CN104844744B - A kind of resin to cephalosporin with specific adsorption and preparation method thereof - Google Patents
A kind of resin to cephalosporin with specific adsorption and preparation method thereof Download PDFInfo
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- CN104844744B CN104844744B CN201510143631.3A CN201510143631A CN104844744B CN 104844744 B CN104844744 B CN 104844744B CN 201510143631 A CN201510143631 A CN 201510143631A CN 104844744 B CN104844744 B CN 104844744B
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- cephalosporin
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- 229930186147 Cephalosporin Natural products 0.000 title claims abstract description 34
- 229940124587 cephalosporin Drugs 0.000 title claims abstract description 34
- 150000001780 cephalosporins Chemical class 0.000 title claims abstract description 34
- 239000011347 resin Substances 0.000 title claims abstract description 30
- 229920005989 resin Polymers 0.000 title claims abstract description 30
- 238000001179 sorption measurement Methods 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000004088 foaming agent Substances 0.000 claims abstract description 19
- 239000000178 monomer Substances 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 14
- 238000010792 warming Methods 0.000 claims abstract description 14
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 10
- 230000008961 swelling Effects 0.000 claims abstract description 10
- 230000002152 alkylating effect Effects 0.000 claims abstract description 9
- 239000002270 dispersing agent Substances 0.000 claims abstract description 8
- 238000004821 distillation Methods 0.000 claims abstract description 8
- 239000003999 initiator Substances 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
- 238000005727 Friedel-Crafts reaction Methods 0.000 claims abstract description 6
- 238000010557 suspension polymerization reaction Methods 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 4
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 4
- 239000000725 suspension Substances 0.000 claims abstract description 4
- 239000002841 Lewis acid 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
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical group C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 8
- 108010010803 Gelatin Proteins 0.000 claims description 7
- 238000010533 azeotropic distillation Methods 0.000 claims description 7
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances 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
- WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-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
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical group ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 6
- 229940073608 benzyl chloride Drugs 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 238000007605 air drying Methods 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 235000019400 benzoyl peroxide Nutrition 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
- 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
- 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
- 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
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 2
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 claims description 2
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 235000014121 butter Nutrition 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 150000004816 dichlorobenzenes Chemical class 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 229920005610 lignin Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 claims 1
- 238000012216 screening Methods 0.000 claims 1
- 239000003463 adsorbent Substances 0.000 abstract description 6
- 229920000642 polymer Polymers 0.000 abstract 1
- 229920001577 copolymer Polymers 0.000 description 14
- 239000011159 matrix material Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 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 description 9
- 239000000047 product Substances 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 239000004519 grease Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000002612 dispersion medium Substances 0.000 description 5
- 238000004900 laundering Methods 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000002250 absorbent Substances 0.000 description 3
- 230000002745 absorbent Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- 238000002156 mixing Methods 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
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 238000006243 chemical reaction Methods 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
- 239000012535 impurity Substances 0.000 description 2
- -1 methyl tert-butyl Chemical group 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 239000000126 substance 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 a kind of resin to cephalosporin with specific adsorption and preparation method thereof, and described polymeric adsorbent is prepared using suspension polymerisation, and preparation method is:After monomer, crosslinking agent, pore-foaming agent, initiator are mixed with water, in the presence of conventional dispersant, suspension polymerization, 75 85 DEG C of suspension polymerization temperatures, polymerization reaction time 10 16 hours are carried out；Gained polymerizate is by distillation, drying process；The polymer of drying and atent solvent are added into reactor swelling together, lewis acid is added at room temperature, alkylating reagent is added dropwise, is warming up to 40 50 DEG C and carries out Friedel-Crafts and react 12 16 hours, washed through solvent, wash and obtain cephalosporin specific adsorption resin.Cephalosporin polymeric adsorbent is made to cephalosporin specific adsorption, adsorbance is big, purity is high in methods described.
Description
Technical field
The present invention relates to a kind of new type functional polymeric sorbent, and in particular to a kind of to have spy to cephalosporin
Resin of opposite sex absorption and preparation method thereof.
Background technology
The yield of cephalosporins accounts for more than the 60% of world's antibiotic yield, and China's cephalosporin yield accounts for
More than the 80% of Gross World Product.It is typically produced by fermentation method, and what the extraction of Cephalosporin C fermentation liquid used is resin
Method, macroporous absorbent resin extraction cephalosporin have the features such as easy to operate, product is pollution-free, and production cost is low, and yield is high.
But there is also the contradiction that this adsorbance and selectivity can not be taken into account for existing macroporous absorbent resin.Macroporous absorbent resin is to cephalo
Rhzomorph C absorption mainly forms π-π effects by phenyl ring and cephalosporin, carries out suction-operated.The density for improving phenyl ring can be with
Its π-π effect is improved, so as to improve the absorption of cephalosporin.Existing is to use post-crosslinking method, increases the crosslinking of resin
Degree, reduced bore, is improved than surface method to reach to cephalosporin high adsorption capacity purpose.But carry high-ratio surface while
Reduced bore, it strengthens other impurities absorption affinity 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, the absorption
The specific surface area of resin is in 1000-2000m2/ g, pore volume is in 1.5-2.5ml/g.Preparation method is：First dispersant is dissolved in scattered
In medium, the mixture being made up of monomer, pore-foaming agent and polymerization initiator is added, 60-100 DEG C of suspension polymerization temperatures, reacts 5-
10h, obtain Crosslinked Macroporous copolymer matrix；Macroporous copolymer matrix is used into lewis acid catalyst 50- in the presence of inert media
120 DEG C are handled, and crosslink reaction again inside the base.The special macropore of cephalosporin adsorbing and extracting of the present invention is inhaled
Attached resin has compared with high adsorption rate, good to target product selectivity, is easy to parse and regenerates, the cephalosporin product of extraction is pure
The defects of degree is high, but the resinoid existence and stability is poor, cephalosporin purity is relatively low.
The content of the invention
The present invention is in order to overcome the shortcomings of that existing polymeric adsorbent adsorbance can not be taken into account with selectivity, there is provided a kind of enemy
Spore rhzomorph C has the resin of specific adsorption, and adsorption head C copolymers are prepared from preferable pore system, then using virtue
Fragrant class alkylating reagent is described so as to improve phenyl ring density in the case where not changing aperture to copolymer Friedel-Crafts
Adsorbent has specific absorption to cephalosporin.
To realize goal of the invention, the technical scheme that the present invention is just gone is as follows：
A kind of preparation method for preparing the resin to cephalosporin with specific adsorption, methods described include following steps
Suddenly：
(1) suspension polymerisation
After monomer, crosslinking agent, pore-foaming agent, initiator are mixed with water, in the presence of dispersants, it is anti-to carry out suspension polymerisation
Should, 75-85 DEG C of suspension polymerization temperatures, polymerization reaction time 10-16 hours；Azeotropic distillation removes pore-foaming agent, into condensate liquid not
Containing grease, stop distillation, after being down to room temperature, water washing spheroid 3~5 times, drain moisture, then heated-air drying to moisture
Less than 1.0%, sieve 30-60 mesh spheroids；
Described pore-foaming agent is that chlorobenzene, dichloroethanes, toluene, dimethylbenzene, n-butanol, methyl isobutyl carbinol, acetic acid are secondary
Fourth
One or more of mixtures in ester；
Described initiator is benzoyl peroxide or lauroyl peroxide；
Described dispersant is one or several kinds of mixtures in gelatin, cellulose family, polyvinyl alcohol, lignin；
Described monomer is selected from divinylbenzene；
Described crosslinking agent is selected from divinylbenzene；
Described pore-foaming agent is monomer and the 180%-300% of crosslinking agent gross weight；
Described initiator is monomer and the 1%-2% of crosslinking agent gross weight；
Described water is the 160%-250% of monomer, pore-foaming agent and crosslinking agent gross weight；
Described dispersant is the 1.6%-2.5% of monomer, pore-foaming agent and crosslinking agent gross weight；
(2) friedel-craft is alkylated
The spheroid of step (1) drying and atent solvent are added into reactor swelling together, lewis acid is added at room temperature, drips
Add alkylating reagent, be added dropwise, be warming up to 40-50 DEG C of progress Friedel-Crafts alkylation 12-16 hour, washed through solvent, water
Wash to obtain cephalosporin specific adsorption resin；
Described swelling time is 1.5-2 hours；
Described atent solvent is dichloroethanes, dichloropropane, nitrobenzene, chlorobenzene or dichloro-benzenes；
Described lewis acid catalyst is selected from alchlor, ferric trichloride, zinc chloride, butter of tin or boron trifluoride；
Described alkylating reagent is benzyl chloride, 1- (chloromethyl) naphthalene, 2- (chloromethyl) naphthalene；
The time of described dropwise addition alkylating reagent is 1.5-3 hours；
Described cleaning solvent is that one or several kinds of mixtures are obtained in acetone, ethanol, methanol；
The amount of described cleaning solvent is the 400%-600% of dry bulb weight；
The amount of described atent 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 increase of cephalosporin polymeric adsorbent prepared by the present invention, is examined through specific surface instrument TriStar 3000
Survey, it is possible to find its microcellular structure is substantially unchanged compared with non-Friedel-Crafts.Prepared by the present invention has suction to cephalosporin
Attached resin can not only remain larger aperture, and add phenyl ring density, so as to realize its high adsorption capacity, high selectivity
Energy.π-π the effects of phenyl ring are improved, to cephalosporin adsorbance up to 60g/L and purity is up to more than 95%.Resin stability
Height, contamination resistance are strong, steady performance.
Brief description of the drawings
Fig. 1 is the change of micropore distribution before and after alkylation
Embodiment
With reference to embodiment, the present invention will be further described.
Embodiment 1
100g (80% content) divinylbenzene, 100g toluene and 50g sec-butyl acetates and 1.0g benzoyl peroxides will be contained
The monomer mixture of formyl is added in the dispersion medium solution being made up of 500ml salt-free waters, 5g gelatin, and stirring makes into certain big
Small symmetrical liquid drop, heat up 80 DEG C, react 12 hours.Then water is drained, rejoins water, be warming up to 50-60 DEG C of stirring and wash
After washing three times, add 500ml water and be warming up to azeotropic distillation removal pore-foaming agent (toluene and sec-butyl acetate), into condensate liquid almost
Without grease, stop distillation.After being down to room temperature, massive laundering washs spheroid, drains moisture, then heated-air drying to moisture
Less than 1.0%, 30-60 mesh spheroids are sieved, produce Crosslinked Macroporous copolymer matrix 95g.
95g Crosslinked Macroporous copolymer matrix obtained above is added in 450ml nitrobenzene, stirring at normal temperature swelling 2 is small
When, then add 50g alchlors, heating 45 DEG C, 2 hours in benzyl chloride 95g, insulation reaction 16 hours is added dropwise.Cooling, will
Nitrobenzene is drained, and adds 500ml ethanol, is stirred 30 minutes, is drained；500ml ethanol is added again, is stirred 30 minutes, is drained.Add
Enter a large amount of salt-free water washings to clarifying, it is cephalosporin specific adsorption resin to produce the light yellow target products of 270g.
Embodiment 2
100g (80% content) divinylbenzene, 90g toluene and 150g methyl isobutyl carbinols and 1.0g peroxides will be contained
The monomer mixture for changing benzoyl is added in the dispersion medium solution being made up of 500ml salt-free waters, 5g gelatin, and stirring makes into one
Determine the symmetrical liquid drop of size, heat up 75 DEG C, react 12 hours.Then water is drained,.Then water is drained, rejoins water, risen
Temperature to 50-60 DEG C of agitator treating three times after, add 500ml water be warming up to azeotropic distillation remove pore-foaming agent (toluene and methyl tert-butyl
Base methanol), grease is practically free of into condensate liquid, stops distillation.Cooling, massive laundering wash spheroid, drain moisture, Ran Houre
Air-dry dry to moisture below 1.0%, sieve 30-60 mesh spheroids, produce Crosslinked Macroporous copolymer matrix 90g.
90g Crosslinked Macroporous copolymer matrix obtained above is added in 570ml dichloroethanes, stirring at normal temperature swelling 2
Hour, 50g iron chloride is added at room temperature, is then started that benzyl chloride 90g is added dropwise, about 2 hours time, 48 is warming up to after being added dropwise
DEG C, react 15 hours.300g brown target product cephalosporin specific adsorption trees are made with reference to embodiment 1 in remaining operation
Fat.
Embodiment 3
100g (80% content) divinylbenzene, 150g toluene and 70g hexones and 1.0g peroxides will be contained
The monomer mixture for changing benzoyl is added in the dispersion medium solution being made up of 500ml salt-free waters, 5g gelatin, and stirring makes into one
Determine the symmetrical liquid drop of size, heat up 75 DEG C, react 12 hours..Then water is drained, rejoins water, be warming up to 50-60 DEG C and stir
After mixing washing three times, add 500ml water and be warming up to azeotropic distillation removal pore-foaming agent (toluene and methyl isobutyl carbinol), to condensation
Grease is practically free of in liquid, stops distillation.Cooling, massive laundering wash spheroid, drain moisture, then heated-air drying to moisture
Less than 1.0%, 30-60 mesh spheroids are sieved, produce Crosslinked Macroporous copolymer matrix 85g.
85g Crosslinked Macroporous copolymer matrix obtained above is added in 510ml dichloroethanes, stirring at normal temperature swelling 2
Hour, 30g iron chloride is added at room temperature, is then started that 1- (chloromethyl) naphthalene 90g is added dropwise, about 2 hours time, is risen after being added dropwise
Temperature is reacted 15 hours to 48 DEG C.Remaining operation is made 255g brown target products cephalosporin specificity and inhaled with reference to embodiment 1
Attached resin.
Embodiment 4
100g (80% content) divinylbenzene, 90g toluene and 150g methyl isobutyl alcohols and 1.0g peroxidating will be contained
The monomer mixture of lauroyl is added in the dispersion medium solution being made up of 500ml salt-free waters, 5g gelatin, and stirring makes into certain
The symmetrical liquid drop of size, heat up 75 DEG C, react 12 hours.Then water is drained,.Then water is drained, rejoins water, heated up
To 50-60 DEG C of agitator treating three times after, add 500ml water be warming up to azeotropic distillation remove pore-foaming agent (toluene and methyl-isobutyl
Methanol), grease is practically free of into condensate liquid, stops distillation.Cooling, massive laundering wash spheroid, drain moisture, then hot blast
Dry to moisture below 1.0%, sieve 30-60 mesh spheroids, produce Crosslinked Macroporous copolymer matrix 95g.
95g Crosslinked Macroporous copolymer matrix obtained above is added in 570ml dichloroethanes, stirring at normal temperature swelling 2
Hour, 50g iron chloride is added at room temperature, is then started that benzyl chloride 90g is added dropwise, about 2 hours time, 48 is warming up to after being added dropwise
DEG C, react 15 hours.305g brown target product cephalosporin specific adsorption trees are made with reference to embodiment 1 in remaining operation
Fat.
Embodiment 5
100g (80% content) divinylbenzene, 150g toluene and 50g dimethylbenzene and 1.0g benzoyl peroxides will be contained
Monomer mixture be added in the dispersion medium solution being made up of 500ml salt-free waters, 5g gelatin, stirring make into a certain size
Symmetrical liquid drop, heat up 75 DEG C, react 12 hours.Then water is drained,.Then water is drained, rejoins water, be warming up to 50-
60 DEG C of agitator treatings three times after, add 500ml water be warming up to azeotropic distillation remove pore-foaming agent (toluene and methyl isobutyl carbinol),
Grease is practically free of into condensate liquid, stops distillation.Cooling, massive laundering washs spheroid, drains moisture, and then heated-air drying is extremely
Below moisture 1.0%, 30-60 mesh spheroids are sieved, produce Crosslinked Macroporous copolymer matrix 80g.
80g Crosslinked Macroporous copolymer matrix obtained above is added in 480ml dichloroethanes, stirring at normal temperature swelling 2
Hour, 25g iron chloride is added at room temperature, is then started that benzyl chloride 90g is added dropwise, about 2 hours time, 48 is warming up to after being added dropwise
DEG C, react 15 hours.250g brown target product cephalosporin specific adsorption trees are made with reference to embodiment 1 in remaining operation
Fat.
Sample result is analyzed
1, the physical characterization of resin
Assay method：Pore volume, than surface, aperture and micropore distribution there is specific surface instrument TriStar 3000 to detect；Water
Divide and determined according to national standard GB/T5757.
Fig. 1 is the change that embodiment 1 is alkylated front and rear micropore distribution, detects, can send out through specific surface instrument TriStar 3000
Its existing microcellular structure is substantially unchanged compared with non-Friedel-Crafts, and objectively responding out phenyl ring density by resin infrared spectrum increases
Add.Illustrate that the obtained cephalosporin polymeric adsorbent of the present invention can not only remain larger aperture, and add phenyl ring density, from
And realize its high selectivity, high adsorption capacity purpose.
Table 1 is alkylated front and rear physical and chemical performance
2 resins are verified in cephalosporin adsorption effect
Experimental method：
Cephalosporin C fermentation liquid of the potency 10,000 or so is taken, pH adjusts upper prop absorption between 2.6-2.8, and adsorption flow rate is
1BV/h；After the salt-free water washings of 2BV；Then parsed with strippant, parsing flow velocity is 0.5BV/h；1BV is used after parsing
Salt-free water water top.Collect absorption to mix, wash mixing, parsing mixing, water top biased sample efficient liquid phase measure potency, count
Calculate the data such as adsorbance, desorption quantity.As a result following table：
The obtained resin of the present invention of table 2 contrasts with commercial resins enemy's cephalosporin adsorption experiment
| Adsorbance 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- resins；DCPC, DOCPC are two kinds of main impurity of Cephalosporin C fermentation liquid.
It the foregoing is only several specific implementation forms of the present invention, it is noted that for ordinary skill people
For member, many deformations can also be made and improved.All deformations or improvement without departing from described in claim are regarded as this
The scope of invention.
Claims (2)
- A kind of 1. preparation method for preparing the resin to cephalosporin with specific adsorption, it is characterised in that methods described bag Include following step：(1) suspension polymerisationAfter monomer, crosslinking agent, pore-foaming agent, initiator are mixed with water, in the presence of dispersants, suspension polymerization is carried out, hanged Floating 75-85 DEG C of polymerization temperature, polymerization reaction time 10-16 hours；Azeotropic distillation removes pore-foaming agent, and oily is free of into condensate liquid Thing, stop distillation, be cooled to room temperature, water washing spheroid 3~5 times, drain moisture, heated-air drying to moisture is below 1.0%, screening 30-60 mesh spheroids；Described pore-foaming agent is chlorobenzene, dichloroethanes, toluene, dimethylbenzene, n-butanol, methyl isobutyl carbinol, sec-butyl acetate In one or more of mixtures；Described initiator is benzoyl peroxide or lauroyl peroxide；Described dispersant is one or several kinds of mixtures in gelatin, cellulose family, polyvinyl alcohol, lignin；Described monomer is selected from divinylbenzene；Described crosslinking agent is selected from divinylbenzene；(2) friedel-craft is alkylatedThe spheroid of step (1) drying and atent solvent are added into reactor swelling together, lewis acid is added at room temperature, alkane is added dropwise Base reagent, after being added dropwise, 40-50 DEG C of progress Friedel-Crafts alkylation 12-16 hour is warming up to, washs, wash through solvent Obtain cephalosporin specific adsorption resin；Described swelling time is 1.5-2 hours；Described atent solvent is dichloroethanes, dichloropropane, nitrobenzene, chlorobenzene or dichloro-benzenes；Described lewis acid catalyst is selected from alchlor, ferric trichloride, zinc chloride, butter of tin or boron trifluoride；Described alkylating reagent is benzyl chloride, 1- (chloromethyl) naphthalene, 2- (chloromethyl) naphthalene；The time of described dropwise addition alkylating reagent is 1.5-3 hours；Described cleaning solvent is that one or several kinds of mixtures are obtained in acetone, ethanol, methanol；The amount of described cleaning solvent is the 400%-600% of dry bulb weight；The amount of described atent solvent is dry bulb weight 500%-700%；Described lewis acidic amount is the 30%-100% of dry bulb weight；The amount of described alkylating reagent is dry bulb weight 30%-100%.
- 2. the preparation method as claimed in claim 1 for preparing the resin to cephalosporin with specific adsorption, its feature exist In described pore-foaming agent is monomer and the 180%-300% of crosslinking agent gross weight；Described initiator is that monomer and crosslinking agent are total The 1%-2% of weight；Described water is the 160%-250% of monomer, pore-foaming agent and crosslinking agent gross weight；Described dispersant is The 1.6%-2.5% of monomer, pore-foaming agent and crosslinking agent gross weight.
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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 |
| 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 |
| 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 |
| 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 |
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| CN101288841A (en) * | 2008-06-11 | 2008-10-22 | 山东鲁抗立科药物化学有限公司 | Macroporous adsorption resin special for extracting cephalosporin C and its preparation method |
| 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 |
| CN103772573A (en) * | 2014-02-24 | 2014-05-07 | 山东鲁抗立科药业有限公司 | Ultrahigh cross-linked macro-porous adsorption resin applicable to removal of patulin |
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| CN101288841A (en) * | 2008-06-11 | 2008-10-22 | 山东鲁抗立科药物化学有限公司 | Macroporous adsorption resin special for extracting cephalosporin C and its preparation method |
| 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 |
| CN103772573A (en) * | 2014-02-24 | 2014-05-07 | 山东鲁抗立科药业有限公司 | Ultrahigh cross-linked macro-porous adsorption resin applicable to removal of patulin |
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