Process for purifying para-dioxanone by reaction

Abstract

The present application relates to a kind of methods for purifying p-dioxycyclohexanone by reaction, comprising the following steps: (1) adding impurity removal reagent to p-dioxycyclohexanone crude product, bubbling by N2, and carrying out impurity removal reaction; (2) removing solid by further processing after the material after reaction impurity removal, to obtain purified p-dioxycyclohexanone; wherein, in step (1), the impurity removal reagent is alkali or basic metal oxide. By adding impurity removal reagent to p-dioxycyclohexanone crude product to remove impurities containing active hydrogen groups such as hydroxyl, carboxyl and other groups in p-dioxycyclohexanone, and then removing solid by means of vacuum distillation, rectification, filtration, centrifugation and other methods, refined p-dioxycyclohexanone product is obtained. The process of the present application is simple, has low energy consumption, low operating cost, can meet the requirements of industrial large-scale production, and the purity of the refined p-dioxycyclohexanone prepared can reach more than 99.9%, which can meet the requirements of downstream applications.

Description

Technical Field

[0001] This invention relates to a method for purifying dioxane, specifically a method for purifying dioxane by removing impurities through reaction. Background Technology

[0002] p-Dioxane, with its six-membered ring structure, is the monomer for synthesizing poly(p-dioxane). Poly(p-dioxane) has unique biodegradability, biocompatibility, and bioabsorbability, making it widely used in the field of medical biodegradable materials. Currently, the most widely used method for producing p-dioxane is a one-step synthesis using diethylene glycol as a raw material via cyclization and dehydrogenation. However, due to factors such as reaction efficiency, byproducts, and the purity of the raw materials, the synthesized p-dioxane has low purity and contains a large number of impurities containing active hydrogen. These impurities generate numerous active centers during polymerization, causing continuous chain transfer and eventual termination of the polymer's active chains. Therefore, to increase the molecular weight of poly(p-dioxane), the key is to improve the purity of the p-dioxane monomer and remove as many active hydrogen impurities as possible.

[0003] Currently, there are four main methods for purifying p-dioxanone monomer: The first method involves repeatedly dissolving the crude p-dioxanone monomer at high temperatures and recrystallizing it at low temperatures using a suitable organic solvent. European patents EP0617029A1 and EP0617029B1 disclose the specific process steps of this purification method. However, because the crystallization temperature of p-dioxanone monomer is relatively low, approximately 26°C, purification using recrystallization requires temperatures as low as -20°C or even lower, making the operation inconvenient. Furthermore, the yield of p-dioxanone monomer purified by recrystallization is very low. Therefore, this method of purifying p-dioxanone monomer through repeated recrystallization results in excessively high preparation costs. The second method involves repeated vacuum distillation of the p-dioxanone monomer, collecting distillate fractions within a certain boiling range under a certain vacuum. This method is not very effective for purifying p-dioxanone monomer, as some impurities with boiling points close to p-dioxanone, such as ethylene glycol, are difficult to remove by distillation. The third method involves adding strong active hydrogen removal reagents such as calcium hydride (CaH2), sodium hydride (NaH), lithium hydride (LiH), aluminum hydride (AlH3), and lithium aluminum hydride (AlH4Li) to p-dioxanone, combined with distillation or fractional distillation, to effectively remove moisture and active hydrogen groups such as hydroxyl and carboxyl groups from the crude p-dioxanone monomer. This type of purification method for p-dioxanone is reported in patents CN110028658A and CN105622912A. However, the strong active hydrogen removal reagents used in this method are unstable, costly, and can promote the polymerization of p-dioxanone, while also generating solid waste. The fourth method involves adding reagents and catalysts to p-dioxanone to react with impurities, followed by distillation to remove the impurities. For example, KR100196097B1 reported a method of adding MDI [diphenylmethane diisocyanate or methylene bis-(4-)phenyl-isocyanate] to p-dioxanone and adding trivalent amine DMDEE (dimorpholinodiethyl ether) as a catalyst. After the reaction is completed, the mixture is then distilled under reduced pressure to remove hydroxyl compounds from p-dioxanone. This method requires a large number of reagents and is therefore costly.

[0004] As mentioned above, existing purification processes for p-dioxanone suffer from drawbacks such as high cost and poor efficiency. P-dioxanone used as a polymerization monomer requires a purity of 99.9% or higher. To meet the application requirements of p-dioxanone, a highly efficient, feasible, and economical purification method is needed. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for purifying p-dioxanone that has low energy consumption, low production cost, and is easy to operate, and can meet the requirements of large-scale industrial production.

[0006] The basic principle of the reaction purification method for dioxane described in this application is to add a purification reagent to crude dioxane, so that it reacts with impurities containing active hydrogen groups such as hydroxyl and carboxyl groups in the crude dioxane. The solid is then removed by vacuum distillation, rectification, filtration, centrifugation, etc. The purity of the purified dioxane can reach more than 99.9%.

[0007] The method for purifying p-dioxanone by reaction described in this application specifically includes the following steps: (1) Add a purification reagent to the crude p-dioxanone and carry out a purification reaction; (2) The material after the reaction and impurity removal is further processed to remove the solids and obtain purified p-dioxanone.

[0008] During the reaction in step (1), N2 is bubbled through at a rate of 50~200 mL / min. In step (1), the impurity removal reagent is an alkali or an alkaline metal oxide, selected from any one or more of NaOH, KOH, Ca(OH)2, Mg(OH)2, Na2O, K2O, ZnO, CaO, MgO, and BaO; In step (1), the purity of crude dioxane is 97%~99%; In step (1), the applicant found through research that adding too little impurity removal reagent resulted in slow effects, while adding too much increased raw material and separation costs. Based on extensive research and experimentation, this application limits the amount of impurity removal reagent added to 0.1-10 wt% of crude PDO, preferably 1-5 wt%. In step (1), the applicant discovered through research that if the reaction temperature is too high, PDO will undergo side reactions such as oligomerization. Based on extensive research and experiments, this application controls the reaction temperature in step 1) at 30~120℃, preferably 30~60℃; In step (1), the applicant found through research that an excessively long reaction time wasted time and that PDO itself would undergo side reactions. Based on extensive research and experimentation, this application controls the reaction time in step 1) to 0.5~20 h, preferably 0.5~10 h; In step (2), the method for removing solids is selected from one of vacuum distillation, rectification, filtration, and centrifugation.

[0009] This invention removes impurities containing active hydrogen groups such as hydroxyl and carboxyl groups from crude p-dioxanone through reaction purification. The solid is then removed by vacuum distillation, rectification, filtration, and centrifugation to obtain purified p-dioxanone. This method overcomes the drawbacks of traditional methods, such as high energy consumption and production costs associated with multiple distillations; high costs, demanding conditions, environmental pollution, and health hazards associated with solution crystallization using organic solvents; and high costs and instability associated with using strong active hydrogen removal reagents such as calcium hydride (CaH2), sodium hydride (NaH), lithium hydride (LiH), aluminum hydride (AlH3), and lithium aluminum hydride (AlH4Li). This invention features a simple process flow, low energy consumption, and low operating costs, meeting the requirements of large-scale industrial production. The purified p-dioxanone obtained can achieve a purity of over 99.9%, satisfying downstream application requirements. Detailed Implementation

[0010] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention. Example 1

[0011] 100 g of crude p-dioxanone with a purity of 97.57% was added to a round-bottom flask, along with 1 g of CaO. N2 was bubbled through the flask at a rate of 50 mL / min, and the reaction was carried out at 60 °C for 1 h. The reactants were filtered to remove solids, yielding the final product, weighing 91 g with a yield of 91%. Gas chromatography analysis by Agilent Gas Chromatography showed a purity of 99.92%. Example 2

[0012] 200 g of crude p-dioxanone with a purity of 98.01% was added to a round-bottom flask, along with 10 g of K₂O. N₂ was bubbled through the flask at a rate of 60 mL / min, and the reaction was carried out at 50 °C for 3 h. The reactants were then transferred to a centrifuge to remove solids, yielding a final product of 190 g (95% yield). Gas chromatography analysis by Agilent Gas Chromatography showed a purity of 99.94%. Example 3

[0013] 1 kg of crude p-dioxanone with a purity of 98.97% was added to a reaction vessel, along with 30 g of MgO. N2 was bubbled through the vessel at a rate of 100 mL / min, and the reaction was carried out at 40 °C for 5 h. The reactants were then transferred to a vacuum distillation apparatus for vacuum distillation. The distillation temperature was controlled at 130 °C, and the absolute pressure was controlled at 5 mbar. The distillate was collected to obtain the final product, weighing 936 g with a yield of 93.6%. Gas chromatography analysis by Agilent Gas Chromatography showed that the product purity was 99.98%. Example 4

[0014] Five kilograms of crude p-dioxanone with a purity of 97.12% were added to a reaction vessel, along with 100 g of Mg(OH)₂. N₂ was bubbled through the vessel at a rate of 200 mL / min, and the reaction was carried out at 40°C for 6 h. The reactants were then transferred to a vacuum distillation apparatus for vacuum distillation. The distillation temperature was controlled at 150°C, and the absolute pressure at 10 mbar. The distillate was collected to obtain the final product, weighing 4.6 kg with a yield of 92%. Gas chromatography analysis by Agilent Gas Chromatography showed a purity of 99.91%. Example 5

[0015] Five kilograms of crude p-dioxanone with a purity of 98.43% were added to a reaction vessel, along with 125 g of NaOH. N2 was bubbled through the vessel at a rate of 200 mL / min, and the reaction was carried out at 50°C for 6 h. The reactants were then transferred to a distillation column to remove solids and heavy components, yielding a final product of 4.7 kg (94% yield). Gas chromatography analysis by Agilent Gas Chromatography confirmed a purity of 99.95%. Example 6

[0016] 10 kg of crude p-dioxanone with a purity of 99.0% was added to a reaction vessel, along with 100 g of CaO. N2 was bubbled through the vessel at a rate of 200 mL / min, and the reaction was carried out at 30°C for 10 h. The reactants were then transferred to a distillation column to remove solids and heavy components, yielding a final product of 9.3 kg (93% yield). Gas chromatography analysis by Agilent Gas Chromatography confirmed a purity of 99.99%.

[0017] Comparative Example 1: 200 g of crude p-dioxanone with a purity of 94.31% was added to a round-bottom flask, along with 5 g of CaO. N2 was bubbled through the flask at a rate of 70 mL / min, and the reaction was carried out at 50 °C for 3 h. The reactants were then transferred to a centrifuge to remove solids, yielding a final product of 175 g (87.5% yield). Gas chromatography analysis by Agilent Gas Chromatography showed a purity of 97.23%.

[0018] Comparative Example 2: 1 kg of crude p-dioxanone with a purity of 98.97% was added to a round-bottom flask, along with 100 g of CaO. N2 was bubbled through the flask at a rate of 100 mL / min, and the reaction was carried out at 110 °C for 5 h. The solids were removed by distillation to obtain the final product, weighing 840 g with a yield of 84%. Gas chromatography analysis by Agilent Gas Chromatography showed a purity of 96.32%.

[0019] Comparative Example 3: 1 kg of crude p-dioxanone with a purity of 98.20% was added to a reaction vessel, along with 25 g of AlH4Li. N2 was bubbled through the vessel at a rate of 100 mL / min, and the reaction was carried out at 40 °C for 5 h. The reactants were then transferred to a vacuum distillation apparatus for vacuum distillation. The distillation temperature was controlled at 130 °C, and the absolute pressure was controlled at 5 mbar. The distillate was collected to obtain the final product, weighing 860 g with a yield of 86.0%. Gas chromatography analysis by Agilent Gas Chromatography showed that the product purity was 99.72%.

Claims

1. A method for purifying p-dioxanone by reaction, comprising the following steps: (1) Add a purification reagent to crude p-dioxanone, and bubble with N2 to carry out the purification reaction; (2) The material after the reaction and impurity removal is further processed to remove the solids and obtain purified p-dioxanone; In step (1), the impurity removal reagent is an alkali or an alkaline metal oxide.

2. The method for purifying p-dioxanone by reaction according to claim 1, characterized in that, Step 1) During the reaction, N2 is bubbled through at a rate of 50~200 mL / min.

3. The method for purifying p-dioxanone by reaction according to claim 1, characterized in that, The alkali or alkaline metal oxide is selected from any one or more of NaOH, KOH, Ca(OH)2, Mg(OH)2, Na2O, K2O, ZnO, CaO, MgO, and BaO.

4. The method for purifying p-dioxanone by reaction according to claim 1, characterized in that, In step (1), the purity of crude dioxane is 97%~99%.

5. The method for purifying p-dioxanone by reaction according to claim 1, characterized in that, In step (1), the amount of the impurity removal reagent added is 0.1 to 10 wt% of the crude dioxane, preferably 1 to 5 wt%.

6. The method for purifying p-dioxanone by reaction according to claim 1, characterized in that, In step (1), the reaction temperature is 30~120℃, preferably 30~60℃.

7. The method for purifying p-dioxanone by reaction according to claim 1, characterized in that, In step (1), the reaction time is 0.5 to 20 h, preferably 0.5 to 10 h.

8. The method for purifying p-dioxanone by reaction according to claim 1, characterized in that, In step (2), the method for removing solids is selected from one of vacuum distillation, rectification, filtration, and centrifugation.