CN116870883A - Preparation method of liquid chromatography organosilicon hybrid porous resin microsphere, microsphere and application - Google Patents
Preparation method of liquid chromatography organosilicon hybrid porous resin microsphere, microsphere and application Download PDFInfo
- Publication number
- CN116870883A CN116870883A CN202310222331.9A CN202310222331A CN116870883A CN 116870883 A CN116870883 A CN 116870883A CN 202310222331 A CN202310222331 A CN 202310222331A CN 116870883 A CN116870883 A CN 116870883A
- Authority
- CN
- China
- Prior art keywords
- microsphere
- porous resin
- liquid chromatography
- microspheres
- gamma
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000004005 microsphere Substances 0.000 title claims abstract description 117
- 239000011347 resin Substances 0.000 title claims abstract description 46
- 229920005989 resin Polymers 0.000 title claims abstract description 46
- 238000004811 liquid chromatography Methods 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims description 19
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims abstract description 50
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 24
- XDLMVUHYZWKMMD-UHFFFAOYSA-N 3-trimethoxysilylpropyl 2-methylprop-2-enoate Chemical compound CO[Si](OC)(OC)CCCOC(=O)C(C)=C XDLMVUHYZWKMMD-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000004132 cross linking Methods 0.000 claims abstract description 15
- 239000002245 particle Substances 0.000 claims abstract description 8
- 238000010558 suspension polymerization method Methods 0.000 claims abstract description 4
- 229920001577 copolymer Polymers 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 54
- 239000011148 porous material Substances 0.000 claims description 34
- 238000005406 washing Methods 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 230000008961 swelling Effects 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 239000000178 monomer Substances 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 13
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 12
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 229910052710 silicon Inorganic materials 0.000 claims description 12
- 239000010703 silicon Substances 0.000 claims description 12
- 239000002270 dispersing agent Substances 0.000 claims description 11
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 10
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 10
- 239000003381 stabilizer Substances 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 108010010803 Gelatin Proteins 0.000 claims description 7
- 229920000159 gelatin Polymers 0.000 claims description 7
- 239000008273 gelatin Substances 0.000 claims description 7
- 235000019322 gelatine Nutrition 0.000 claims description 7
- 235000011852 gelatine desserts Nutrition 0.000 claims description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 238000009210 therapy by ultrasound Methods 0.000 claims description 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 4
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 claims description 4
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 claims description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 abstract description 5
- 230000004048 modification Effects 0.000 abstract description 5
- 238000000926 separation method Methods 0.000 abstract description 5
- 238000004458 analytical method Methods 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 229920000642 polymer Polymers 0.000 description 11
- 239000012071 phase Substances 0.000 description 10
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 7
- 239000011159 matrix material Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 229910000077 silane Inorganic materials 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 229910001220 stainless steel Inorganic materials 0.000 description 5
- 239000010935 stainless steel Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229920000620 organic polymer Polymers 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- NKSJNEHGWDZZQF-UHFFFAOYSA-N ethenyl(trimethoxy)silane Chemical compound CO[Si](OC)(OC)C=C NKSJNEHGWDZZQF-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 241000544066 Stevia Species 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 2
- 229960000878 docusate sodium Drugs 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- QWMJEUJXWVZSAG-UHFFFAOYSA-N (4-ethenylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=C)C=C1 QWMJEUJXWVZSAG-UHFFFAOYSA-N 0.000 description 1
- UUEWCQRISZBELL-UHFFFAOYSA-N 3-trimethoxysilylpropane-1-thiol Chemical compound CO[Si](OC)(OC)CCCS UUEWCQRISZBELL-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229920000779 poly(divinylbenzene) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- PNOXUQIZPBURMT-UHFFFAOYSA-M potassium;3-(2-methylprop-2-enoyloxy)propane-1-sulfonate Chemical compound [K+].CC(=C)C(=O)OCCCS([O-])(=O)=O PNOXUQIZPBURMT-UHFFFAOYSA-M 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000012799 strong cation exchange Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/282—Porous sorbents
- B01J20/285—Porous sorbents based on polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28016—Particle form
- B01J20/28019—Spherical, ellipsoidal or cylindrical
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28057—Surface area, e.g. B.E.T specific surface area
- B01J20/28066—Surface area, e.g. B.E.T specific surface area being more than 1000 m2/g
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28069—Pore volume, e.g. total pore volume, mesopore volume, micropore volume
- B01J20/28076—Pore volume, e.g. total pore volume, mesopore volume, micropore volume being more than 1.0 ml/g
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28078—Pore diameter
- B01J20/28083—Pore diameter being in the range 2-50 nm, i.e. mesopores
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F212/34—Monomers containing two or more unsaturated aliphatic radicals
- C08F212/36—Divinylbenzene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F230/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
- C08F230/04—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal
- C08F230/08—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal containing silicon
- C08F230/085—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal containing silicon the monomer being a polymerisable silane, e.g. (meth)acryloyloxy trialkoxy silanes or vinyl trialkoxysilanes
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention relates to an organosilicon hybridized porous resin microsphere for liquid chromatography, which is a polydivinylbenzene-gamma-methacryloxypropyl trimethoxysilane porous resin microsphere, in particular to a copolymer of divinylbenzene and gamma-methacryloxypropyl trimethoxysilane, and the particle size of the microsphere is 30-40 mu m. The specific surface area of the original microsphere is 600-900 m 2 After crosslinking treatment, the specific surface area can reach 1000 to the upper1200m 2 And/g. The method for preparing the resin microsphere by using the suspension polymerization method is simple and easy to amplify. The prepared original microsphere has good mechanical strength and contains a large number of reaction sites for modification, and the modification can be carried out according to different requirements, so that the original microsphere is suitable for different separation systems.
Description
Technical Field
The invention relates to the field of liquid chromatographic column matrixes, in particular to an organosilicon hybrid porous resin microsphere applied to liquid chromatography and a preparation method thereof.
Background
The high performance liquid chromatography is one of the most commonly used methods in modern analytical chemistry, has the advantages of high efficiency, high speed, high sensitivity and the like, and can be used in a plurality of scientific fields such as quality control, medicine analysis, clinical test, environmental monitoring and the like. The separation principle of high performance liquid chromatography is based on the difference of affinity of the compound to be separated to the stationary phase and the mobile phase, so that the chromatographic column is the core of a liquid chromatography system, and the research of chromatographic packing becomes the most abundant, active and creative part of the chromatographic research.
Liquid chromatography packing is largely divided into inorganic silica gel matrix, organic polymer matrix and organic-inorganic hybrid matrix. The silica gel matrix has high mechanical strength, good thermal stability and easy regulation and control of pore structure. However, silica matrices have a narrow pH tolerance range and are at risk of dissolution when used in alkaline mobile phases.
Organic polymer matrices can be broadly classified as polyacrylamides, polystyrenes, polymethacrylates, with polystyrenes being the most widely used. The polymer matrix has a wide range of pH applications compared to silica gel matrices, and even washing the column with a strong base solution such as sodium hydroxide does not affect its chromatographic performance. However, organic polymers have their fatal disadvantages in that they have poor mechanical strength and cannot withstand high column pressures in terms of their physicochemical properties.
In order to solve the disadvantage of poor mechanical strength, the most common method is to prepare an organosilicon hybrid polymer from an organic polymer and a silicon-containing reagent. Analytical Chemistry,2009,81 (9), 3529-3536 (non-patent document 1) discloses a method for producing an organic-inorganic hybrid polymer monolith having hydrophilic properties using vinyltrimethoxysilane, methyl orthosilicate and acrylamide; analytical Chemistry,2010,82 (7), 2907-2915 (non-patent document 2) discloses a method for producing a hybrid monolith having strong anion exchange properties using vinyltrimethoxysilane, methyl orthosilicate and N, N-trimethyl-3- (2-methallylanilide) -1-propanammonium chloride as precursors; chemical Communications,2011,47 (34), 9675-9677 (non-patent document 3) discloses a method for producing a hybrid monolithic column having boric acid affinity using 3- (methacryloyloxy) propyl trimethoxysilane, methyl orthosilicate and 4-vinylphenylboronic acid as precursors; electrophoresis,2013,34 (4), 510-517 (non-patent document 4) discloses a method for producing a hybrid monolithic column having both strong cation exchange and reverse phase retention mechanisms using mercaptopropyl trimethoxysilane, methyl orthosilicate and potassium 3-sulfopropyl methacrylate as precursors; analytical Chemistry,2011,83 (9), 3616-3622 (non-patent document 5) discloses a method for synthesizing a cyclodextrin derivative hybrid monolithic column using vinyltrimethoxysilane and methyl orthosilicate as organic monomers using a double bond-containing cyclodextrin derivative.
In the preparation of organic-inorganic hybrid polymer microspheres, patent literature (application No. 201110263262.3) discloses a method for preparing non-porous organic-inorganic hybrid polymer microspheres for ion chromatography using styrene and 3-trimethoxy propyl methacrylate. However, since the nonporous microspheres are not as effective as porous materials in actual sample chromatographic separations, a simple synthetic method is needed to prepare high strength porous organic-inorganic hybrid polymer microspheres.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to provide a preparation method of the organosilicon hybrid resin microsphere for liquid chromatography. The invention aims to provide the microsphere prepared by the method. Another technical problem to be solved by the present invention is to provide an application of the microsphere.
The technical scheme of the invention is that the preparation method of the organic silicon hybrid porous resin microsphere for liquid chromatography is a suspension polymerization method and comprises the following steps:
(1) Adding a dispersing agent and a stabilizing agent into water at 50-70 ℃ and stirring for dissolution; the mass fractions of the dispersing agent and the stabilizing agent are 0.5% -2%; the dispersing agent is selected from one or more than one of the following components: sodium docusate, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, sodium dodecyl sulfate, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium dodecyl benzene sulfonate; the stabilizer is selected from one or more than one of the following components: sodium docusate, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, sodium dodecyl sulfate, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium dodecyl benzene sulfonate;
(2) Taking a certain amount of dimethylbenzene, divinylbenzene, gamma-methacryloxypropyl trimethoxysilane and azobisisobutyronitrile, and uniformly mixing;
the volume ratio of divinylbenzene to gamma-methacryloxypropyl trimethoxysilane is 7:3 to 9:1, the dosage of the dimethylbenzene is 1.5 to 3 times of the volume of the divinylbenzene and the gamma-methacryloxypropyl trimethoxysilane; the dosage of the azodiisobutyronitrile is 0.5 to 1.5 percent of the total mass of the comonomer; the total mass of the comonomer is the sum of the mass of the divinylbenzene monomer and the gamma-methacryloxypropyl trimethoxysilane monomer;
(3) Adding the organic phase uniformly mixed in the step (2) into a reactor of the step (1), wherein: the volume ratio of the total volume of the organic phase to the volume of water is 1: 3-1: 5, a step of; reacting for 10-50 minutes, then continuously heating to 70-80 ℃ to continue reacting for 8-12 hours, and finally washing with hot water and ethanol respectively to obtain microspheres;
(4) Adding the microsphere obtained in the step (3) into tetrahydrofuran, and continuing swelling for 10-14 hours after ultrasonic treatment for 1-30 minutes; the proportion of the microsphere to tetrahydrofuran is as follows: 1:10 to 1:15 (g/mL);
(5) Adding ammonia water into the reaction bottle in the step (4), fully stirring, standing, and finally washing with water and ethanol to obtain the microsphere.
In the step (1), the dispersing agent can have various choices, which mainly affect the particle size of the microspheres, and different dispersing agents can be selected to try according to the size of the target microspheres; stabilizers are also selected in many ways, but gelatin has a relatively good morphology to stabilize the microspheres. Dispersants and stabilizers are generally not clearly distinguished, many substances being both dispersants and stabilizers themselves. The dispersant and the stabilizer are different substances, so that the effect is better.
In step (2), the 4 components are mutually soluble organic phases, and in step (3), the organic phase is added into the aqueous phase in step 1, and the final reaction system is a two-phase mixed system of organic phase and aqueous phase. The preparation method of the microsphere is essentially free radical thermal initiated polymerization reaction, and the comonomer is single molecule with unsaturated bond, and the polymer microsphere is further obtained by polymerizing into long chain; azobisisobutyronitrile is used as a radical initiator, and its effect is to initiate polymerization, and the amount of azobisisobutyronitrile used affects the particle size and particle size distribution of the final microspheres, so that a proper amount is required. Both the silane monomer and the divinylbenzene monomer are comonomers.
In the step (3), washing is performed by hot water and then ethanol.
According to the preparation method of the organic silicon hybrid porous resin microsphere for liquid chromatography, the reaction time of the step (3) is preferably 30-50 minutes.
According to the preparation method of the organic silicon hybrid porous resin microsphere for liquid chromatography, preferably, the stirring in the step (5) is ultrasonic stirring for 15-30 minutes; and (3) standing for 18-36 hours in the step (5).
According to the preparation method of the organic silicon hybrid porous resin microsphere for liquid chromatography, in the step (5), preferably, the volume ratio of the ammonia water to the tetrahydrofuran is 1: 15-1: 20.
according to the preparation method of the organic silicon hybrid porous resin microsphere for liquid chromatography, the step (5) is preferably followed by a post-crosslinking method; the post-crosslinking method comprises the following steps:
dispersing the microspheres in 1, 2-dichloroethane, swelling for 6-10 hours, adding anhydrous ferric trichloride, heating to 70-90 ℃ for reaction for 7-9 hours, washing with ethanol after the reaction, washing with dilute hydrochloric acid, washing with water to neutrality, and drying to obtain the target product.
Further, the mass ratio of the 1, 2-dichloroethane, anhydrous ferric trichloride and the microspheres is 4-7:0.2-0.5:0.5-2.
The invention also provides a microsphere obtained by the preparation method of the organosilicon hybridized porous resin microsphere for liquid chromatography, wherein the microsphere is a copolymer of divinylbenzene and gamma-methacryloxypropyl trimethoxysilane; the specific surface area of the obtained original microsphere is 600-900 m 2 Per gram, pore volume of 0.8-1.4 cm 3 And/g, average pore diameter of 5-8 nm. Has good thermal stability and can resist the pressure of at least 3500 psi.
The invention also provides a microsphere obtained by the preparation method of the organosilicon hybridized porous resin microsphere for liquid chromatography, and the specific surface area of the organosilicon hybridized porous resin microsphere obtained after the crosslinking treatment is 1000-1200 m 2 Per gram, pore volume of 1.2-1.8 cm 3 And/g, average pore diameter of 5-8 nm. The microspheres have good thermal stability and are capable of withstanding pressures of at least 3500 psi. The mechanical strength of the microspheres after the cross-linking treatment is significantly better than that obtainable from the pressure-flow graph in the figures.
Preferably, the particle diameter of the microspheres is 30 to 40. Mu.m.
The invention provides application of the microsphere in liquid chromatography. In particular as liquid chromatography packing.
The invention specifically relates to preparation and application of polydivinylbenzene-gamma-methacryloxypropyl trimethoxysilane porous resin microspheres.
The prepared microspheres are porous resin microspheres, and the silane monomers are added, so that the silane monomers also contain unsaturated bonds and can be copolymerized with the divinylbenzene monomers to form polymers, so that the polymer skeleton contains silicon elements, the mechanical strength of the resin microspheres can be improved, and the final resin microspheres have proper specific surface area and better mechanical strength by adjusting the proportion of the silane monomers to the divinylbenzene monomers. On the other hand, the final polymerized resin microsphere skeleton contains a large number of silicon-oxygen bonds, so that condensation reaction is easy to occur, and a new chemical bond can be formed between a polymer long chain and a long chain in the skeleton, namely, the crosslinking degree is improved, and the mechanical strength of the resin microsphere is further improved while the crosslinking degree is improved. At the same time, the microsphere contains a large number of reaction sites for modification, and different modification can be carried out according to different separation systems. As the adopted monomer is divinylbenzene, the two unsaturated bonds have different activities, so that the skeleton of the final resin microsphere contains a large number of unreacted carbon-carbon double bonds, friedel-crafts alkylation reaction can be carried out under the catalysis of Lewis acid, new chemical bonds are formed between long chains of the polymer in the skeleton, the crosslinking degree is improved again, and the specific surface area and the mechanical strength of the resin microsphere are further improved. The resin microsphere can be used in alkaline environment for a long time, and can be used as a preferred matrix in an environment where a silica gel matrix is not applicable.
The porous resin microsphere prepared by the invention has two main points of physicochemical properties, namely a porous structure and better mechanical strength. The mechanical strength effect is shown in the various pressure-flow diagrams in the figures. The linear relationship between pressure and flow rate demonstrates that the resin microspheres can withstand the pressures tested. Meanwhile, the resin microspheres relate to the process of filling the resin microspheres into a chromatographic column in chromatographic application, after filling, the resin microspheres with different mechanical strengths can present different pressures at the same flow rate in liquid chromatography, the mechanical strength is weaker and higher pressure is presented, namely, the linear relation in a pressure-flow rate diagram has a larger slope, and the difference of the mechanical strengths among the different resin microspheres can be compared through the comparison of the slopes.
Drawings
FIG. 1 is a thermal weight loss curve of the resin microspheres prepared in example 1.
FIG. 2 is a scanning electron microscope image of the resin microspheres prepared in example 1.
FIG. 3 is a thermal weight loss curve of the resin microspheres prepared in example 4.
FIG. 4 is a scanning electron microscope image of the resin microspheres prepared in example 4.
FIG. 5 is a graph of flow rate versus column pressure for a chromatographic column packed in example 7.
FIG. 6 is a graph of flow rate versus column pressure for a chromatographic column packed in example 8.
FIG. 7 is a graph of flow rate versus column pressure for a chromatographic column packed in example 9.
Fig. 8 is a chromatogram of example 10 for separation and purification of stevia extract, and fig. 8a and 8b are respectively taken from the left and right of fig. 8.
Detailed Description
Specific embodiments of the method for preparing the organosilicon hybrid porous resin microsphere for high performance liquid chromatography are provided below.
Example 1
Step (1) adding 1080mL of pure water, 5.4g of docusate sodium and 5.4g of gelatin into a 2000mL three-neck flask, and stirring at 70 ℃ for 20 minutes to completely dissolve the docusate sodium and the gelatin;
step (2) another beaker is taken, 240mL of dimethylbenzene, 108mL of divinylbenzene, 12mL of gamma-methacryloxypropyl trimethoxysilane and 0.6g of AIBN are added and mixed uniformly;
and (3) adding the organic phase which is uniformly mixed in the step (2) into the step (1), reacting for 40 minutes at 70 ℃, and then raising the temperature to 80 ℃ for further reacting for 8 hours. After the reaction is finished, cleaning the microspheres with hot water, then cleaning the microspheres with ethanol, and finally drying to obtain the microspheres;
step (4) dispersing 60g of the microsphere prepared in the step (3) into 600mL of tetrahydrofuran, carrying out ultrasonic treatment for 15 minutes, and standing and swelling for 12 hours;
adding 30mL of ammonia water, stirring for 15 minutes while performing ultrasonic treatment, standing for 24 hours, washing with water and ethanol after the reaction is finished, and finally drying to obtain a target product;
by analysis with a specific surface analyzer, a specific surface area of 811m was measured 2 /g，Pore volume of 1.32cm 3 /g, average pore size 7.11nm;
analysis by thermogravimetric analyzer, the result is shown in figure 1, and the decomposition temperature of the microsphere is 287 ℃;
the results of the analysis by a scanning electron microscope are shown in FIG. 2, and the average particle diameter is 33. Mu.m.
Example 2
In the step (2) of example 1, 108mL of divinylbenzene, 12mL of gamma-methacryloxypropyl trimethoxysilane were replaced with 96mL of divinylbenzene, 24mL of gamma-methacryloxypropyl trimethoxysilane, and the other steps were carried out in the same manner as in example 1, and the specific surface area was 747m by analysis using a specific surface area analyzer 2 Per g, pore volume of 1.09cm 3 And/g, average pore diameter of 6.27nm.
Example 3
In the step (2) of example 1, 108mL of divinylbenzene, 12mL of gamma-methacryloxypropyl trimethoxysilane were replaced with 84mL of divinylbenzene, 36mL of gamma-methacryloxypropyl trimethoxysilane, and the other steps were carried out in the same manner as in example 1, and the specific surface area was 639m by analysis using a specific surface area analyzer 2 Per g, pore volume of 0.88cm 3 And/g, average pore diameter of 5.60nm.
Example 4
50g of the microspheres prepared in example 1 were dispersed in 275mL of 1, 2-dichloroethane and allowed to stand and swell for 6 hours. Adding 7.5g of anhydrous ferric trichloride after swelling, adding nitrogen for protection, heating to 80 ℃ for reaction for 8 hours, washing with ethanol after the reaction is finished, washing with dilute hydrochloric acid for several times, washing with water to be neutral, and finally drying to obtain a target product;
the specific surface area was 1071m by analysis with a specific surface analyzer 2 Per g, pore volume of 1.76cm 3 /g, average pore size 7.51nm;
analysis by a thermogravimetric analyzer, the result is shown in fig. 3, and the decomposition temperature of the microspheres is 276 ℃;
the analysis by a scanning electron microscope gave an average particle size of 33 μm as shown in FIG. 4.
Example 5
50g of the microspheres prepared in example 2 were dispersed in 275ml of 1, 2-dichloroethane and allowed to stand for swelling for 6h. After swelling, 7.5g of anhydrous ferric trichloride is added, nitrogen is added for protection, the temperature is raised to 80 ℃ for reaction for 8 hours, ethanol is used for washing after the reaction is finished, dilute hydrochloric acid is used for washing for several times, water is used for washing to be neutral, and finally the target product is obtained after drying. The specific surface area was 1079m by analysis with a specific surface analyzer 2 Per g, pore volume of 1.49cm 3 /g, average pore size of 6.39nm;
example 6
50g of the microspheres prepared in example 3 were dispersed in 275ml of 1, 2-dichloroethane and allowed to stand for swelling for 6h. After swelling, 7.5g of anhydrous ferric trichloride is added, nitrogen is added for protection, the temperature is raised to 80 ℃ for reaction for 8 hours, ethanol is used for washing after the reaction is finished, dilute hydrochloric acid is used for washing for several times, water is used for washing to be neutral, and finally the target product is obtained after drying. The specific surface area was 1019m by analysis with a specific surface analyzer 2 Per g, pore volume of 1.22cm 3 /g, average pore size 5.57nm;
example 7
The microspheres obtained in step (3) of examples 1,2 and 3 and the polydivinylbenzene microspheres were packed into 4.6X250i.d.mm stainless steel chromatography columns, respectively, using ethanol as a mobile phase, and column pressures at different flow rates were recorded to obtain FIG. 5. After the silane is added, the chromatographic column shows lower column pressure under the same mobile phase, and has good mechanical strength.
Example 8
The final microspheres obtained in step (5) of examples 1,2 and 3 were packed into 4.6X250i.d.mm stainless steel chromatography columns, respectively, using isopropanol as a mobile phase, and column pressures at different flow rates were recorded to obtain FIG. 6. After the silane was crosslinked by hydrolytic condensation, the column pressure was lower than that of the silane without crosslinking, and it was confirmed that the mechanical strength was further improved after the hydrolytic condensation crosslinking.
Example 9
The microspheres obtained in examples 4, 5 and 6 were packed into 4.6X250i.d.mm stainless steel chromatography columns, respectively, using 50% isopropyl alcohol aqueous solution as mobile phase, and column pressures at different flow rates were recorded to obtain FIG. 7. After the post-crosslinking treatment, the chromatographic column shows lower column pressure, which proves that the mechanical strength can be further improved by the post-crosslinking.
Example 10
As shown in FIG. 8, the result of separating and purifying the stevia extract as an actual sample by using the 4.6X105 i.d.mm stainless steel chromatographic column provided with the microspheres prepared in example 5 shows that the content of rebaudioside A is improved from 26.14% to 58.53% by analyzing the component B, and the microsphere has a certain separating and purifying capability.
FIG. 8 (a) shows a 4.6X105 i.d.mm stainless steel column packed with microspheres prepared in example 5, under the following conditions:
the mobile phase is water/ethanol, the flow rate is 1.0mL/min, and the detection wavelength is 290nm
0min-10min water 100%
Ethanol 0% -25% in 10-20 min
Ethanol 25% for 20min-25min
25-30 min ethanol 25% -30%
Ethanol 30% for 30min-35min
Ethanol 30% -45% in 35min-50min
Ethanol 45% for 50min-55min
55min-65min ethanol 45% -90%
65min-80min ethanol 90%
FIG. 8 (b) shows a C18 column (4.6X105 i.d.mm) as the column under the following conditions:
the mobile phase is water/acetonitrile, the flow rate is 1.0mL/min, and the detection wavelength is 210nm
Acetonitrile/water 0min-20 min: 20/80 to 60/40;
example 11
Step (1) adding 1080mL of pure water, 6g of polyvinyl alcohol and 6g of sodium docusate into a 2000mL three-neck flask, and stirring at 70 ℃ for 20 minutes to completely dissolve the sodium docusate and the polyvinyl alcohol;
step (2) another beaker is taken, 162mL of dimethylbenzene, 97mL of divinylbenzene, 11mL of gamma-methacryloxypropyl trimethoxysilane and 0.7g of AIBN are added and mixed uniformly;
and (3) adding the organic phase which is uniformly mixed in the step (2) into the step (1), reacting for 40 minutes at 70 ℃, and then raising the temperature to 80 ℃ for further reacting for 8 hours. After the reaction is finished, cleaning the microspheres with hot water, then cleaning the microspheres with ethanol, and finally drying to obtain the microspheres;
step (4) 50g of the microsphere prepared in step (3) is dispersed into 800mL of tetrahydrofuran, ultrasonic is carried out for 20 minutes, and then standing and swelling are carried out for 14 hours;
adding 50mL of ammonia water, stirring for 20 minutes while performing ultrasonic treatment, standing for 30 hours, washing with water and ethanol after the reaction is finished, and finally drying to obtain a target product;
the specific surface area was measured to be 678m by analysis with a specific surface analyzer 2 Per g, pore volume of 1.07cm 3 /g, average pore size of 6.48nm;
example 12
In the step (2) of example 11, 97mL of divinylbenzene, 11mL of gamma-methacryloxypropyl trimethoxysilane were replaced with 86mL of divinylbenzene, 22mL of gamma-methacryloxypropyl trimethoxysilane, and the other steps were carried out as in example 11, and the specific surface area was determined to be 610m by analysis using a specific surface area analyzer 2 Per g, pore volume of 0.82cm 3 And/g, average pore diameter of 5.29nm.
Example 13
In the step (2) of example 11, 97mL of divinylbenzene, 11mL of gamma-methacryloxypropyl trimethoxysilane were replaced with 76mL of divinylbenzene, 32mL of gamma-methacryloxypropyl trimethoxysilane, and the other steps were carried out in the same manner as in example 11, and the specific surface area was 493m by analysis using a specific surface area analyzer 2 Per g, pore volume of 0.58cm 3 And/g, average pore diameter of 4.35nm.
Example 14
50g of the microspheres prepared in example 11 were dispersed in 275ml of 1, 2-dichloroethane and allowed to stand for swelling for 6h. Adding 7.5g of anhydrous ferric trichloride after swelling, adding nitrogen for protection, heating to 80 ℃ for reaction for 8 hours, washing with ethanol after the reaction is finished, washing with dilute hydrochloric acid for several times, washing with water to be neutral, and finally drying to obtain a target product;
the specific surface area was 1175m by analysis with a specific surface analyzer 2 Per g, pore volume of 2.31cm 3 /g, average pore size of 8.34nm;
example 15
50g of the microspheres prepared in example 12 were dispersed in 275ml of 1, 2-dichloroethane and allowed to stand for swelling for 6h. Adding 7.5g of anhydrous ferric trichloride after swelling, adding nitrogen for protection, heating to 80 ℃ for reaction for 8 hours, washing with ethanol after the reaction is finished, washing with dilute hydrochloric acid for several times, washing with water to be neutral, and finally drying to obtain a target product;
the specific surface area was 1197m by analysis with a specific surface analyzer 2 Per g, pore volume of 2.21cm 3 /g, average pore size of 8.13nm;
example 16
50g of the microspheres prepared in example 13 were dispersed in 275ml of 1, 2-dichloroethane and allowed to stand for swelling for 6h. Adding 7.5g of anhydrous ferric trichloride after swelling, adding nitrogen for protection, heating to 80 ℃ for reaction for 8 hours, washing with ethanol after the reaction is finished, washing with dilute hydrochloric acid for several times, washing with water to be neutral, and finally drying to obtain a target product;
the specific surface area was 1026m by analysis with a specific surface analyzer 2 Per g, pore volume of 1.49cm 3 /g, average pore size of 6.66nm;
the invention adopts a suspension polymerization method, has simple method and is easy to amplify. The porous resin microsphere with better mechanical strength can be obtained by the method, contains a large number of reaction sites for modification, can be modified according to different requirements, and is suitable for different separation systems.
Claims (10)
1. A preparation method of organosilicon hybridized porous resin microspheres for liquid chromatography is characterized in that: the preparation method is a suspension polymerization method and comprises the following steps:
(1) Adding a dispersing agent and a stabilizing agent into water at 50-70 ℃ and stirring for dissolution; the mass fractions of the dispersing agent and the stabilizing agent are 0.5% -2%; the dispersing agent is selected from one or more than one of the following components: sodium docusate, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, sodium dodecyl sulfate, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium dodecyl benzene sulfonate; the stabilizer is selected from one or more than one of the following components: sodium docusate, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, sodium dodecyl sulfate, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium dodecyl benzene sulfonate;
(2) Taking a certain amount of dimethylbenzene, divinylbenzene, gamma-methacryloxypropyl trimethoxysilane and azobisisobutyronitrile, and uniformly mixing;
the volume ratio of divinylbenzene to gamma-methacryloxypropyl trimethoxysilane is 7:3 to 9:1, the dosage of the dimethylbenzene is 1.5 to 3 times of the volume of the divinylbenzene and the gamma-methacryloxypropyl trimethoxysilane; the dosage of the azodiisobutyronitrile is 0.5 to 1.5 percent of the total mass of the comonomer; the total mass of the comonomer is the sum of the mass of the divinylbenzene monomer and the gamma-methacryloxypropyl trimethoxysilane monomer;
(3) Adding the organic phase uniformly mixed in the step (2) into a reactor of the step (1), wherein: the volume ratio of the total volume of the organic phase to the volume of water is 1: 3-1: 5, a step of; reacting for 10-50 minutes, then continuously heating to 70-80 ℃ to continue reacting for 8-12 hours, and finally washing with hot water and ethanol respectively to obtain microspheres;
(4) Adding the microsphere obtained in the step (3) into tetrahydrofuran, and continuing swelling for 10-14 hours after ultrasonic treatment for 1-30 minutes; the proportion of the microsphere to tetrahydrofuran is as follows: 1:10 to 1:15 (g/mL);
(5) Adding ammonia water into the reaction bottle in the step (4), fully stirring, standing, and finally washing with water and ethanol to obtain the microsphere.
2. The method for preparing the organic silicon hybrid porous resin microsphere for liquid chromatography according to claim 1, wherein the method comprises the following steps: the reaction time in the step (3) is 30-50 minutes.
3. The method for preparing the organic silicon hybrid porous resin microsphere for liquid chromatography according to claim 1, wherein the method comprises the following steps: the stirring in the step (5) is ultrasonic stirring, and the ultrasonic stirring is carried out for 15-30 minutes; and (3) standing for 18-36 hours in the step (5).
4. The method for preparing the organic silicon hybrid porous resin microsphere for liquid chromatography according to claim 1, wherein the method comprises the following steps: in the step (5), the volume ratio of the ammonia water to the tetrahydrofuran is 1: 15-1: 20.
5. the method for preparing the organic silicon hybrid porous resin microsphere for liquid chromatography according to claim 1, wherein the method comprises the following steps: the step (5) is followed by a post-crosslinking method; the post-crosslinking method comprises the following steps:
dispersing the microspheres in 1, 2-dichloroethane, swelling for 6-10 hours, adding anhydrous ferric trichloride, heating to 70-90 ℃ for reaction for 7-9 hours, washing with ethanol after the reaction, washing with dilute hydrochloric acid, washing with water to neutrality, and drying to obtain the target product.
6. The method for preparing the organic silicon hybrid porous resin microsphere for liquid chromatography according to claim 5, wherein the method comprises the following steps: the mass ratio of the 1, 2-dichloroethane, anhydrous ferric trichloride and the microspheres is 4-7:0.2-0.5:0.5-2.
7. The microsphere prepared by the preparation method of the organosilicon hybridized porous resin microsphere for liquid chromatography as claimed in claim 1, which is characterized in that: the microsphere is a copolymer of divinylbenzene and gamma-methacryloxypropyl trimethoxysilane; the specific surface area of the obtained original microsphere is 600-900 m 2 Per gram, pore volume of 0.8-1.4 cm 3 And/g, average pore diameter of 5-8 nm.
8. A liquid chromatograph according to claim 5The microsphere prepared by the preparation method of the organosilicon hybridized porous resin microsphere is characterized in that: the specific surface area of the organosilicon hybridized porous resin microsphere obtained after the crosslinking treatment is 1000-1200 m 2 Per gram, pore volume of 1.2-1.8 cm 3 And/g, average pore diameter of 5-8 nm.
9. The microsphere prepared by the preparation method of the organosilicon hybridized porous resin microsphere for liquid chromatography according to claim 7 or 8, wherein the microsphere is characterized in that: the particle size of the microsphere is 30-40 mu m.
10. Use of the microsphere according to claim 7 or 8 in liquid chromatography.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310222331.9A CN116870883A (en) | 2023-03-09 | 2023-03-09 | Preparation method of liquid chromatography organosilicon hybrid porous resin microsphere, microsphere and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310222331.9A CN116870883A (en) | 2023-03-09 | 2023-03-09 | Preparation method of liquid chromatography organosilicon hybrid porous resin microsphere, microsphere and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116870883A true CN116870883A (en) | 2023-10-13 |
Family
ID=88255560
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310222331.9A Pending CN116870883A (en) | 2023-03-09 | 2023-03-09 | Preparation method of liquid chromatography organosilicon hybrid porous resin microsphere, microsphere and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116870883A (en) |
-
2023
- 2023-03-09 CN CN202310222331.9A patent/CN116870883A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Svec et al. | Monolithic stationary phases for capillary electrochromatography based on synthetic polymers: designs and applications | |
| Plunkett et al. | Molecularly imprinted polymers on silica: selective supports for high-performance ligand-exchange chromatography | |
| CA1046451A (en) | Chromatography solid support | |
| US5453185A (en) | Column with macroporous polymer media | |
| EP0763064B1 (en) | A method of manufacturing particles, and particles that can be produced in accordance with the method | |
| Guyot | Polymer supports with high accessibility | |
| Haginaka et al. | Uniform-sized molecularly imprinted polymer material for (S)-propranolol | |
| JPH021747A (en) | Macro-porous polymer film and its preparation | |
| EP0288006B1 (en) | Process for producing crosslinked polymer particles | |
| US20050065282A1 (en) | Post-modification of a porous support | |
| EP1226870B1 (en) | Anion exchanger, process for producing the same, and its use | |
| Ding et al. | Advancements in the preparation of high-performance liquid chromatographic organic polymer monoliths for the separation of small-molecule drugs | |
| CN1079229A (en) | Crosslinked methacrylic anhydride copolymers | |
| JP2005510609A5 (en) | ||
| KR20000017535A (en) | A polymer packing material for liquid chromatography and a producing method thereof | |
| JP3158186B2 (en) | Alkyl group-containing porous resin, production method thereof and use thereof | |
| Li et al. | Chiral stationary phase based on cellulose derivative coated polymer microspheres and its separation performance | |
| KR101333577B1 (en) | Process for making improved chromatography media and method of use | |
| CN116870883A (en) | Preparation method of liquid chromatography organosilicon hybrid porous resin microsphere, microsphere and application | |
| CN114931934B (en) | Grafted cation exchange chromatographic column filler and preparation method thereof | |
| JP2008264732A (en) | Porous ion exchanger and manufacturing method thereof | |
| Ihara et al. | Linear polystyrene-grafted silica gels for high-performance liquid chromatography | |
| WO2019110318A1 (en) | Porous materials, method for producing same and uses thereof | |
| JP3657448B2 (en) | Polymer packing material for liquid chromatography and process for producing the same | |
| CN113019349A (en) | Preparation method of anion chromatographic stationary phase |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |