阅读说明：本技术 一种单分散多孔聚合物微球的制备方法 (Preparation method of monodisperse porous polymer microspheres ) 是由 王艳艳 郭峰豪 丁园园 陈志勇 于 2020-11-02 设计创作，主要内容包括：本发明涉及一种微米级单分散多孔聚合物微球的制备方法,是以甲基丙烯酸缩水甘油酯为单体,以二乙烯基苯为交联剂,聚合得到；微球粒径为2～10μm,多分散系数为1.01～1.05,微球表面积在2～500 m～2/g之间可控。制备方法,包括步骤如下：将烯烃单体、二乙烯基苯和引发剂一起加入到以乙腈与四氢呋喃组成的二元溶剂体系中混合均匀,置于不锈钢反应釜中,通入氮气后密封,于油浴中升温聚合,反应温度控制在82～90℃,反应时间3-5小时；得到的反应产物经洗涤、干燥,即得；本发明所得微米级微球,粒径单分散,表面积高,机械强度高；制备过程简单,反应条件安全可靠,反应迅速,耗时短,固含量高,制备过程环保,易于工业化生产。(The invention relates to a preparation method of micron-sized monodisperse porous polymer microspheres, which is obtained by polymerizing glycidyl methacrylate serving as a monomer and divinylbenzene serving as a crosslinking agent; the particle size of the microspheres is 2-10 mu m, the polydispersity is 1.01-1.05, and the surface area of the microspheres is 2-500 m 2 The concentration/g is controllable. The preparation method comprises the following steps: olefin monomer, divinyl benzene and initiator are added into a binary solvent system consisting of acetonitrile and tetrahydrofuran together and mixed evenlyPlacing the mixture in a stainless steel reaction kettle, introducing nitrogen, sealing, heating in an oil bath for polymerization, controlling the reaction temperature at 82-90 ℃ and the reaction time for 3-5 hours; washing and drying the obtained reaction product to obtain the catalyst; the micron-sized microspheres obtained by the invention have monodisperse particle size, high surface area and high mechanical strength; the preparation process is simple, the reaction conditions are safe and reliable, the reaction is rapid, the time consumption is short, the solid content is high, the preparation process is environment-friendly, and the industrial production is easy to realize.)

1. A micron-sized monodisperse porous polymer microsphere is prepared by polymerizing unsaturated olefin such as glycidyl methacrylate, methyl methacrylate, methacrylic acid, hydroxyethyl methacrylate and the like serving as monomers, divinyl benzene (DVB) serving as a cross-linking agent and a binary solvent system consisting of acetonitrile, toluene, tetrahydrofuran, isopropanol, water and the like serving as a solvent; the particle size of the microspheres is 2-10 mu m, the polydispersity coefficient is 1.01-1.05, and the surface area of the microspheres measured by a nitrogen adsorption method is 2-500 m²The concentration/g is controllable.

2. A method for preparing the highly crosslinked monodisperse epoxy group-containing polymer microsphere of claim 1, comprising the steps of:

adding unsaturated olefin such as glycidyl methacrylate, methyl methacrylate, methacrylic acid, hydroxyethyl methacrylate and the like, divinyl benzene (DVB) and an initiator into a binary solvent system consisting of acetonitrile, toluene, tetrahydrofuran, isopropanol, water and the like, uniformly mixing, placing into a stainless steel reaction kettle, introducing nitrogen, sealing, heating in an oil bath for polymerization, controlling the reaction temperature at 82-90 ℃, and reacting for 3-5 hours; washing and drying the obtained reaction product to obtain the catalyst.

3. The method according to claim 2, wherein the olefin monomer is Glycidyl Methacrylate (GMA) and the molar ratio of the glycidyl methacrylate to Divinylbenzene (DVB) is (2-80): 100, more preferably (10 to 30): 100.

4. the method according to claim 2, wherein the ratio of the initiator to the total mass of the olefin monomer and the Divinylbenzene (DVB) is (1-12): 100, more preferably (7 to 10): 100.

5. the method according to claim 2, wherein the binary solvent system is a binary solvent of acetonitrile and toluene or tetrahydrofuran, and more preferably, the binary solvent system of acetonitrile and tetrahydrofuran, the volume ratio of which is 100: (1 to 40), more preferably 100: (8-15).

6. The method of claim 2, wherein the initiator is azobisisobutyronitrile.

7. The preparation method according to claim 2, wherein the temperature is controlled at 82-90 ℃, more preferably 85 ℃; the reaction time is 3-5 hours, and the preferable time is 4 hours; the heating mode is oil bath or water bath heating.

8. The method according to claim 2, wherein the washing detergent is ethanol, and the drying temperature is 50 ℃ and the washing detergent is dried to a constant weight.

9. A preparation method of micron-sized monodisperse porous polymer microspheres comprises the following steps:

adding 3.70 ml of divinylbenzene, 0.87 ml of glycidyl methacrylate and 0.35 g of azobisisobutyronitrile into 28.92ml of acetonitrile and 1.52 ml of tetrahydrofuran, mixing, adding into a polytetrafluoroethylene lining of a stainless steel reaction kettle, introducing nitrogen for 5 min, removing oxygen, and sealing; then placing the mixture in an oil bath, setting the temperature of the oil bath to be 85 ℃, and reacting for 4 hours; stopping heating, washing with 50 ml ethanol, drying to constant weight to obtain micron-sized fractionThe average particle size of the dispersed porous polymer microspheres is 5.13 mu m, the polydispersity is 1.05, and the surface area (determined by a nitrogen adsorption method) is 434.4 m²/g。

Technical Field

The invention relates to a preparation method of micron-sized monodisperse porous polymer microspheres, belonging to the technical field of high molecular materials.

Background

Monodisperse polymeric microspheres refer to spherical polymeric materials with highly uniform particle size. The monodisperse polymer microsphere can be used as a core component of high performance liquid chromatography, namely a filler of a liquid chromatography column, and can realize rapid analysis and industrial-scale purification and separation of target molecules such as organic compounds, natural products, proteins, polypeptides and the like. Compared with silica gel matrix filler, the polymer microsphere matrix has the advantages of wide pH tolerance range, low nonspecific adsorption and easy surface modification.

Precipitation polymerization is the only method for preparing micron-sized monodisperse polymer microspheres without any auxiliary agent. The porous monodisperse polymer microspheres prepared by precipitation polymerization are reported in the literature, the obtained microspheres have pure surfaces and are beneficial to treatment, the particle size is 2-10 mu m, and the surface area is several-800 m²Controllable in terms of/g, and suitable as chromatographic media (see: Wen-Hui Li, Harald D.H. Stover, Journal of Polymer Science A1998, 36, 1543-. However, in order to ensure uniformity of particle size, in the above precipitation polymerization, the solid content of the monomer is low (2% to 5% by weight input ratio), the yield of the microspheres is low (usually below 50%), the solvent consumption is large, and the method is not suitable for large-scale industrial production.

Chinese patent documents CN102898572A and CN1047886092A disclose a method for preparing monodisperse microspheres by solvent thermal bonding precipitation polymerization, and the method has high monomer input and high microsphere yield. However, the method adopts a single solvent system, and the obtained microspheres have small surface area and low adsorption capacity, so that the method is not beneficial to application in chromatographic packing.

Disclosure of Invention

In order to solve the problems and the defects of the prior art, the invention provides a preparation method of micron-sized monodisperse porous polymer microspheres; the method is prepared by introducing a binary solvent system and adopting solvent thermal combination precipitation polymerization.

The technical scheme of the invention is as follows:

a micron-sized monodisperse porous polymer microsphere is prepared by polymerizing unsaturated olefin such as glycidyl methacrylate, methyl methacrylate, methacrylic acid, hydroxyethyl methacrylate and the like serving as monomers, Divinylbenzene (DVB) serving as a cross-linking agent and a binary solvent system consisting of acetonitrile, toluene, tetrahydrofuran, propanol, water and the like serving as a solvent; the particle size of the microspheres is 2-10 mu m, the polydispersity is 1.01-1.05, and the surface area determined by a nitrogen adsorption method is 2-500 m²/g；

A preparation method of micron-sized monodisperse porous polymer microspheres comprises the following steps:

adding unsaturated olefin such as glycidyl methacrylate, methyl methacrylate, methacrylic acid, hydroxyethyl methacrylate and the like, divinyl benzene (DVB) and an initiator into a binary solvent system consisting of acetonitrile, toluene, tetrahydrofuran, isopropanol, water and the like, uniformly mixing, placing into a stainless steel reaction kettle, introducing nitrogen, sealing, heating in an oil bath for polymerization, controlling the reaction temperature at 82-90 ℃, and reacting for 3-5 hours; washing and drying the obtained reaction product to obtain the catalyst.

According to the present invention, preferably, the olefin monomer is glycidyl methacrylate, and the molar ratio of the glycidyl methacrylate to Divinylbenzene (DVB) is (2 to 80): 100, more preferably (10 to 30): 100, respectively;

preferably, the ratio of the initiator to the total mass of the olefin monomer and the Divinylbenzene (DVB) is (1-12): 100, more preferably (7 to 10): 100, respectively;

preferably, the ratio of the solvent to the total mass of the olefin monomer and Divinylbenzene (DVB) is 100: (2 to 30), more preferably 100: (18-25).

Preferably, the binary solvent system is a binary solvent composed of acetonitrile and toluene or tetrahydrofuran, and more preferably, the binary solvent system of acetonitrile and tetrahydrofuran, the volume ratio of which is 100: (1 to 40), more preferably 100: (8-15).

According to the present invention, preferably, the initiator is azobisisobutyronitrile.

According to the invention, preferably, the temperature is controlled to be 82-90 ℃, and more preferably 85 ℃; the reaction time is 3-5 hours, and the preferable time is 4 hours; the heating mode is oil bath or water bath heating.

According to the invention, preferably, the washing detergent is ethanol, the drying temperature is 50 ℃, and the washing detergent is dried to constant weight.

According to the present invention, most preferably, a method for preparing micron-sized monodisperse porous polymer microspheres comprises the following steps:

adding 3.70 ml of divinylbenzene, 0.87 ml of glycidyl methacrylate and 0.35 g of azobisisobutyronitrile into 28.92ml of acetonitrile and 1.52 ml of tetrahydrofuran, mixing, adding into a polytetrafluoroethylene lining of a stainless steel reaction kettle, introducing nitrogen for 5 min, removing oxygen, and sealing; then placing the mixture in an oil bath, setting the temperature of the oil bath to be 85 ℃, and reacting for 4 hours; stopping heating, washing with 50 ml ethanol, and drying to constant weight to obtain micron-sized monodisperse porous polymer microspheres. The average particle size is 5.13 mu m, the polydispersity is 1.05, the yield is 64.4%, and the surface area (determined by nitrogen adsorption method) is 434.4 m²/g。

The micron-sized monodisperse porous polymer microspheres prepared by the method have micron-sized particle sizes, average particle sizes of 2-10 mu m, polydispersity numbers of 1.01-1.05 and surface areas of 2-500 m²The/g is controllable, and the monodispersity and the spherical character are good.

The invention has the following beneficial effects:

1. the micron-sized monodisperse porous polymer microspheres prepared by the method have the advantages of several microns of particle size, monodispersity of particle size, high surface area and high mechanical strength, and are suitable for chromatographic packing;

2. the preparation method has the advantages of simple preparation process, safe and reliable reaction conditions, rapid reaction, short time consumption, high solid content, high yield of the polymer microspheres, environment-friendly preparation process and easy industrial production;

3. the invention has cheap and easily obtained raw materials and low production cost.

Drawings

FIG. 1 is a nitrogen adsorption-desorption curve of porous polymeric microspheres prepared in examples 1-5 of the present invention.

FIG. 2 is a comparison of pore performance of porous microspheres made in examples 1-5 of the present invention.

Detailed Description

The present invention will be further described with reference to the following examples and drawings, but is not limited thereto.

The divinylbenzene monomer used in the examples was divinylbenzene 80 (trade name, indicating that the divinylbenzene content was 80% by mass and the vinylethylbenzene content was 20%), which was commercially available from alatin reagent (china) ltd. Glycidyl methacrylate monomer, available from alatin reagent (china) limited. The yields in the examples are weight yields based on the total amount of glycidyl methacrylate and Divinylbenzene (DVB) charged.

Example 1

A preparation method of micron-sized monodisperse porous polymer microspheres comprises the following steps:

4.08 ml of divinylbenzene monomer, 0.96 ml of glycidyl methacrylate and 0.38 g of azobisisobutyronitrile are added into 27.24 ml of acetonitrile and 2.72 ml of toluene, mixed and dissolved, added into a polytetrafluoroethylene lining of a stainless steel reaction kettle, introduced with nitrogen for 15 min, and sealed after oxygen is removed; then placing the mixture in an oil bath, setting the temperature of the oil bath to be 85 ℃, and reacting for 4 hours; stopping heating, washing with 50 ml ethanol, and drying at 50 ℃ to constant weight to obtain the polymer microsphere. The average particle size was 5.26 μm, the polydispersity was 1.07, the yield was 66.9%, and the surface area (determined by nitrogen adsorption) was 357.8 m²/g。

Example 2

A preparation method of micron-sized monodisperse porous polymer microspheres comprises the following steps:

3.70 ml of divinylbenzene monomer, 0.87 ml of glycidyl methacrylate and 0.35 g of azobisisobutyronitrile are added into 28.92ml of acetonitrile and 1.52 ml of tetrahydrofuran, after being mixed, the mixture is added into a polytetrafluoroethylene lining of a stainless steel reaction kettle, and nitrogen is introduced into the polytetrafluoroethylene liningIntroducing gas for 15 min, removing oxygen, and sealing; then placing the mixture in an oil bath, setting the temperature of the oil bath to be 85 ℃, and reacting for 4 hours; stopping heating, washing with 50 ml ethanol, and drying at 50 ℃ to constant weight to obtain the polymer microsphere. The average particle size is measured to be 5.13 mu m, the polydispersity is 1.05, and the yield is 64.4%; the surface area (determined by nitrogen adsorption method) is 434.4 m²/g。

Example 3

A preparation method of micron-sized monodisperse porous polymer microspheres comprises the following steps:

4.06 ml of divinylbenzene monomer, 0.95 ml of glycidyl methacrylate and 0.38 g of azobisisobutyronitrile are added into 27.27 ml of acetonitrile to neutralize 2.73 ml of propanol, mixed and dissolved, added into a polytetrafluoroethylene lining of a stainless steel reaction kettle, introduced with nitrogen for 15 min, and sealed after oxygen is removed; then placing the mixture in an oil bath, setting the temperature of the oil bath to be 85 ℃, and reacting for 4 hours; stopping heating, washing with 50 ml ethanol, and drying at 50 ℃ to constant weight to obtain the polymer microsphere. The average particle size was found to be 6.13 μm, the polydispersity was found to be 1.05, the yield was 50.6%, and the surface area (determined by nitrogen adsorption) was 262.5 m²/g。

Example 4

A preparation method of micron-sized monodisperse porous polymer microspheres comprises the following steps:

4.07 ml of divinylbenzene monomer, 0.95 ml of glycidyl methacrylate and 0.38 g of azobisisobutyronitrile are added into 29.40 ml of acetonitrile and 0.59 ml of water, mixed and dissolved, added into a polytetrafluoroethylene lining of a stainless steel reaction kettle, introduced with nitrogen for 15 min, and sealed after oxygen is removed; then placing the mixture in an oil bath, setting the temperature of the oil bath to be 85 ℃, and reacting for 4 hours; stopping heating, washing with 50 ml ethanol, and drying at 50 ℃ to constant weight to obtain the polymer microsphere. The average particle size was 4.11 μm, the polydispersity was 1.02, the yield was 55.9%, and the surface area (determined by nitrogen adsorption) was 14.8 m²/g。

Example 5 (comparative example)

A preparation method of micron-sized monodisperse porous polymer microspheres comprises the following steps:

adding 3.70 ml of divinylbenzene monomer, 0.87 ml of glycidyl methacrylate and 0.35 g of azobisisobutyronitrile into 30.44 ml of acetonitrile, mixing, adding into a polytetrafluoroethylene lining of a stainless steel reaction kettle, introducing nitrogen for 15 min, removing oxygen, and sealing; then placing the mixture in an oil bath, setting the temperature of the oil bath to be 85 ℃, and reacting for 4 hours; stopping heating, washing with 50 ml ethanol, and drying at 50 ℃ to constant weight to obtain the polymer microsphere. The average particle size was 4.11 μm, the polydispersity was 1.02, the yield was 55.9%, and the surface area (determined by nitrogen adsorption) was 14.8 m²/g。