CN104844744A - Resin with specific adsorption for cephalosporin C and preparation method therefor - Google Patents
Resin with specific adsorption for cephalosporin C and preparation method therefor Download PDFInfo
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- 239000011347 resin Substances 0.000 title claims abstract description 35
- 229920005989 resin Polymers 0.000 title claims abstract description 35
- 238000001179 sorption measurement Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- HOKIDJSKDBPKTQ-GLXFQSAKSA-N cephalosporin C Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 title abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000000178 monomer Substances 0.000 claims abstract description 19
- 238000004821 distillation Methods 0.000 claims abstract description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 10
- 238000010557 suspension polymerization reaction Methods 0.000 claims abstract description 10
- 230000008961 swelling Effects 0.000 claims abstract description 10
- 238000005406 washing Methods 0.000 claims abstract description 9
- 239000012442 inert solvent Substances 0.000 claims abstract description 7
- 239000003999 initiator Substances 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 230000029936 alkylation Effects 0.000 claims abstract description 6
- 238000005804 alkylation reaction Methods 0.000 claims abstract description 6
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 4
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 claims abstract description 3
- 239000002841 Lewis acid Substances 0.000 claims abstract description 3
- 239000002270 dispersing agent Substances 0.000 claims abstract description 3
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 3
- 230000035484 reaction time Effects 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 36
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- 229930186147 Cephalosporin Natural products 0.000 claims description 32
- 229940124587 cephalosporin Drugs 0.000 claims description 32
- 150000001780 cephalosporins Chemical class 0.000 claims description 32
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical group C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 18
- 238000010792 warming Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 12
- 230000002152 alkylating effect Effects 0.000 claims description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 claims description 7
- 108010010803 Gelatin Proteins 0.000 claims description 7
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 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
- 238000007601 warm air drying Methods 0.000 claims description 7
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 6
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical group Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 6
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 6
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical group ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 6
- 239000006185 dispersion Substances 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- 238000004140 cleaning Methods 0.000 claims description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- XMWGTKZEDLCVIG-UHFFFAOYSA-N 1-(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1 XMWGTKZEDLCVIG-UHFFFAOYSA-N 0.000 claims description 3
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 claims description 3
- 239000011968 lewis acid catalyst Substances 0.000 claims description 3
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 3
- KNKRKFALVUDBJE-UHFFFAOYSA-N 1,2-dichloropropane Chemical compound CC(Cl)CCl KNKRKFALVUDBJE-UHFFFAOYSA-N 0.000 claims description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- MPCHQYWZAVTABQ-UHFFFAOYSA-N 2-(chloromethyl)naphthalene Chemical compound C1=CC=CC2=CC(CCl)=CC=C21 MPCHQYWZAVTABQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 abstract description 4
- 229920000642 polymer Polymers 0.000 abstract 2
- 239000003431 cross linking reagent Substances 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 239000004088 foaming agent Substances 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 229920001577 copolymer Polymers 0.000 description 12
- 239000011159 matrix material Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- 239000003463 adsorbent Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000002612 dispersion medium Substances 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 230000000274 adsorptive effect Effects 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000004900 laundering Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- ZSDSQXJSNMTJDA-UHFFFAOYSA-N trifluralin Chemical compound CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O ZSDSQXJSNMTJDA-UHFFFAOYSA-N 0.000 description 3
- URYAFVKLYSEINW-UHFFFAOYSA-N Chlorfenethol Chemical compound C=1C=C(Cl)C=CC=1C(O)(C)C1=CC=C(Cl)C=C1 URYAFVKLYSEINW-UHFFFAOYSA-N 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000002594 sorbent Substances 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000012262 fermentative production Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N iso-butyl alcohol Natural products CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
- 229940035429 isobutyl alcohol Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- -1 methyl isobutyl Chemical group 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Landscapes
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Cephalosporin Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention discloses resin with specific adsorption for cephalosporin C and a preparation method therefor. The adsorption resin is prepared by adopting suspension polymerization. The preparation method comprises the steps of: after mixing a monomer, a cross-linking agent, a pore-foaming agent, an initiator and water, performing a suspension polymerization reaction under the condition of the existence of a conventional dispersing agent, wherein the suspension polymerization temperature is 75 to 85 DEG C and the polymerization reaction time is 10 to 16 hours; carrying out distillation and drying treatment on the obtained polymer; adding the dried polymer and an inert solvent into a reactor together for swelling, adding lewis acid at room temperature, dropwise adding an alkylation reagent, heating to 40 to 50 DEG C to perform a friedel-crafts alkylation reaction for 12 to 16 hours, and carrying out solvent washing and washing to obtain the cephalosporin C specific adsorption resin. The cephalosporin C specific adsorption resin prepared by the method has specific adsorption for cephalosporin C, and is large in adsorption quantity and high in purity.
Description
Technical field
The present invention relates to a kind of new type functional polymeric sorbent, be specifically related to a kind of to cephalosporin resin with specific adsorption and preparation method thereof.
Background technology
The output of cephalosporins accounts for more than 60% of world's antibiotic yield, and China's cephalosporin output has accounted for more than 80% of Gross World Product.It is generally by fermentative Production, and the extraction of Cephalosporin C fermentation liquid use is all resin methods, and macroporous adsorbent resin extracts cephalosporin and has easy and simple to handle, and product is pollution-free, and production cost is low, productive rate high.But also there is the contradiction that this adsorptive capacity and selectivity can not be taken into account in existing macroporous adsorbent resin.Macroporous adsorbent resin mainly forms π-π effect by phenyl ring and cephalosporin to the absorption of cephalosporin, carries out adsorption.The density improving phenyl ring can improve its π-π effect, thus improves the absorption of cephalosporin.Existing is all cross-linking methods after adopting, and increases cross-linkage of resin, reduced bore, improves specific surface method and reaches cephalosporin high adsorption capacity object.But improve specific surface simultaneously also reduced bore, it strengthens other impurity absorption power in filtrate, causes the purity of cephalosporin in desorbed solution low.
CN10128884 discloses a kind of macroporous adsorption resin special for extracting cephalosporin C and preparation method thereof, and the specific surface area of this polymeric adsorbent is at 1000-2000m
2/ g, pore volume is at 1.5-2.5ml/g.Preparation method is: be first dissolved in dispersion medium by dispersion agent, adds the mixture be made up of monomer, pore-creating agent and polymerization starter, suspension polymerization temperatures 60-100 DEG C, and reaction 5-10h, obtains Crosslinked Macroporous copolymer matrix; Macroporous copolymer matrix processed with lewis acid catalyst 50-120 DEG C under inert media exists, again there is crosslinking reaction in portion in the substrate.Cephalosporin adsorbing and extracting macroporous adsorbent resin special of the present invention has comparatively high adsorption rate, good to target product selectivity, be easy to resolve and regeneration, the cephalosporin product purity of extraction is high, but the defect such as this resinoid existence and stability is poor, cephalosporin purity is on the low side.
Summary of the invention
The deficiency that the present invention can not take into account to overcome existing polymeric adsorbent adsorptive capacity and selectivity, provide a kind of resin cephalosporin to specific adsorption, desirable pore system is selected to prepare adsorption head C multipolymer, then adopt aromatics alkylating reagent to multipolymer Friedel-Crafts, thus improving phenyl ring density when not changing aperture, described sorbent material has specific absorption to cephalosporin.
For realizing goal of the invention, the technical scheme that the present invention just goes is as follows:
Prepare a preparation method for resin cephalosporin to specific adsorption, described method comprises the steps:
(1) suspension polymerization
After monomer, linking agent, pore-creating agent, initiator being mixed with water, in the presence of dispersants, carry out suspension polymerization, suspension polymerization temperatures 75-85 DEG C, polymerization reaction time 10-16 hour; Component distillation removes pore-creating agent, and not containing oily matter to phlegma, stop distillation, after being down to room temperature, water washing spheroid 3 ~ 5 times, drains moisture, and then warm air drying is to moisture less than 1.0%, screening 30-60 order spheroid;
Described pore-creating agent is chlorobenzene, ethylene dichloride, toluene, dimethylbenzene, propyl carbinol, methyl isobutyl carbinol, acetic acid Zhong Ding
The mixture of one or more in ester;
Described initiator is benzoyl peroxide or lauroyl peroxide;
Described dispersion agent is one or several the mixture in gelatin, cellulose family, polyvinyl alcohol, xylogen;
Described monomer is selected from divinylbenzene;
Described linking agent is selected from divinylbenzene;
Described pore-creating agent is the 180%-300% of monomer and linking agent gross weight;
Described initiator is the 1%-2% of monomer and linking agent gross weight;
Described water is the 160%-250% of monomer, pore-creating agent and linking agent gross weight;
Described dispersion agent is the 1.6%-2.5% of monomer, pore-creating agent and linking agent gross weight;
(2) Fu-Ke alkylation
The spheroid that step (1) is dried is added together with inert solvent reactor swelling, Lewis acid is added under room temperature, drip alkylating reagent, dropwise, be warming up to 40-50 DEG C and carry out Friedel-Crafts alkylation 12-16 hour, obtain cephalosporin specific adsorption resin through solvent wash, washing;
Described swelling time is 1.5-2 hour;
Described inert solvent is ethylene dichloride, propylene dichloride, oil of mirbane, chlorobenzene or dichlorobenzene;
Described lewis acid catalyst is selected from aluminum chloride, iron trichloride, zinc chloride, tin tetrachloride or boron trifluoride;
Described alkylating reagent is benzyl chlorine, 1-(chloromethyl) naphthalene, 2-(chloromethyl) naphthalene;
The time of described dropping alkylating reagent is 1.5-3 hour;
Described cleaning solvent is obtain one or several mixtures in acetone, ethanol, methyl alcohol;
The amount of described cleaning solvent is the 400%-600% of dry bulb weight;
The amount of described inert solvent is the 500%-700% of dry bulb weight;
Described lewis acidic amount is the 30%-100% of dry bulb weight;
The amount of described alkylating reagent is the 30%-100% of dry weight.
The phenyl ring density of cephalosporin polymeric adsorbent prepared by the present invention increases, and detects, can find that its microvoid structure is substantially unchanged compared with non-Friedel-Crafts through specific surface instrument TriStar 3000.Prepared by the present invention can not only remain larger aperture to the resin that cephalosporin has absorption, and adds phenyl ring density, thus realizes its high adsorption capacity, highly selective performance.π-π the effect of raising phenyl ring, can reach 60g/L to cephalosporin adsorptive capacity and purity can reach more than 95%.Resin stability is high, contamination resistance is strong, steady performance.
Accompanying drawing explanation
Fig. 1 is the change of micropore distribution before and after alkylation
Embodiment
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1
Monomer mixture containing 100g (80% content) divinylbenzene, 100g toluene and 50g sec-butyl acetate and 1.0g benzoyl peroxide is joined in the dispersion medium solution be made up of 500ml salt-free water, 5g gelatin, stir the symmetrical liquid drop making into a certain size, heat up 80 DEG C, react 12 hours.Then water is drained, rejoin water, after being warming up to 50-60 DEG C of agitator treating three times, adding 500ml water and be warming up to component distillation and remove pore-creating agent (toluene and sec-butyl acetate), hardly containing oily matter to phlegma, stop distillation.After being down to room temperature, massive laundering washs spheroid, drains moisture, and then warm air drying is to moisture less than 1.0%, and screening 30-60 order spheroid, obtains Crosslinked Macroporous copolymer matrix 95g.
Join in 450ml oil of mirbane by 95g Crosslinked Macroporous copolymer matrix obtained above, swelling 2 hours of stirring at normal temperature, then adds 50g aluminum chloride, heats up 45 DEG C, dropwises benzyl chlorine 95g in 2 hours, insulation reaction 16 hours.Cooling, drains oil of mirbane, adds 500ml ethanol, stir 30 minutes, drain; Again add 500ml ethanol, stir 30 minutes, drain.Add the washing of a large amount of salt-free water to clarification, obtaining the light yellow target product of 270g is cephalosporin specific adsorption resin.
Embodiment 2
Monomer mixture containing 100g (80% content) divinylbenzene, 90g toluene and 150g methyl isobutyl carbinol and 1.0g benzoyl peroxide is joined in the dispersion medium solution be made up of 500ml salt-free water, 5g gelatin, stir the symmetrical liquid drop making into a certain size, heat up 75 DEG C, react 12 hours.Then water is drained.Then water is drained, rejoin water, after being warming up to 50-60 DEG C of agitator treating three times, adding 500ml water and be warming up to component distillation and remove pore-creating agent (toluene and methyl isobutyl carbinol), hardly containing oily matter to phlegma, stop distillation.Cooling, massive laundering washs spheroid, drains moisture, and then warm air drying is to moisture less than 1.0%, and screening 30-60 order spheroid, obtains Crosslinked Macroporous copolymer matrix 90g.
Join in 570ml ethylene dichloride by 90g Crosslinked Macroporous copolymer matrix obtained above, swelling 2 hours of stirring at normal temperature, adds 50g iron(ic) chloride under room temperature, then starts to drip benzyl chlorine 90g, about 2 hours time, is warming up to 48 DEG C after dropwising, and reacts 15 hours.All the other operations, with reference to embodiment 1, obtain 300g brown target product cephalosporin specific adsorption resin.
Embodiment 3
Monomer mixture containing 100g (80% content) divinylbenzene, 150g toluene and 70g hexone and 1.0g benzoyl peroxide is joined in the dispersion medium solution be made up of 500ml salt-free water, 5g gelatin, stir the symmetrical liquid drop making into a certain size, heat up 75 DEG C, react 12 hours.。Then water is drained, rejoin water, after being warming up to 50-60 DEG C of agitator treating three times, adding 500ml water and be warming up to component distillation and remove pore-creating agent (toluene and methyl isobutyl carbinol), hardly containing oily matter to phlegma, stop distillation.Cooling, massive laundering washs spheroid, drains moisture, and then warm air drying is to moisture less than 1.0%, and screening 30-60 order spheroid, obtains Crosslinked Macroporous copolymer matrix 85g.
Join in 510ml ethylene dichloride by 85g Crosslinked Macroporous copolymer matrix obtained above, swelling 2 hours of stirring at normal temperature, adds 30g iron(ic) chloride under room temperature, then start to drip 1-(chloromethyl) naphthalene 90g, about 2 hours time, after dropwising, be warming up to 48 DEG C, react 15 hours.All the other operations, with reference to embodiment 1, obtain 255g brown target product cephalosporin specific adsorption resin.
Embodiment 4
Monomer mixture containing 100g (80% content) divinylbenzene, 90g toluene and 150g methyl isobutyl alcohol and 1.0g lauroyl peroxide is joined in the dispersion medium solution be made up of 500ml salt-free water, 5g gelatin, stir the symmetrical liquid drop making into a certain size, heat up 75 DEG C, react 12 hours.Then water is drained.Then water is drained, rejoin water, after being warming up to 50-60 DEG C of agitator treating three times, adding 500ml water and be warming up to component distillation and remove pore-creating agent (toluene and methyl isobutyl carbinol), hardly containing oily matter to phlegma, stop distillation.Cooling, massive laundering washs spheroid, drains moisture, and then warm air drying is to moisture less than 1.0%, and screening 30-60 order spheroid, obtains Crosslinked Macroporous copolymer matrix 95g.
Join in 570ml ethylene dichloride by 95g Crosslinked Macroporous copolymer matrix obtained above, swelling 2 hours of stirring at normal temperature, adds 50g iron(ic) chloride under room temperature, then starts to drip benzyl chlorine 90g, about 2 hours time, is warming up to 48 DEG C after dropwising, and reacts 15 hours.All the other operations, with reference to embodiment 1, obtain 305g brown target product cephalosporin specific adsorption resin.
Embodiment 5
Monomer mixture containing 100g (80% content) divinylbenzene, 150g toluene and 50g dimethylbenzene and 1.0g benzoyl peroxide is joined in the dispersion medium solution be made up of 500ml salt-free water, 5g gelatin, stir the symmetrical liquid drop making into a certain size, heat up 75 DEG C, react 12 hours.Then water is drained.Then water is drained, rejoin water, after being warming up to 50-60 DEG C of agitator treating three times, adding 500ml water and be warming up to component distillation and remove pore-creating agent (toluene and methyl isobutyl carbinol), hardly containing oily matter to phlegma, stop distillation.Cooling, massive laundering washs spheroid, drains moisture, and then warm air drying is to moisture less than 1.0%, and screening 30-60 order spheroid, obtains Crosslinked Macroporous copolymer matrix 80g.
Join in 480ml ethylene dichloride by 80g Crosslinked Macroporous copolymer matrix obtained above, swelling 2 hours of stirring at normal temperature, adds 25g iron(ic) chloride under room temperature, then starts to drip benzyl chlorine 90g, about 2 hours time, is warming up to 48 DEG C after dropwising, and reacts 15 hours.All the other operations, with reference to embodiment 1, obtain 250g brown target product cephalosporin specific adsorption resin.
Sample result is analyzed
1, the physical characterization of resin
Measuring method: pore volume, specific surface, aperture and micropore distribution all have specific surface instrument TriStar 3000 to detect; Moisture measures according to GB GB/T5757.
Fig. 1 is the change of micropore distribution before and after embodiment 1 alkylation, detects, can find that its microvoid structure is substantially unchanged compared with non-Friedel-Crafts through specific surface instrument TriStar 3000, and objectively responding out phenyl ring density by resin infrared spectrum increases.Illustrate that the present invention obtains cephalosporin polymeric adsorbent and can not only remain larger aperture, and add phenyl ring density, thus realize its highly selective, high adsorption capacity object.
Physical and chemical performance before and after table 1 alkylation
2 resins are verified at cephalosporin adsorption effect
Experimental technique:
Get the Cephalosporin C fermentation liquid of tiring about 10,000, pH adjusts upper prop absorption between 2.6-2.8, and adsorption flow rate is 1BV/h; After 2BV salt-free water washing; Then resolve with strippant, parsing flow velocity is 0.5BV/h; With the salt-free water water top of 1BV after parsing.Collect absorption mixing, washing mixing, resolve mixing, water top biased sample high performance liquid phase measures and tires, calculate the data such as adsorptive capacity, desorption quantity.Result following table:
Table 2 the present invention obtains resin and the correct cephalosporin adsorption experiment of commercial resins contrasts
| Adsorptive capacity g/mL | Parsing amount g/mL | Desorption efficiency % | DCPC％ | DOCPC％ | CPC％ | |
| Embodiment 1 | 58.6 | 58.0 | 99.0 | 0.48 | 0.35 | 98.3 |
| Embodiment 2 | 62.1 | 61.4 | 98.9 | 0.52 | 0.38 | 97.6 |
| Embodiment 3 | 58.8 | 57.6 | 99.3 | 0.31 | 0.28 | 98.8 |
| Embodiment 4 | 58.8 | 57.2 | 97.3 | 0.38 | 0.30 | 97.5 |
| Embodiment 5 | 59.2 | 58.8 | 98.0 | 0.41 | 0.39 | 97.1 |
| Commercial resins | 60.3 | 58.8 | 97.5 | 1.35 | 1.16 | 92.6 |
Note: the volume of BV-resin; DCPC, DOCPC are the main two kinds of impurity of Cephalosporin C fermentation liquid.
The foregoing is only several concrete forms of implementation of the present invention, it should be pointed out that to those skilled in the art, many distortion and improvement can also be made.All do not exceed distortion described in claim or improve all should be considered as scope of the present invention.
Claims (3)
1. prepare a preparation method for resin cephalosporin to specific adsorption, it is characterized in that, described method comprises the steps:
(1) suspension polymerization
After monomer, linking agent, pore-creating agent, initiator being mixed with water, in the presence of dispersants, carry out suspension polymerization, suspension polymerization temperatures 75-85 DEG C, polymerization reaction time 10-16 hour; Component distillation removes pore-creating agent, and not containing oily matter to phlegma, stop distillation, be cooled to room temperature, water washing spheroid 3 ~ 5 times, drains moisture, and warm air drying, to moisture less than 1.0%, sieves 30-60 order spheroid;
Described pore-creating agent is the mixture of one or more in chlorobenzene, ethylene dichloride, toluene, dimethylbenzene, propyl carbinol, methyl isobutyl carbinol, sec-butyl acetate;
Described initiator is benzoyl peroxide or lauroyl peroxide;
Described dispersion agent is one or several the mixture in gelatin, cellulose family, polyvinyl alcohol, xylogen;
Described monomer is selected from divinylbenzene;
Described linking agent is selected from divinylbenzene;
(2) Fu-Ke alkylation
The spheroid that step (1) is dried is added together with inert solvent reactor swelling, Lewis acid is added under room temperature, drip alkylating reagent, after dropwising, be warming up to 40-50 DEG C and carry out Friedel-Crafts alkylation 12-16 hour, obtain cephalosporin specific adsorption resin through solvent wash, washing;
Described swelling time is 1.5-2 hour;
Described inert solvent is ethylene dichloride, propylene dichloride, oil of mirbane, chlorobenzene or dichlorobenzene;
Described lewis acid catalyst is selected from aluminum chloride, iron trichloride, zinc chloride, tin tetrachloride or boron trifluoride;
Described alkylating reagent is benzyl chlorine, 1-(chloromethyl) naphthalene, 2-(chloromethyl) naphthalene;
The time of described dropping alkylating reagent is 1.5-3 hour;
Described cleaning solvent is obtain one or several mixtures in acetone, ethanol, methyl alcohol.
2. prepare the preparation method of resin cephalosporin to specific adsorption as claimed in claim 1, it is characterized in that, the amount of described cleaning solvent is the 400%-600% of dry bulb weight; The amount of described inert solvent is the 500%-700% of dry bulb weight;
Described lewis acidic amount is the 30%-100% of dry bulb weight; The amount of described alkylating reagent is the 30%-100% of dry bulb weight.
3. prepare the preparation method of resin cephalosporin to specific adsorption as claimed in claim 1, it is characterized in that, described pore-creating agent is the 180%-300% of monomer and linking agent gross weight; Described initiator is the 1%-2% of monomer and linking agent gross weight; Described water is the 160%-250% of monomer, pore-creating agent and linking agent gross weight; Described dispersion agent is the 1.6%-2.5% of monomer, pore-creating agent and linking agent gross weight.
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| CN108355626A (en) * | 2018-03-02 | 2018-08-03 | 中国科学院广州能源研究所 | A kind of modified styrene absorption resin, preparation method and its ligno-cellulose hydrolysate it is refined on application |
| CN108707247A (en) * | 2018-03-22 | 2018-10-26 | 安徽皖东树脂科技有限公司 | The preparation method of resin for antibiotic purification |
| CN109589947A (en) * | 2018-11-27 | 2019-04-09 | 艾美科健（中国）生物医药有限公司 | One kind macroporous adsorbent resin preparation method thereof of polystyrene containing polyphenol hydroxyl and application |
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| CN101987291A (en) * | 2010-11-05 | 2011-03-23 | 山东鲁抗立科药物化学有限公司 | Macropore adsorption resin as well as preparation method and application thereof |
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| CN108355626A (en) * | 2018-03-02 | 2018-08-03 | 中国科学院广州能源研究所 | A kind of modified styrene absorption resin, preparation method and its ligno-cellulose hydrolysate it is refined on application |
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| CN108707247A (en) * | 2018-03-22 | 2018-10-26 | 安徽皖东树脂科技有限公司 | The preparation method of resin for antibiotic purification |
| CN109589947A (en) * | 2018-11-27 | 2019-04-09 | 艾美科健（中国）生物医药有限公司 | One kind macroporous adsorbent resin preparation method thereof of polystyrene containing polyphenol hydroxyl and application |
| CN109589947B (en) * | 2018-11-27 | 2021-11-30 | 艾美科健（中国）生物医药有限公司 | Preparation method and application of polystyrene macroporous adsorption resin containing polyphenol hydroxyl groups |
| CN111036180A (en) * | 2019-12-05 | 2020-04-21 | 安徽皖东树脂科技有限公司 | Preparation process of macroporous adsorption resin for extracting noble metal and rare metal |
| CN111036180B (en) * | 2019-12-05 | 2022-07-12 | 安徽皖东树脂科技有限公司 | Preparation process of macroporous adsorption resin for extracting noble metal and rare metal |
| CN114682229A (en) * | 2022-03-29 | 2022-07-01 | 西安蓝深新材料科技有限公司 | Boron adsorption resin and preparation method and application thereof |
| CN114682229B (en) * | 2022-03-29 | 2023-04-25 | 西安蓝深新材料科技股份有限公司 | Boron adsorption resin and preparation method and application thereof |
| CN116535731A (en) * | 2023-06-12 | 2023-08-04 | 西安蓝深新材料科技股份有限公司 | Adsorption resin, preparation method thereof and application thereof in cephalosporin C extraction |
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