Preparation method of sulfonate

Abstract

The invention provides a preparation method of sulfonate, which comprises the following steps: carrying out condensation reaction on cholic acid and N, N-dimethyl-1, 3-diaminopropane under the action of a catalyst by utilizing a micro-channel fixed bed reaction device to obtain an intermediate 1, and reacting with a sulfonating reagent to obtain the sulfonate. According to the invention, no highly toxic or sensitizing reagent is used, so that the safety coefficient is high; cholic acid and amine are catalyzed to be directly condensed through a fixed bed device loaded with solid superacid, so that the reaction steps are simplified, the use amount of amine is reduced, and the material atom utilization rate is high; through the micro-channel fixed bed reaction device, the mass and heat transfer efficiency is high, the retention time is short, the reaction temperature is stable, the obtained product is high in purity, and the reaction post-treatment is simple.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing sulfonate. Background Art

[0002] As a surfactant, sulfonate can effectively reduce the surface tension of liquids and change the surface properties of liquids, making it easier for liquids to wet other surfaces. The core feature of sulfonates is the sulfonate group (SO 3 - ) combines with other groups inside the molecule to form an internal salt structure, which makes it show excellent interfacial activity in the aqueous phase. Sulfonates are widely used in various cleaning products such as detergents and detergents due to their excellent surface activity.

[0003] Take CHAPS as an example. 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid inner salt (CHAPS) is a typical zwitterionic surfactant. It was designed in 1980 for membrane protein catalysis. As a bile salt derivative, CHAPS not only has a sterol head with three hydrophilic hydroxyl groups, but also has a flexible tail containing a zwitterionic aminothiobetaine part. These characteristics enable CHAPS to form micelles in aqueous solution. As the most commonly used protein cleavage reagent, CHAPS helps maintain the conformation and function of proteins and reduce denaturation; it has low toxicity and is suitable for biomedical research; it is stable under physiological conditions, etc.

[0004]

[0005] The main reported preparation methods of CHAPS are as follows:

[0006] Patent CN116063371A discloses a method for synthesizing 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid inner salt, which uses readily available raw material bile acid as a starting material, and obtains the final product 3-[3-(cholamidopropyl)dimethylamino]propanesulfonic acid inner salt through three steps of esterification, aminolysis and quaternary ammonium salt formation.

[0007] US20170320906A1 discloses a compound for treating Clostridium difficile, which uses cholic acid and acetyl chloride as starting materials, and obtains cholic acid benzyl amide, N-(4-aminobutyl) cholic acid amide, N-[3-(cyclohexylamino)propyl] cholic acid amide and other substances through esterification and amine ester exchange.

[0008] CN111040014A discloses a method for preparing CHAPSO, wherein CHAPSO is obtained by sequentially esterifying, amine transesterifying and salifying taurocholic acid, ethyl chloroformate and 3-dimethylaminopropylamine.

[0009] CN117645646 A discloses a method for synthesizing 3-(cholamidopropyl)-1,1-dimethylamine, which uses cholic acid as a raw material and alkyl chloroformate as an activator to react to generate a mixed acid anhydride, and then the mixed acid anhydride and N,N-dimethyl-1,3-diaminopropane undergo a nucleophilic substitution reaction to generate 3-(cholamidopropyl)-1,1-dimethylamine.

[0010] In summary, the current methods for synthesizing CHAPS and CHAPSO all use bile acid as the raw material, and finally obtain CHAPS and CHAPSO through esterification, amine ester exchange, and salt formation. These routes have low atomic utilization, long reaction time, high energy consumption, use of allergenic and highly toxic raw materials such as EDCI and ethyl chloroformate, and produce a large amount of waste liquid, which is highly polluting. Therefore, these routes are not economical and practical synthetic routes.

[0011] Therefore, how to provide a method for preparing sulfonates with a high safety factor, no use of highly toxic and allergenic reagents, high material atomic utilization, high mass transfer and heat transfer efficiency, short residence time, and stable reaction temperature has become an urgent problem to be solved. Summary of the invention

[0012] In view of the shortcomings of the prior art, the object of the present invention is to provide a method for preparing sulfonates. The preparation method provided by the present invention has a high safety factor, does not use highly toxic and sensitizing reagents, has a high material atomic utilization rate, high mass transfer and heat transfer efficiency, short residence time, and stable reaction temperature. To achieve this invention object, the present invention adopts the following technical solutions:

[0013] The object of the present invention is to provide a method for preparing a sulfonate, which comprises using a microchannel fixed bed reaction device to carry out a condensation reaction of bile acid and N,N-dimethyl-1,3-diaminopropane under the action of a catalyst to obtain an intermediate 1, and then reacting the intermediate with a sulfonating agent to obtain the sulfonate;

[0014]

[0015] Wherein, X is H or a hydroxyalkyl group, and the number of carbon atoms in the hydroxyalkyl group is not greater than 10.

[0016] Specifically, the catalyst is a solid catalyst, including one or more of AlPO, TiPO, ZrPO, NbPO, polystyrene sulfonic acid resin, and perfluorosulfonic acid resin.

[0017] Specifically, the sulfonating agent is selected from sultone, At least one of the following, wherein X is Cl, Br or I, m=2-10, R is hydroxyl, -CH 2 OH, -C 2 H 5 One of OH;

[0018] Preferably, the sulfonating agent is propane sultone, cyclohexane sultone, cyclopentane sultone, Sodium 3-chloro-2-hydroxypropanesulfonate, Sodium 3-chloro-2-hydroxymethylpropanesulfonate, One of them.

[0019] Specifically, the microchannel fixed bed reaction device comprises a preheater, a fixed bed reactor, and a microchannel reactor which are arranged in sequence, and the microchannel reactor comprises a plurality of microchannel modules, a preheater, and a delay device which are arranged in sequence and connected in series.

[0020] Preferably, the number of the microchannel modules is 1-5, and the number of the delay devices is 1-6.

[0021] More preferably, the number of the microchannel modules is 2-3, and the number of the delay devices is 3-5.

[0022] More preferably, the microchannel modules and the delay devices can be arranged alternately.

[0023] Preferably, cholic acid and N,N-dimethyl-1,3-diaminopropane are respectively prepared into corresponding tetrahydrofuran solutions and preheated at a temperature of 55 to 65°C.

[0024] More preferably, the preheated tetrahydrofuran solution of bile acid and the tetrahydrofuran solution of N,N-dimethyl-1,3-diaminopropane are respectively introduced into the fixed bed reactor for condensation reaction to obtain intermediate 1, the reaction temperature is 95-105°C, the pressure is 1.5-2.5 MPa, and the residence time is 40-60 min; further preferably, the reaction temperature can be 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C or 105°C, and the reaction pressure can be 1.5 MPa, 1.6 MPa, 1.7 MPa, 1.8 MPa, 1.9 The pressure can be as follows: MPa, 2.0 MPa, 2.1 MPa, 2.2 MPa, 2.3 MPa, 2.4 MPa or 2.5 MPa, and the residence time can be 40 min, 41 min, 42 min, 43 min, 44 min, 45 min, 46 min, 47 min, 48 min, 49 min, 50 min, 51 min, 52 min, 53 min, 54 min, 55 min, 56 min, 57 min, 58 min, 59 min or 60 min, but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are equally applicable.

[0025] Preferably, the intermediate 1 and the sulfonated reagent are preheated and introduced into a microchannel reactor for reaction, the reaction temperature is 60-65°C, the pressure is 1.5-2.5 MPa, and the residence time is 30-45 min; more preferably, the reaction temperature can be 60°C, 61°C, 62°C, 63°C, 64°C or 65°C, the reaction pressure can be 1.5 MPa, 1.6 MPa, 1.7 MPa, 1.8 MPa, 1.9 MPa, 2.0 MPa, 2.1 MPa, 2.2 MPa, 2.3 MPa, 2.4 MPa or 2.5 MPa, and the residence time can be 30 min, 31 min, 32 min, 33 min, 34 min, 35 min, 36 min, 37 min, 38 min, 39 min, 40 min, 41 min, 42 min, 43 min, 44 min or 45 min, but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0026] Specifically, the molar ratio of the bile acid, N,N-dimethyl-1,3-diaminopropane and the sulfonation reagent is 1:(1.05-1.10):(1.05-1.10).

[0027] Compared with the prior art, the present invention provides a method for preparing propane sulfonate, which has the following beneficial effects: no highly toxic and sensitizing reagents are used, and the safety factor is high; a fixed bed device loaded with a solid superacid is used to catalyze the direct condensation of bile acid and amine, thereby simplifying the reaction steps, reducing the amount of amine used, and achieving high material atom utilization; a microchannel fixed bed reaction device is used, and the mass transfer and heat transfer efficiency is high, the residence time is short, the reaction temperature is stable, the obtained product has high purity, and the post-reaction treatment is simple.

[0028] Figure content

[0029] Attached Figure 1 This is a simple schematic diagram of a microchannel fixed bed reaction device according to Example 1 of the present invention;

[0030] Attached Figure 2 This is a simple schematic diagram of a microchannel fixed bed reaction device according to Example 4 of the present invention;

[0031] Attached Figure 3 This is a simple schematic diagram of a microchannel fixed bed reaction device according to Example 5 of the present invention;

[0032] Attached Figure 4 This is a simple schematic diagram of a microchannel fixed bed reaction device according to Example 6 of the present invention;

[0033] Attached Figure 5 This is a simple schematic diagram of a microchannel fixed bed reaction device according to Example 8 of the present invention;

[0034] Among them: 1. Heat exchanger; 2. Fixed bed reactor; 3. Microchannel module; 4. Delay device. DETAILED DESCRIPTION

[0035] In order to further explain the technical means and effects adopted by the present invention, the technical solution of the present invention is further described below in conjunction with the preferred embodiments of the present invention, but the present invention is not limited to the scope of the embodiments.

[0036] Example 1

[0037] The present embodiment provides a method for preparing propane sulfonate. The microchannel fixed bed reaction device includes a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor, which are arranged in sequence. The microchannel reactor includes a microchannel module 3, a microchannel module 3, a delay 4, a delay 4, and a delay 4, which are arranged in series in sequence.

[0038] The specific steps are as follows:

[0039] Cholic acid and N,N-dimethyl-1,3-diaminopropane were respectively prepared into corresponding tetrahydrofuran solutions and preheated to 60° C. Cholic acid tetrahydrofuran solution (0.735 mol / L) and N,N-dimethyl-1,3-diaminopropane tetrahydrofuran solution (0.771 mol / L) were respectively introduced into fixed bed reactor 2 through metering pumps at flow rates of 10 mL / min and 9.8 mL / min for condensation reaction. The reaction temperature was 100° C., the pressure was 2 MPa, and the residence time was 40 min to obtain a tetrahydrofuran solution of intermediate 1. Then, the tetrahydrofuran solution of intermediate 1 and the tetrahydrofuran solution of propane sultone (0.386 mol / L) were preheated to 60°C and introduced into a microchannel reactor for reaction, wherein the flow rate of the tetrahydrofuran solution of propane sultone was 9.9 mL / min, the reaction temperature was 60°C, the pressure was 2 MPa, the reaction residence time was 30 min, and finally bile acid was completely converted. The reaction solution was decompressed and desolventized to obtain 412.4 g of crude product, ethanol was added and heated to dissolve, crystallized at 5°C for 2 h, filtered and dried to obtain 388 g of white crystalline powder, i.e. Yield: 86%, purity: 99.5%.

[0040] Example 2

[0041] This example provides a method for preparing propane sulfonate, which is basically the same as Example 1, except that the fixed bed reactor is loaded with a solid acid catalyst polystyrene sulfonic acid resin, and finally 379g of white crystalline powder is obtained, i.e. Yield: 84%, purity: 99.3%.

[0042] Example 3

[0043] This example provides a method for preparing propanesulfonate, which is basically the same as Example 1, except that the fixed bed reactor is loaded with a solid acid catalyst ZrPO, and finally 401.5 g of white crystalline powder is obtained, namely Yield: 89%, purity: 99.6%.

[0044] Example 4

[0045] This embodiment provides a method for preparing propane sulfonate, which is basically the same as that of Embodiment 1, except that the microchannel fixed bed reaction device comprises a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor arranged in sequence, and the microchannel reactor comprises a microchannel module 3, a microchannel module 3, a delay 4, a delay 4, a delay 4, and a delay 4 arranged in series in sequence, and finally 415 g of white crystalline powder is obtained, that is, Yield: 92%, purity: 99.6%.

[0046] Example 5

[0047] This embodiment provides a method for preparing propane sulfonate, which is basically the same as that of Embodiment 1, except that the microchannel fixed bed reaction device comprises a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor arranged in sequence, and the microchannel reactor comprises a microchannel module 3, a delay device 4, a delay device 4, a microchannel module 3, a delay device 4, and a delay device 4 arranged in series in sequence, and finally 424 g of white crystalline powder is obtained, that is, Yield: 94%, purity: 99.6%.

[0048] Example 6

[0049] This embodiment provides a method for preparing propane sulfonate, which is basically the same as Example 1, except that the microchannel fixed bed reaction apparatus comprises a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor arranged in sequence, and the microchannel reactor comprises a microchannel module 3, a microchannel module 3, a delay 4, a delay 4, a delay 4, a delay 4, a delay 4, a delay 4, and a delay 4 arranged in series in sequence, and finally 379g of white crystalline powder is obtained, that is, Yield: 84%, purity: 99.6%.

[0050] Example 7

[0051] The present embodiment provides a method for preparing propane sulfonate. The microchannel fixed bed reaction device includes a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor, which are arranged in sequence. The microchannel reactor includes a microchannel module 3, a microchannel module 3, a delay 4, a delay 4, and a delay 4, which are arranged in series in sequence.

[0052] The specific steps are as follows:

[0053] Cholic acid and N,N-dimethyl-1,3-diaminopropane were respectively prepared into corresponding tetrahydrofuran solutions and preheated to 60° C. Cholic acid tetrahydrofuran solution (0.735 mol / L) and N,N-dimethyl-1,3-diaminopropane tetrahydrofuran solution (0.771 mol / L) were respectively introduced into a fixed bed reactor through metering pumps at flow rates of 10 mL / min and 9.8 mL / min for condensation reaction. The reaction temperature was 105° C., the pressure was 2 MPa, and the residence time was 60 min to obtain a tetrahydrofuran solution of intermediate 1. Then, the tetrahydrofuran solution of intermediate 1 and the tetrahydrofuran solution of sodium 3-chloro-2-hydroxypropanesulfonate (0.386 mol / L) were preheated to 60°C and introduced into a microchannel reactor for reaction, wherein the flow rate of the tetrahydrofuran solution of sodium 3-chloro-2-hydroxypropanesulfonate was 9.9 mL / min, the reaction temperature was 60°C, the pressure was 2 MPa, the reaction residence time was 30 min, and finally bile acid was completely converted. The reaction solution was decompressed and desolventized to obtain 409.5 g of crude product, ethanol was added and heated to dissolve, crystallized at 5°C for 2 h, filtered and dried to obtain 383 g of white crystalline powder, i.e. Yield: 83%, purity: 99.4%.

[0054] Example 8

[0055] This embodiment provides a method for preparing propane sulfonate, which is basically the same as Example 7, except that the microchannel fixed bed reaction device includes a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor arranged in sequence, and the microchannel reactor includes a microchannel module 3, a delay device 4, a microchannel module 3, a delay device 4, a microchannel module 3, a delay device 4, and a delay device 4 arranged in series in sequence; and finally 415.3 g of white crystalline powder is obtained, that is, Yield: 90%, purity: 99.4%.

[0056] Example 9

[0057] The present embodiment provides a method for preparing propane sulfonate. The microchannel fixed bed reaction device includes a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor, which are arranged in sequence. The microchannel reactor includes a microchannel module 3, a microchannel module 3, a delay 4, a delay 4, and a delay 4, which are arranged in series in sequence.

[0058] The specific steps are as follows:

[0059] Cholic acid and N,N-dimethyl-1,3-diaminopropane were respectively prepared into corresponding tetrahydrofuran solutions and preheated to 60°C. The tetrahydrofuran solution of cholic acid (0.735 mol / L) and the tetrahydrofuran solution of N,N-dimethyl-1,3-diaminopropane (0.771 mol / L) were respectively introduced into the fixed bed reactor through metering pumps at flow rates of 10 mL / min and 9.8 mL / min for condensation reaction. The reaction temperature was 100°C, the pressure was 2 MPa, and the residence time was 50 min to obtain a tetrahydrofuran solution of intermediate 1. Then, the tetrahydrofuran solution of intermediate 1, The tetrahydrofuran solution (0.386 mol / L) was preheated to 60°C and introduced into the microchannel reactor for reaction. The flow rate of tetrahydrofuran solution was 9.9 mL / min, the reaction temperature was 60°C, the pressure was 2 MPa, the residence time was 30 min, and finally bile acid was completely converted. The reaction solution was decompressed and desolventized to obtain 424 g of crude product, ethanol was added to heat and dissolve, crystallized at 5°C for 2 h, filtered and dried to obtain 396 g of white crystalline powder, i.e. Yield: 82%, purity: 99.4%.

[0060] Example 10

[0061] The present embodiment provides a method for preparing propane sulfonate. The microchannel fixed bed reaction device includes a preheater 1, a fixed bed reactor 2 loaded with a solid acid catalyst AlPO, and a microchannel reactor, which are arranged in sequence. The microchannel reactor includes a microchannel module 3, a microchannel module 3, a delay 4, a delay 4, and a delay 4, which are arranged in series in sequence.

[0062] The specific steps are as follows:

[0063] Cholic acid and N,N-dimethyl-1,3-diaminopropane were respectively prepared into corresponding tetrahydrofuran solutions and preheated to 65°C. The tetrahydrofuran solution of cholic acid (0.735 mol / L) and the tetrahydrofuran solution of N,N-dimethyl-1,3-diaminopropane (0.771 mol / L) were respectively introduced into the fixed bed reactor through metering pumps at flow rates of 10 mL / min and 9.8 mL / min for condensation reaction. The reaction temperature was 100°C, the pressure was 2 MPa, and the residence time was 55 min to obtain a tetrahydrofuran solution of intermediate 1. Then, the tetrahydrofuran solution of intermediate 1, The tetrahydrofuran solution (0.386 mol / L) was preheated to 60°C and introduced into the microchannel reactor for reaction. The flow rate of tetrahydrofuran solution was 9.9 mL / min, the reaction temperature was 60°C, the pressure was 2 MPa, the reaction residence time was 30 min, and finally bile acid was completely converted. The reaction solution was decompressed and desolventized to obtain 418 g of crude product, ethanol was added to heat and dissolve, crystallized at 5°C for 2 h, filtered and dried to obtain 392 g of white crystalline powder, i.e. Yield: 85%, purity: 99.6%.

[0064] The applicant declares that the present invention illustrates the preparation method of a propane sulfonate salt of the present invention through the above-mentioned embodiment, but the present invention is not limited to the above-mentioned embodiment, that is, it does not mean that the present invention must rely on the above-mentioned embodiment 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.

[0065] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0066] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A method for preparing a sulfonate, characterized in that: Using a microchannel fixed bed reaction device, cholic acid and N,N-dimethyl-1,3-diaminopropane are subjected to a condensation reaction under the action of a catalyst to obtain an intermediate 1, which is then reacted with a sulfonating agent to obtain the sulfonate; Wherein, X is H or a hydroxyalkyl group, and the number of carbon atoms in the hydroxyalkyl group is not greater than 10.

2. The preparation method according to claim 1, characterized in that: The catalyst is a solid catalyst, including one or more of AlPO, TiPO, ZrPO, NbPO, polystyrene sulfonic acid resin, and perfluorosulfonic acid resin.

3. The preparation method according to claim 1, characterized in that: The sulfonating agent is selected from sultone, At least one of, wherein X is Cl, Br or I, m=2-10, and R is one of hydroxyl, -CH2OH, and -C2H5OH; Preferably, the sulfonating agent is propane sultone, cyclohexane sultone, cyclopentane sultone, One of them.

4. The preparation method according to claim 1, characterized in that: The microchannel fixed bed reaction device comprises a preheater, a fixed bed reactor and a microchannel reactor which are arranged in sequence. The microchannel reactor comprises a plurality of microchannel modules, a preheater and a delay device which are arranged in sequence and connected in series.

5. The preparation method according to claim 4, characterized in that: The number of the microchannel modules is 1-5, and the number of the delay devices is 1-6.

6. The preparation method according to claim 5, characterized in that: The number of the microchannel modules ranges from 2 to 3, and the number of the delay devices ranges from 3 to 5.

7. The preparation method according to claim 4, characterized in that: Cholic acid and N,N-dimethyl-1,3-diaminopropane are respectively prepared into corresponding tetrahydrofuran solutions and preheated at a temperature of 55 to 65°C.

8. The preparation method according to claim 5, characterized in that: The preheated tetrahydrofuran solution of bile acid and the tetrahydrofuran solution of N,N-dimethyl-1,3-diaminopropane are respectively introduced into the fixed bed reactor to carry out condensation reaction to obtain intermediate 1. The reaction temperature is 95-105° C., the pressure is 1.5-2.5 MPa, and the residence time is 40-60 min.

9. The preparation method according to claim 4, characterized in that: The intermediate 1 and the sulfonation reagent are preheated separately and introduced into a microchannel reactor for reaction at a reaction temperature of 60 to 65° C., a pressure of 1.5 to 2.5 MPa, and a residence time of 30 to 45 min.

10. The preparation method according to claim 1, characterized in that: The molar ratio of the bile acid, N,N-dimethyl-1,3-diaminopropane and the sulfonation reagent is 1:(1.05-1.10):(1.05-1.10).

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