Preparation method of methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate

Abstract

The invention relates to the technical field of polymer chemical synthesis, in particular to a preparation method of methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate. A two-step synthesis method is adopted and comprises the following steps: firstly, carrying out ethoxylation reaction on methacrylic acid or acrylic acid and ethylene oxide in the presence of a catalyst to generate a methacrylic acid polyethylene glycol ester intermediate or an acrylic acid polyethylene glycol ester intermediate; and carrying out end capping on the intermediate, alkali and halomethane through a Williamson ether synthesis reaction to obtain high-purity methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate. The invention overcomes the problems of high reaction temperature, low conversion rate, insufficient product purity and easy polymerization of methacrylate or acrylate in the traditional transesterification method, and overcomes the defects of long synthetic route steps and high cost in the prior art. The method has the advantages of mild process conditions, controllable molecular weight and high product purity, and is suitable for the fields of biomedical materials, cosmetics, polymer emulsifiers and the like.

Description

Technical Field

[0001] This invention relates to the field of polymer chemistry and functional monomer synthesis technology, specifically to a method for preparing methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate. Background Technology

[0002] Methoxylated polyethylene glycol methacrylate and methoxylated polyethylene glycol acrylate are important functional acrylate monomers. Their molecular structure consists of a polymerizable methacryloyloxy group at one end and a biocompatible methoxy-terminated polyethylene glycol chain at the other end. These monomers are widely used in biomedical materials (such as drug carriers, hydrogels, and tissue engineering scaffolds), high-performance coatings, and polycarboxylate superplasticizers.

[0003] Currently, the main industrial method for preparing methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate is transesterification, which involves reacting methyl methacrylate or methyl acrylate with methoxy polyethylene glycol in the presence of a catalyst. Existing technologies typically require the prior synthesis of methoxy polyethylene glycol, followed by esterification with methacrylic acid or acrylic acid. This process is lengthy and costly. For example, patent applications CN101117378A and CN101289533A use polyethylene glycol monomethyl ether and methacrylic acid or acrylic acid as raw materials, with p-toluenesulfonic acid or concentrated sulfuric acid as catalysts for esterification. In this method, methacrylic acid or acrylic acid readily undergoes self-polymerization, and the reaction generates a large amount of water, which must be removed. This process is complex and requires sophisticated equipment.

[0004] Therefore, developing a method for preparing methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate that is simple in procedure, mild in conditions, and produces high-purity products has significant industrial application value. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a novel two-step method for preparing methoxylated polyethylene glycol methacrylate or methoxylated polyethylene glycol acrylate. This method uses methacrylic acid or acrylic acid and ethylene oxide as starting materials, generates an intermediate through direct ethoxylation, and then capsifies the intermediate via a highly efficient Williamson ether synthesis reaction. The process is short, the conditions are mild, and the product has high purity.

[0006] The technical solution of the present invention is as follows: A method for preparing methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate, comprising the following steps: Step 1, Ethoxylation reaction: Add methacrylic acid or acrylic acid, catalyst, and polymerization inhibitor to a reaction vessel, stir thoroughly at 80-130℃ under inert gas protection, then slowly introduce ethylene oxide into the vessel, controlling the pressure to not exceed 0.5 MPa, and react until the system pressure no longer decreases. After aging, cool to obtain polyethylene glycol methacrylic acid intermediate or polyethylene glycol acrylate intermediate. Step 2, End-capping reaction: The polyethylene glycol methacrylate intermediate or polyethylene glycol acrylate intermediate obtained in Step 1 is reacted with a nucleophile and halomethane at 40-90℃ to synthesize Williamson ether for 2-8 hours to generate the target product methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate.

[0007] In the preparation method described above, in step 1, the molar ratio of methacrylic acid or acrylic acid to ethylene oxide is 1:n, where n is the average number of additions of ethylene oxide, and the value of n ranges from 4 to 60.

[0008] In the above preparation method, in step 1, the catalyst is an alkaline catalyst selected from at least one of sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium ethoxide; the amount of the catalyst used is 0.1%-3.0% of the mass of methacrylic acid or acrylic acid.

[0009] In the above preparation method, in step 1, the polymerization inhibitor is hydroquinone, phenothiazine, polymerization inhibitor 701 piperidinol oxide, p-tert-butylcatechol, etc., and the amount of the polymerization inhibitor is 0.1%-3.0% of the mass of methacrylic acid or acrylic acid.

[0010] In the preparation method described above, in step 2, the nucleophile is at least one of sodium hydride, sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium phenolate; the molar ratio of methacrylic acid or acrylic acid to the nucleophile is 1:0.5-1.0.

[0011] In the above preparation method, in step 2, the halomethane is iodomethane, chloromethane, or bromomethane; the molar ratio of methacrylic acid or acrylic acid to halomethane is 1:1.0-2.0.

[0012] In the preparation method described above, in step 2, the Williamson ether synthesis reaction is carried out in a solvent, which is an aprotic polar solvent selected from at least one of N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran.

[0013] In the preparation method described above, after the Williamson ether synthesis reaction is completed in step 2, a post-processing step is also included: cooling the reaction solution to room temperature, filtering to remove solid salt, and then removing the solvent and unreacted halomethane by vacuum distillation to obtain a crude product; the crude product is purified to obtain high-purity methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate.

[0014] The methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate prepared according to the above preparation method has the following general molecular formula: CH2=C(CH3)C(O)O-(CH2CH2O) n -CH3 or CH2=CH-C(O)O-(CH2CH2O) n -CH3, where n is an integer between 5 and 50.

[0015] The beneficial effects of this invention are: 1. Simple and efficient route: Polyethylene glycol chains are directly constructed from basic chemical raw materials such as methacrylic acid or acrylic acid and ethylene oxide, avoiding the step of pre-synthesizing methoxy polyethylene glycol, simplifying the process and reducing costs.

[0016] 2. Mild reaction conditions: Both steps of the reaction are carried out at lower temperatures (ethoxylation 80-130℃, end-capping reaction 40-90℃), which reduces energy consumption and side reactions caused by high temperatures (such as double bond polymerization).

[0017] 3. High product purity: End-capping via Williamson ether synthesis results in high reaction specificity and conversion rate. Combined with column chromatography purification, a product with a purity greater than 99% can be obtained, which is superior to the approximately 92% purity of the traditional transesterification method.

[0018] 4. Strong controllability of molecular weight: By precisely controlling the molar ratio of methacrylic acid or acrylic acid to ethylene oxide (1:n, n=4-60), a series of products with different chain lengths (n value) can be easily prepared to meet different application needs.

[0019] 5. Wide range of applications: The resulting products can be used to prepare biocompatible medical devices, cosmetics with excellent moisturizing properties, and highly efficient polymer emulsifiers. Detailed Implementation

[0020] The present invention will be further described below with reference to embodiments, but the scope of protection of the present invention is not limited thereto.

[0021] A method for preparing methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate includes the following steps: (1) Ethoxylation reaction: Methacrylic acid or acrylic acid, along with a catalyst and polymerization inhibitor, are added to a high-pressure reactor equipped with a stirrer, thermometer, and gas inlet / outlet. The air inside the reactor is replaced with nitrogen. Stirring is started at 80-130℃, and then metered ethylene oxide is slowly introduced, controlling the reaction pressure to not exceed 0.5 MPa. The reaction endpoint is determined by monitoring the pressure. When the pressure no longer decreases, the mixture is kept at this temperature for 0.5-1 hour to obtain polyethylene glycol methacrylate intermediates or polyethylene glycol acrylate intermediates.

[0022] (2) End-capping reaction: The intermediate obtained in step (1) is transferred to a reaction flask under normal pressure, and solvent and alkali are added. The mixture is activated at 40-90℃ for 0.5-1 hours to generate alkoxide active species. Then, halomethane is added dropwise, and the reaction is carried out at this temperature for 2-8 hours. After the reaction is completed, the product is purified by cooling, filtration, vacuum distillation, and column chromatography to obtain the final product methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate.

[0023] Example 1: Preparation of methoxylated polyethylene glycol methacrylate with n≈10

[0024] (1) Ethoxylation reaction

[0025] 172.2 g (2.0 mol) of methacrylic acid, 0.9 g of sodium hydroxide, 0.9 g of potassium hydroxide (1.0 wt% of the methacrylic acid content), 0.17 g of hydroquinone and 0.17 g of phenothiazine (0.2 wt% of the methacrylic acid content) were added to a 2 L autoclave. The autoclave was purged three times with nitrogen gas at 0.5 MPa. Stirring was started and the temperature was raised to 95 °C. Then, 880 g (20.0 mol) of ethylene oxide was slowly introduced, controlling the pressure inside the autoclave to not exceed 0.35 MPa, for approximately 4 hours. After the introduction was complete, stirring was continued at 110 °C until the pressure no longer decreased, and then the mixture was allowed to mature for another 0.5 hours. The mixture was cooled to room temperature to obtain the polyethylene glycol methacrylic acid intermediate CH2=C(CH3)C(O)O-(CH2CH2O). 10 -OH.

[0026] (2) End-capping reaction

[0027] All the above intermediates were transferred to a 4L three-necked flask, and 1L of N,N-dimethylformamide (DMF) was added as a solvent, along with 96g of sodium hydride (0.56 wt% of the amount of methacrylic acid). The mixture was activated at 30°C for 1 hour under nitrogen protection with stirring. Then, 338g of iodomethane (120% of the molar amount of methacrylic acid) was slowly added dropwise. After the addition was complete, the temperature was raised to 50°C to carry out the Williamson ether synthesis reaction for 4 hours.

[0028] After the reaction was complete, the reaction solution was cooled to room temperature, and the generated sodium iodide solid was removed by filtration. The filtrate was then subjected to vacuum distillation at 50°C to recover DMF and unreacted iodomethane. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 2 / 1, v / v) to give a colorless, transparent liquid product, methoxy polyethylene glycol methacrylate (CH2=C(CH3)C(O)O-(CH2CH2O)). 10 -CH3), with a purity of 99.2% and a conversion rate of 96.4%.

[0029] Example 2: Preparation of methoxylated polyethylene glycol methacrylate with n≈25

[0030] (1) Ethoxylation reaction

[0031] The procedure was the same as in Example 1. The raw materials were: 86.1 g (1.0 mol) methacrylic acid, 1.72 g potassium hydroxide (2.0 wt% of the methacrylic acid), 0.13 g of polymerization inhibitor p-tert-butylcatechol, 0.13 g of phenothiazine (0.3 wt% of the methacrylic acid), and 1100.0 g (25.0 mol) ethylene oxide. The reaction temperature was 100°C, and the pressure was controlled to not exceed 0.4 MPa.

[0032] (2) End-capping reaction

[0033] The procedure was the same as in Example 1. The obtained intermediate was dissolved in 800 mL of tetrahydrofuran (THF), and 27 g of sodium methoxide and 27 g of hydroxide (0.62 wt% of methacrylic acid) were added. The mixture was activated at 40 °C for 0.5 h. Then, 155 g of iodomethane (110% of methacrylic acid by mol) was added dropwise, and the Williamson ether synthesis reaction was carried out at 40 °C for 6 h. The post-treatment and purification methods were the same as in Example 1, yielding a colorless, transparent, viscous liquid product, methoxy polyethylene glycol methacrylate (CH2=C(CH3)C(O)O-(CH2CH2O)). 25 -CH3), with a purity of 98.8% and a conversion rate of 95.9%.

[0034] Example 3: Preparation of methoxylated polyethylene glycol acrylate with n≈10

[0035] (1) Ethoxylation reaction

[0036] Add 144 g (2.0 mol) of acrylic acid, 1.0 g of sodium hydroxide, 0.44 g of sodium methoxide (1.0 wt% of acrylic acid), 0.22 g of polymerization inhibitor 701 (piperidinol oxide), and 0.22 g of p-tert-butylcatechol (0.3 wt% of acrylic acid) to a 2 L autoclave. Purge the autoclave three times with nitrogen at 0.5 MPa. Start stirring and heat to 95 °C, then slowly introduce 880 g (20.0 mol) of ethylene oxide, controlling the pressure inside the autoclave to not exceed 0.4 MPa, for approximately 4 hours. After the purging is complete, continue stirring at 115 °C until the pressure no longer decreases, and then allow to mature for another 0.5 hours. Cool to room temperature to obtain the polyethylene glycol acrylate intermediate CH2=CC(O)O-(CH2CH2O). 10 -OH.

[0037] (2) End-capping reaction

[0038] All the above intermediates were transferred to a 4L three-necked flask, and 1L of N,N-dimethylformamide (DMF) was added as a solvent, along with 96g of sodium hydride (0.56 wt% of the amount of acrylic acid). The mixture was activated at 30°C for 1 hour under nitrogen protection with stirring. Then, 111g of chloromethane (110% of the molar amount of acrylic acid) was slowly added dropwise. After the addition was complete, the temperature was raised to 50°C and the reaction was carried out for 4 hours.

[0039] After the reaction was complete, the reaction solution was cooled to room temperature and filtered to remove the generated sodium iodide solid. The filtrate was then subjected to vacuum distillation at 50°C to recover DMF and unreacted iodomethane. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 2 / 1, v / v) to give methoxy polyethylene glycol acrylate (CH2=CC(O)O-(CH2CH2O)). 10 -CH3), with a purity of 99.3% and a conversion rate of 95.3%.

[0040] Example 4: Preparation of methoxylated polyethylene glycol acrylate with n≈30

[0041] (1) Ethoxylation reaction

[0042] The procedure was the same as in Example 3. The raw materials were: 72 g (1.0 mol) acrylic acid, 1.44 g potassium hydroxide (2.0 wt% of acrylic acid), 0.15 g of polymerization inhibitor p-tert-butylcatechol, 0.15 g of phenothiazine (0.4 wt% of acrylic acid), and 1320.0 g (30.0 mol) ethylene oxide. The reaction temperature was 100°C, and the pressure was controlled to not exceed 0.45 MPa.

[0043] (2) End-capping reaction

[0044] The procedure was the same as in Example 3. The obtained intermediate was dissolved in 800 mL of tetrahydrofuran (THF), and 27 g of sodium methoxide and 27 g of hydroxide (0.62 wt% of acrylic acid) were added. The mixture was activated at 40 °C for 0.5 h. Then, 123.5 g of methyl bromo (130% of acrylic acid by weight) was added dropwise, and the reaction was carried out at 45 °C for 6 h. The post-treatment and purification methods were the same as in Example 1, yielding methoxy polyethylene glycol acrylate (CH2=CC(O)O-(CH2CH2O)). 30 -CH3), the purity was determined to be 98.9%, and the conversion rate was 94.4%.

[0045] Table 1 shows a comparison of the reaction pressure, reaction temperature, and yield between the above-described embodiments and the comparative examples. Table 1

[0046] Conclusion: The methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate prepared by the method provided in this invention has milder reaction conditions, is more convenient to operate, and does not require steps such as dripping, intermediate aeration, catalyst replenishment, or controlled reflux. The product has higher purity and conversion rate.

Claims

1. A method for preparing methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate, characterized in that, Includes the following steps: Step 1, Ethoxylation reaction: Add methacrylic acid or acrylic acid, catalyst, and polymerization inhibitor to a reaction vessel, stir thoroughly at 80-130℃ under inert gas protection, then slowly introduce ethylene oxide into the vessel, controlling the pressure to not exceed 0.5 MPa, and react until the system pressure no longer decreases. After aging, cool to obtain polyethylene glycol methacrylic acid intermediate or polyethylene glycol acrylate intermediate. Step 2, End-capping reaction: The polyethylene glycol methacrylate intermediate or polyethylene glycol acrylate intermediate obtained in Step 1 is reacted with a nucleophile and halomethane at 40-90℃ to synthesize Williamson ether for 2-8 hours to generate the target product methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate.

2. The preparation method according to claim 1, characterized in that, In step 1, the molar ratio of methacrylic acid or acrylic acid to ethylene oxide is 1:n, where n is the average number of additions of ethylene oxide, and the value of n ranges from 4 to 60.

3. The preparation method according to claim 1, characterized in that, In step 1, the catalyst is an alkaline catalyst, selected from at least one of sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium ethoxide; the amount of the catalyst used is 0.1%-3.0% of the mass of methacrylic acid or acrylic acid.

4. The preparation method according to claim 1, characterized in that, In step 1, the polymerization inhibitor is hydroquinone, phenothiazine, polymerization inhibitor 701 piperidinol oxide, p-tert-butylcatechol, etc., and the amount of the polymerization inhibitor is 0.1%-3.0% of the mass of methacrylic acid or acrylic acid.

5. The preparation method according to claim 1, characterized in that, In step 2, the nucleophile is at least one of sodium hydride, sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium phenolate; the molar ratio of methacrylic acid or acrylic acid to the nucleophile is 1:0.5-1.

0.

6. The preparation method according to claim 1, characterized in that, In step 2, the halomethane is iodomethane, chloromethane, or bromomethane; the molar ratio of methacrylic acid or acrylic acid to halomethane is 1:1.0-2.

0.

7. The preparation method according to claim 1, characterized in that, In step 2, the Williamson ether synthesis reaction is carried out in a solvent, which is an aprotic polar solvent selected from at least one of N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran.

8. The preparation method according to claim 1, characterized in that, In step 2, after the Williamson ether synthesis reaction is completed, a post-processing step is also included: the reaction solution is cooled to room temperature, the solid salt is removed by filtration, and the solvent and unreacted halomethane are removed by vacuum distillation to obtain the crude product; the crude product is purified to obtain high-purity methoxy polyethylene glycol methacrylate or methoxy polyethylene glycol acrylate.

9. A methoxylated polyethylene glycol methacrylate or methoxylated polyethylene glycol acrylate prepared by the preparation method according to any one of claims 1-7, characterized in that, Its general molecular formula is: CH2=C(CH3)C(O)O-(CH2CH2O) n -CH3 or CH2=CH-C(O)O-(CH2CH2O) n -CH3, where n is an integer between 5 and 50.

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