阅读说明：本技术 一种水溶性高分子冠醚的制备方法 (Preparation method of water-soluble high-molecular crown ether ) 是由 杨文茂 王勇 余翔 唐磊 马龙 王玉莹 何伦云 于 2020-11-17 设计创作，主要内容包括：本发明公开了一种聚乙二醇单甲醚苯并冠醚的制备方法,属于高分子合成技术领域。采用mPEG-COOH为原料,经过HOSu活化,在低温条件下和氨基苯并冠醚反应得到聚乙二醇单甲醚五乙烯六胺粗品,混合溶剂重结晶得到聚乙二醇单甲醚五乙烯六胺纯品。此路线都为市场上常见原料,经过两步的得到粗品后,重结晶即可达到HPLC纯度99.0％,非常适合工业化放大生产。(The invention discloses a preparation method of polyethylene glycol monomethyl ether benzocrown ether, belonging to the technical field of polymer synthesis. mPEG-COOH is adopted as a raw material, is activated by HOSu, reacts with aminobenzene crown ether at low temperature to obtain a crude product of polyethylene glycol monomethyl ether pentaethylene hexamine, and is recrystallized by mixed solvent to obtain a pure product of polyethylene glycol monomethyl ether pentaethylene hexamine. The route is common raw materials in the market, after the crude product is obtained through two steps, the purity of HPLC (high performance liquid chromatography) can reach 99.0% through recrystallization, and the method is very suitable for industrial large-scale production.)

1. A water-soluble high-molecular crown ether is characterized by having the following structure:

2. a method for producing a water-soluble polymer crown ether according to claim 1, characterized in that:

the method comprises the following steps:

step one, mPEG-COOH and HOSu react in an organic solvent A in the presence of a catalyst to obtain mPEG-OSu;

secondly, reacting mPEG-OSu with aminobenzene crown ether in the presence of organic base to obtain a high-molecular water-soluble crown ether crude product;

and thirdly, adding the crude polymer water-soluble crown ether product into an organic solvent B, heating, dissolving, adding the solvent B, precipitating, filtering and drying to obtain a pure polymer water-soluble crown ether product.

3. The method for producing a water-soluble polymer crown ether according to claim 1, characterized in that: the mPEG has a molecular weight of 2000 or 5000.

4. The method for producing a water-soluble polymer crown ether according to claim 2, characterized in that: in the first step, the organic solvent A is selected from chlorine-containing solvents or dehydrating solvents.

5. The method for producing a water-soluble polymer crown ether according to claim 4, characterized in that: in the first step, the chlorine-containing solvent is selected from one or more of dichloromethane, 1, 2-dichloroethane, chloroform and chlorobenzene; the dehydration solvent comprises one or more of n-hexane, cyclohexane, toluene and dioxane.

6. The method for producing a water-soluble polymer crown ether according to claim 2, characterized in that: in the first step, the catalyst is DIC or B (C)₆F₅)₃(ii) a When catalyst DIC is adopted, the molar ratio of mPEG-COOH, HOSu and DIC is 1:1-1.2: 1-1.5; the reaction solvent is a chlorine-containing solvent; by using B (C)₆F₅)₃When the molar ratio of mPEG-COOH, HOSu and DIC is 1:1-1.2: 0.02-0.2; the reaction solvent is a dehydration solvent.

7. The method for producing a water-soluble polymer crown ether according to claim 2, characterized in that: in the second step, the organic base is selected from triethylamine, pyridine or diisopropylethylamine.

8. The method for producing a water-soluble polymer crown ether according to claim 2, characterized in that: and thirdly, the organic solvent B is selected from acetone, and the organic solvent C is selected from cyclopentyl methyl ether, tetrahydrofuran or tert-butyl methyl ether.

9. The method for producing a water-soluble polymer crown ether according to claim 2, characterized in that: and the third step is drying at 40-60 ℃ under vacuum and reduced pressure.

10. The method for producing a water-soluble polymer crown ether according to any one of claims 2 to 9, characterized in that: the product is sealed and stored for a long time by filling inert gas.

Technical Field

The invention relates to a preparation method of a crown ether material, in particular to a preparation method of polyethylene glycol monomethyl ether benzo crown ether.

Background

The wide application of nuclear energy brings various conveniences to human beings and also brings huge health threats, a large amount of radioactive wastes are often generated in the process of using the nuclear energy, the degradation time of the wastes is long, serious environmental pollution is easily caused, and how to safely and effectively treat the radioactive wastes becomes a key factor for restricting the sustainable development of the nuclear energy.

In recent years, nuclear power is developed vigorously due to large energy density and little pollution, and greenhouse gases caused by emission are avoided, however, spent fuel is inevitably generated in nuclear power operation. The high level waste liquid (HLLW) produced by the post-treatment of spent fuel is a highly acidic, highly radioactive and highly toxic mixed solution.

The degradation time of the high-level radioactive waste liquid is long, so that serious environmental pollution is easily caused, how to safely and effectively treat the radioactive waste becomes a key factor for restricting the sustainable development of nuclear energy, and the common methods for treating the high-level radioactive waste liquid comprise an adsorption method, an ion exchange method and a membrane separation method, the number of devices involved in the methods is large, and the treatment process steps are complex;

when high-level radioactive waste liquid is treated, radioactive pollution is caused when the waste liquid passes through equipment or a structure, so that the more the equipment is, the more the process steps are complicated, and the more serious the pollution is, therefore, the equipment number is reduced as much as possible, and the treatment process flow is shortened.

The invention content is as follows:

the invention aims to provide a preparation method of water-soluble high-molecular crown ether, which has the following structure:

the preparation route is as follows:

mPEG-COOH is adopted as a raw material, and is activated to react with aminobenzene crown ether at low temperature, so that a product with the liquid phase purity of 99 percent is obtained by a crystallization method. The route has low cost and is suitable for industrial scale-up production.

The invention relates to a preparation method of water-soluble high-molecular crown ether, which comprises the following steps:

step one, mPEG-COOH and HOSu react in an organic solvent A in the presence of a catalyst to obtain mPEG-OSu;

secondly, reacting mPEG-OSu with aminobenzene crown ether in the presence of organic base to obtain a high-molecular water-soluble crown ether crude product;

and thirdly, adding the crude polymer water-soluble crown ether product into an organic solvent B, heating, dissolving, adding the solvent B, precipitating, filtering and drying to obtain a pure polymer water-soluble crown ether product.

Further, in the above technical solution, the mPEG has a molecular weight selected from 2000 or 5000.

Further, in the above technical solution, the organic solvent a is selected from chlorine-containing solvents, such as dichloromethane, 1, 2-dichloroethane, chloroform, chlorobenzene, and the like.

Further, in the above technical solution, the organic base is selected from triethylamine, pyridine or diisopropylethylamine.

Further, in the above technical solution, the organic solvent B is selected from acetone, and the organic solvent C is selected from cyclopentyl methyl ether, tetrahydrofuran, tert-butyl methyl ether, and the like.

Further, in the technical scheme, the drying is carried out in an oven at 40 ℃ under vacuum and reduced pressure.

Further, in the technical scheme, the product is hermetically stored for a long time by re-introducing inert gas.

The specific implementation mode is as follows:

example 1:

in the first step, the intermediate mPEG2000-OSu is prepared:

a white pasty solid, mPEG2000-COOH, having a hydroxyl value of 28.1mgKOH/g (199.7g,0.1mol) was transferred with 3.5L DCM to a 20L dry kettle with stirring. HOSu (12.08g,0.105mol) is accurately weighed and added in three batches, and after the materials are completely dissolved, an ice bath is opened to reduce the temperature to 5-10 ℃ in the kettle. When the temperature in the kettle is 5-10 ℃, dropping DIC (13.63g,0.108mol) by using a constant-pressure dropping funnel, wherein the temperature is increased, and the dropping speed is controlled so that the temperature in the kettle does not exceed 25 ℃ and the dropping is finished within 30 min. The funnel and the neck were rinsed with 500mL DCM for 30min in ice bath, the ice bath was removed and the reaction was carried out at room temperature for 10-16 h. After the reaction was complete, a large amount of white needle crystals formed in the kettle, which was filtered over celite in a buchner funnel, the filter cake was rinsed with a small amount of DCM, and the combined filtrates were spin-dried to give 194.4g of a white paste solid in 92.4% yield.

The second step is that: preparation of water-soluble high-molecular crown ether

5L of THF was added to the reaction vessel, 18-aminobenzcrown ether (38.3g,0.117mol) was weighed out accurately, stirring was started and the ice bath was opened. DIEA (45.23g,0.35mol) was weighed out accurately, diluted with 200mL THF and added slowly. When the temperature in the kettle was reduced to 0-5 deg.C, the white pasty solid obtained in the above step, MPEG-OSu (189.9g,0.09mol), was dissolved in 5L THF, slowly added dropwise over 2 h. The funnel and the vial mouth were rinsed with 500mL of DCM, kept in ice bath for 30min, the ice bath was removed, and the reaction was allowed to proceed overnight at room temperature. After the reaction was completed, the reaction solution in the kettle was a white suspension, and THF was evaporated at 40 ℃ in a 5L rotary evaporator. Stopping reducing the pressure, adding 1L of acetone into a rotary evaporation bottle, filling nitrogen, keeping the temperature at 40 ℃, rotating for 30min until the solids are completely dispersed in an acetone solution, supplementing 500mL of acetone if the solids cannot be dispersed, transferring the rotary evaporation bottle into a 50L round bottom reaction kettle after the solids in the rotary evaporation bottle are not agglomerated, quickly dropwise adding 3L-3.5L of methyl tert-butyl ether at room temperature under the protection of nitrogen, separating out white solids, stirring at room temperature for crystallization for 1h, filtering, leaching a filter cake with a 1L of acetone/methyl tert-butyl ether mixed solvent of 1:3, drying the filter cake in a reduced-pressure oven at 40 ℃ for 24h, and taking out the filter cake to obtain 175.6g of polyethylene glycol monomethyl ether benzocrown ether with a yield of 84%. Charging nitrogen gas for low-temperature storage.

Example 2:

in the first step, the intermediate mPEG2000-OSu is prepared:

a white pasty solid, mPEG2000-COOH, having a hydroxyl value of 28.1mgKOH/g (199.7g,0.1mol), was transferred with 3.5L of chloroform to a 20L dry autoclave, and stirring was started. HOSu (12.08g,0.105mol) is accurately weighed and added in three batches, and after the materials are completely dissolved, an ice bath is opened to reduce the temperature to 5-10 ℃ in the kettle. When the temperature in the kettle is 5-10 ℃, dropping DIC (13.63g,0.108mol) by using a constant-pressure dropping funnel, wherein the temperature is increased, and the dropping speed is controlled so that the temperature in the kettle does not exceed 25 ℃ and the dropping is finished within 30 min. The funnel and the bottle mouth are washed by 500mL of chloroform, kept for 30min under ice bath, removed from the ice bath and reacted for 10-16h at room temperature. After the reaction was complete, a large amount of white needle crystals were formed in the kettle, filtered over celite in a buchner funnel, the filter cake was rinsed with a small amount of chloroform, and the combined filtrates were spin-dried to give 196.4g of a white paste-like solid in 93.1% yield.

The second step is that: preparation of water-soluble high-molecular crown ether

5L of THF was added to the reaction vessel, 17-aminobenzcrown ether (38.3g,0.117mol) was weighed out accurately, stirring was started and the ice bath was opened. Pyridine (24.52g,0.31mol) was weighed out accurately, diluted with 200mL THF and added slowly. When the temperature in the kettle was reduced to 0-5 deg.C, the white pasty solid obtained in the above step, MPEG-OSu (189.9g,0.09mol), was dissolved in 5L THF, slowly added dropwise over 2 h. The funnel and the vial mouth were rinsed with 500mL of DCM, kept in ice bath for 30min, the ice bath was removed, and the reaction was allowed to proceed overnight at room temperature. After the reaction was completed, the reaction solution in the kettle was a white suspension, and THF was evaporated at 40 ℃ in a 5L rotary evaporator. Stopping reducing pressure, adding 1L of acetone into a rotary evaporation bottle, filling nitrogen, keeping the temperature at 40 ℃, rotating for 30min until the solids are completely dispersed in an acetone solution, supplementing 500mL of acetone if the solids cannot be dispersed, transferring the rotary evaporation bottle into a 50L round bottom reaction kettle after the solids in the rotary evaporation bottle do not agglomerate, quickly dropwise adding 3L-3.5L of cyclopentyl methyl ether at room temperature under the protection of nitrogen, separating out white solids, stirring at room temperature for crystallization for 1h, filtering, leaching a filter cake with a 1L of acetone/cyclopentyl methyl ether 1:3 mixed solvent, drying the filter cake in a reduced-pressure oven at 40 ℃ for 24h, taking out the filter cake, obtaining 145.9g of polyethylene glycol monomethyl ether benzocrown, obtaining the yield of 69.8%, filling nitrogen, and storing at low temperature.

Example 3:

in the first step, the intermediate mPEG5000-OSu is prepared:

the white pasty solid mPEG5000-COOH having a hydroxyl value of 10.9mgKOH/g (514.8g,0.1mol) was transferred to a 20L dry autoclave with 8L of 1, 2-dichloroethane, and stirring was started. HOSu (12.08g,0.105mol) is accurately weighed and added in three batches, and after the materials are completely dissolved, an ice bath is opened to reduce the temperature to 5-10 ℃ in the kettle. When the temperature in the kettle is 5-10 ℃, dropping DIC (13.63g,0.108mol) by using a constant-pressure dropping funnel, wherein the temperature is increased, and the dropping speed is controlled so that the temperature in the kettle does not exceed 25 ℃ and the dropping is finished within 30 min. The funnel and the mouth of the bottle were rinsed with 1.5L of 1, 2-dichloroethane, kept in ice bath for 30min, the ice bath was removed, and the reaction was carried out at room temperature for 10-16 h. After the reaction was completed, a large amount of white needle crystals were formed in the kettle, filtered through celite in a buchner funnel, the filter cake was rinsed with a small amount of 1, 2-dichloroethane, and the combined filtrates were spin-dried to obtain 478.7g of a white paste solid with a yield of 91%.

The second step is that: preparation of water-soluble high-molecular crown ether

5L of THF was added to the reaction vessel, 18-aminobenzcrown ether (38.3g,0.117mol) was weighed out accurately, stirring was started and the ice bath was opened. Triethylamine (36.43g,0.36mol) was weighed out accurately, diluted with 200mL of THF and added slowly. When the temperature in the kettle was reduced to 0-5 deg.C, the white pasty solid obtained in the above step, MPEG-OSu (473.5g,0.09mol), was dissolved in 5L THF, slowly added dropwise over 2 h. The funnel and the vial mouth were rinsed with 500mL of DCM, kept in ice bath for 30min, the ice bath was removed, and the reaction was allowed to proceed overnight at room temperature. After the reaction was completed, the reaction solution in the kettle was a white suspension, and THF was evaporated at 40 ℃ in a 5L rotary evaporator. Stopping reducing pressure, adding 1L of acetone into a rotary evaporation bottle, filling nitrogen, keeping the temperature at 40 ℃, rotating for 30min until the solids are completely dispersed in an acetone solution, supplementing 500mL of acetone if the solids cannot be dispersed, transferring the rotary evaporation bottle into a 50L round bottom reaction kettle after the solids in the rotary evaporation bottle do not agglomerate, quickly dropwise adding 5L-5.5L of tetrahydrofuran at room temperature under the protection of nitrogen, separating out white solids, stirring at room temperature for crystallization for 1h, filtering, leaching a filter cake with a 2L of acetone/tetrahydrofuran 1:3 mixed solvent, drying the filter cake in a reduced-pressure oven at 40 ℃ for 24h, taking out the filter cake to obtain 361.6g of polyethylene glycol monomethyl ether benzocrown, wherein the yield is 73.4%, filling nitrogen and storing at low temperature.

The foregoing embodiments have described the general principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the present invention, and that various changes and modifications may be made without departing from the scope of the principles of the present invention, and the invention is intended to be covered by the appended claims.