Water-soluble morpholine lactamide acrylate bio-based monomers and polymers thereof

Abstract

The application discloses a water-soluble morpholine lactic amide acrylate bio-based monomer and a polymer thereof, and belongs to the technical field of bio-based polymers.The application uses a lactic acid derived green solvent (methyl lactate, ethyl lactate, propyl lactate, butyl lactate and the like) and morpholine to synthesize morpholine lactic amide ester (MML) through amine ester exchange under solvent-free mild conditions, then synthesizes a polymerizable morpholine lactic amide acrylate monomer (MMLA) through acylation reaction and tests the performance through various means.The research finds that the water-soluble bio-based monomer (MMLA) of the morpholine lactic amide acrylate developed by the application has lower toxicity than traditional acrylate monomers and can be polymerized in a more environmentally friendly system, and the water-soluble polymer obtained after polymerization has high glass transition temperature and good thermal stability, and the water-soluble polymer with lower biological toxicity and good stability has application prospects in the development of biomedical fields.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of bio-based polymers, and particularly relates to a water-soluble morpholine lactamide acrylate bio-based monomer and a polymer thereof. BACKGROUND

[0002] In recent years, the importance of environmental protection and sustainable development has been increasing, and the use of renewable resources to develop materials that can replace traditional petrochemical materials is becoming more and more urgent, so renewable bio-based polymers have received extensive attention. At present, there are many problems to be solved in the synthesis of bio-based polymers, including developing more kinds of environmentally friendly bio-based monomers, effectively controlling the performance of polymer materials, and making polymer materials high-performance. At present, scientists have prepared many kinds of polymerizable monomers using various biomass raw materials such as terpenes, lactic acid, lignin, etc., and synthesized bio-based polymers through various polymerization methods. However, most of the lactic acid-based monomers reported in the literature are not soluble in water, and environmentally unfriendly organic solvents are used in polymerization, which does not meet the concept of green chemistry. Therefore, it is necessary to develop water-soluble bio-based monomers for polymerization in aqueous solution. SUMMARY

[0003] In order to obtain more renewable and environmentally friendly bio-based monomers that can be polymerized in aqueous solution, the purpose of the present application is to provide a water-soluble morpholine lactamide acrylate bio-based monomer and a polymer thereof.

[0004] To achieve the above-mentioned purpose of the present application, the following technical solutions are provided:

[0005] The water-soluble morpholine lactamide acrylate bio-based monomer according to the present application has a structural formula (I) as shown below, and the polymers thereof have structural formulas (II) and (III) as shown below:

[0006]

[0007] In the compound of structural formula (III), X is an N, P, O or S atom;

[0008] R1 is a C1-C12 cyano group, a C1-C12 alkyl group, a C1-C12 ester group or a C6-C30 aryl group;

[0009] R2 is a C1-C8 alkyl group, a C6-C30 aryl group, a C5-C24 heteroaryl group (the heteroatoms in the heteroaryl group are at least one of N, O and S);

[0010] R3 is a C1-C8 alkyl group, a C6-C30 aryl group, a C5-C24 heteroaryl group (the heteroatoms in the heteroaryl group are at least one of N, O and S);

[0011] n is a positive integer, representing the number of polymerization units;

[0012] The reaction is shown below:

[0013]

[0014] Synthesis of the compound of structural formula (I): 1 mole of lactic acid ester (methyl lactate, ethyl lactate, propyl lactate, butyl lactate, etc.) is directly mixed with 1.1-1.3 moles of morpholine, 0.01-0.1 moles of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is added as a catalyst for the lactic acid ester, and the mixture is stirred at 25-40°C for 60-80 hours. After the reaction is completed, the product is concentrated by rotary evaporation, the obtained liquid is purified by column chromatography using ethyl acetate as an eluent, the eluent is removed by rotary evaporation, and the precursor morpholine lactate (MML) is obtained. 1 mole of the precursor morpholine lactate (MML) is dissolved in super-dry dichloromethane under a stream of argon, 1-1.5 moles of triethylamine is added, and the mixture is stirred uniformly at 0-10°C under an oxygen-free condition for 10-40 minutes. Then, 1-1.5 moles of acryloyl chloride is slowly added dropwise, and the mixture is stirred at room temperature for 10-20 hours. The product is filtered off, the obtained filtrate is washed and dried, the drying agent is filtered off, the solvent is removed by rotary evaporation, the obtained liquid is purified by column chromatography using ethyl acetate and n-hexane (volume ratio 5:1) as an eluent, the eluent is removed by rotary evaporation, and the morpholine lactamide acrylate (MMLA) monomer of structural formula (I) is obtained;

[0015] Synthesis of the compound of structural formula (II): 1 mole of the morpholine lactamide acrylate (MMLA) monomer is uniformly mixed with 0.0025-0.05 moles of an oil-soluble radical initiator (an oil-soluble thermal initiator, a photoinitiator, or an oxidation-reduction initiator such as azobisisobutyronitrile, azobisisoheptyl nitrile, azobisisopentyl nitrile, azobiscyclohexyl cyanide, dimethyl azobisbutyrate, etc.) in dimethyl sulfoxide, and the oxygen is removed by argon replacement for 20-60 minutes. Then, the mixture is placed in an oil bath at 60-80°C and reacted for 5-10 hours. After the reaction is completed, the reaction liquid is exposed to air to quench the reaction, and the polymorpholine lactamide acrylate of structural formula (II) is obtained.

[0016] Synthesis of compound of structural formula (III): chain transfer reagent (one of bis-thioesters, trithiocarbonates, dithio-carbonamates and xanthates), morpholine lactamide acrylate (MMLA) monomer, water-soluble radical initiator (4,4'-azobis(4-cyanopentanoic acid), azobisimidoformate hydrochloride, azobisimidazole hydrochloride and other water-soluble thermal initiators, photoinitiators and redox initiators) are mixed uniformly with water to configure a reaction solution, argon gas replacement method is used to remove oxygen for 20-60 minutes, and then the reaction solution is placed in an oil bath at 60-80 DEG C for 10-24 hours; after the reaction is completed, the reaction solution is exposed to air to quench the reaction, so that the poly-morpholine lactamide acrylate of structural formula (III) with controllable dispersity is obtained; wherein: the solid content of the polymerization solution is 10%-100%, the molar ratio of the chain transfer reagent, the monomer and the radical initiator is 1:10-2000:0.01-0.5.

[0017] The present application uses lactic acid derived green solvent (lactate) and morpholine to synthesize morpholine lactam ester through amine ester exchange under solvent-free mild conditions, and then synthesizes polymerizable morpholine lactamide acrylate through acylation reaction and tests the performance of the polymer synthesized through various means. Compared with most of the lactic acid-based monomers reported at present, the water-soluble morpholine lactamide acrylate bio-based monomer (MMLA) prepared in the present application has lower toxicity (derived from the bio-based raw material itself, compared with the raw material derived from fossil fuels, has lower toxicity, in addition, the monomer synthesized in the present application is water-soluble, thus has lower toxicity) and can be polymerized in an environmentally friendly water system, and the water-soluble polymer obtained after polymerization has high glass transition temperature and good thermal stability (example 3 is polymerized in an aqueous solution, the system before and after polymerization is homogeneous, thus it is proved that the polymer is water-soluble), the water-soluble polymer with lower biological toxicity and good stability can be prepared into biocompatible hydrogel dressing, thus reducing the toxic effect of the material on the biological epidermis, and thus has the application prospect in the field of biomedicine. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 The mass spectrum of the monomer MMLA of example 1 of the present application is shown in Figure 3. 1 H NMR chart;

[0019] Figure 2 The mass spectrum of the monomer MMLA of example 1 of the present application is shown in Figure 3. 13 C NMR chart;

[0020] Figure 3 The mass spectrum of the monomer MMLA of example 1 of the present application is shown in Figure 3. Figures 1-3 The successful synthesis and purification of MMLA are illustrated;

[0021] Figure 4GPC plot of the product PMMLA of Example 2 of the present application, from which we obtain the molecular weight and dispersity of the polymorpholine lactamide acrylate obtained by conventional free radical polymerization;

[0022] Figure 5 DSC plot of the product PMMLA of Example 2 of the present application, from which we obtain the glass transition temperature of the polymorpholine lactamide acrylate; 1 HNMR plot, from which we determine that the polymorpholine lactamide acrylate is completely purified according to the present application;

[0023] Figure 6 DSC plot of the product PMMLA of Example 2 of the present application, from which we obtain the glass transition temperature of the polymorpholine lactamide acrylate;

[0024] Figure 7 TGA plot of the product PMMLA of Example 2 of the present application, from which we obtain the thermal decomposition temperature of the polymorpholine lactamide acrylate;

[0025] Figure 8 GPC plot of the product PMMLA of Example 3 of the present application; 50 from which we obtain the molecular weight and dispersity of the polymorpholine lactamide acrylate obtained by RAFT polymerization with controlled dispersity. DETAILED DESCRIPTION

[0026] In order to make the purpose, technical scheme of the present application more clear, the essential content of the present application is introduced below combined with specific examples; the examples listed in the present application are only used to illustrate the present application, and are not used to limit the scope of the present application.

[0027] Example 1: Synthesis of morpholine lactamide acrylate

[0028] First, synthesize the precursor morpholine lactate (MML): mix morpholine (17.42 g, 0.24 mol), methyl lactate (24.98 g, 0.2 mol) and DBU (3.04 g, 0.02 mol) uniformly in a flask, and stir at 40°C for 3 days. After the reaction is completed, concentrate the product by rotary evaporation, purify the obtained liquid by column chromatography (ethyl acetate), then remove the eluent by rotary evaporation, and finally obtain 28.64 g of yellowish liquid MML with a yield of 89.9%. The structural formula is as follows:

[0029]

[0030] Subsequently, monomer morpholine lactamide acrylate MMLA was synthesized: MML (15.9 g, 0.1 mol) was dissolved in 50 mL of super-dry dichloromethane under argon gas flow, and triethylamine (12.14 g, 0.12 mol) was added. The mixed solution was stirred for 30 minutes after being uniformly mixed at 5°C under anaerobic conditions, and then acryloyl chloride (10.86 g, 0.12 mol) was slowly added dropwise. After the addition was completed, the reaction solution was raised to room temperature and stirred overnight. The product was filtered to remove the solid, and the filtrate was washed with hydrochloric acid aqueous solution (1M), saturated sodium bicarbonate solution, and saturated sodium chloride solution, respectively. After washing, the organic phase was dried over anhydrous magnesium sulfate, and the magnesium sulfate was removed by filtration. The solvent was removed from the organic phase by rotary evaporation, and the obtained liquid was purified by column chromatography (ethyl acetate: n-hexane 5:1, v / v). The eluent was then removed by rotary evaporation, and finally 8.28 g of yellowish liquid MMLA was obtained, with a yield of 41.6%. The structural formula is as follows:

[0031]

[0032] In this example, the product characterization results are shown in Figure 1 , Figure 2 , Figure 3 , indicating that the product with the target structure was obtained.

[0033] Example 2:

[0034] a) Synthesis of poly-morpholine lactamide acrylate PMMLA

[0035] Morpholine lactamide acrylate MMLA (0.2995 g, 1.4 mmol), azobisisobutyronitrile AIBN (0.58 mg, 3.5 μmol), and dimethyl sulfoxide DMSO (700 mL) were added to a 4 mL dry glass bottle. The glass bottle was sealed and deoxygenated for 30 minutes using the argon gas replacement method. After deoxygenation, the bottle was placed in a 70°C oil bath for 10 hours. After opening the bottle cap to quench the reaction, poly-morpholine lactamide acrylate (PMMLA) was obtained. Nuclear magnetic resonance testing showed that the monomer conversion rate was greater than 99%.

[0036] Experimental test analysis:

[0037] The PMMLA prepared in this example 2 was tested. According to the signal peak integral area of the hydrogen corresponding to the double bond on the monomer morpholine lactamide acrylate, the monomer conversion rate was greater than 99% by nuclear magnetic resonance testing. Gel permeation chromatography GPC testing showed that the M n,GPC = 30.45 kg / mol, See Figure 4 .

[0038] b) Thermal property test of poly-morpholine lactamide acrylate

[0039] The PMMLA polymer sample was dried overnight in a 60°C vacuum drying oven to remove the solvent. NMR analysis revealed the absence of monomer and solvent peaks in the purified sample. Thermal performance testing was then performed. The NMR spectrum of the purified polymer is shown below. Figure 5 .

[0040] Differential scanning calorimetry (DSC) was performed on the dried and purified polymer sample of this embodiment. PMMLA (5.92 mg) was weighed, and the test temperature range was set to -50 to 200 °C with a heating rate of 10 °C / min. The test was conducted under a nitrogen atmosphere for two cycles, with a 2-minute holding time after each temperature change. After the test, the data was analyzed and a DSC curve was plotted. We obtained the glass transition temperature of PMMLA as 73 °C. (See also...) Figure 6 This indicates that the product has a high glass transition temperature.

[0041] Thermogravimetric analysis was performed on the dried and purified polymer sample. 6.74 mg of PMMLA was weighed, and the test temperature range was set to room temperature to 200 °C, with a heating rate of 10 °C / min. Analysis of the data after the test showed that the thermal decomposition temperature of PMMLA was 318 °C. See [link to relevant documentation]. Figure 7 This indicates that the product has good thermal stability. Example 3: Polymorpholine lactamide acrylate (PMMLA) 50 RAFT aggregation

[0042] Morpholin-lactamide acrylate (MMLA) (0.3866 g, 1.81 mmol), chain transfer reagent 4-((((2-carboxyethyl)thio)thiocarbonyl)thio)-4-cyanopentanoic acid (CTPA) (0.0112 g, 36.43 μmol), 4,4'-azobis(4-cyanopentanoic acid) ACVC (2.035 mg, 7.26 μmol), and water (H2O) (600 mL) were added to a 4 mL dry glass bottle to prepare a polymerization solution with a solid content of 40%. After sealing the glass bottle, the oxygen was removed by argon purging for 30 minutes. After deoxygenation, the solution was placed in a 70°C oil bath and reacted for 20 hours. The reaction was then quenched by opening the bottle cap to obtain polymorpholino-lactamide acrylate (PMMLA) with controllable dispersibility. 50 NMR spectroscopy showed that the monomer conversion rate was greater than 99%. The polymer structure is as follows:

[0043]

[0044] The PMMLA prepared in this embodiment 50 Testing was conducted, and the integrated area of ​​the signal peak corresponding to the double bond hydrogens on the morpholine lactamide acrylate monomer, measured by NMR, showed that the monomer conversion rate was greater than 99%. Gel permeation chromatography (GPC) analysis indicated that the polymer PMMLA... 50 M n,GPC= 2.56 kg / mol, See Figure 8 .

[0045] RAFT polymers containing different substituents as shown in structural formula (III) can also be obtained using chain transfer agents of other structures.

Claims

1. A water-soluble morpholine lactamide acrylate bio-based monomer, having a structure as shown in the following formula, 。 2.A water-soluble morpholine lactamide acrylate bio-based polymer, having a structure as shown in one of the following formulas: ； (II) (IV) n is a positive integer, representing the number of polymerization units.

3. The method of making a water soluble morpholine lactamide acrylate bio-based monomer of claim 1, characterized by: 1.1-1.3 moles of morpholine are directly mixed with 1 mole of lactate ester, 0.01-0.1 moles of 1,8-diazabicyclo[5.4.0]undec-7-ene is added as a catalyst for the lactate ester, and the mixture is stirred at 25-40 ℃ for 60-80 hours. After the reaction is completed, the product is concentrated by rotary evaporation, the obtained liquid is purified by column chromatography using ethyl acetate as an eluent, the eluent is removed by rotary evaporation, and a precursor morpholine lactate ester is obtained. 1 mole of the precursor morpholine lactate ester is dissolved in super-dry dichloromethane under a flow of argon, 1-1.5 moles of triethylamine is added, and the mixture is stirred uniformly at 0-10 ℃ under an oxygen-free condition for 10-40 minutes. Then, 1-1.5 moles of acryloyl chloride is slowly added dropwise, and the mixture is reacted at room temperature for 10-20 hours. The product is filtered to remove the solid, the obtained filtrate is washed and dried, the drying agent is removed by filtration, the solvent is removed by rotary evaporation, the obtained liquid is purified by column chromatography using ethyl acetate and n-hexane (5:1 by volume) as an eluent, the eluent is removed by rotary evaporation, and a morpholine lactamide acrylate monomer having a structure as shown in the following formula (I) is obtained.

4. The method of making a water soluble morpholine lactam acrylate bio-based monomer according to claim 3, wherein: The lactate ester is methyl lactate, ethyl lactate, propyl lactate, or butyl lactate.

5. The method of making water soluble morpholine lactamide acrylate bio-based polymer of claim 2, characterized by: 1 mole of the morpholine lactamide acrylate monomer having a structure as shown in the formula (I) is mixed uniformly with 0.0025-0.05 moles of an oil-soluble radical initiator in dimethyl sulfoxide, the oxygen is removed by an argon replacement method for 20-60 minutes, and the mixture is placed in an oil bath at 60-80 ℃ for 5-10 hours. After the reaction is completed, the reaction liquid is exposed to air to quench the reaction, and a poly-morpholine lactamide acrylate having a structure as shown in the formula (II) is obtained. 。 6. The process for the preparation of water soluble morpholine lactamide acrylate bio-based polymer as claimed in claim 5 wherein: The oil-soluble radical initiator is azobisdimethylvaleronitrile, azobisdimethylvaleronitrile, azobisdimethylvaleronitrile, azobiscyclohexylcarbonitrile, or azobisdimethylvaleronitrile.

7. The process for the preparation of water soluble morpholine lactamide acrylate bio-based polymer as claimed in claim 2, wherein the process comprises of: The chain transfer agent, the morpholine lactamide acrylate monomer having a structure as shown in the formula (I), and the water-soluble radical initiator are mixed uniformly to configure a reaction liquid, the oxygen is removed by an argon replacement method for 20-60 minutes, and the mixture is placed in an oil bath at 60-80 ℃ for 10-24 hours. After the reaction is completed, the reaction liquid is exposed to air to quench the reaction, and a poly-morpholine lactamide acrylate having a structure as shown in the formula (IV) is obtained, wherein the solid content of the polymerization solution is 10%-100%, the molar ratio of the chain transfer agent, the monomer, and the radical initiator is 1:10-2000:0.01-0.

5. 。 8. The method of making water soluble morpholine lactamide acrylate bio-based polymer according to claim 7, wherein: The chain transfer agent is 4-((((2-carboxyethyl)thio)thiocarbonyl)thio)-4-cyanopentanoic acid.

9. The method of making water soluble morpholine lactam acrylate bio-based polymer according to claim 7, wherein: The water-soluble radical initiator is 4,4'-azobis(4-cyanopentanoic acid), azobisdimethylvaleronitrile, or azobisdimethylvaleronitrile.

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