Method for synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid or salt thereof by using micro-channel continuous flow process and micro-channel reaction device

Abstract

The invention provides a method for synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid or salt thereof by using a micro-channel continuous flow process, which comprises the following steps: mixing and preheating an aqueous solution of sodium hydroxyethyl sulfonate and alkali, and respectively introducing the mixture and preheated N-hydroxyethylpiperazine into a micro-channel reaction device for reaction to obtain 4-hydroxyethylpiperazine ethanesulfonate; and then introducing into an acidification module, and reacting to obtain the 4-hydroxyethylpiperazine ethanesulfonic acid. According to the invention, full mixing of materials is realized through the micro-channel reaction module, and the materials are reacted completely in cooperation with the delay reactor, so that 4-hydroxyethylpiperazine ethanesulfonic acid or salt thereof with the purity up to 99% or above and the conversion rate up to 99% or above is obtained, pipeline reaction and kettle reaction in the prior art are replaced, and the production cost is reduced. The problems that the reaction is insufficient, separation and purification are difficult due to reaction substrates, industrialization is difficult to achieve and the like are solved, VOC emission is reduced, and the process is safer, more environmentally friendly and more environmentally friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemistry, and specifically relates to a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by using a microchannel continuous flow process and a microchannel reaction device. Background Art

[0002] Piperazine sulfonic acid buffers are zwitterionic biological buffers, such as piperazine sulfonic acid buffers including 4-hydroxyethylpiperazineethanesulfonic acid (HEPES), 4-hydroxyethylpiperazinepropanesulfonic acid (HEPPS), 3-(hydroxyethylpiperazine)-2-hydroxypropanesulfonic acid (HEPPSO) and their corresponding sodium salts HEPES-Na, HEPPS-Na, HEPPSO-Na, etc., which have good buffering capacity within a certain pH range and can maintain a constant pH of the solution system for a long time.

[0003] In the prior art, Wuhan Desheng Biochemical Technology Co., Ltd. discloses a method for preparing 4-hydroxyethylpiperazineethanesulfonic acid by using a kettle method, using hydroxyethylpiperazine, sodium chloroethanesulfonate and sodium hydroxide as raw materials, and refluxing until the reaction is completed. After cooling, ion exchange resin H + Desalting and purifying by chromatography column; adding acid to adjust pH, and cooling by alcohol precipitation to obtain yellow HEPES crude product. Then, after post-treatment, 4-hydroxyethylpiperazineethanesulfonic acid product can be obtained. Although this autoclave preparation method has a high product yield and high product purity, it is cumbersome to operate and produces sodium chloride as a by-product; in particular, the reaction product is yellow, and post-treatment is troublesome. Even after post-treatment, the transmittance of the obtained product is poor, and the economic benefit is poor.

[0004] The patent with the public announcement number CN112159367B discloses a method for preparing 4-hydroxyethylpiperazineethanesulfonic acid, which adopts a pipeline continuous production system, uses sodium hydroxyethyl sulfonate, hydroxyethylpiperazine, and liquid caustic soda as raw materials, and the reaction liquid after the reaction is exchanged with a hydrogen-type cation exchange resin, and 4-hydroxyethylpiperazineethanesulfonic acid is obtained by post-treatment. The patent adopts a pipeline continuous production process to replace the batch reaction of kettle type, which saves costs and reduces energy consumption. The process system is stable, but the mass transfer and heat transfer effects in the pipeline are not good, the synthesis rate is low, and a long reaction pipeline is required, which is difficult to achieve industrialization.

[0005] In summary, the above problems exist in the preparation process of 4-hydroxyethylpiperazineethanesulfonic acid, which hinders the large-scale application of 4-hydroxyethylpiperazineethanesulfonic acid; therefore, the industry urgently needs a method for efficiently preparing 4-hydroxyethylpiperazineethanesulfonic acid or its salt to solve the problems in the prior art. Summary of the invention

[0006] In view of the deficiencies in the prior art, the object of the present invention is to provide a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt using a microchannel continuous flow process and a microchannel reaction device. The method achieves efficient mixing and heat conduction of materials at the molecular level, so that the reaction materials are fully mixed, the reaction is more complete, the reaction conversion rate is further improved, the process operation is safe and controllable, and no by-products are generated, so as to obtain high-purity and high-quality 4-hydroxyethylpiperazineethanesulfonic acid and its salt.

[0007] To achieve this object, the present invention adopts the following technical solutions:

[0008] The first object of the present invention is to provide a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by using a microchannel continuous flow process, comprising the following steps: mixing an aqueous solution of sodium isethionate and a base to form a mixed solution, preheating the mixed solution, and introducing the mixed solution and the preheated N-hydroxyethylpiperazine into a microchannel reaction device for reaction to obtain 4-hydroxyethylpiperazineethanesulfonic acid salt.

[0009] Specifically, the reaction temperature is 150-220° C., the reaction pressure is 1-3 Mpa, and the reaction residence time is 10-60 min.

[0010] Specifically, the alkali is an aqueous alkali solution with a mass concentration of 35-45%, and the mass concentration of sodium hydroxyethyl sulfonate in the aqueous solution of sodium hydroxyethyl sulfonate is 55-65%;

[0011] Wherein, the reaction temperature can be 150°C, 160°C, 170°C, 180°C, 190°C, 200°C, 210°C or 220°C, etc., the reaction pressure can be 1Mpa, 2Mpa or 3Mpa, etc., the reaction residence time can be 10min, 20min, 30min, 40min, 50min or 60min, etc., but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0012] The alkali may be an aqueous alkali solution having a mass concentration of 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44% or 45%, etc. The mass concentration of sodium hydroxyethyl sulfonate in the aqueous solution of sodium hydroxyethyl sulfonate may be 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64% or 65%, etc., but is not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0013] Preferably, the base is one selected from sodium hydroxide and potassium hydroxide.

[0014] Specifically, the mass ratio of the aqueous solution of sodium isethionate to the aqueous alkali solution is 1:(0.03-0.15).

[0015] Specifically, the mass ratio of the mixed liquid to the N-hydroxyethylpiperazine is 1:(0.24-0.8).

[0016] In a specific embodiment of the present invention, in a small test, the flow rate of the mixed solution is 13.3-40.0 g / min, and the flow rate of the N-hydroxyethylpiperazine is 6.82-18.8 g / min;

[0017] In a specific embodiment of the present invention, industrially, the flow rate of the mixed liquid is 1500-5500 g / min, and the flow rate of N-hydroxyethylpiperazine is 800-3000 g / min.

[0018] The flow rates of the specific mixed solution and N-hydroxyethylpiperazine depend on the actual reaction scale and are not limited to the numerical ranges listed above. Other numerical ranges not listed are also applicable. The embodiment of the present invention is tested according to the flow rate range provided by the small test process.

[0019] Specifically, the preheating temperature of the mixed solution is 60-80°C, and the preheating temperature of the N-hydroxyethylpiperazine is 80-90°C.

[0020] The preheating temperature of the mixed liquid can be 60°C, 65°C, 70°C, 75°C or 80°C, etc., and the preheating temperature of the N-hydroxyethylpiperazine can be 80°C, 85°C or 90°C, etc., but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0021] Specifically, the microchannel reaction device comprises at least two microchannel modules arranged in series, at least one delayed reactor, and a condenser, wherein the delayed reactor is arranged behind the microchannel module adjacent to the condenser and / or between two microchannel modules, and the condenser is arranged at the discharge port of the microchannel reaction device;

[0022] Preferably, the number of the microchannel modules is 1-10, and the number of the delayed reactors is 1-10;

[0023] More preferably, the number of the microchannel modules is 4-6, and the number of the delayed reactors is 4-6.

[0024] Specifically, the microchannel reaction device further comprises a first metering pump disposed between the first microchannel module and the last microchannel module, and N-hydroxyethylpiperazine is introduced again into the microchannel reaction device through the first metering pump.

[0025] Specifically, the microchannel reaction device further comprises an acidification module disposed behind the condenser, and acid is added to the acidification module to obtain 4-hydroxyethylpiperazineethanesulfonic acid;

[0026] Preferably, the acid is one selected from formic acid, glacial acetic acid and oxalic acid.

[0027] The second object of the present invention is to provide a microchannel reaction device used in the above method, the microchannel reaction device comprising at least two microchannel modules arranged in series, at least one delayed reactor, and a condenser, wherein the condenser is arranged at the discharge port of the microchannel reaction device, and the delayed reactor is arranged behind the microchannel module closest to the discharge port and / or between two microchannel modules;

[0028] Preferably, the microchannel reaction device further comprises a first metering pump, and the first metering pump is arranged between the first microchannel module and the last microchannel module;

[0029] Preferably, the microchannel reaction device further comprises an acidification module arranged behind the condenser.

[0030] Preferably, the microchannel reaction device further comprises a second metering pump arranged before the first microchannel module. In the present invention, there are two second metering pumps, which are arranged in parallel and are used to inject the mixed solution and N-hydroxyethylpiperazine into the microchannel module respectively.

[0031] The first microchannel module mentioned in the present invention refers to the microchannel module closest to the raw material inlet; the last microchannel module refers to the microchannel module closest to the condenser adjacent to the discharge port.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] The invention provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by using a microchannel continuous flow process and a microchannel reaction device. The microchannel reaction module realizes full mixing of materials, and cooperates with a time-delay reactor to make the materials react completely, thereby obtaining 4-hydroxyethylpiperazineethanesulfonic acid or its salt with a purity of up to 99% and a conversion rate of up to 99%. The method replaces the pipeline reaction and kettle reaction in the prior art, solves the problems of insufficient reaction, difficulty in separation and purification due to reaction substrates, difficulty in industrialization, etc., reduces VOC emissions, and makes the process safer, greener and more environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Attached Figure 1 This is a schematic diagram of a device according to Embodiment 1 of the present invention;

[0035] Attached Figure 2 This is a schematic diagram of a device according to Embodiment 8 of the present invention;

[0036] Attached Figure 3 is a schematic diagram of a device according to Embodiment 9 of the present invention;

[0037] Attached Figure 4 is a schematic diagram of a device according to embodiment 10 of the present invention;

[0038] Attached Figure 5 is a schematic diagram of a device according to embodiment 11 of the present invention;

[0039] Among them, 1-the second metering pump; 2-the microchannel module; 3-the delayed reactor; 4-the condenser; 5-the first metering pump; 6-the acidification module. DETAILED DESCRIPTION

[0040] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0041] Example 1

[0042] The present embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, wherein the microchannel reaction device comprises two second metering pumps arranged in parallel, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, and a condenser, such as Figure 1 shown.

[0043] The synthesis method is as follows: a 50% sodium hydroxyethyl sulfonate aqueous solution and a 30% sodium hydroxide aqueous solution are mixed at a mass ratio of 1:0.08 to form a mixed solution, which is then preheated to 60° C., and N-hydroxyethylpiperazine is preheated to 80° C. for later use;

[0044] The mixed liquid was injected into the microchannel reaction device at 19.95 g / min and N-hydroxyethylpiperazine at 8.98 g / min by a metering pump. The raw materials were kept in the microchannel reaction device for 18 min at 180 ° C and 1 MPa. The reaction mother liquor containing sodium 4-hydroxyethylpiperazine ethanesulfonate was obtained after being discharged from the condenser at an outlet temperature of 92 ° C. The conversion rate of sodium 4-hydroxyethylpiperazine ethanesulfonate was calculated to be 99.52% by ELSD analysis. The reaction liquid was concentrated and distilled, and ethanol was dispersed and separated. The mother liquor was concentrated and applied to obtain a white solid powder of sodium 4-hydroxyethylpiperazine ethanesulfonate with a yield of 91.94% and a purity of 99.65%. The microchannel continuous flow process device can be operated continuously for at least 10 months.

[0045] Example 2

[0046] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 1, except that the mixed solution and N-hydroxyethylpiperazine are fed at 19.95 g / min and 8.28 g / min, and the conversion rate of sodium hydroxyethyl sulfonate is calculated to be 99.12% by ELSD analysis, and the reaction solution is concentrated and distilled by ethanol dispersion separation, and the mother liquor is concentrated and reused to obtain a white solid powder of sodium 4-hydroxyethylpiperazine ethanesulfonate, with a yield of 88.51% and a purity of 99.00%. It has been verified by experiments that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0047] Example 3

[0048] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazine ethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 1, except that the mixed solution and N-hydroxyethylpiperazine are fed at 21.95 g / min and 8.98 g / min, and the conversion rate of sodium hydroxyethyl sulfonate is calculated to be 99.08% by ELSD analysis, and the reaction solution is concentrated and distilled by ethanol dispersion separation, and the mother liquor is concentrated and reused to obtain a white solid powder of sodium 4-hydroxyethylpiperazine ethanesulfonate, with a yield of 86.32% and a purity of 99.05%. It has been verified by experiments that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0049] Example 4

[0050] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 1, except that the mass ratio of sodium hydroxyethyl sulfonate aqueous solution to sodium hydroxide aqueous solution is changed to 1:0.15, and the conversion rate of sodium hydroxyethyl sulfonate is calculated to be 99.08% by ELSD analysis, and the reaction solution is concentrated and distilled to ethanol dispersion separation, and the mother liquor is concentrated and reused to obtain 4-hydroxyethylpiperazineethanesulfonic acid sodium white solid powder, with a yield of 92.12% and a purity of 99.63%. It has been verified by experiments that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0051] Example 5

[0052] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 1, except that the reaction temperature in the microchannel reaction device is 160°C, and the conversion rate of sodium hydroxyethyl sulfonate is calculated to be 99.03% by ELSD analysis, and the reaction solution is concentrated and distilled to disperse and separate ethanol, and the mother liquor is concentrated and reused to obtain a white solid powder of sodium 4-hydroxyethylpiperazineethanesulfonate with a yield of 86.12% and a purity of 98.85%. It has been verified by experiments that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0053] Example 6

[0054] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 1, except that the reaction pressure in the microchannel reaction device is 0.6MPa, and the conversion rate of sodium hydroxyethyl sulfonate is calculated to be 99.15% by ELSD analysis, and the reaction solution is concentrated, distilled, and separated by ethanol dispersion, and 4-hydroxyethylpiperazineethanesulfonic acid sodium white solid powder is obtained with a yield of 84.16% and a purity of 98.98%. It has been verified by experiments that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0055] Example 7

[0056] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 1, except that the residence time of the reaction in the microchannel reaction device is 25 minutes, and the conversion rate of sodium hydroxyethyl sulfonate is calculated to be 99.64% by ELSD analysis, and the reaction solution is concentrated, distilled, and separated by ethanol dispersion to obtain a white solid powder of sodium 4-hydroxyethylpiperazineethanesulfonate, with a yield of 92.03% and a purity of 99.31%. It has been verified experimentally that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0057] Example 8

[0058] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which are basically the same as those in Embodiment 1, except that the microchannel reaction device includes two second metering pumps, a microchannel module, a microchannel module, a microchannel module, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a microchannel module, a microchannel module, and a condenser, which are sequentially arranged in parallel. Figure 2As shown. After the reaction, the conversion rate of sodium hydroxyethyl sulfonate was calculated to be 99.58% by ELSD analysis. The reaction solution was concentrated and distilled, and ethanol was dispersed and separated. The mother liquor was concentrated and reused to obtain 4-hydroxyethylpiperazine ethanesulfonate sodium white solid powder with a yield of 92.38% and a purity of 99.43%. It has been verified by experiments that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0059] Example 9

[0060] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 7, except that a time-delay reactor is added, and the microchannel reaction device includes two second metering pumps arranged in parallel, a microchannel module, a microchannel module, a microchannel module, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a microchannel module, a condenser, and the like. Figure 3 As shown. Through ELSD analysis, the conversion rate of sodium hydroxyethyl sulfonate was calculated to be 99.59%. The reaction solution was concentrated, distilled, and separated by ethanol dispersion to obtain a white solid powder of sodium 4-hydroxyethylpiperazine ethanesulfonate with a yield of 92.41% and a purity of 99.23%. Experimental verification shows that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0061] Example 10

[0062] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which are basically the same as Example 1, except that the microchannel reaction device also includes a first metering pump arranged between the first microchannel module and the second microchannel module.

[0063] The microchannel reaction device includes two second metering pumps arranged in parallel, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a first metering pump, a microchannel module, a time-delay reactor, a microchannel module, and a condenser. Figure 4 shown.

[0064] A 50% sodium isethionate aqueous solution and a 30% sodium hydroxide aqueous solution are mixed at a mass ratio of 1:0.08 to form a mixed solution, which is then preheated to 70° C.; N-hydroxyethylpiperazine is preheated to 80° C. for later use;

[0065] The mixed liquid was injected into the microchannel reaction device at 19.95 g / min and N-hydroxyethylpiperazine at 8.98 g / min, respectively. Then, N-hydroxyethylpiperazine was added between the third microchannel module and the fourth microchannel module at 1.12 g / min by a second metering pump. At 180°C and 1 MPa, the raw material stayed in the microchannel reaction device for 18 minutes. The material was then discharged from the condenser at an outlet temperature of 92°C to obtain a reaction mother liquor containing sodium 4-hydroxyethylpiperazine ethanesulfonate. The mother liquor was concentrated and applied. After ELSD analysis, the conversion rate of sodium 4-hydroxyethylpiperazine ethanesulfonate was calculated to be 99.57%. The reaction liquid was concentrated, distilled, and dispersed in ethanol to obtain a white solid powder of sodium 4-hydroxyethylpiperazine ethanesulfonate with a yield of 91.88% and a purity of 99.36%. The microchannel continuous flow process device was verified by experiments to be able to operate continuously for at least 10 months.

[0066] Embodiment 11

[0067] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 1, except that the microchannel reaction device also includes an acidification module arranged after the condenser.

[0068] The microchannel reaction device includes two second metering pumps arranged in parallel, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a microchannel module, a time-delay reactor, a microchannel module, a condenser, and an acidification module. Figure 5 shown.

[0069] A 50% sodium isethionate aqueous solution and a 30% sodium hydroxide aqueous solution are mixed at a mass ratio of 1:0.08 to form a mixed solution, which is then preheated to 70° C.; N-hydroxyethylpiperazine is preheated to 70° C. for later use;

[0070] The mixed liquid was injected into the microchannel reaction device at 19.95 g / min and N-hydroxyethylpiperazine at 8.98 g / min by a metering pump. The raw materials were kept in the microchannel reaction device for 18 min at 180 ° C and 1 MPa. The reaction mother liquor containing sodium 4-hydroxyethylpiperazine ethanesulfonate was obtained by discharging through a condenser at an outlet temperature of 92 ° C. The reaction mother liquor was concentrated and reused, and then the temperature was condensed to room temperature by a condenser. The reaction liquid containing sodium 4-hydroxyethylpiperazine ethanesulfonate was passed through an acidification module. Glacial acetic acid was added to the acidification module at 16.97 g / min to obtain a reaction liquid containing 4-hydroxyethylpiperazine ethanesulfonic acid. The reaction liquid was concentrated and reused. The reaction liquid was acidified for 1 h, concentrated and distilled, and then methanol was refluxed and dispersed for recrystallization. The white solid powder of 4-hydroxyethylpiperazine ethanesulfonic acid was obtained by filtration. The yield was 85.92% and the titration content was 99.92%. The microchannel continuous flow process device can be operated continuously for at least 10 months.

[0071] Example 12

[0072] This embodiment provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process and a microchannel reaction device, which is basically the same as Example 10, except that formic acid is introduced into the microchannel acidification module at 9.69 g / min, the reaction solution is acidified for 1 hour, and after concentration and distillation, methanol reflux dispersion, recrystallization and filtration are used to obtain a white solid powder of 4-hydroxyethylpiperazineethanesulfonic acid, with a yield of 85.83% and a titration content of 98.93%. It has been experimentally verified that the microchannel continuous flow process device can operate continuously for at least 10 months.

[0073] The following is a table of product testing data in Examples 1-12

[0074]

[0075] In Examples 1-12, the solubility test of the product was carried out by preparing a 1M aqueous solution of the product, which was all colorless and clear.

[0076] The present invention provides a method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by using a microchannel continuous flow process and a microchannel reaction device. The microchannel reaction module realizes full mixing of materials, and cooperates with a time-delay reactor to make the materials react completely, thereby obtaining 4-hydroxyethylpiperazineethanesulfonic acid or its salt with a purity of up to 99% and a conversion rate of up to 99%. The method replaces the pipeline reaction and kettle reaction in the prior art, solves the problems of insufficient reaction, difficulty in separation and purification due to reaction substrates, difficulty in industrialization, etc., reduces VOC emissions, and makes the process safer and more environmentally friendly.

[0077] The applicant declares that the present invention uses the above-mentioned embodiments to illustrate the method and microchannel reaction device for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt by a microchannel continuous flow process, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for synthesizing 4-hydroxyethylpiperazineethanesulfonic acid or its salt using a microchannel continuous flow process, characterized in that: The method comprises the following steps: mixing an aqueous solution of sodium hydroxyethyl sulfonate and a base to form a mixed solution, preheating the mixed solution, and introducing the mixed solution and the preheated N-hydroxyethyl piperazine into a microchannel reaction device for reaction to obtain 4-hydroxyethyl piperazine ethanesulfonate.

2. The method according to claim 1, characterized in that: The reaction temperature is 150-220° C., the reaction pressure is 1-3 MPa, and the reaction residence time is 10-60 min.

3. The method according to claim 1 or 2, characterized in that: The alkali is an aqueous alkali solution with a mass concentration of 35-45%, and the mass concentration of sodium hydroxyethyl sulfonate in the aqueous solution of sodium hydroxyethyl sulfonate is 55-65%; Preferably, the base is one selected from sodium hydroxide and potassium hydroxide.

4. The method according to any one of claim 3, characterized in that: The mass ratio of the aqueous solution of sodium hydroxyethyl sulfonate to the aqueous alkali solution is 1:(0.03-0.15).

5. The method according to any one of claims 1 to 4, characterized in that: The mass ratio of the mixed liquid to the N-hydroxyethylpiperazine is 1:(0.24-0.8).

6. The method according to any one of claims 1 to 5, characterized in that: The preheating temperature of the mixed solution is 60-80°C, and the preheating temperature of the N-hydroxyethylpiperazine is 80-90°C.

7. The method according to any one of claims 1 to 6, characterized in that: The microchannel reaction device comprises at least two microchannel modules arranged in series, at least one time-delay reactor, and a condenser, wherein the condenser is arranged at the discharge port of the microchannel reaction device, and the time-delay reactor is arranged behind the microchannel module adjacent to the condenser and / or between two microchannel modules; Preferably, the number of the microchannel modules is 1-10, and the number of the delayed reactors is 1-10; More preferably, the number of the microchannel modules is 4-6, and the number of the delayed reactors is 4-6.

8. The method according to claim 7, characterized in that: The microchannel reaction device further comprises a first metering pump disposed between the first microchannel module and the last microchannel module, and N-hydroxyethylpiperazine is introduced again into the microchannel reaction device through the first metering pump.

9. The method according to claim 7 or 8, characterized in that: The microchannel reaction device further comprises an acidification module disposed behind the condenser, and acid is added to the acidification module to obtain 4-hydroxyethylpiperazineethanesulfonic acid; Preferably, the acid is one selected from formic acid, glacial acetic acid and oxalic acid.

10. A microchannel reaction device used in the method according to any one of claims 1 to 9, characterized in that: The microchannel reaction device comprises at least two microchannel modules arranged in series, at least one time-delay reactor, and a condenser, wherein the condenser is arranged at the discharge port of the microchannel reaction device, and the time-delay reactor is arranged behind the microchannel module closest to the discharge port and / or between two microchannel modules; Preferably, the microchannel reaction device further comprises a first metering pump, and the first metering pump is arranged between the first microchannel module and the last microchannel module; Preferably, the microchannel reaction device further comprises an acidification module arranged behind the condenser.

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