Preparation method of sodium picosulfate

Abstract

The invention discloses a preparation method of sodium picosulfate, and relates to the technical field of medicine preparation. The preparation method of the sodium picosulfate comprises the following steps: by taking 2, 6-dichlorophenol and 2-pyridylaldehyde as raw materials, carrying out condensation reaction under the action of strong acid, carrying out dechlorination reduction by using Ni / Al-SiO2 to obtain 4, 4-(2-pyridylmethylene)-phenol, and carrying out sulfation on the 4, 4-(2-pyridylmethylene)-phenol and chlorosulfonic acid to obtain the sodium picosulfate. The Ni / Al-SiO2 nano litchi-shaped structure adopted by the invention has large specific surface area and surface activity, Ni, Al and SiO2 have excellent catalytic effect on dechlorination and hydrogenation of benzene rings, chlorinated impurities can be effectively reduced, and the purpose of improving the yield of sodium picosulfate is achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparation, and specifically relates to a preparation method of sodium picosulfate. Background Art

[0002] Sodium picosulfate, chemically named sodium 4,4'-(pyridine-2-ylmethylene) bis(phenolate) disulfate, is a constipation treatment drug developed by DeAngeli Company in Italy. Its efficacy is mainly based on being decomposed by colonic microbial sulfatase into active bisphenol metabolites, promoting intestinal peristalsis and inhibiting water absorption in the intestine, producing a mild laxative effect, and can be used for various constipation, postoperative adjuvant defecation, promoting defecation after administration of contrast agents, and excluding intestinal contents before surgery, etc.

[0003] The Chinese patent application with the publication number CN 112851574A discloses that using phenol and 2-pyridinecarboxaldehyde as raw materials, a condensation reaction is carried out under the action of strong acid to obtain 4,4'-(pyridin-2-yl-methylene) bisphenol, and then the target product is obtained through esterification and salification reactions. This route uses phenol as the starting material, and is prone to generating isomeric impurities: 2-[(4-hydroxyphenyl)-2-pyridylmethyl] phenol and 2,2'-(2-pyridylmethylene) diphenol, and the separation and purification are difficult, resulting in a low yield of the target product.

[0004] The US patent application with the publication number US3558643A discloses that using 2,6-dichlorophenol (bromide) and 2-pyridinecarboxaldehyde as raw materials, a condensation reaction is also carried out under the action of strong acid, followed by sulfuric acid esterification with chlorosulfonic acid, and then dechlorination reduction is carried out using nickel-aluminum alloy to obtain sodium picosulfate. However, when carrying out sulfuric acid esterification with chlorosulfonic acid, there are halogen atoms at both ortho positions of the hydroxyl group. Due to the influence of steric hindrance effect, the reaction temperature is relatively high, and subsequent dechlorination reduction using nickel-aluminum alloy is required, resulting in a low yield. Summary of the Invention

[0005] Aiming at the deficiencies existing in the prior art, the purpose of the present invention is to provide a preparation method of sodium picosulfate.

[0006] To achieve the above purpose, the present invention is realized through the following technical solutions:

[0007] A preparation method of sodium picosulfate, using 2,6-dichlorophenol and 2-pyridinecarboxaldehyde as raw materials, carrying out a condensation reaction under the action of strong acid, using Ni / Al-SiO2 for dechlorination reduction to obtain 4,4-(2-pyridylmethylene)-phenol, then carrying out sulfuric acid esterification with chlorosulfonic acid to obtain a crude product, and obtaining sodium picosulfate through recrystallization; the Ni / Al-SiO2 is prepared by the following method:

[0008] S1: Heat the triethanolamine aqueous solution to 70 - 90 °C, and successively add polyvinylpyrrolidone, sodium dodecyl sulfate, and tetraethoxysilane, stir, add NaA1O2, increase the pressure to 0.1 - 0.3 MPa, react for 4 - 6 h, and obtain Al - SiO2 through post - treatment and calcination;

[0009] S2: Mix nickel nitrate, Al - SiO2, and deionized water evenly, add hydrazine hydrate, heat to 60 - 100 °C, react for 2 - 5 h, and obtain Ni / Al - SiO2 through post - treatment.

[0010] In the step S1, the molar ratio of triethanolamine, polyvinylpyrrolidone, sodium dodecyl sulfate, tetraethoxysilane, and NaA1O2 is 1:(2 - 3):(2.5 - 3.2):20:(1 - 2).

[0011] In the step S2, the mass ratio of nickel nitrate, Al - SiO2, and hydrazine hydrate is 1:(8 - 12):(1.44 - 2).

[0012] A preparation method of sodium picosulfate, comprising the following steps:

[0013] S1: Under ice - bath, drop concentrated sulfuric acid into the DMF solution of 2,6 - dichlorophenol, drop in 2 - pyridinecarboxaldehyde, react for 1 - 2 h, raise the temperature to 30 - 40 °C and react for 6 - 18 h, and obtain intermediate 1 through post - treatment; the reaction equation is shown as follows:

[0014]

[0015] S2: Mix intermediate 1 with sodium hydroxide solution evenly, add Ni / Al - SiO2 at room temperature and react for 12 - 24 h, and obtain intermediate 2 through post - treatment; the reaction equation is shown as follows:

[0016]

[0017] S3: Mix pyridine, intermediate 2, and chlorosulfonic acid evenly, heat to 40 - 60 °C and react for 10 - 15 h, and obtain the crude product; the reaction equation is shown as follows:

[0018]

[0019] S4: Mix water, alcohol solution, and the crude product evenly, heat to reflux, and recrystallize to obtain sodium picosulfate.

[0020] In the step S1, the mass ratio of 2,6 - dichlorophenol, concentrated sulfuric acid, and 2 - pyridinecarboxaldehyde is (3 - 4.5):(3 - 5):1.

[0021] In the step S2, the concentration of the sodium hydroxide solution is 15 - 30 wt%.

[0022] In the step S2, the mass ratio of the intermediate 1 to Ni / Al-SiO2 in the feed is 1:(0.02 - 0.2).

[0023] In the step S3, the molar ratio of the intermediate 2 to chlorosulfonic acid in the feed is 1:(2.1 - 3).

[0024] In the step S4, the alcohol solution is one of methanol, ethanol, and isopropyl alcohol.

[0025] In the step S4, the mass ratio of water, alcohol solvent, and sodium picosulfate in the feed is 1:9:(4 - 6).

[0026] Due to the above technical solutions, the beneficial effects of the present invention include:

[0027] (1) The nano-litchi-like structure of Ni / Al-SiO2 adopted in the present invention has a large specific surface area and surface activity. Ni, Al, and SiO2 have excellent catalytic effects on the dechlorination and hydrogenation of the benzene ring, effectively reducing the impurity of chlorinated substances and achieving the purpose of improving the yield of intermediate 2.

[0028] (2) The starting material 2,6-dichlorophenol adopted in the present invention has a wide source, sufficient market supply, and is cheap and easy to obtain; and it can reduce the generation of isomer impurities and improve the yield of sodium picosulfate. Description of the Drawings

[0029] Figure 1 It is the TEM image of Ni / Al-SiO2 prepared in Example 2. Detailed Embodiments

[0030] The following is further illustrated in conjunction with embodiments, but the present invention is not limited to these embodiments.

[0031] Preparation of Ni / Al-SiO2 in Example 1:

[0032] S1: Stir 1 mol of triethanolamine and 1000 ml of deionized water, heat up to 70 °C, and sequentially add 2 mol of polyvinylpyrrolidone, 2.5 mol of sodium dodecyl sulfate, and 20 mol of tetraethoxysilane and stir for 2 h. Then add 1 mol of NaA1O2, increase the pressure to 0.1 MPa, react for 6 h, filter, wash with deionized water twice (500 ml each time), and vacuum dry at 70 °C for 10 h. The obtained solid is calcined at 550 °C for 6 hours to obtain Al-SiO2;

[0033] S2: Mix 100 g of nickel nitrate, 800 g of Al-SiO2, and 2400 ml of deionized water evenly. Add 144 g of hydrazine hydrate, heat up to 60 °C, react for 5 h, filter, wash with deionized water twice (500 ml each time), wash with 500 ml of acetone, and dry at 60 °C for 5 h to obtain Ni / Al-SiO2.

[0034] Preparation of Ni / Al-SiO2 in Example 2:

[0035] S1: Stir 1 mol of triethanolamine and 1000 ml of deionized water, heat up to 80 °C, successively add 2.4 mol of polyvinylpyrrolidone, 3 mol of sodium dodecyl sulfate, and 20 mol of tetraethoxysilane, stir for 2 h, add 1.6 mol of NaA1O2, increase the pressure to 0.2 MPa, react for 5 h, filter, wash with deionized water twice (500 ml each time), dry under vacuum at 70 °C for 10 h, and calcine the obtained solid at 550 °C for 6 hours to obtain Al-SiO2;

[0036] S2: Mix 100 g of nickel nitrate, 1000 g of Al-SiO2, and 2500 ml of deionized water evenly. Add 180 g of hydrazine hydrate, heat up to 80 °C, react for 3 h, filter, wash with deionized water twice (500 ml each time), wash with 500 ml of acetone, and dry at 60 °C for 5 h to obtain Ni / Al-SiO2.

[0037] Preparation of Ni / Al-SiO2 in Example 3:

[0038] S1: Stir 1 mol of triethanolamine and 1000 ml of deionized water, heat up to 90 °C, successively add 3 mol of polyvinylpyrrolidone, 3.2 mol of sodium dodecyl sulfate, and 20 mol of tetraethoxysilane, stir for 2 h, add 2 mol of NaA1O2, increase the pressure to 0.3 MPa, react for 4 h, filter, wash with deionized water twice (500 ml each time), dry under vacuum at 70 °C for 10 h, and calcine the obtained solid at 550 °C for 6 hours to obtain Al-SiO2;

[0039] S2: Mix 100 g of nickel nitrate, 1200 g of Al-SiO2, and 3000 ml of deionized water evenly. Add 200 g of hydrazine hydrate, heat up to 100 °C, react for 2 h, filter, wash with deionized water twice (500 ml each time), wash with 500 ml of acetone, and dry at 60 °C for 5 h to obtain Ni / Al-SiO2.

[0040] Preparation of sodium picosulfate in Example 4:

[0041] S1: Under an ice bath, add 1000 ml of DMF and 300 g of 2,6-dichlorophenol to a reaction flask and stir. Slowly add 280 g of concentrated sulfuric acid dropwise. The addition is completed in 30 min. Then add 100 g of 2-pyridinecarboxaldehyde dropwise. The addition is completed in 30 min and the reaction proceeds for 1 h. The temperature is raised to 30 °C and the reaction proceeds for 18 h. Cool to 0 °C and add 5 M NaOH solution dropwise to adjust the pH to 8. Stir for 30 min, then filter by suction. Wash the filter cake with 100 ml of deionized water and dry it under vacuum at 70 °C for 10 h to obtain Intermediate 1, with a mass of 353.66 g, a yield of 91.2%, and a liquid-phase purity of 99.84%. The 1H NMR data are as follows: 1 HNMR(500MHz,Chloroform-d)δ8.60(dd,J=4.5,1.7Hz,1H),7.78(td,J=7.2,1.7Hz,1H),7.62(ddd,J=7.1,4.4,1.3Hz,1H),7.45-7.37(m,5H),6.06-6.02(m,1H),5.37(s,2H).

[0042] S2: Dissolve 100 g of Intermediate 1 in 600 ml of 15 wt% sodium hydroxide solution, add 2 g of Ni / Al-SiO2 (prepared in Example 1) at room temperature, and react for 24 h. Filter. Adjust the pH of the filtrate to 7 with 10 wt% hydrochloric acid aqueous solution, then filter. Wash the filter cake with 300 ml of deionized water and dry it under vacuum at 70 °C for 10 h to obtain Intermediate 2, with a mass of 62.7 g, a yield of 93.9%, and a liquid-phase purity of 99.91%. The 1H NMR data are as follows: 1 HNMR(500MHz,Chloroform-d)δ8.60(dd,J=4.5,1.7Hz,1H),7.78(td,J=7.2,1.7Hz,1H),7.62(ddd,J=7.1,4.4,1.3Hz,1H),7.50-7.44(m,4H),7.43-7.35(m,3H),6.81-6.77(m,4H),5.75(d,J=1.0Hz,1H).;

[0043] S3: Under an ice bath, add 1000 ml of pyridine and 1 mol of Intermediate 2 to a reaction flask. Slowly add 2.1 mol of chlorosulfonic acid dropwise. The addition is completed in 30 min. Slowly raise the temperature to 40 °C and react for 15 h. Pour the reaction solution into 2000 ml of ice water, adjust the pH to 10 with 30 wt% sodium hydroxide solution, wash with 500 ml of dichloromethane. Distill the aqueous phase under reduced pressure at 60 °C for 2 h. Add 1200 ml of ethanol dropwise to the residue and stir to crystallize. Filter by suction. Wash the filter cake with 500 ml of ethanol and dry at 60 °C for 6 h to obtain 435.0 g of crude picrosulfate sodium, with a yield of 87.10%.

[0044] S4: Add 40 g of the crude product, 10 g of water, and 90 g of methanol into a reaction flask, stir, heat up to reflux until clear, keep warm for 0.5 h, cool down to 0 °C for crystallization for 2 h, filter, and wash with 50 ml of methanol to obtain 34.08 g of sodium picosulfate, with a yield of 85.20% and a liquid phase purity of 99.95%.

[0045] Preparation of sodium picosulfate in Example 5:

[0046] S1: Under ice bath, add 1000 ml of DMF and 400 g of 2,6-dichlorophenol into a reaction flask, stir, slowly dropwise add 420 g of concentrated sulfuric acid, finish dropping in 30 min, dropwise add 100 g of 2-pyridinecarboxaldehyde, finish dropping in 30 min, react for 1.5 h, raise the temperature to 35 °C and react for 15 h, cool down to 0 °C, dropwise add 5M NaOH solution to adjust the pH = 8, stir for 30 min, filter by suction, wash the filter cake with 100 ml of deionized water, and dry in vacuum at 70 °C for 10 h to obtain Intermediate 1, with a mass of 369.2 g, a yield of 95.2%, and a liquid phase purity of 99.90%;

[0047] S2: Dissolve 100 g of Intermediate 1 in 600 ml of 25 wt% sodium hydroxide solution, add 15 g of Ni / Al-SiO2 (prepared in Example 2) at room temperature and react for 18 h, filter, adjust the pH of the filtrate to 7 with 10 wt% hydrochloric acid aqueous solution, filter, wash the filter cake with 300 ml of deionized water, and dry in vacuum at 70 °C for 10 h to obtain Intermediate 2, 64.7 g, with a yield of 96.8% and a liquid phase purity of 99.93%;

[0048] S3: Under ice bath, add 1000 ml of pyridine and 1 mol of Intermediate 2 into a reaction flask, slowly dropwise add 2.5 mol of chlorosulfonic acid, finish dropping in 30 min, slowly raise the temperature to 50 °C and react for 12 h, pour the reaction solution into 2000 ml of ice water, adjust the pH = 11 with 30 wt% sodium hydroxide solution, wash with 400 ml of dichloromethane, distill the aqueous phase under reduced pressure at 60 °C for 2 h, add 1200 ml of ethanol dropwise to the residue and stir for crystallization, filter by suction, wash the filter cake with 500 ml of ethanol, and dry at 60 °C for 6 h to obtain 444.0 g of crude sodium picosulfate, with a yield of 88.90%;

[0049] S4: Add 50 g of the crude product, 10 g of water, and 90 g of ethanol into a reaction flask, stir, heat up to reflux until clear, keep warm for 0.5 h, cool down to 0 °C for crystallization for 3 h, filter, and wash with 50 ml of ethanol to obtain 45.05 g of sodium picosulfate, with a yield of 90.1% and a liquid phase purity of 99.94%.

[0050] Preparation of sodium picosulfate in Example 6:

[0051] S1: Under an ice bath, add 1000 ml of DMF and 450 g of 2,6-dichlorophenol to a reaction flask and stir. Slowly add dropwise 500 g of concentrated sulfuric acid. The addition is completed in 30 min. Then add dropwise 100 g of 2-pyridinecarboxaldehyde. The addition is completed in 30 min. React for 2 h, raise the temperature to 40 °C and react for 6 h. Cool to 0 °C, add dropwise 5 M NaOH solution to adjust the pH to 8, stir for 30 min, filter by suction. Wash the filter cake with 100 ml of deionized water and dry it under vacuum at 70 °C for 10 h to obtain 364.9 g of Intermediate 1, with a yield of 94.1% and a liquid phase purity of 99.89%;

[0052] S2: Dissolve 100 g of Intermediate 1 in 600 ml of 30 wt% sodium hydroxide solution, add 20 g of Ni / Al-SiO2 (prepared in Example 3) at room temperature and react for 12 h. Filter. Adjust the pH of the filtrate to 7 with 10 wt% hydrochloric acid aqueous solution, filter. Wash the filter cake with 300 ml of deionized water and dry it under vacuum at 70 °C for 10 h to obtain 63.2 g of Intermediate 2, with a yield of 94.6% and a liquid phase purity of 99.90%;

[0053] S3: Under an ice bath, add 1000 ml of pyridine and 1 mol of Intermediate 2 to a reaction flask. Slowly add dropwise 3 mol of chlorosulfonic acid. The addition is completed in 30 min. Slowly raise the temperature to 60 °C and react for 10 h. Pour the reaction solution into 2000 ml of ice water, adjust the pH to 11 with 30 wt% sodium hydroxide solution, wash with 500 ml of dichloromethane. Distill the aqueous phase under reduced pressure at 60 °C for 2 h. Add dropwise 1200 ml of ethanol to the residue and stir for crystallization. Filter by suction. Wash the filter cake with 500 ml of ethanol and dry it at 60 °C for 6 h to obtain 427.5 g of crude sodium picosulfate, with a yield of 85.60%;

[0054] S4: Add 60 g of the crude product, 10 g of water and 90 g of isopropanol to a reaction flask and stir. Heat up to reflux until clear, keep warm for 0.5 - 1 h, cool down to 5 °C and crystallize for 3 h. Filter, and wash with 50 ml of isopropanol to obtain 52.02 g of sodium picosulfate, with a yield of 86.70% and a liquid phase purity of 99.92%.

[0055] Comparative Example 1

[0056] The preparation method of Intermediate 2 is basically the same as that in Example 5, except that the Ni / Al-SiO2 (prepared in Example 2) in Step S2 is replaced with a nickel catalyst prepared by the following method:

[0057] Mix 100 g of nickel nitrate and 2000 ml of deionized water evenly, add 180 g of hydrazine hydrate, raise the temperature to 80 °C and react for 3 h. Filter, wash with deionized water twice (500 ml each time), wash with 500 ml of acetone and dry at 60 °C for 5 h to obtain the nickel catalyst.

[0058] 40.5 g of intermediate was obtained with a yield of 60.6% and a liquid-phase purity of 99.78%.

[0059] Comparative Example 2

[0060] The preparation method of Intermediate 2 was basically the same as that of Example 5, except that the Ni / Al-SiO2 (prepared in Example 2) in Step S2 was replaced with a Ni / SiO2 catalyst prepared by the following method:

[0061] 1 mol of triethanolamine and 1000 ml of deionized water were stirred and heated to 80 °C. Then, 1.8 mol of polyvinylpyrrolidone, 3 mol of sodium dodecyl sulfate, and 20 mol of tetraethoxysilane were added successively and stirred for 2 h. 1.6 mol of nickel nitrate was added, the pressure was raised to 0.2 MPa, and the reaction was carried out for 5 h. After filtration, it was washed twice with deionized water (500 ml each time), dried in vacuum at 70 °C for 10 h. The obtained solid was calcined in a hydrogen atmosphere at 550 °C for 6 h to obtain the Ni-SiO2 catalyst.

[0062] 52.7 g of intermediate was obtained with a yield of 78.9% and a liquid-phase purity of 99.87%.

[0063] Comparative Example 3

[0064] The preparation method of Intermediate 2 was basically the same as that of Example 5, except that the Ni / Al-SiO2 (prepared in Example 2) in Step S1 was replaced with a Ni / Al-SiO2 catalyst prepared by the following method:

[0065] S1: 1 mol of triethanolamine and 1000 ml of deionized water were stirred and heated to 80 °C. Then, 1.8 mol of polyvinylpyrrolidone, 3 mol of sodium dodecyl sulfate, and 20 mol of tetraethoxysilane were added successively and stirred for 2 h. 1.6 mol of NaA1O2 was added, the pressure was raised to 0.2 MPa, and the reaction was carried out for 5 h. After filtration, it was washed twice with deionized water (500 ml each time), dried in vacuum at 70 °C for 10 h. The obtained solid was calcined at 550 °C for 6 h to obtain Al-SiO2;

[0066] S2: 100 g of nickel nitrate, 1000 g of Al-SiO2, and 2000 ml of deionized water were mixed evenly and stirred for 12 h. The water was evaporated by heating to 80 °C. The obtained solid was calcined at 500 °C for 3 h and then reduced at 500 °C in a hydrogen atmosphere for 2 h to obtain the Ni / Al-SiO2 catalyst.

[0067] 57.3 g of intermediate was obtained with a yield of 85.8% and a liquid-phase purity of 99.91%.

[0068] In the examples and comparative examples of this application, the polyvinylpyrrolidone used had a Mw of 360,000. The hydrazine hydrate used in the examples and comparative examples of this application was an aqueous solution of 40 wt%, and the ethanol was absolute ethanol.

[0069] As can be seen from Examples 4, 5, and 6, the method for preparing sodium picosulfate of the present invention has a high yield. The reason is that: for the Ni / Al-SiO2 prepared in the present invention to adsorb the reaction substrate, the synergistic effect of nickel and aluminum can change the electronic structure on the catalyst surface, thereby enhancing the adsorption capacity for the substrate; nickel, as the main active center, can activate hydrogen molecules, dissociating them into active hydrogen atoms (H*), and the activated hydrogen atoms react with the molecules adsorbed on the catalyst surface, gradually replacing the chlorine atoms with hydrogen atoms. After the chlorine atoms are substituted, the active sites of nickel provide electrons or stabilize the transition state, and the generated chloride ions are removed from the catalyst surface.

[0070] During the preparation of Ni / Al-SiO2, through the action of auxiliary agents such as triethanolamine, polyvinylpyrrolidone, and sodium dodecyl sulfate, tetraethoxysilane and NaAlO2 fully react to form an Al-SiO2 support. Subsequently, nickel is loaded on this support, enabling nickel to be dispersed on the support in the form of nanoparticles with relatively high activity. This structure is conducive to improving the activity and stability of the catalyst. The interaction between nickel particles and the support can prevent the nickel particles from aggregating during the reaction, thereby maintaining a relatively high catalytic activity. The nano-lychee-like structure has a large specific surface area and surface activity, which can effectively improve the reaction efficiency.

[0071] Comparative Example 1 is a comparative example different from Example 5. The difference is that the nickel catalyst used in Comparative Example 1 was directly prepared by reacting nickel nitrate with hydrazine hydrate without the support of a carrier. The nickel particles may aggregate during the reaction, resulting in a reduction in active sites and relatively low catalytic activity. In addition, lacking the protection of the carrier, the nickel particles are more likely to sinter and deactivate during high-temperature or long-term reactions, and the stability is poor.

[0072] The Ni / SiO2 catalyst used in Comparative Example 2 uses SiO2 as the carrier, and nickel is loaded on SiO2 through a similar preparation method, which can provide a certain dispersing effect for the nickel particles, thereby improving the activity and stability of the catalyst.

[0073] In Comparative Example 3, the Ni / Al-SiO2 catalyst was synthesized by impregnation during the preparation process, and then the Ni / Al-SiO2 catalyst was synthesized by calcination and reduction. For the catalyst synthesized by this method, the nickel specific surface area is small, the active sites are small, and the driving force for the catalytic reaction is less than that of the catalysts prepared in Examples 1-3 of this application.

[0074] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. However, for those of ordinary skill in the art, within the scope of the technical solution of the present invention, any equivalent changes made by using the technical content disclosed above, such as slight modifications, refinements, and evolutions, are all equivalent embodiments of the present invention. At the same time, any equivalent changes, modifications, and evolutions made to the above embodiments based on the essential technology of the present invention still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A preparation method of sodium picosulfate, characterized in that: Using 2,6-dichlorophenol and 2-pyridinecarboxaldehyde as raw materials, a condensation reaction is carried out, and Ni / Al-SiO2 is used for hydrodechlorination to obtain 4,4-(2-pyridylmethylene)-phenol, which is then subjected to sulfuric acid esterification with chlorosulfonic acid to obtain sodium picosulfate; The Ni / Al-SiO2 is prepared by the following method: S1: Heat the aqueous triethanolamine solution to 70-90 °C, successively add polyvinylpyrrolidone, sodium dodecyl sulfate, tetraethoxysilane and stir, add NaA1O2, increase the pressure to 0.1-0.3 MPa, react for 4-6 h, and obtain Al-SiO2 after post-treatment and calcination; S2: Mix nickel nitrate, Al-SiO2 and deionized water evenly, add hydrazine hydrate, heat to 60-100 °C, react for 2-5 h, and obtain Ni / Al-SiO2 after post-treatment.

2. The preparation method of sodium picosulfate according to claim 1, characterized in that, In the step S1, the molar ratio of triethanolamine, polyvinylpyrrolidone, sodium dodecyl sulfate, tetraethoxysilane, and NaA1O2 is 1:(2-3):(2.5-3.2):20:(1-2).

3. The preparation method of sodium picosulfate according to claim 1, characterized in that, In the step S2, the mass ratio of nickel nitrate, Al-SiO2 and hydrazine hydrate is 1:(8-12):(1.44-2).

4. The preparation method of sodium picosulfate according to claim 1, wherein, It includes the following steps: S1: Under ice bath, drop concentrated sulfuric acid into the DMF solution of 2,6-dichlorophenol, drop 2-pyridinecarboxaldehyde, react for 1-2 h, raise the temperature to 30-40 °C and react for 6-18 h, and obtain intermediate 1 after post-treatment; S2: Mix intermediate 1 with sodium hydroxide solution evenly, add Ni / Al-SiO2 at room temperature and react for 12-24 h, and obtain intermediate 2 after post-treatment; S3: Mix pyridine, intermediate 2 and chlorosulfonic acid evenly, heat to 40-60 °C and react for 10-15 h, and obtain the crude product after post-treatment; S4: Mix water, alcohol solution and the crude product evenly, heat to reflux, and recrystallize to obtain sodium picosulfate.

5. The preparation method of sodium picosulfate according to claim 4, characterized in that, In the step S1, the mass ratio of 2,6-dichlorophenol, concentrated sulfuric acid and 2-pyridinecarboxaldehyde is (3-4.5):(2.8-5):

1.

6. The preparation method of sodium picosulfate according to claim 4, characterized in that, In the step S2, the concentration of the sodium hydroxide solution is 15-30 wt%.

7. A method for preparing sodium picosulfate according to claim 4, characterized in that, In the step S2, the mass ratio of intermediate 1 and Ni / Al-SiO2 is 1:(0.02-0.2).

8. A method for preparing sodium picosulfate according to claim 4, characterized in that, In the step S3, the molar ratio of intermediate 2 and chlorosulfonic acid is 1:(2.1-3).

9. The preparation method of sodium picosulfate according to claim 4, characterized in that, In the step S4, the alcohol solution is one of methanol, ethanol and isopropanol.

10. A method for preparing sodium picosulfate according to claim 4, characterized in that, In the step S4, the mass ratio of water, alcohol solvent and sodium picosulfate is 1:9:(4-6).

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