855B - Synthesis method of 4-hydroxyethyl piperazine ethanesulfonic acid - Google Patents
Synthesis method of 4-hydroxyethyl piperazine ethanesulfonic acid Download PDFInfo
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- CN112028855B CN112028855B CN202010899312.6A CN202010899312A CN112028855B CN 112028855 B CN112028855 B CN 112028855B CN 202010899312 A CN202010899312 A CN 202010899312A CN 112028855 B CN112028855 B CN 112028855B
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Abstract
The invention provides a synthesis method of 4-hydroxyethyl piperazine ethanesulfonic acid. The synthesis method comprises the steps of mixing 2-chloroethyl sodium sulfonate, N-hydroxyethyl piperazine, an alkaline agent and water to prepare a mixed solution; and (3) neutralizing and acidifying the mixed solution, adding an extracting agent for extraction, recrystallizing, washing and drying the solid to obtain the 4-hydroxyethyl piperazine ethanesulfonic acid. The synthesis method has the advantages of high synthesis yield, high product purity and less wastewater output, and can be used for industrial production.
Description
Technical Field
The invention relates to a synthesis method of a compound, in particular to a synthesis method of 4-hydroxyethyl piperazine ethanesulfonic acid, belonging to the technical field of compound synthesis.
Background
4-hydroxyethyl piperazine ethanesulfonic acid, also known as 4-hydroxyethyl piperazine ethanesulfonic acid, abbreviated as HEPES. Is a Good's buffer with a pH buffer range of 6.8-8.2.HEPES is easily soluble in water, does not undergo a precipitation reaction with polyvalent metal ions, and the dissociation is little affected by its concentration, temperature, ion composition or medium salinity.
In analytical tests, in many reactions such as complexometric titration and spectrophotometry, the pH value of the solution is required to be kept within a range to ensure the color change of the indicator, the color development of the developer and the like, and these conditions are all achieved by adding a certain amount of buffer solution, so that the buffer solution is a reagent frequently required in analytical tests.
In the existing method for synthesizing the HEPE buffer solution, the desalting process is generally carried out in a resin exchange mode. However, the amount of wastewater generated by the desalting method is large, and the amount of wastewater is about 20 tons to 30 tons per ton of product wastewater.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a method for synthesizing 4-hydroxyethyl piperazine ethanesulfonic acid, which has high synthesis yield, high product purity and small wastewater amount.
In order to achieve the technical purpose, the invention firstly provides a synthesis method of 4-hydroxyethyl piperazine ethanesulfonic acid, which comprises the following steps:
mixing 2-chloroethyl sodium sulfonate, N-hydroxyethyl piperazine, an alkaline agent and water, and carrying out mixed reaction for 2-4 h at the temperature of 90-105 ℃ to obtain a mixed solution;
performing primary solid-liquid separation on the mixed solution, taking liquid for distillation separation, performing secondary solid-liquid separation after the distillation separation, adding acid into the solution after the secondary solid-liquid separation for neutralization, wherein the pH value of the neutralized mixed solution is 6.5-7.5;
adding activated carbon into the neutralized solution for decoloring;
acidifying the decolorized solution, wherein the pH of the acidified mixed solution is 4.5-5.5;
adding an extracting agent into the acidified solution at 40-80 ℃ for extraction, performing solid-liquid separation after extraction, taking liquid for crystallization and solid-liquid separation, and recrystallizing, washing and drying the solid obtained by solid-liquid separation to obtain the 4-hydroxyethyl piperazine ethanesulfonic acid.
The synthesis method of the 4-hydroxyethyl piperazine ethanesulfonic acid comprises the step of preparing a mixed solution.
In a specific embodiment of the invention, when the mixed solution is prepared, the feeding molar ratio of the 2-chloroethyl sodium sulfonate, the N-hydroxyethyl piperazine, the alkaline agent and the water is 1:1:0.5:20.
the synthesis method of the 4-hydroxyethyl piperazine ethanesulfonic acid comprises the step of separating the mixed solution.
Wherein, the mixed solution is subjected to solid-liquid separation for the first time, and solid impurities after the solid-liquid separation for the first time are directly discharged; carrying out distillation separation on the liquid subjected to the primary solid-liquid separation, and taking the liquid left after the distillation separation as a mixed solution; carrying out secondary solid-liquid separation on the mixed solution, and directly washing and drying solid obtained by the secondary solid-liquid separation to obtain food-grade/industrial-grade sodium chloride; and adding acid to neutralize the filtrate obtained by the secondary solid-liquid separation.
The synthesis method of the 4-hydroxyethyl piperazine ethanesulfonic acid comprises the step of neutralizing the mixed solution. Specifically, the mixed solution is neutralized by an acid solution, and after the mixed solution is neutralized by the acid, the pH value of the mixed solution is 7.
In a specific embodiment of the present invention, the acid used for neutralization may be one or a combination of several of formic acid, acetic acid, propionic acid, sulfuric acid and hydrochloric acid.
The synthesis method of the 4-hydroxyethyl piperazine ethanesulfonic acid comprises the step of decoloring the neutralized solution. The decolorization is mainly to add active carbon into the solution, and after the decolorization treatment, the waste active carbon is directly discharged and recycled.
The synthesis method of the 4-hydroxyethyl piperazine ethanesulfonic acid comprises the step of acidifying the decolored solution. After acidifying the mixed solution, the pH of the mixed solution was 5. Wherein, the solid which is acidified for solid-liquid separation is directly washed and dried to obtain the food-grade/industrial-grade salt.
In one embodiment of the present invention, the acid used for acidification and the acid used for neutralization may be one or a combination of formic acid, acetic acid, propionic acid, sulfuric acid and hydrochloric acid.
The synthesis method of the 4-hydroxyethyl piperazine ethanesulfonic acid comprises the step of extracting and purifying acidified liquid. Through extraction and desalination, the purity of a target product can be effectively improved while the output of wastewater is effectively reduced.
Wherein, after extraction, solid-liquid separation is carried out, and the solid obtained by the solid-liquid separation can be directly mixed with the solid obtained by the solid-liquid separation after acidification, and the food grade/industrial grade salt is obtained after washing and drying. Crystallizing the liquid subjected to the primary solid-liquid separation, performing the secondary solid-liquid separation, recrystallizing the solid subjected to the secondary solid-liquid separation, washing and drying to obtain 4-hydroxyethyl piperazine ethanesulfonic acid; and (3) separating the liquid obtained by the secondary solid-liquid separation by using an extracting agent, wherein the extracting agent is reused, the wastewater is subjected to environment-friendly treatment, and the residual solution is used as a mixed solution for reuse.
In one embodiment of the invention, the crystallization temperature is-10 ℃ to 10 ℃ and the crystallization time is 0.5h to 3h.
In a specific embodiment of the present invention, the extraction agent used is one or more of dioxane, cyclohexane, methanol, ethanol, butanol, and benzene.
Specifically, when one of the substances is used as the extractant, the molar ratio of dioxane to 4-hydroxyethyl piperazine ethanesulfonic acid is 3-5 (preferably 4; the molar ratio of cyclohexane to 4-hydroxyethylpiperazine ethanesulfonic acid is 5-10 (preferably 6; the molar ratio of methanol to 4-hydroxyethylpiperazine ethanesulfonic acid is 15-25 (preferably 20; the molar ratio of ethanol to 4-hydroxyethylpiperazine ethanesulfonic acid is 10-20 (preferably 12; the molar ratio of butanol to 4-hydroxyethylpiperazine ethanesulfonic acid is 7-15 (preferably 8; the molar ratio of benzene to 4-hydroxyethylpiperazine ethanesulfonic acid is 5-10 (preferably 6.
In a further embodiment of the invention, when the extractant is a mixture of dioxane and butanol, the molar ratio of dioxane to 4-hydroxyethylpiperazine ethanesulfonic acid is 1-3:1 (preferably 2.
In a further embodiment of the invention, when the extraction agent is a mixture of dioxane and ethanol, the molar ratio of dioxane to 4-hydroxyethylpiperazine ethanesulfonic acid is 1-3:1 (preferably 2.
In a further embodiment of the invention, where the extractant is a mixture of dioxane and methanol, the molar ratio of dioxane to 4-hydroxyethylpiperazine ethanesulfonic acid is 1 to 3 (preferably 2:1, the molar ratio of methanol to 4-hydroxyethylpiperazine ethanesulfonic acid is 9-11 (preferably 10.
In a further embodiment of the invention, when the extractant is a mixture of cyclohexane and butanol, the molar ratio of cyclohexane to 4-hydroxyethylpiperazine ethanesulfonic acid is 2 to 4:1 (preferably 3:1 (preferably 3.
In a further embodiment of the invention, when the extracting agent is a mixture of cyclohexane and ethanol, the molar ratio of cyclohexane to 4-hydroxyethylpiperazine ethanesulfonic acid is 2-4:1 (preferably 3:1 (preferably 6.
In a further embodiment of the invention, when the extractant is a mixture of cyclohexane and methanol, the molar ratio of cyclohexane to 4-hydroxyethylpiperazine ethanesulfonic acid is 2 to 4:1 (preferably 3:1 (preferably 10.
The synthesis method of 4-ethoxyl piperazine ethanesulfonic acid has less wastewater output, and each ton of product wastewater is about 0.5 ton; the product yield is high (more than or equal to 85.0 percent) and the product purity is high (more than or equal to 99.5 percent).
Drawings
FIG. 1 is a partial process flow diagram of a method for synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid according to an embodiment of the present invention;
FIG. 2 is a partial process flow diagram of a method of synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid according to an embodiment of the present invention;
FIG. 3 is a partial process flow diagram of a method of synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid according to an embodiment of the present invention;
FIG. 4 is a partial process flow diagram of a method for synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid according to an embodiment of the present invention;
FIG. 5 is an IR spectrum of 4-hydroxyethylpiperazine ethanesulfonic acid of example 1;
FIG. 6 is a UV absorption spectrum of 4-hydroxyethylpiperazine ethanesulfonic acid of example 1.
Detailed Description
Examples
The embodiment provides a method for synthesizing 4-hydroxyethyl piperazine ethanesulfonic acid, and the specific process is shown in fig. 1 to 4 (fig. 1 to 4 are connected in series to form a complete 4-hydroxyethyl piperazine ethanesulfonic acid synthesis process), and the method comprises the following steps:
mixing 2-chloroethyl sodium sulfonate (fed by a solid feeding system), N-hydroxyethyl piperazine (fed by a metering tank), an alkaline agent (fed by the metering tank) and water (fed by an overhead tank), and mixing and reacting at 90-105 ℃ for 3 hours to obtain a mixed solution; the feeding molar ratio of the 2-chloroethyl sodium sulfonate, the N-hydroxyethyl piperazine, the alkaline agent (liquid alkali) and the water is 1:1:0.5:20;
carrying out primary solid-liquid separation on the mixed solution, and directly discharging solid impurities after the primary solid-liquid separation; carrying out distillation separation on the liquid subjected to the primary solid-liquid separation, wherein the liquid subjected to the distillation separation is used as a mixed solution; carrying out secondary solid-liquid separation after distillation separation, and directly washing and drying solid obtained by the secondary solid-liquid separation to obtain food-grade/industrial-grade sodium chloride;
adding acid (fed by a metering tank) into the filtrate obtained by the secondary solid-liquid separation for neutralization, wherein the pH value of the neutralized mixed solution is 7;
adding active carbon for decoloring; after the decolorization treatment, directly discharging and recycling the waste active carbon;
acidifying the decolored solution, wherein the pH of the acidified mixed solution is 5; wherein, the solid obtained by acidification and solid-liquid separation is directly washed and dried to obtain food-grade/industrial salt;
adding an extracting agent (different embodiments are shown in table 1) into the acidified solution at 60 ℃ for extraction, performing solid-liquid separation after extraction, directly mixing the solid obtained by solid-liquid separation after acidification, washing and drying to obtain the food-grade/industrial-grade salt. Crystallizing the liquid obtained by the first solid-liquid separation (the crystallization temperature is 5 ℃ and the time is 1 hour), carrying out the second solid-liquid separation, and recrystallizing, washing and drying the solid obtained by the second solid-liquid separation to obtain 4-hydroxyethyl piperazine ethanesulfonic acid; and (3) separating the liquid obtained by the secondary solid-liquid separation by using an extracting agent, wherein the extracting agent is reused, the wastewater is subjected to environment-friendly treatment, and the residual solution is used as a mixed solution for reuse.
The 4-hydroxyethylpiperazine ethanesulfonic acid obtained in example 1 was also subjected to infrared and ultraviolet absorption tests, and the obtained curves are shown in fig. 5 and 6, and it can be determined from fig. 5 and 6 that the substance is 4-hydroxyethylpiperazine ethanesulfonic acid.
TABLE 1
Note: the values in Table 1 are the molar ratio of each substance to 4-hydroxyethylpiperazine ethanesulfonic acid.
Comparative example 5
Comparative example 5 differs from example 3 in that: and (3) neutralizing and acidifying the mixed solution, and desalting by adopting a resin exchange technology.
The products of examples 1 to 6, and comparative examples 1 to 5 were analyzed, and the yield and purity of the objective product were analyzed, and the results are shown in table 2.
TABLE 2
The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (1)
1. A synthesis method of 4-hydroxyethyl piperazine ethanesulfonic acid comprises the following steps:
mixing 2-chloroethyl sodium sulfonate, N-hydroxyethyl piperazine, an alkaline agent and water, and carrying out mixed reaction for 3 hours at the temperature of 90-105 ℃ to obtain a mixed solution; the feeding molar ratio of the 2-chloroethyl sodium sulfonate to the N-hydroxyethyl piperazine to the alkaline agent to the water is 1:1:0.5:20; the alkaline agent is liquid alkali;
carrying out primary solid-liquid separation on the mixed solution, and directly discharging solid impurities after the primary solid-liquid separation; carrying out distillation separation on the liquid subjected to the primary solid-liquid separation, wherein the liquid subjected to the distillation separation is used as a mixed solution; carrying out secondary solid-liquid separation after distillation separation, and directly washing and drying solid obtained by the secondary solid-liquid separation to obtain food-grade/industrial-grade sodium chloride;
adding acid into the filtrate obtained by the secondary solid-liquid separation for neutralization, wherein the pH value of the neutralized mixed solution is 7;
adding active carbon for decoloring; after the decolorization treatment, directly discharging and recycling the waste activated carbon;
acidifying the decolorized solution, wherein the pH of the acidified mixed solution is 5; wherein, the solid which is acidified for solid-liquid separation is directly washed and dried to obtain food-grade/industrial salt;
adding an extracting agent into the acidified solution at 60 ℃ for extraction, performing solid-liquid separation after extraction, directly mixing the solid obtained by the solid-liquid separation after the solid-liquid separation with the solid obtained by the solid-liquid separation after the acidification, washing and drying to obtain food-grade/industrial salt; crystallizing the liquid obtained by the first solid-liquid separation at 5 ℃ for 1 hour, carrying out the second solid-liquid separation, and recrystallizing, washing and drying the solid obtained by the second solid-liquid separation to obtain 4-hydroxyethyl piperazine ethanesulfonic acid; separating the liquid obtained by the secondary solid-liquid separation with an extracting agent, wherein the extracting agent is reused, the wastewater is subjected to environment-friendly treatment, and the residual solution is reused as a mixed solution;
the extractant is a mixture consisting of dioxane and butanol, and the molar ratio of the extractant to the 4-hydroxyethyl piperazine ethanesulfonic acid is 2:3:1.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20060089509A1 (en) * | 2003-09-16 | 2006-04-27 | Carroll Glenn T | Preparation of substituted alkanesulfonates from 2-hydroxyalkanesulfonates |
| CN110683995A (en) * | 2019-09-17 | 2020-01-14 | 苏州亚科科技股份有限公司 | Piperazine ethanesulfonic acid derivative preparation method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20060089509A1 (en) * | 2003-09-16 | 2006-04-27 | Carroll Glenn T | Preparation of substituted alkanesulfonates from 2-hydroxyalkanesulfonates |
| CN110683995A (en) * | 2019-09-17 | 2020-01-14 | 苏州亚科科技股份有限公司 | Piperazine ethanesulfonic acid derivative preparation method |
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