Method for preparing monodisperse crosslinked polymer microspheres by RAFT dispersion polymerization

Abstract

The present invention belongs to the field of polymer microsphere preparation, and specifically relates to a method for preparing monodisperse cross-linked polymer microspheres by RAFT dispersion polymerization. First, a macromolecular RAFT agent, a monomer, an organic amine, an initiator, a cross-linking agent, an organic solvent and deionized water are added to a three-necked flask, stirred and dissolved, vacuumed and passed with argon, and the reaction obtains a cross-linked polymer microsphere dispersion. The polymer microsphere dispersion is diluted with a mixed solution of ethanol and water, and then centrifuged and washed, and circulated three times to remove unreacted monomers and initiators, and dried to obtain white powdery cross-linked polymer microspheres. The present invention adopts RAFT dispersion polymerization to prepare cross-linked polymer microspheres, does not need to add dispersants and stabilizers, the product is pure, and the surface of the microspheres is smooth. By adding organic amines, the stability of the polymerization system can be effectively adjusted, and monodisperse, highly cross-linked, adjustable particle size and narrowly distributed polymer microspheres can be prepared.

Description

Technical Field

[0001] The invention belongs to the field of polymer microsphere preparation, and particularly relates to a method for preparing monodisperse cross-linked polymer microspheres by adopting RAFT dispersion polymerization. Background Art

[0002] Micron-sized monodisperse cross-linked polymer microspheres have the characteristics of large specific surface area, strong adsorption, excellent heat resistance and solvent resistance, and high surface activity. They occupy an increasingly important position in applications in bioengineering, medical immunology, microelectronics, analytical chemistry, and catalysts.

[0003] Monodisperse polymer microspheres are often prepared by dispersion polymerization. However, it is difficult to prepare micron-sized monodisperse microspheres with regular morphology and high cross-linking degree by traditional dispersion polymerization, and a large amount of stabilizer is usually required. For example, Wei et al. used dispersion polymerization and cross-linker post-drip addition to prepare micron-sized carboxylated polystyrene cross-linked microspheres. When the cross-linker dosage was 1 wt% and the dispersant dosage was 6 wt%, the microspheres obtained had regular morphology and good monodispersity (Polymer Bulletin, 2016(6):56-62). Although this cross-linker post-drip addition method can reduce the influence of the cross-linker on the nucleation stage, the steps are cumbersome, and a large amount of stabilizer adheres to the surface of the microspheres, which is difficult to remove.

[0004] The one-step preparation of cross-linked polymer microspheres can be regulated by adding a chain transfer agent. In the active controlled free radical polymerization reaction, the addition of a directional agent can simultaneously control the molecular weight and the regularity of the three-dimensional structure, produce a polymer chain with uniform structure, and avoid the intramolecular cross-linking and microgels of traditional free radical polymerization. For example, Wang et al. used dodecyl mercaptan as a chain transfer agent and prepared monodisperse cross-linked polystyrene microspheres with a cross-linker content of 1wt% by one-step dispersion polymerization. When the dispersant content was 20wt%, the microspheres had good monodispersity. (Polymers for Advanced Technologies, 2020, 31(3): 407-414). Yuan Yuan et al. used dithiocarbonate as a chain transfer agent to prepare cross-linked polymer microspheres by RAFT soap-free emulsion polymerization. No stabilizer was required. The microspheres prepared had good monodispersity only when the cross-linker content was as low as 2% of the total monomer volume (Journal of Inspection and Quarantine, 2020, 30(01): 83-85). Summary of the Invention

[0005] The present invention aims to provide a method for preparing polymer microspheres with controllable particle size, monodispersity, and a high degree of crosslinking. This method solves the problems of poor polymerization process stability, uneven microsphere dispersion, low degree of crosslinking, and difficulty in removing stabilizers in the prior art. By using a macromolecular RAFT agent and adding an organic amine to control the dispersion polymerization process, the aggregation and fusion of particles during the polymerization process are effectively avoided, and the stability of the polymerization system is improved, thereby preparing polymer microspheres with regular morphology, monodispersity, and high degree of crosslinking. The preparation method of the present invention has the advantages of readily available raw materials, simple operation, good monodispersity of the resulting polymer microspheres, and a high degree of crosslinking.

[0006] To achieve the above object, the present invention is implemented through the following technical solutions:

[0007] The method for preparing monodisperse cross-linked polymer microspheres by RAFT dispersion polymerization is as follows:

[0008] 1. Add the macromolecular RAFT agent, monomer, organic amine, initiator, crosslinker, organic solvent, and deionized water to a three-necked flask, stir and dissolve. Vacuum and purge with argon for three cycles. Allow the reaction to proceed at a constant temperature. Sample and measure the conversion. Stop the reaction when the conversion reaches 90% or higher to obtain a dispersion of crosslinked polymer microspheres.

[0009] The structural formula of the macromolecular RAFT agent is:

[0010]

[0011] in: The structural formula represents one or more of polyacrylic acid, polymethacrylic acid, polyglycidyl acrylate, and polyglycidyl methacrylate.

[0012] The structural formula represents: one or both of polystyrene and polymethyl methacrylate.

[0013] Where 0≤m, n≤300.

[0014]

[0015] The molecular weight of the macromolecular RAFT agent is 500 to 20,000 g / mol, and the usage thereof is 0.1% to 50% of the monomer mass.

[0016] The monomer is one or more of styrene, methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, and isooctyl acrylate, and its usage is 10% to 90% of the total mass of the system.

[0017] The organic amine is one or more of tetraethylammonium hydroxide, tetrapropylammonium hydroxide, tetrabutylammonium hydroxide, tetraoctylammonium hydroxide, tetrabutylammonium bromide, diethylamine, triethylamine, diethylenetriamine, and triethylenetetramine. The amount used is 0.1% to 10% of the total mass of the system.

[0018] The initiator is one or more of azobisisobutyronitrile, azobisisoheptanenitrile and azobisisobutyramidine hydrochloride, and the content thereof is 0.02% to 10% of the monomer mass.

[0019] The crosslinking agent is one or more of tripropylene glycol diacrylate, divinylbenzene, trimethylol triacrylate, ethylene glycol dimethacrylate and allyl methacrylate, and the amount used is 0.5% to 20% of the monomer mass.

[0020] The organic solvent is one or more of propylene glycol methyl ether, ethanol, methanol, ethyl acetate, acetonitrile, toluene, acetone, tetrahydrofuran, and dioxane. The weight ratio of the solvent to deionized water is 40 / 60 to 100 / 0, and the dosage is 10% to 500% of the total mass of the system.

[0021] The reaction temperature is 40-120°C, and the reaction time is 0.2-24h.

[0022] 2. The resulting polymer microsphere dispersion was diluted with a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1 (mass ratio)), followed by three cycles of centrifugation and washing to remove unreacted monomers and initiator. The mixture was then dried at 40°C to obtain white powdery cross-linked polymer microspheres. The powdery cross-linked polymer microspheres were dispersed in an organic solvent or water to obtain a cross-linked polymer microsphere dispersion.

[0023] The organic solvent is one or more of ethanol, methanol, acetonitrile, propylene glycol methyl ether, ethyl acetate, acetone, toluene, and tetrahydrofuran. The mass ratio of the solvent to deionized water is 0 / 100 to 100 / 0, and the amount used is 10% to 2000% of the total mass of the microspheres.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] (1) The present invention adopts RAFT dispersion polymerization to prepare cross-linked polymer microspheres, which does not require the addition of dispersants and stabilizers. The product is pure and the surface of the microspheres is smooth.

[0026] (2) The present invention can effectively adjust the stability of the polymerization system by adding organic amines, and can prepare monodisperse, highly cross-linked, and narrowly distributed polymer microspheres with adjustable particle size. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1These are scanning electron micrographs of cross-linked polymer microspheres prepared in Example 7, Example 16, and Comparative Example 1 of the present invention, wherein: (a) Comparative Example 1: no tetraethylammonium hydroxide was added; (b) Example 7: tetraethylammonium hydroxide was added; and (c) Example 16: tetrabutylammonium hydroxide was added.

[0028] Figure 2 These are scanning electron micrographs of cross-linked polymer microspheres prepared in Examples 5, 6, 7, and 8 of the present invention; wherein, (a) Example 5: Mn = 2000 g / mol; (b) Example 6: Mn = 5000 g / mol; (c) Example 7: Mn = 10000 g / mol; (d) Example 8: Mn = 20000 g / mol.

[0029] Figure 3 Scanning electron micrographs of cross-linked polymer microspheres prepared in Examples 7, 11, 12, 13, and 14 of the present invention; St / PAA-RAFT ratios are: (a) Example 11: 3 / 1; (b) Example 12: 4 / 1; (c) Example 7: 5 / 1; (d) Example 13: 6 / 1; (e) Example 14:

[0030] 7 / 1.

[0031] Figure 4 These are scanning electron micrographs of the cross-linked polymer microspheres prepared in Examples 7 and 15 of the present invention; wherein the initiator contents are: (a) Example 7: 0.6%; (b) Example 15: 1%.

[0032] Figure 5 This is a scanning electron microscope image of the cross-linked polymer microspheres prepared in Example 22 of the present invention. DETAILED DESCRIPTION

[0033] The preferred embodiments of the present invention will be described in detail below with reference to specific examples.

[0034] Example 1

[0035] Design and synthesis of a macromolecular RAFT agent PAA-RAFT with a molecular weight of 2000 g / mol

[0036] 0.46 g (0.0013 mol) of 2-[(dodecylsulfanyl)thioacyl]-2-methylpropanoic acid, 2.50 g (0.0347 mol) of acrylic acid, 0.0456 g (0.2775 mmol) of azobisisobutyronitrile, and 11.84 g of propylene glycol methyl ether were weighed and added to a 100 mL three-necked flask. The mixture was evacuated and purged with argon and reacted at 70°C. A sample was taken to measure the conversion. The reaction was stopped when the conversion reached 80%, yielding a yellow, transparent liquid.

[0037] By using the same synthesis steps and adjusting the molar ratio of acrylic acid to 2-[(dodecylsulfanyl)thioacyl]-2-methylpropionic acid, macromolecular RAFT agents PAA-RAFT with molecular weights of 5000, 10000, and 20000 g / mol can be prepared.

[0038] Example 2

[0039] Design and synthesis of a macromolecular RAFT agent PAA-b-PS-RAFT with a molecular weight of 10000 g / mol

[0040] Weigh 14.80 g (0.0015 mol) of the macromolecular RAFT agent PAA-RAFT (Mn = 2000 g / mol), 10.00 g (0.0960 mol) of styrene, 0.0631 g (0.3841 mmol) of azobisisobutyronitrile, and 8.64 g of propylene glycol methyl ether into a 100 mL three-necked flask. Vacuum and purge with argon and react at 70°C. Samples were taken for conversion measurement. The reaction was stopped when the conversion reached 80%, yielding a yellow, transparent liquid.

[0041] Example 3

[0042] Design and synthesis of a macromolecular RAFT agent PAA-co-PS-RAFT with a molecular weight of 10000 g / mol

[0043] 0.46 g (0.0013 mol) of 2-[(dodecylsulfanyl)thioacyl]-2-methylpropanoic acid, 2.50 g (0.0347 mol) of acrylic acid, 10.00 g (0.0960 mol) of styrene, 0.0429 g (0.2614 mmol) of azobisisobutyronitrile, and 8.64 g of propylene glycol methyl ether were added to a 100 mL three-necked flask. The mixture was evacuated, purged with argon, and reacted at 70°C. A sample was taken for conversion measurement. The reaction was stopped when the conversion reached 80%, yielding a yellow, transparent liquid.

[0044] Example 4

[0045] Design and synthesis of a macromolecular RAFT agent PGMA-co-PMMA-RAFT with a molecular weight of 10000 g / mol

[0046] 0.23 g (0.0007 mol) of 2-[(dodecylsulfanyl)thioacyl]-2-methylpropanoic acid, 4.73 g (0.0333 mol) of glycidyl methacrylate, 7.77 g (0.0776 mol) of methyl methacrylate, 0.0364 g (0.2217 mmol) of azobisisobutyronitrile, 30.23 g of ethyl acetate, and 0.5 g of anisole were added to a 100 mL three-necked flask, evacuated, purged with argon, and reacted at 70°C. Samples were taken for conversion measurement. The reaction was stopped when the conversion reached 80%, yielding a yellow, transparent liquid.

[0047] Example 5

[0048] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=2000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0049] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 4.47 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0050] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0051] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 705 nm, with a coefficient of variation (CV) of 0.034, calculated from 100 selected points in the SEM image.

[0052] Example 6

[0053] Monodisperse microspheres were prepared with a mass ratio of styrene to PAA-RAFT (Mn=5000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0054] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 4.47 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0055] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0056] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 707 nm, with a coefficient of variation (CV) of 0.040, as determined by scanning electron microscopy at 100 points.

[0057] Example 7

[0058] Monodisperse microspheres were prepared with a mass ratio of styrene to PAA-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine in an amount of 3.5% of the total mass of the system.

[0059] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 4.47 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0060] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0061] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and then measured by scanning electron microscopy. The average particle size of the microspheres was 787 nm, with a coefficient of variation (CV) of 0.029, calculated from 100 selected points in the SEM image.

[0062] Example 8

[0063] Monodisperse microspheres were prepared with a mass ratio of styrene to PAA-RAFT (Mn=20000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0064] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 4.47 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0065] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0066] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 1879 nm, with a coefficient of variation (CV) of 0.092, as determined by scanning electron microscopy at 100 points.

[0067] Example 9

[0068] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-b-PS-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0069] 0.67 g (0.0400 mmol) of the macromolecular RAFT agent PAA-b-PS-RAFT, 2.00 g (0.0192 mol) of styrene, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 0.87 g (0.0015 mol) of tetraethylammonium hydroxide aqueous solution, 15.73 g of propylene glycol methyl ether, and 6.26 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0070] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0071] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 64 nm, with a coefficient of variation (CV) of 0.079, as determined by scanning electron microscopy at 100 points.

[0072] Example 10

[0073] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-co-PS-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0074] 0.67 g (0.0400 mmol) of the macromolecular RAFT agent PAA-co-PS-RAFT, 2.00 g (0.0192 mol) of styrene, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 0.87 g (0.0015 mol) of tetraethylammonium hydroxide aqueous solution, 15.73 g of propylene glycol methyl ether, and 6.26 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0075] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0076] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and then measured by scanning electron microscopy. The average particle size of the microspheres was 1840 nm, with a coefficient of variation (CV) of 0.149, calculated from 100 selected points in the SEM image.

[0077] Example 11

[0078] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 3 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0079] 3.00 g (0.0003 mol) of the macromolecular RAFT agent PAA-RAFT, 1.80 g (0.0173 mol) of styrene, 0.14 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0105 g (0.0639 mmol) of azobisisobutyronitrile, 4.90 g (0.0084 mol) of tetraethylammonium hydroxide aqueous solution, 13.63 g of propylene glycol methyl ether, and 3.20 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken and the conversion was measured. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0080] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0081] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slides were dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 500 nm, with a coefficient of variation (CV) of 0.058, as determined by scanning electron microscopy at 100 points.

[0082] Example 12

[0083] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 4 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0084] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 1.60 g (0.0154 mol) of styrene St, 0.13 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0093 g (0.0567 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 11.82 g of propylene glycol methyl ether, and 3.31 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0085] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0086] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 639 nm, with a coefficient of variation (CV) of 0.062, as determined by scanning electron microscopy at 100 points.

[0087] Example 13

[0088] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 6 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0089] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.40 g (0.0230 mol) of styrene St, 0.19 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0140 g (0.0853 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 17.24 g of propylene glycol methyl ether, and 5.63 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0090] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0091] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and then measured by scanning electron microscopy. The average particle size of the microspheres was 883 nm, with a coefficient of variation (CV) of 0.090, as determined by selecting 100 points from the SEM image.

[0092] Example 14

[0093] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 7 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine.

[0094] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.80 g (0.0269 mol) of styrene St, 0.22 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0269 g (0.1638 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 19.97 g of propylene glycol methyl ether, and 6.80 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0095] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0096] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and then measured by scanning electron microscopy. The average particle size of the microspheres was 1014 nm, with a coefficient of variation (CV) of 0.059, calculated from 100 selected points in the SEM image.

[0097] Example 15

[0098] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, tetraethylammonium hydroxide as the organic amine, and an initiator azobisisobutyronitrile added in an amount of 1% of the monomer mass.

[0099] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.02 g (0.1218 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 4.47 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a polymer microsphere dispersion.

[0100] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0101] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and then measured by scanning electron microscopy. The average particle size of the microspheres was 1057 nm, with a coefficient of variation (CV) of 0.060, as determined by scanning electron microscopy at 100 points.

[0102] Example 16

[0103] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetrabutylammonium hydroxide as the organic amine.

[0104] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 5.76 g (0.0056 mol) of tetrabutylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 2.59 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a polymer microsphere dispersion.

[0105] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0106] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 657 nm, with a coefficient of variation (CV) of 0.116, calculated from 100 selected points in the SEM image.

[0107] Example 17

[0108] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine in an amount of 5% of the total mass of the system.

[0109] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 4.63 g (0.0079 mol) of tetraethylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 3.44 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a polymer microsphere dispersion.

[0110] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0111] Example 18

[0112] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and tetraethylammonium hydroxide as the organic amine in an amount of 8% of the total mass of the system.

[0113] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 7.41 g (0.0126 mol) of tetraethylammonium hydroxide aqueous solution, 14.53 g of propylene glycol methyl ether, and 1.35 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a polymer microsphere dispersion.

[0114] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0115] Example 19

[0116] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 5 / 1 and an alcohol / water ratio of 60 / 40.

[0117] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 12.22 g of propylene glycol methyl ether, and 6.77 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0118] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0119] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then dispensed onto a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres, calculated from 100 points of the SEM image, was 679 nm, with a coefficient of variation (CV) of 0.186.

[0120] Example 20

[0121] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 5 / 1 and an alcohol / water ratio of 80 / 20.

[0122] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 16.83 g of propylene glycol methyl ether, and 2.16 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0123] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0124] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 538 nm, with a coefficient of variation (CV) of 0.125, calculated from 100 selected points in the SEM image.

[0125] Example 21

[0126] Monodisperse microspheres were prepared with a mass ratio of styrene to macromolecular RAFT agent PAA-RAFT (Mn=10000 g / mol) of 5 / 1 and an alcohol / water ratio of 90 / 10.

[0127] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, and 19.14 g of propylene glycol methyl ether were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres.

[0128] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0129] One drop of polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and subjected to scanning electron microscopy. The average particle size of the microspheres was 1213 nm, with a coefficient of variation (CV) of 0.313, calculated from 100 points of the SEM image.

[0130] Example 22

[0131] Monodisperse microspheres were prepared with a mass ratio of styrene to the macromolecular RAFT agent PGMA-co-PMMA-RAFT (Mn=10000 g / mol) of 5 / 1 and an alcohol / water ratio of 70 / 30.

[0132] 1.33 g (0.0002 mol) of the macromolecular RAFT agent PGMA-co-PMMA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 3.27 g (0.0056 mol) of tetraethylammonium hydroxide aqueous solution, 15.20 g of propylene glycol methyl ether, and 4.47 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated, purged with argon, and reacted at 70°C. Samples were taken to measure the conversion. The reaction was stopped when the conversion reached 90%, yielding a polymer microsphere dispersion.

[0133] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), then centrifuged and washed three times to remove unreacted monomers and initiators, and finally dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0134] One drop of the polymer microsphere dispersion was added to 10 g of deionized water, dispersed ultrasonically, and then applied to a clean 5 x 5 mm glass slide. The slide was dried at 40°C and then measured by scanning electron microscopy. The average particle size of the microspheres was 265 nm, with a coefficient of variation (CV) of 0.069, as determined by scanning electron microscopy at 100 points.

[0135] Comparative Example 1

[0136] Monodisperse microspheres were prepared with a mass ratio of styrene to PAA-RAFT (Mn=10000 g / mol) of 5 / 1, an alcohol / water ratio of 70 / 30, and no organic amine added.

[0137] 2.00 g (0.0002 mol) of the macromolecular RAFT agent PAA-RAFT, 2.00 g (0.0192 mol) of styrene St, 0.16 g (8% of the monomer weight) of the crosslinker tripropylene glycol diacrylate, 0.0117 g (0.0711 mmol) of azobisisobutyronitrile, 14.53 g of propylene glycol methyl ether, and 6.91 g of deionized water were added to a three-necked flask and stirred until completely dissolved. The mixture was then evacuated and purged with argon. The reaction was carried out at 70°C, and the conversion was measured by sampling. The reaction was stopped when the conversion reached 90%, yielding a dispersion of crosslinked polymer microspheres. A gel-like substance was observed in the system.

[0138] 10 g of the cross-linked polymer microsphere dispersion was diluted with 20 g of a mixed solution of ethanol and water (ethanol / deionized water = 1 / 1), centrifuged, and washed three times to remove unreacted monomers and initiators. The mixture was then dispersed in 9 g of deionized water to obtain a cross-linked polymer microsphere dispersion with a solid content of 10%.

[0139] Add one drop of polymer microsphere dispersion to 10g of deionized water, disperse with ultrasound, and drop onto a clean 5×5mm glass slide. Dry at 40°C and measure with a scanning electron microscope. Scanning electron microscopy shows that the particles are poorly spherical and aggregated.

[0140] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

Claims

1. A monodisperse cross-linked polymer microsphere prepared by RAFT dispersion polymerization, characterized in that: The preparation method of the monodisperse cross-linked polymer microspheres comprises the following steps: (1) Add the macromolecular RAFT agent, monomer, organic amine, initiator, crosslinking agent, organic solvent and deionized water into a three-necked flask, stir and dissolve, evacuate and pass argon, cycle three times, then react, take samples to measure the conversion rate, stop the reaction when the conversion rate reaches more than 90%, and obtain a cross-linked polymer microsphere dispersion; (2) diluting the polymer microsphere dispersion with a mixed solution of ethanol and water, then centrifuging and washing for three cycles to remove unreacted monomers and initiators, and drying at 40°C to obtain white powdery cross-linked polymer microspheres. The powdery cross-linked polymer microspheres are dispersed in an organic solvent or water to obtain a cross-linked polymer microsphere dispersion; The organic amine is one or more of tetraethylammonium hydroxide, tetrapropylammonium hydroxide, tetrabutylammonium hydroxide, tetraoctylammonium hydroxide, tetrabutylammonium bromide, diethylamine, triethylamine, diethylenetriamine, and triethylenetetramine, and its usage is 0.1% to 10% of the total mass of the system.

2. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The structural formula of the macromolecular RAFT agent in step (1) is: ， in: Representative structural formula: one or more of polyacrylic acid, polymethacrylic acid, polyglycidyl acrylate, and polyglycidyl methacrylate; The structural formula represents: one or both of polystyrene and polymethyl methacrylate, wherein 0≤m, n≤300.

3. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The macromolecular RAFT agent in step (1) has a molecular weight of 500 to 20,000 g / mol and is used in an amount of 0.1% to 50% of the monomer mass.

4. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The monomers in step (1) are one or more of styrene, methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, and isooctyl acrylate, and the amount thereof is 10% to 90% of the total mass of the system.

5. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The initiator in step (1) is one or more of azobisisobutyronitrile, azobisisoheptanenitrile, and azobisisobutyramidine hydrochloride, and its content is 0.02% to 10% of the monomer mass.

6. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The cross-linking agent in step (1) is one or more of tripropylene glycol diacrylate, divinylbenzene, trimethylol triacrylate, ethylene glycol dimethacrylate, and allyl methacrylate, and its usage is 0.5% to 20% of the monomer mass.

7. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The organic solvent in step (1) is one or more of propylene glycol methyl ether, ethanol, methanol, ethyl acetate, acetonitrile, toluene, acetone, tetrahydrofuran, and dioxane, the weight ratio of the organic solvent to deionized water is 40 / 60~100 / 0, and the amount used is 10%~500% of the total mass of the system.

8. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The reaction temperature of step (1) is 40-120°C, and the reaction time is 0.2-24 h.

9. The monodisperse cross-linked polymer microspheres prepared by RAFT dispersion polymerization according to claim 1, characterized in that: The weight ratio of ethanol to deionized water in the mixed solution of step (2) is 1:1.

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