CN112174912B - Preparation method of piperazine-N, N' -di (2-ethanesulfonic acid) - Google Patents
Preparation method of piperazine-N, N' -di (2-ethanesulfonic acid) Download PDFInfo
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- CN112174912B CN112174912B CN202011108048.6A CN202011108048A CN112174912B CN 112174912 B CN112174912 B CN 112174912B CN 202011108048 A CN202011108048 A CN 202011108048A CN 112174912 B CN112174912 B CN 112174912B
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- piperazine
- sodium hydroxide
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- filter cake
- ethanesulfonic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention provides a preparation method of piperazine-N, N' -di (2-ethanesulfonic acid), which comprises the following steps: putting 40g of piperazine, 40g of methanol, 1g of copper powder and 800g of dichloroethane into a three-necked flask, and heating to reflux; slowly dripping sodium hydroxide methanol solution into a three-mouth bottle for reaction for 4 hours; 300g of water is added into a three-mouth bottle, and the temperature is raised to 95 ℃; 174g of sodium sulfite and 300g of water are put into a three-mouth bottle for thermal insulation reaction for 6 hours, and the first filtrate is obtained by filtration and is cooled to room temperature; adding 150g of concentrated hydrochloric acid into the first filtrate to adjust the pH value of the solution to be between 1 and 2, and filtering to obtain a first filter cake; putting the first filter cake into a beaker, adding 700g of pure water, slowly adding 28g of sodium hydroxide product until the product is completely dissolved, and filtering to obtain a second filtrate; adding 80g of concentrated hydrochloric acid into the second filtrate to adjust the pH value of the solution to be between 2 and 3, stirring for 10 minutes, and filtering to obtain a second filter cake; and drying the second filter cake at 70-80 ℃ to obtain white piperazine-N, N' -di (2-ethanesulfonic acid) powder. The piperazine-N, N' -di (2-ethanesulfonic acid) provided by the invention has a simple process.
Description
Technical Field
The invention relates to the technical field of biological pharmacy, in particular to a preparation method of piperazine-N, N' -di (2-ethanesulfonic acid).
Background
PIPES, chinese name piperazine-N, N' -bis (2-ethanesulfonic acid), is one of the ethanesulfonic acid buffer salt series, chemically and enzymatically stable, and can be applied to cell culture work because its pKa at 37℃is close to physiological pH.
In the related art, the preparation of piperazine-N, N '-bis (2-ethanesulfonic acid) generally requires the preparation of sodium chloroethanesulfonate, and then the sodium chloroethanesulfonate is reacted to generate piperazine-N, N' -bis (2-ethanesulfonic acid), and the preparation process is complex, and the purification of the sodium chloroethanesulfonic acid is also required, so that the total preparation time is long.
Therefore, it is necessary to provide a novel process for the preparation of piperazine-N, N' -bis (2-ethanesulfonic acid) to solve the above-mentioned problems.
Disclosure of Invention
The invention aims to overcome the technical problems and provide a preparation method of piperazine-N, N' -di (2-ethanesulfonic acid) with simple preparation process.
In order to achieve the above object, the present invention provides a preparation method of piperazine-N, N' -bis (2-ethanesulfonic acid), comprising the steps of:
s1: putting 40g of piperazine, 40g of methanol, 1g of copper powder and 800g of dichloroethane into a three-necked flask, and heating to reflux;
s2: dissolving 37g of sodium hydroxide into 200g of methanol to obtain sodium hydroxide methanol solution, slowly dripping the sodium hydroxide methanol solution into the three-mouth bottle, and reacting for 4 hours after the sodium hydroxide methanol solution is dripped;
s3: 300g of water is added into the three-mouth bottle, the three-mouth bottle is continuously heated to recover dichloroethane and methanol, and the temperature is continuously raised to 95 ℃ after the recovery is finished;
s4: 174g of sodium sulfite and 300g of water are put into the three-necked flask, the reaction is carried out for 6 hours under the condition of heat preservation, the first filtrate is obtained after filtration, and the first filtrate is cooled to the room temperature;
s5: adding 150g of concentrated hydrochloric acid into the first filtrate to adjust the pH value of the solution to be between 1 and 2, and filtering to obtain a first filter cake;
s6: putting the first filter cake into a beaker, adding 700g of pure water, slowly adding 28g of sodium hydroxide product until the product is completely dissolved, and filtering again to obtain a second filtrate;
s7: adding 80g of concentrated hydrochloric acid into the second filtrate to adjust the pH value of the solution to be between 2 and 3, stirring for 10 minutes, and filtering to obtain a second filter cake;
s8: and drying the second filter cake at 70-80 ℃ to obtain white piperazine-N, N' -di (2-ethanesulfonic acid) powder.
Preferably, the three-necked bottle is a 1000ml three-necked bottle.
Preferably, in the step S2, "slowly dropping the sodium hydroxide methanol solution into the three-necked flask" is specifically: the sodium methoxide methanol solution was added to a dropping funnel and then slowly dropped into the three-necked flask.
Preferably, the dropping time of the sodium hydroxide methanol solution in the step S2 is more than 2 hours.
Preferably, the dichloroethane and methanol recovered in step S3 can be reused.
Compared with the related art, the preparation method of piperazine-N, N '-di (2-ethanesulfonic acid) provided by the invention adopts a one-pot method to prepare piperazine-N, N' -di (2-ethanesulfonic acid), so that the process of preparing sodium chloroethanesulfonate is omitted, the overall reaction time is shorter, and the cost is also saved.
Detailed Description
The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The invention provides a preparation method of piperazine-N, N' -di (2-ethanesulfonic acid), which comprises the following steps:
s1: 40g of piperazine, 40g of methanol, 1g of copper powder, 800g of dichloroethane were placed in a three-necked flask and heated to reflux.
In this embodiment, the three-mouth bottle is a 1000ml three-mouth bottle, and the raw materials are directly added into the three-mouth bottle in a one-pot method, so that the process of preparing and purifying sodium chloroethanesulfonate in the related art is omitted, and the process is simple.
S2: 37g of sodium hydroxide was dissolved in 200g of methanol to obtain a sodium hydroxide methanol solution, and then the sodium hydroxide methanol solution was slowly dropped into the three-necked flask, and the reaction was carried out for 4 hours after the dropping of the sodium hydroxide methanol solution was completed.
In the step S2, "slowly dropping the sodium hydroxide methanol solution into the three-mouth bottle" is specifically: the sodium methoxide methanol solution was added to a dropping funnel and then slowly dropped into the three-necked flask. The dropping time of the sodium hydroxide methanol solution in the step S2 is more than 2 hours.
S3: 300g of water is added into the three-mouth bottle, the heating is continued to recover dichloroethane and methanol, and the temperature is continuously raised to 95 ℃ after the recovery is finished.
The dichloroethane and methanol recovered in the step S3 can be reused, so that the waste of materials is avoided, and the production cost is reduced.
S4: 174g of sodium sulfite and 300g of water are put into the three-necked flask, the reaction is carried out for 6 hours under the heat preservation, the first filtrate is obtained after filtration, and the first filtrate is cooled to the room temperature.
S5: 150g of concentrated hydrochloric acid is added into the first filtrate to adjust the pH value of the solution to be between 1 and 2, and the first filter cake is obtained after filtration.
S6: the first filter cake was placed in a beaker, 700g of pure water was added, then 28g of sodium hydroxide product was slowly added until complete dissolution, and filtration was again carried out to obtain a second filtrate.
S7: and adding 80g of concentrated hydrochloric acid into the second filtrate to adjust the pH value of the solution to be between 2 and 3, stirring for 10 minutes, and filtering to obtain a second filter cake.
S8: and drying the second filter cake at 70-80 ℃ to obtain white piperazine-N, N' -di (2-ethanesulfonic acid) powder.
134g of piperazine-N, N '-di (2-ethane sulfonic acid) can be prepared according to the proportion, the calculated yield is 95%, and the prepared piperazine-N, N' -di (2-ethane sulfonic acid) nuclear magnetic data are consistent with those in related documents.
Compared with the related art, the preparation method of piperazine-N, N '-di (2-ethanesulfonic acid) provided by the invention adopts a one-pot method to prepare piperazine-N, N' -di (2-ethanesulfonic acid), so that the process of preparing sodium chloroethanesulfonate is omitted, the overall reaction time is shorter, and the cost is also saved.
While the invention has been described with respect to the above embodiments, it should be noted that modifications can be made by those skilled in the art without departing from the inventive concept, and these are all within the scope of the invention.
Claims (5)
1. A method for preparing piperazine-N, N' -di (2-ethane sulfonic acid), which is characterized by comprising the following steps:
s1: putting 40g of piperazine, 40g of methanol, 1g of copper powder and 800g of dichloroethane into a three-necked flask, and heating to reflux;
s2: dissolving 37g of sodium hydroxide into 200g of methanol to obtain sodium hydroxide methanol solution, slowly dripping the sodium hydroxide methanol solution into the three-mouth bottle, and reacting for 4 hours after the sodium hydroxide methanol solution is dripped;
s3: 300g of water is added into the three-mouth bottle, the three-mouth bottle is continuously heated to recover dichloroethane and methanol, and the temperature is continuously raised to 95 ℃ after the recovery is finished;
s4: 174g of sodium sulfite and 300g of water are put into the three-necked flask, the reaction is carried out for 6 hours under the condition of heat preservation, the first filtrate is obtained after filtration, and the first filtrate is cooled to the room temperature;
s5: adding 150g of concentrated hydrochloric acid into the first filtrate to adjust the pH value of the solution to be between 1 and 2, and filtering to obtain a first filter cake;
s6: putting the first filter cake into a beaker, adding 700g of pure water, slowly adding 28g of sodium hydroxide product until the product is completely dissolved, and filtering again to obtain a second filtrate;
s7: adding 80g of concentrated hydrochloric acid into the second filtrate to adjust the pH value of the solution to be between 2 and 3, stirring for 10 minutes, and filtering to obtain a second filter cake;
s8: and drying the second filter cake at 70-80 ℃ to obtain white piperazine-N, N' -di (2-ethanesulfonic acid) powder.
2. The process for the preparation of piperazine-N, N' -bis (2-ethanesulfonic acid) according to claim 1, wherein the three-necked flask is a 1000ml three-necked flask.
3. The method for preparing piperazine-N, N' -bis (2-ethane sulfonic acid) according to claim 1, wherein "slowly dropping the sodium hydroxide methanol solution into the three-necked flask" in the step S2 is specifically: the sodium methoxide methanol solution was added to a dropping funnel and then slowly dropped into the three-necked flask.
4. The process for producing piperazine-N, N' -bis (2-ethanesulfonic acid) according to claim 3, wherein the dropping time of the sodium hydroxide methanol solution in the step S2 is more than 2 hours.
5. The process for the preparation of piperazine-N, N' -bis (2-ethanesulfonic acid) according to claim 1, wherein the dichloroethane and methanol recovered in step S3 are reusable.
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| CN202011108048.6A CN112174912B (en) | 2020-10-16 | 2020-10-16 | Preparation method of piperazine-N, N' -di (2-ethanesulfonic acid) |
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| CN202011108048.6A CN112174912B (en) | 2020-10-16 | 2020-10-16 | Preparation method of piperazine-N, N' -di (2-ethanesulfonic acid) |
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| CN112174912B true CN112174912B (en) | 2023-08-22 |
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- 2020-10-16 CN CN202011108048.6A patent/CN112174912B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| 卞克建等.磺酸型生物缓冲剂的合成.化学试剂.1997,19(3),第162～164页. * |
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