Synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid
The HEPES synthesis system, which uses a synthesis kettle, a separation tank, and multiple crystallization steps, solves the problems of high wastewater treatment and resin regeneration costs in HEPES production, and achieves high-purity, high-yield HEPES production.
Patent Information
- Application Number
- CN202422382298.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-29
- Publication Date
- 2025-12-09
- Estimated Expiration
- 2034-09-29
AI Technical Summary
The existing HEPES synthesis process generates a large amount of difficult-to-treat saline wastewater, and the ion exchange resin needs to be repeatedly regenerated, consuming a large amount of acid and alkali. The product purity is not high and the cost is high.
By employing equipment such as synthesis kettles, separatory tanks, and concentration crystallization kettles, and by controlling reaction conditions and multiple crystallization steps, combined with drying treatment, efficient synthesis of HEPES can be achieved.
It reduces wastewater discharge, lowers resin regeneration costs, improves product purity and yield, and reduces production costs.
Smart Images
Figure CN223641824U_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic preparation technology, specifically relating to a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid. Background Technology
[0002] 4-Hydroxyethylpiperazine ethanesulfonic acid (HEPES) is an important hydrogen ion buffer with good buffering capacity in the pH range of 6.8–8.2, enabling it to maintain a constant pH for a relatively long period. The concentration used is 10–50 mmol / L; generally, a culture medium containing 20 mmol / L of HEPES provides good buffering capacity and has no cytotoxic effects.
[0003] The common method for separating and purifying HEPES is to first convert the sodium, potassium, or ammonium salts of HEPES by acidification, then use the weak basicity of the nitrogen atom on the piperazine ring in the HEPES molecular structure to exchange HEPES ions onto a cation exchange resin. Then, a large amount of water is used to remove sulfate and sodium ions, followed by the exchange of HEPES with ammonia. Finally, HEPES is obtained through neutralization, concentration, and crystallization. The main problems with this method are: (1) a large amount of difficult-to-treat saline wastewater is generated during the production process, causing serious environmental pollution; (2) the ion exchange resin needs to be repeatedly regenerated, consuming a large amount of acid and alkali; (3) the purity of the obtained product is not high enough, and further separation and purification are required; (4) the purification yield per unit mass of ion exchange resin is low, and the lifespan is short, resulting in high cost. Utility Model Content
[0004] The purpose of this invention is to solve the problems of the prior art and provide a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid. N-hydroxyethylpiperazine is added to the synthesis reactor through the N-hydroxyethylpiperazine inlet pipe. Sodium 2-chloroethylsulfonate and sodium bicarbonate are added through the feed inlet, followed by water addition through the first water inlet pipe. The stirring device on the synthesis reactor is started, and the first heating jacket heats the reactor to the reaction temperature. After a period of reaction, the material flows through the first discharge pipe and is cooled to room temperature by the first cooler before being discharged into a separatory tank. Water is added through the second water inlet pipe to wash the oil phase, which then flows out through the solvent recovery pipe. The aqueous phase flows through... The aqueous phase flows through the first transfer tank and into the first concentration crystallization vessel. Hydrochloric acid and methanol then flow in sequentially through the hydrochloric acid inlet and the first methanol inlet. The second heating jacket heats the material to the reflux temperature. After refluxing for a period of time, the second heating jacket stops heating to allow for primary crystallization. The crystallized material flows through the third discharge pipe into the plate and frame filter press to obtain waste salt filter cake and the second aqueous phase. The second aqueous phase flows through the second transfer tank and into the second concentration crystallization vessel. Methanol then flows in through the second methanol inlet for secondary crystallization. The material flows through the fourth discharge pipe into the centrifuge to obtain 4-hydroxyethylpiperazine ethanesulfonic acid product.
[0005] This utility model is achieved through the following technical solution:
[0006] A synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid includes a synthesis vessel. The synthesis vessel is equipped with a first water inlet pipe, an N-hydroxyethylpiperazine inlet pipe, a n-butanol inlet pipe, a feed port, a first heating jacket, and a first discharge pipe. A first cooler and a separating tank are sequentially arranged on the first discharge pipe. A second water inlet pipe and a second discharge pipe are arranged on the separating tank. A three-way valve is arranged on the second discharge pipe, which is connected to a solvent recovery pipe and an aqueous phase discharge pipe. A first transfer tank and a first concentration crystallization vessel are sequentially arranged on the aqueous phase discharge pipe. A second heating jacket, a hydrochloric acid inlet pipe, a first methanol inlet pipe, and a third discharge pipe are arranged on the first concentration crystallization vessel. A plate and frame filter press, a second transfer tank, and a second concentration crystallization vessel are sequentially arranged on the third discharge pipe. A third heating jacket, a second methanol inlet pipe, and a fourth discharge pipe are arranged on the second concentration crystallization vessel. A centrifuge is arranged on the fourth discharge pipe.
[0007] Preferably, the synthesis reactor is provided with a first gas outlet pipe, and a second cooler is provided on the first gas outlet pipe. The second cooler is connected to the synthesis reactor through a first condensate return pipe.
[0008] Preferably, the first heating jacket, the second heating jacket, and the third heating jacket are each provided with a steam inlet pipe and a condensate outlet pipe, the steam inlet pipe is provided with a steam valve, and the condensate outlet pipe is provided with a drain valve.
[0009] Preferably, temperature sensors are installed on the synthesis vessel, the first concentration crystallization vessel, and the second concentration crystallization vessel.
[0010] Preferably, valves are provided on the first water inlet pipe, the N-hydroxyethylpiperazine inlet pipe, the n-butanol inlet pipe, the first discharge pipe, the second water inlet pipe, the second discharge pipe, the solvent recovery pipe, the aqueous phase discharge pipe, the hydrochloric acid inlet pipe, the first methanol inlet pipe, the third discharge pipe, the second methanol inlet pipe, and the fourth discharge pipe.
[0011] Preferably, flow meters are installed on the first water inlet pipe, the N-hydroxyethylpiperazine inlet pipe, the n-butanol inlet pipe, the second water inlet pipe, the hydrochloric acid inlet pipe, the first methanol inlet pipe, and the second methanol inlet pipe.
[0012] Preferably, a transfer pump is installed on the first discharge pipe, the aqueous phase discharge pipe, and the third discharge pipe.
[0013] Preferably, a dryer is also included.
[0014] Preferably, the separating tank, the first concentration crystallization vessel, and the second concentration crystallization vessel are sequentially provided with a second gas outlet pipe, a third gas outlet pipe, and a fourth gas outlet pipe.
[0015] Preferably, a third cooler is provided on the third exhaust pipe, and a second condenser is provided on the third cooler, the second condenser being connected to the first buffer tank; a fourth cooler is provided on the fourth exhaust pipe, and a third condenser is provided on the fourth cooler, the third condenser being connected to the second buffer tank.
[0016] Compared with the prior art, this utility model has the following advantages and beneficial effects:
[0017] I. This utility model provides a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid. N-hydroxyethylpiperazine is added into the synthesis reactor through the N-hydroxyethylpiperazine inlet pipe. Sodium 2-chloroethylsulfonate and sodium bicarbonate are added through the feed inlet, followed by water through the first water inlet pipe and n-butanol through the n-butanol inlet pipe. The stirring device on the synthesis reactor is started, and the first heating jacket heats up to the reaction temperature. After reacting for a period of time, the material flows through the first discharge pipe and is cooled to room temperature by the first cooler before being discharged into the separatory tank. Water is added through the second water inlet pipe to wash the oil phase, which flows out through the solvent recovery pipe. The aqueous phase... After flowing through the first transfer tank via the aqueous phase outlet pipe, it flows into the first concentration and crystallization vessel. Hydrochloric acid and methanol then flow in sequentially through the hydrochloric acid inlet pipe and the first methanol inlet pipe. The second heating jacket heats up to the reflux temperature. After refluxing for a period of time, the second heating jacket stops heating to allow for primary crystallization. After crystallization, the material flows into the plate and frame filter press through the third outlet pipe to obtain waste salt filter cake and the second aqueous phase. The second aqueous phase flows through the second transfer tank and into the second concentration and crystallization vessel. Methanol then flows into the second methanol inlet pipe for secondary crystallization. The material flows into the centrifuge through the fourth outlet pipe to obtain the 4-hydroxyethylpiperazine ethanesulfonic acid product.
[0018] II. The present invention provides a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid, wherein flow meters and valves are installed on the first water inlet pipe, the N-hydroxyethylpiperazine inlet pipe, the n-butanol inlet pipe, the second water inlet pipe, the hydrochloric acid inlet pipe, the first methanol inlet pipe, and the second methanol inlet pipe to facilitate the precise addition of each material.
[0019] III. The present invention provides a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid, wherein the setting of the dryer further removes moisture from the 4-hydroxyethylpiperazine ethanesulfonic acid product. Attached Figure Description
[0020] Figure 1 This is a schematic diagram of the structure of this utility model;
[0021] Figure 2 This is a schematic diagram of the structure of Embodiment 2 of this utility model;
[0022] The components are as follows: 110, Synthesis vessel; 120, Separating tank; 130, First cooler; 140, First transfer tank; 150, First concentration and crystallization vessel; 160, Plate and frame filter press; 170, Second transfer tank; 180, Second concentration and crystallization vessel; 190, Centrifuge; 200, Second cooler; 210, Third cooler; 220, First buffer tank; 230, Fourth cooler; 240, Second buffer tank; 250, Dryer; 1, First water inlet pipe; 2, N-hydroxyethylpiperazine inlet pipe; 3, n-butanol inlet pipe; 4, Feed inlet; 5, First heating jacket; 6, First discharge pipe; 7, ... 8. Second water inlet pipe; 9. Second discharge pipe; 10. Three-way valve; 11. Solvent recovery pipe; 12. Aqueous phase discharge pipe; 13. Second heating jacket; 14. Hydrochloric acid inlet pipe; 15. First methanol inlet pipe; 16. Third discharge pipe; 17. Second methanol inlet pipe; 18. Fourth discharge pipe; 19. First vent pipe; 20. First condensate return pipe; 21. Third heating jacket; 22. Steam inlet pipe; 23. Condensate discharge pipe; 24. Steam valve; 25. Drain valve; 26. Transfer pump; 27. Second vent pipe; 28. Third vent pipe; 29. Second condenser pipe; 30. Third condenser pipe. Detailed Implementation
[0023] The present invention will be further described in detail below with reference to the embodiments, but the implementation of the present invention is not limited thereto.
[0024] Example 1
[0025] like Figure 1 As shown, this embodiment provides a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid, including a synthesis reactor 110. The synthesis reactor 110 is equipped with a first water inlet pipe 1, an N-hydroxyethylpiperazine inlet pipe 2, a n-butanol inlet pipe 3, a feed port 4, a first heating jacket 5, and a first discharge pipe 6. A first cooler 130 and a separatory tank 120 are sequentially arranged on the first discharge pipe 6. A second water inlet pipe 7 and a second discharge pipe 8 are arranged on the separatory tank 120. A three-way valve 9 is arranged on the second discharge pipe 8, and the three-way valve 9 is connected to a solvent recovery pipe 10 and an aqueous phase outlet pipe 11, respectively. The aqueous phase outlet pipe 11 is connected to the first transfer tank 140 and the first concentration crystallization vessel 150, which are arranged in sequence. The first concentration crystallization vessel 150 is equipped with a second heating jacket 12, a hydrochloric acid inlet pipe 13, a first methanol inlet pipe 14 and a third discharge pipe 15. The third discharge pipe 15 is equipped with a plate and frame filter press 160, a second transfer tank 170 and a second concentration crystallization vessel 180, which are arranged in sequence. The second concentration crystallization vessel 180 is equipped with a third heating jacket 20, a second methanol inlet pipe 16 and a fourth discharge pipe 17. The fourth discharge pipe 17 is equipped with a centrifuge 190.
[0026] Example 2
[0027] like Figure 2 As shown, the difference between this embodiment and Embodiment 1 is that, as Figure 2 As shown, the synthesis vessel 110 is provided with a first gas outlet pipe 18, and a second cooler 200 is provided on the first gas outlet pipe 18. The second cooler 200 is connected to the synthesis vessel 110 through a first condensate return pipe 19.
[0028] The first heating jacket 5, the second heating jacket 12 and the third heating jacket 20 are each provided with a steam inlet pipe 21 and a condensate outlet pipe 22. The steam inlet pipe 21 is provided with a steam valve 23 and the condensate outlet pipe 22 is provided with a drain valve 24.
[0029] Temperature sensors are installed on the synthesis vessel 110, the first concentration crystallization vessel 150, and the second concentration crystallization vessel 180.
[0030] Valves are provided on the first water inlet pipe 1, N-hydroxyethylpiperazine inlet pipe 2, n-butanol inlet pipe 3, first discharge pipe 6, second water inlet pipe 7, second discharge pipe 8, solvent recovery pipe 10, aqueous phase discharge pipe 11, hydrochloric acid inlet pipe 13, first methanol inlet pipe 14, third discharge pipe 15, second methanol inlet pipe 16, and fourth discharge pipe 17.
[0031] Flow meters are installed on the first water inlet pipe 1, the N-hydroxyethylpiperazine inlet pipe 2, the n-butanol inlet pipe 3, the second water inlet pipe 7, the hydrochloric acid inlet pipe 13, the first methanol inlet pipe 14, and the second methanol inlet pipe 16.
[0032] Among them, the first discharge pipe 6, the water phase discharge pipe 11 and the third discharge pipe 15 are all equipped with a transfer pump 25.
[0033] This also includes a 250-type dryer.
[0034] The liquid separator 120, the first concentration crystallization vessel 150 and the second concentration crystallization vessel 180 are respectively provided with a second vent pipe 26, a third vent pipe 27 and a fourth vent pipe 28.
[0035] The third outlet pipe 27 is equipped with a third cooler 210, and the third cooler 210 is equipped with a second condenser pipe 29, which is connected to the first buffer tank 220. The fourth outlet pipe 28 is equipped with a fourth cooler 230, and the fourth cooler 230 is equipped with a third condenser pipe 30, which is connected to the second buffer tank 240. Both the first buffer tank 220 and the second buffer tank 240 are equipped with vacuum pumps.
[0036] Compared with the prior art, this utility model has the following advantages and beneficial effects:
[0037] I. This utility model provides a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid. N-hydroxyethylpiperazine is added into the synthesis reactor 110 through the N-hydroxyethylpiperazine inlet pipe 2. Sodium 2-chloroethylsulfonate and sodium bicarbonate are added through the feed inlet 4. Water is then added through the first water inlet pipe 1, and n-butanol is added through the n-butanol inlet pipe 3. The stirring device on the synthesis reactor 110 is started, and the first heating jacket 5 is heated to the reaction temperature. After reacting for a period of time, the material flows through the first discharge pipe 6 and is cooled to room temperature by the first cooler 130 before being discharged into the separatory tank 120. Water is added through the second water inlet pipe 7 to wash the oil phase. The oil phase flows out through the solvent recovery pipe 10, and the aqueous phase flows out through the aqueous phase outlet pipe 1. After passing through the first transfer tank 140, the material flows into the first concentration crystallization kettle 150. It then flows into hydrochloric acid and methanol sequentially through the hydrochloric acid inlet pipe 13 and the first methanol inlet pipe 14. The second heating jacket 12 is heated to the reflux temperature. After reflux for a period of time, the second heating jacket 12 stops heating to carry out primary crystallization. After crystallization, the material flows into the plate and frame filter press 160 through the third discharge pipe 15 to obtain waste salt filter cake and the second aqueous phase. The second aqueous phase flows into the second concentration crystallization kettle 180 after passing through the second transfer tank 170. It then flows into methanol through the second methanol inlet pipe 16 for secondary crystallization. The material flows into the centrifuge 190 through the fourth discharge pipe 17 to obtain the 4-hydroxyethylpiperazine ethanesulfonic acid product.
[0038] II. The present invention provides a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid, wherein flow meters and valves are provided on the first water inlet pipe 1, the N-hydroxyethylpiperazine inlet pipe 2, the n-butanol inlet pipe 3, the second water inlet pipe 7, the hydrochloric acid inlet pipe 13, the first methanol inlet pipe 14, and the second methanol inlet pipe 16, so as to facilitate the precise addition of each material.
[0039] III. The present invention provides a synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid, wherein the setting of the dryer 250 further removes moisture from the 4-hydroxyethylpiperazine ethanesulfonic acid product.
[0040] Example 3
[0041] This embodiment uses the 4-hydroxyethylpiperazine ethanesulfonic acid synthesis system described in Example 2. 100 kg of N-hydroxyethylpiperazine is added into the synthesis vessel 110 through the N-hydroxyethylpiperazine inlet pipe 2; 202 kg of sodium 2-chloroethylsulfonate and 64 kg of sodium bicarbonate are added through the feed inlet 4; 200 kg of water is added through the first water inlet pipe 1; and 400 kg of n-butanol is added through the n-butanol inlet pipe 3. Under stirring, the temperature is raised to 95°C in the first heating jacket 5, and the reaction is carried out for 6 hours. The initial pH of the reaction is 7-8.
[0042] After the reaction is complete, the first cooler 130 is cooled to room temperature, and the mixture is separated in the separator 120. 50 kg of water is added through the second water inlet pipe 7 to wash the n-butanol phase twice. The aqueous phase flows into the first concentration crystallization kettle 150. 130 kg of hydrochloric acid is added through the hydrochloric acid inlet pipe 13 to adjust the pH to 3-4. The mixture is concentrated until there are no fractions. 750 kg of methanol is added through the first methanol inlet pipe 14 and heated to 65°C through the second heating jacket 12. Then the second heating jacket 12 stops heating, and crystallization is carried out once in the first concentration crystallization kettle 150. The crystallized material is filtered through the plate and frame filter press 160 to obtain waste salt filter cake and aqueous phase.
[0043] The aqueous phase obtained from the plate and frame filter press 160 flows into the second concentration and crystallization kettle 180. 800 kg of methanol is added through the second methanol inlet pipe 16 and heated to 65°C through the third heating jacket 20. Heating is then stopped in the third heating jacket 20, and secondary crystallization occurs in the second concentration and crystallization kettle 180. The material after secondary crystallization is filtered through a centrifuge 190 to obtain 4-hydroxyethylpiperazine ethanesulfonic acid. The 4-hydroxyethylpiperazine ethanesulfonic acid product is then dried in a dryer 250. The yield of the 4-hydroxyethylpiperazine ethanesulfonic acid product is 90%, the purity is 98%, and the chloride ion content is 0.13%.
[0044] The above description is merely a preferred embodiment of the present utility model and is not intended to limit the present utility model in any way. Any simple modifications or equivalent changes made to the above embodiments based on the technical essence of the present utility model shall fall within the protection scope of the present utility model.
Claims
1. A synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid, characterized in that: The reactor includes a synthesis vessel (110), which is equipped with a first water inlet pipe (1), an N-hydroxyethylpiperazine inlet pipe (2), a n-butanol inlet pipe (3), a feed port (4), a first heating jacket (5), and a first discharge pipe (6). A first cooler (130) and a separatory tank (120) are sequentially installed on the first discharge pipe (6). A second water inlet pipe (7) and a second discharge pipe (8) are installed on the separatory tank (120). A three-way valve (9) is installed on the second discharge pipe (8). The three-way valve (9) is connected to a solvent recovery pipe (10) and an aqueous phase discharge pipe (11), respectively. The first transfer tank (140) and the first concentration crystallization kettle (150) are arranged in sequence. The first concentration crystallization kettle (150) is equipped with a second heating jacket (12), a hydrochloric acid inlet pipe (13), a first methanol inlet pipe (14) and a third discharge pipe (15). The third discharge pipe (15) is equipped with a plate and frame filter press (160), a second transfer tank (170) and a second concentration crystallization kettle (180) in sequence. The second concentration crystallization kettle (180) is equipped with a third heating jacket (20), a second methanol inlet pipe (16) and a fourth discharge pipe (17). The fourth discharge pipe (17) is equipped with a centrifuge (190).
2. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: The synthesis vessel (110) is provided with a first gas outlet pipe (18), and a second cooler (200) is provided on the first gas outlet pipe (18). The second cooler (200) is connected to the synthesis vessel (110) through a first condensate return pipe (19).
3. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: The first heating jacket (5), the second heating jacket (12) and the third heating jacket (20) are each provided with a steam inlet pipe (21) and a condensate outlet pipe (22). A steam valve (23) is provided on the steam inlet pipe (21) and a drain valve (24) is provided on the condensate outlet pipe (22).
4. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: Temperature sensors are installed on the synthesis vessel (110), the first concentration crystallization vessel (150), and the second concentration crystallization vessel (180).
5. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: Valves are provided on the first water inlet pipe (1), N-hydroxyethylpiperazine inlet pipe (2), n-butanol inlet pipe (3), first discharge pipe (6), second water inlet pipe (7), second discharge pipe (8), solvent recovery pipe (10), aqueous phase discharge pipe (11), hydrochloric acid inlet pipe (13), first methanol inlet pipe (14), third discharge pipe (15), second methanol inlet pipe (16) and fourth discharge pipe (17).
6. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: Flow meters are installed on the first water inlet pipe (1), N-hydroxyethylpiperazine inlet pipe (2), n-butanol inlet pipe (3), second water inlet pipe (7), hydrochloric acid inlet pipe (13), first methanol inlet pipe (14) and second methanol inlet pipe (16).
7. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: A transfer pump (25) is installed on the first discharge pipe (6), the water phase discharge pipe (11) and the third discharge pipe (15).
8. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: It also includes a dryer (250).
9. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 1, characterized in that: The separator (120), the first concentration crystallizer (150), and the second concentration crystallizer (180) are sequentially provided with a second vent pipe (26), a third vent pipe (27), and a fourth vent pipe (28).
10. The synthesis system for 4-hydroxyethylpiperazine ethanesulfonic acid according to claim 9, characterized in that: A third cooler (210) is provided on the third exhaust pipe (27), and a second condenser (29) is provided on the third cooler (210). The second condenser (29) is connected to the first buffer tank (220). A fourth cooler (230) is provided on the fourth exhaust pipe (28), and a third condenser (30) is provided on the fourth cooler (230). The third condenser (30) is connected to the second buffer tank (240).