Method for preparing small molecule substance adsorbing resin by post-crosslinking of gel resin and application thereof

Abstract

The present application relates to the technical field of resin organic synthesis. The method for preparing small molecule substance adsorption resin by post-crosslinking gel resin comprises the following steps: (1) oil phase preparation (2) water phase preparation (3) polymerization (4) chloromethylation: adding white ball resin into a reaction container, swelling by adding chloromethyl ether, stirring to mix uniformly by adding anhydrous zinc chloride, and adding concentrated sulfuric acid drop by drop to react to obtain chloro ball resin; (5) post-crosslinking reaction: adding chloro ball into a container, swelling by adding dichloroethane, stirring to dissolve by adding anhydrous ferric chloride, and heating to react to obtain post-crosslinked resin (6) hydrolysis reaction: adding the post-crosslinked resin into sodium hydroxide solution to perform alkaline hydrolysis. The resin of the present application is prepared into gel resin without using a pore former, then the gel resin is post-crosslinked, the obtained resin has a narrower pore size, a uniform pore structure distribution, more effective pore structures capable of adsorbing small molecules, and greatly improved adsorption capacity for small molecule substances.

Description

TECHNICAL FIELD

[0001] The present application relates to a method for synthesizing resin, and belongs to the technical field of organic synthesis. BACKGROUND

[0002] Gel-type ion exchange resin is a kind of ion exchange resin, which is synthesized by condensation or polymerization of pure monomer mixture, and has a transparent homogeneous gel structure and is commonly used in water treatment. Generally, the spherical matrix is synthesized by suspension copolycondensation or copolymerization process, and then is activated by chemical reaction to introduce ion exchange groups.

[0003] The existing gel-type resin generally uses pore-forming agents to form pores, so the pore size is large and the specific surface area is small, and the obtained resin has a small adsorption capacity for small molecules. SUMMARY

[0004] The purpose of the present application is to provide a method for preparing small molecule adsorption resin by post-crosslinking of gel resin, which has a narrower pore size, a uniform pore structure distribution, more effective pore structures for adsorbing small molecules, and greatly improved adsorption capacity for small molecules.

[0005] To achieve the above purpose, the present application provides the following technical scheme:

[0006] A method for preparing small molecule adsorption resin by post-crosslinking of gel resin, comprising the following steps:

[0007] (1) Oil phase preparation: add divinylbenzene, styrene, methyl acrylate and benzoyl peroxide into a container, stir and mix uniformly to completely dissolve the benzoyl peroxide; (2) Water phase preparation: add purified water, polyvinyl alcohol and sodium chloride into a container, heat to 60℃, and stir at a speed of 100 r / min to completely dissolve the polyvinyl alcohol and sodium chloride; (3) Polymerization: add the oil phase into the water phase, slowly turn on the stirrer to 120±15 r / min after the oil phase is stable, observe the particle size of the white spherical resin, adjust the speed to make the particle size of the resin reach 0.2-1.15 mm, and stabilize the stirring speed; heat to 78℃, observe whether the resin is solidified and shaped every 10 minutes, heat to 85℃ after the resin is shaped, keep the temperature for 4 hours, heat to 90℃ after the temperature keeping is completed, keep the temperature for 2 hours, heat to 95℃ after the temperature keeping is completed, keep the temperature for 6 hours; stop heating after the temperature keeping is completed, naturally cool to below 60℃, take out the resin, wash off the dispersing agent on the surface of the resin with warm water at 45℃, and dry to obtain the white spherical resin.

[0008] Polymerization principle:

[0009] With divinyl benzene as crosslinking agent, styrene and methyl acrylate as monomer, styrene crosslinking provides a large number of benzene ring for the reaction site of chloromethyl ether in the next chlorination process; methyl acrylate polymerization and then hydrolysis provides a large number of carboxyl for the resin, improving the biocompatibility of the resin.

[0010] (4) chloromethylation: the white ball resin is added to the reaction vessel, chloromethyl ether is added to swell, after swelling, anhydrous zinc chloride is added and stirred until uniform, concentrated sulfuric acid is added dropwise, the temperature is raised to 48℃ and kept for 12 hours; the solution in the container is filtered off, anhydrous ethanol is added and stirred for 15 minutes, then anhydrous ethanol is replaced, and this operation is repeated until there is no chloromethyl ether smell, the anhydrous ethanol is washed off with purified water, and the chloro ball resin is obtained after drying.

[0011] Chloromethylation reaction principle:

[0012] Chloromethyl ether is used to soak and swell the white ball resin, so that the resin is in a certain swelling state, and the catalyst anhydrous zinc chloride is added to catalyze the reaction of chloromethyl ether with the benzene ring on the polymer white ball to form chloromethyl; concentrated sulfuric acid is added dropwise, which mainly combines with a small amount of water in the reaction system, and also plays a certain catalytic role.

[0013] (5) post-crosslinking reaction: the chloro ball is added to the container, dichloroethane is added to swell, after swelling, anhydrous ferric chloride is added and stirred to dissolve, the temperature is raised to 80℃ and kept for 18 hours; dichloroethane is recovered by distillation, 2% hydrochloric acid is added to the resin until it is soaked, soaked for 4 hours, the hydrochloric acid is filtered off, 2% hydrochloric acid is added again until it is soaked, soaked for 4 hours, and this operation is repeated 4 times; the resin is loaded into a resin column and washed with purified water from top to bottom until the washing liquid is neutral; the resin is taken out, 1% sodium hydroxide solution is added to the resin until it is soaked, soaked for 4 hours, the sodium hydroxide solution is filtered off, 1% sodium hydroxide solution is added again until it is soaked, soaked for 4 hours, and this operation is repeated 4 times; the resin is loaded into a resin column and washed with purified water from top to bottom until the washing liquid is neutral, and dried for use.

[0014] Post-crosslinking reaction principle:

[0015] The chloro ball is swelled with dichloroethane, and under the catalysis of anhydrous ferric chloride, the benzyl chloride on the benzene ring and the adjacent benzene ring are crosslinked to increase the specific surface area of the product.

[0016] (6) hydrolysis reaction: the post-crosslinked resin is added to the container, sodium hydroxide solution is added and soaked for 4 hours, and alkaline hydrolysis is carried out at 80℃ for 8 hours; the hydrolyzed resin is loaded into a resin column and washed with purified water from top to bottom until the washing liquid is neutral.

[0017] Hydrolysis reaction principle:

[0018] The ester group of methyl acrylate contained in the resin is hydrolyzed under alkaline conditions to generate a carboxylate sodium functional group.

[0019] The mass ratio of divinylbenzene, styrene, methyl acrylate and benzoyl peroxide in the oil phase is 3-8:35-45:2-5:1.

[0020] The mass ratio of purified water, polyvinyl alcohol and sodium chloride in the water phase is 30-40:1-3:1.

[0021] The mass ratio of the oil phase to the water phase is 1:2-4.

[0022] In step (4), the mass-volume ratio of white ball resin, chloromethyl ether, anhydrous zinc chloride and concentrated sulfuric acid is 1-5g:10-15g:1-3g:1ml; the preferred mass-volume ratio is 50g:200g:20g:15ml.

[0023] In step (5), the mass ratio of chloro ball, dichloroethane and anhydrous ferric chloride is 1-5:20-25:1; the preferred mass ratio is 10:70:3.

[0024] In step (6), the mass ratio of the post-crosslinked resin to sodium hydroxide solution is 1:8-12; the preferred mass ratio is 1:10.

[0025] Beneficial effects

[0026] The resin of the present application is first prepared into a gel resin without using a pore-forming agent, and then the gel resin is post-crosslinked, so that the obtained resin has a narrower pore size, a uniform pore structure distribution, more effective pore structures capable of adsorbing small molecules, and greatly improved adsorption capacity for small molecule substances. DETAILED DESCRIPTION

[0027] The effective ingredient content of the raw materials used in the present application is as follows: styrene of 99% styrene, divinylbenzene of 85% divinylbenzene, methyl acrylate of 99% methyl acrylate, and sodium chloride of 95% sodium chloride.

[0028] Example 1

[0029] The method for preparing a small molecule adsorption resin by post-crosslinking a gel resin comprises the following steps: (1) preparing an oil phase: adding 11.76 g of divinylbenzene, 83.24 g of styrene, 5 g of methyl acrylate, and 2 g of benzoyl peroxide to a beaker, stirring and mixing evenly to completely dissolve the benzoyl peroxide, and setting aside for use; (2) preparing an aqueous phase: adding 300 g of purified water, 15 g of polyvinyl alcohol, and 8 g of sodium chloride to a three-necked flask, heating the flask to 60° C., and stirring at a speed of 100 r / min to completely dissolve the dispersant; (3) polymerizing reaction: stopping stirring, adding the oil phase to the three-necked flask, and stirring the flask until the oil phase is stable. Slowly turn on the stirrer to 120±15r / min, observe the particle size of the white ball resin after stirring for a certain period of time, adjust the speed to make the resin particle size reach 0.2-1.15mm, and stabilize the stirring speed; raise the temperature to 78℃, observe every 10 minutes whether the resin is solidified and fixed, raise the temperature to 85℃ after the resin is fixed, and keep it warm for 4 hours. After the insulation is completed, raise the temperature to 90℃ and keep it warm for 2 hours. After the insulation is completed, raise the temperature to 95℃ and keep it warm for 6 hours; after the insulation is completed, stop heating and let the temperature drop naturally to below 60℃, take out the resin, rinse the dispersant on the resin surface with 45℃ warm water, and dry it to obtain the white ball resin for use;

[0030] (4) Chloromethylation: Add 50g of white ball resin to a three-necked flask, add 200g of chloromethyl ether and fully swell for 8 hours. After swelling is completed, add 20g of anhydrous zinc chloride and stir until dissolved and mixed evenly. Add 15ml of 98% concentrated sulfuric acid dropwise, heat to 48°C and keep warm for 12 hours; filter the solution in the three-necked flask, add 200ml of anhydrous ethanol and stir for 15 minutes, then replace with anhydrous ethanol. Repeat this operation until there is no chloromethyl ether smell. Rinse off the anhydrous ethanol with purified water and dry to obtain the white ball resin for use;

[0031] (5) Post-crosslinking reaction: add 50g of chlorine balls to a three-necked flask, add 350g of dichloroethane and fully swell for 4 hours. After swelling is completed, add 15g of anhydrous ferric chloride and stir to dissolve, heat to 80℃ and keep warm for 18 hours; distill and recover dichloroethane, take out the resin, add 2% hydrochloric acid with a mass fraction to the resin until it is covered with the resin and soak for 4 hours, filter out the hydrochloric acid, add 2% hydrochloric acid again and soak for 4 hours, repeat this 4 times; load the resin into a resin column, rinse with purified water from top to bottom until the eluent is neutral; take out the resin, add 1% sodium hydroxide solution with a mass fraction to the resin until it is covered with the resin and soak for 4 hours, filter out the sodium hydroxide solution, add 1% sodium hydroxide solution again and soak for 4 hours, repeat this 4 times; load the resin into a resin column, rinse with purified water from top to bottom until the eluent is neutral, dry and set aside;

[0032] (6) Hydrolysis reaction: 50 g of the post-crosslinked resin was added into a flask, 500 g of 5% sodium hydroxide solution was added to soak for 4 hours, and then the temperature was raised to 80 °C for alkaline hydrolysis for 8 hours. The hydrolyzed resin was loaded into a resin column, and purified water was used for upward elution until the eluate was neutral.

[0033] Adsorption performance detection

[0034] (1) Adsorption performance of sodium pentobarbital

[0035] A 80 mg / L sodium pentobarbital solution was prepared, 25 mL of which was placed in a 50 mL conical flask with a stopper, 1.0 g of the resin prepared in Example 1 (dry weight, or wet state can be converted into dry weight, or the adsorbent after constant weight by normal pressure drying method was directly weighed) was weighed and put into the flask, and the flask was placed in a reciprocating constant temperature water bath shaker at (37 ± 1) °C and shaken at a rate of (60 ± 10) times / min for 2 h of adsorption. The concentrations of the sodium pentobarbital solution before and after adsorption were measured at 240 nm by ultraviolet spectrophotometry, and the decrease rate was calculated according to formula (1):

[0036]

[0037] In the formula:

[0038] c r1 The decrease rate of the sodium pentobarbital solution, %;

[0039] c0The concentration of the sodium pentobarbital solution before adsorption, in units of milligrams per liter (mg / L);

[0040] c t The concentration of the sodium pentobarbital solution after 2 h of adsorption, in units of milligrams per liter (mg / L);

[0041] Note: Wet state can be converted into dry weight, that is, a certain volume of adsorbent is weighed and dried to constant weight, and 1 g of dry weight of adsorbent is equivalent to how many mL of wet state.

[0042] (2) Adsorption performance of creatinine

[0043] A 35 mg / L creatinine solution was prepared, 25 mL of which was placed in a 50 mL conical flask with a stopper, 1.0 g of the resin prepared in Example 1 (dry weight, or wet state can be converted into dry weight, or the adsorbent after constant weight by normal pressure drying method was directly weighed) was weighed and put into the flask, and the flask was placed in a reciprocating constant temperature water bath shaker at (37 ± 1) °C and shaken at a rate of (60 ± 10) times / min for 2 h of adsorption. The concentrations of the creatinine solution before and after adsorption were measured at 232 nm by ultraviolet spectrophotometry, and the decrease rate was calculated according to formula (2):

[0044]

[0045] In the formula:

[0046] c r2 - creatinine solution reduction rate, %;

[0047] c0- creatinine solution concentration before adsorption, in milligrams per liter (mg / L);

[0048] c t - creatinine solution concentration after 2h adsorption, in milligrams per liter (mg / L);

[0049] Test results

[0050] Adsorbent model Adsorption rate of creatinine (%) Adsorption rate of sodium pentobarbital (%) Resin of Example 1 99.5 99.3 AB-8 57.2 64.3 H103 85.7 94.6 D4006 71.6 46.8

[0051] Example 2

[0052] A method for preparing a small molecule adsorbent resin by post-crosslinking of a gel resin, comprising the following steps: (1) oil phase preparation: 16 g of divinylbenzene, 70 g of styrene, 10 g of methyl acrylate, and 2 g of benzoyl peroxide are added into a beaker, stirred and mixed uniformly to completely dissolve the benzoyl peroxide, and then stand by; (2) water phase preparation: 320 g of purified water, 8 g of polyvinyl alcohol, and 8 g of sodium chloride are loaded into a three-necked flask, heated to 60°C, and stirred at a speed of 100 r / min to completely dissolve the dispersant; (3) polymerization reaction: stop stirring, add the oil phase into the three-necked flask, slowly open the stirrer to 120±15 r / min after the oil phase is stable, adjust the stirring speed to make the resin particle size reach 0.2-1.15 mm, and stabilize the stirring speed; heat to 78°C, observe whether the resin is solidified and shaped every 10 minutes, heat to 85°C after the resin is shaped, keep for 4 hours, heat to 90°C after the keeping is completed, keep for 2 hours, heat to 95°C after the keeping is completed, and keep for 6 hours; stop heating after the keeping is completed, naturally cool to below 60°C, take out the resin, and rinse the dispersant on the surface of the resin with 45°C warm water, and dry to obtain white ball resin for standby;

[0053] (4) chloromethylation: 75 g of white ball resin is added into a three-necked flask, 225 g of chloromethyl ether is added to swell for 8 hours, 30 g of anhydrous zinc chloride is added after the swelling is completed, stirred to dissolve and mix uniformly, 15 ml of 98% concentrated sulfuric acid is added dropwise, heated to 48°C and kept for 12 hours; filter out the solution in the three-necked flask, add 200 ml of anhydrous ethanol and stir for 15 minutes, then replace the anhydrous ethanol, and repeat the operation until there is no chloromethyl ether smell, wash the anhydrous ethanol with purified water, and dry to obtain chloro ball resin for standby;

[0054] (5) Post-crosslinking reaction: 75 g of chloromethylated beads were added to a three-necked flask, 300 g of dichloroethane was added to swell for 4 hours, 15 g of anhydrous ferric chloride was added to dissolve after the swelling was completed, and the temperature was raised to 80°C for 18 hours; dichloroethane was recovered by distillation, 2% hydrochloric acid was added to the resin until the resin was soaked, and the hydrochloric acid was filtered out; 2% hydrochloric acid was added again to soak for 4 hours, and the process was repeated 4 times; the resin was loaded into a resin column, and purified water was used to rinse from top to bottom until the rinsing liquid was neutral; the resin was taken out, 1% sodium hydroxide solution was added to the resin until the resin was soaked, and the sodium hydroxide solution was filtered out; 1% sodium hydroxide solution was added again to soak for 4 hours, and the process was repeated 4 times; the resin was loaded into a resin column, and purified water was used to rinse from top to bottom until the rinsing liquid was neutral, and the resin was dried for standby;

[0055] (6) Hydrolysis reaction: 50 g of post-crosslinked resin was added to a three-necked flask, 400 g of 5% sodium hydroxide solution was added to soak for 4 hours, and the temperature was raised to 80°C for 8 hours of alkaline hydrolysis; the hydrolyzed resin was loaded into a resin column, and purified water was used to rinse from top to bottom until the rinsing liquid was neutral.

[0056] Example 3

[0057] The method for preparing a small molecule substance adsorption resin by post-crosslinking of a gel resin comprises the following steps: (1) oil phase preparation: 6 g of divinylbenzene, 90 g of styrene, 4 g of methyl acrylate, and 2 g of benzoyl peroxide were added to a beaker, stirred and mixed uniformly to completely dissolve the benzoyl peroxide, and then set aside; (2) water phase preparation: 240 g of purified water, 24 g of polyvinyl alcohol, and 8 g of sodium chloride were added to a three-necked flask, the temperature was raised to 60°C, and the dispersant was completely dissolved by stirring at a speed of 100 r / min; (3) polymerization reaction: the stirring was stopped, the oil phase was added to the three-necked flask, and after the oil phase was stable, the stirrer was slowly turned on to 120±15 r / min; after a certain period of stirring, the size of the white ball resin particles was observed, the stirring speed was adjusted to 0.2-1.15 mm, and the stirring speed was stabilized; the temperature was raised to 78°C, and every 10 minutes the resin was observed to see if it was solidified and shaped; after the resin was shaped, the temperature was raised to 85°C, and the temperature was maintained for 4 hours; after the temperature was maintained, the temperature was raised to 90°C, and the temperature was maintained for 2 hours; after the temperature was maintained, the temperature was raised to 95°C, and the temperature was maintained for 6 hours; after the temperature was maintained, the heating was stopped, and the temperature was naturally lowered to below 60°C; the resin was taken out, washed with 45°C warm water to remove the dispersant on the surface of the resin, and dried to obtain white ball resin for standby;

[0058] (4) chloromethylation: 45 g of white ball resin was added to a three-necked flask, 150 g of chloromethyl ether was added to swell for 8 hours, after swelling, 15 g of anhydrous zinc chloride was added to stir until dissolved and mixed uniformly, 15 ml of 98% concentrated sulfuric acid was added dropwise, and the temperature was raised to 48°C for 12 hours; the solution in the three-necked flask was filtered out, 200 ml of anhydrous ethanol was added to stir for 15 minutes, and then anhydrous ethanol was replaced, and this operation was repeated until there was no chloromethyl ether smell, and the anhydrous ethanol was washed with purified water, and the chloro ball resin was dried to obtain a chloro ball resin for standby;

[0059] (5) post-crosslinking reaction: 45 g of chloro ball was added to a three-necked flask, 375 g of dichloroethane was added to swell for 4 hours, after swelling, 15 g of anhydrous ferric chloride was added to stir until dissolved, and the temperature was raised to 80°C for 18 hours; dichloroethane was recovered by distillation, the resin was taken out, 2% hydrochloric acid was added to soak the resin for 4 hours, the hydrochloric acid was filtered out, 2% hydrochloric acid was added again to soak for 4 hours, and this operation was repeated 4 times; the resin was loaded into a resin column, and purified water was washed from top to bottom until the washing liquid was neutral; the resin was taken out, 1% sodium hydroxide solution was added to soak the resin for 4 hours, the sodium hydroxide solution was filtered out, 1% sodium hydroxide solution was added again to soak for 4 hours, and this operation was repeated 4 times; the resin was loaded into a resin column, and purified water was washed from top to bottom until the washing liquid was neutral, and was dried for standby;

[0060] (6) hydrolysis reaction: 50 g of post-crosslinked resin was added to a three-necked flask, 600 g of 5% sodium hydroxide solution was added to soak for 4 hours, and the temperature was raised to 80°C for alkaline hydrolysis for 8 hours; the hydrolyzed resin was loaded into a resin column, and purified water was washed from top to bottom until the washing liquid was neutral.

Claims

1. A method for preparing sodium pentobarbital and creatinine adsorption resin by post-crosslinking a gel resin, characterized in that: The following steps are involved: (1) Preparation of oil phase: Add divinylbenzene, styrene, methyl acrylate and benzoyl peroxide into a container, stir and mix evenly to completely dissolve the benzoyl peroxide; the mass ratio of divinylbenzene, styrene, methyl acrylate and benzoyl peroxide is 3-8:35-45:2-5:1; (2) Preparation of water phase: Add purified water, polyvinyl alcohol and sodium chloride into a container, heat to 60℃, stir at 100r / min to completely dissolve the polyvinyl alcohol and sodium chloride; the mass ratio of purified water, polyvinyl alcohol and sodium chloride is 30-40:1-3:1; (3) Polymerization: Add the oil phase into the water phase, and the oil phase and the water phase are mixed. The mass ratio of the water phase is 1:2-4. After the oil phase is stable, slowly turn on the stirrer to 120±15r / min, observe the particle size of the white ball resin, adjust the speed to make the resin particle size reach 0.2-1.15mm, and stabilize the stirring speed; raise the temperature to 78°C, observe every 10 minutes whether the resin is solidified and fixed, raise the temperature to 85°C after the resin is fixed, and keep it warm for 4 hours. After the insulation is completed, raise the temperature to 90°C and keep it warm for 2 hours. After the insulation is completed, raise the temperature to 95°C and keep it warm for 6 hours; after the insulation is completed, stop heating and let the temperature drop naturally to below 60°C, take out the resin, rinse off the dispersant on the resin surface with 45°C warm water, and dry to obtain the white ball resin; (4) Chloromethylation: Add the white ball resin to the reaction vessel, add chloromethyl ether to fully swell it, add anhydrous zinc chloride after swelling is complete, stir until the mixture is uniform, add concentrated sulfuric acid dropwise, heat to 48 ° C and keep warm for 12 hours; filter out the solution in the container, add anhydrous ethanol and stir for 15 minutes, then replace with anhydrous ethanol, repeat this operation until there is no chloromethyl ether smell, wash off the anhydrous ethanol with purified water, and dry to obtain the chloro ball resin; (5) Post-crosslinking reaction: add chlorine balls into a container, add dichloroethane to fully swell, add anhydrous ferric chloride after swelling is complete, stir and dissolve, heat to 80 ° C and keep warm for 18 hours; distill and recover dichloroethane, take out the resin, add 2% hydrochloric acid by mass to the resin until it covers the resin and soak for 4 hours, filter out the hydrochloric acid, add 2% hydrochloric acid by mass again and soak for 4 hours, repeat this 4 times; put the resin into a resin column, rinse with purified water from top to bottom until the eluent is neutral; take out the resin, add 1% sodium hydroxide solution by mass to the resin until it covers the resin and soak for 4 hours, filter out the sodium hydroxide solution, add 1% sodium hydroxide solution by mass again and soak for 4 hours, repeat this 4 times; put the resin into a resin column, rinse with purified water from top to bottom until the eluent is neutral, dry and set aside; (6) Hydrolysis reaction: Add the post-crosslinked resin into a container, add sodium hydroxide solution and soak for 4 hours, then heat to 80°C for alkaline hydrolysis for 8 hours. Load the hydrolyzed resin into a resin column and elute with purified water from top to bottom until the eluent is neutral.

2. The method for preparing pentobarbital sodium and creatinine adsorption resin according to claim 1, wherein: In step (4), the mass volume ratio of white ball resin to chloromethyl ether, anhydrous zinc chloride, and concentrated sulfuric acid is 1-5g:10-15g:1-3g:1mL.

3. The method for preparing pentobarbital sodium and creatinine adsorption resin according to claim 1, wherein: In step (5), the mass ratio of chlorine balls, dichloroethane and anhydrous ferric chloride is 1-5:20-25:

1.

4. The method for preparing pentobarbital sodium and creatinine adsorption resin according to claim 1, wherein: The mass ratio of the post-crosslinked resin to the sodium hydroxide solution in step (6) is 1:8-12.

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