CN103041805A - Preparation method of high-activity palladium-carbon catalyst for synthesis of imipenem antibiotics - Google Patents
Preparation method of high-activity palladium-carbon catalyst for synthesis of imipenem antibiotics Download PDFInfo
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- 239000003054 catalyst Substances 0.000 title claims abstract description 70
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 230000000694 effects Effects 0.000 title abstract description 17
- 238000003786 synthesis reaction Methods 0.000 title abstract description 7
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 title abstract description 5
- 230000015572 biosynthetic process Effects 0.000 title abstract description 5
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 title abstract description 5
- 229960002182 imipenem Drugs 0.000 title abstract description 5
- 239000003242 anti bacterial agent Substances 0.000 title abstract 4
- 229940088710 antibiotic agent Drugs 0.000 title abstract 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 127
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 45
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 37
- 239000007788 liquid Substances 0.000 claims abstract description 15
- 238000006722 reduction reaction Methods 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 29
- 239000002002 slurry Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000009938 salting Methods 0.000 claims description 13
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 12
- CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 claims description 10
- 239000008139 complexing agent Substances 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 239000011148 porous material Substances 0.000 claims description 8
- 238000010521 absorption reaction Methods 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000003610 charcoal Substances 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 230000011218 segmentation Effects 0.000 claims description 6
- 235000017281 sodium acetate Nutrition 0.000 claims description 6
- 239000001632 sodium acetate Substances 0.000 claims description 6
- 239000002250 absorbent Substances 0.000 claims description 5
- 230000002745 absorbent Effects 0.000 claims description 5
- 230000003115 biocidal effect Effects 0.000 claims description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 4
- 150000002611 lead compounds Chemical class 0.000 claims description 4
- 238000002803 maceration Methods 0.000 claims description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
- 238000005660 chlorination reaction Methods 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 239000007791 liquid phase Substances 0.000 claims description 2
- 239000013528 metallic particle Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000002023 wood Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 238000005470 impregnation Methods 0.000 abstract 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 abstract 1
- 239000000654 additive Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000002243 precursor Substances 0.000 abstract 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 abstract 1
- 239000001509 sodium citrate Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000003756 stirring Methods 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000005303 weighing Methods 0.000 description 8
- 239000008367 deionised water Substances 0.000 description 7
- 229910021641 deionized water Inorganic materials 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
- 238000006264 debenzylation reaction Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000004140 cleaning Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- 238000012549 training Methods 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 description 4
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 4
- 229960002260 meropenem Drugs 0.000 description 4
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 235000011091 sodium acetates Nutrition 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 235000011167 hydrochloric acid Nutrition 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 101150003085 Pdcl gene Proteins 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- -1 benzyl ester Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000010970 precious metal Substances 0.000 description 2
- 238000011946 reduction process Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- MRMBZHPJVKCOMA-YJFSRANCSA-N biapenem Chemical compound C1N2C=NC=[N+]2CC1SC([C@@H]1C)=C(C([O-])=O)N2[C@H]1[C@@H]([C@H](O)C)C2=O MRMBZHPJVKCOMA-YJFSRANCSA-N 0.000 description 1
- 229960003169 biapenem Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- ZMLDXWLZKKZVSS-UHFFFAOYSA-N palladium tin Chemical compound [Pd].[Sn] ZMLDXWLZKKZVSS-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention relates to a preparation method of a high-activity palladium-carbon catalyst for synthesis of imipenem antibiotics. According to the preparation method of the high-activity palladium-carbon catalyst for the synthesis of the imipenem antibiotics, ammonium chloropalladite and salts thereof are taken as precursor compounds of an active component, namely palladium, powdered activated carbon is taken as a carrier, additives such as sodium citrate are added into Pd impregnation liquid, and then the Pd impregnation liquid is absorbed onto the activated carbon in a segmenting manner and subjected to wet chemical reduction to obtain the high-activity palladium-carbon catalyst; and the catalyst is used for industrial production of the synthesis of the imipenem antibiotics.
Description
Technical field
The present invention relates to a kind of preparation method of palladium carbon catalyst of high activity, particularly relate to the preparation method of the palladium carbon catalyst of high activity of the synthetic middle debenzylation class protecting group of a kind of penem-like pharmaceutical.
Background technology
Benzyl is important organo-functional group blocking group; because its easy formation, relatively stable and under the condition of gentleness, slough easily under certain condition, so in organic synthesis; be commonly used to protect the compound that contains O-, N-, make respectively corresponding benzyl oxide, benzyl ester and benzylamine after the protection.Benzyl separates with amino or hydroxy functional group in the debenzylation process, becomes toluene after benzyl or the substituted benzyl hydrogenolysis or replaces toluene and slough, and compound itself generally can not produce destruction.An attracting purposes of debenzylation (or benzyloxycarbonyl group) is in the organic synthesis process benzyl (or benzyloxycarbonyl group) and hydroxyl or amido functional group to be separated.According to estimates, in surpassing the building-up process of 1000 kinds of medicines, to carry out the reaction of debenzylation class protecting group.Experience shows that palladium carbon catalyst is the excellent catalysts of debenzylation or benzyloxycarbonyl group.
Penem-like pharmaceutical is to see that take Meropenem structural formula (I), Imipenem see that structural formula (II) and Biapenem see that structural formula (III) etc. is as the carbapenem antibiotic of representative; it is the widest beta-lactam antibiotic of a class antimicrobial spectrum; final step in its chemical synthesis; need to use palladium carbon catalyst to carry out hydrogenolysis; slough benzyl class protecting group, as to nitrobenzyl (PNB), to nitro benzyloxycarbonyl group (PNZ) (the catalytic hydrogenolytic cleavage formula of penem-like pharmaceutical in synthetic seen in reaction).
Chinese patent (CN 101348486A, CN100422184C, CN 101921273 A, CN 101921274 A, CN101921275 A, CN100383142C, CN 100424071C, CN100497349C etc.) relates in the synthetic penem-like pharmaceutical needs to use palladium carbon catalyst, but does not relate to palladium carbon catalyst preparation method's description.
Chinese patent (CN 102133527A) has been mentioned a kind of for synthetic palladium tin Pd/carbon catalyst of Meropenem and preparation method thereof.This catalyst is take powdered activated carbon as carrier, load active component metal Pd and active component Sn.Preparation process through active carbon acid treatment, Pd and Sn compound loaded catalyst precarsor, catalyst precarsor reduces to get catalyst prod after wearing out.The acid treatment active carbon is so that catalyst preparation process lengthens, and product cost raises, and the interpolation of second component Sn is so that from waste catalyst recovery Pd complicated, be unfavorable for the recycling of precious metals pd.
In the building-up process of penem-like pharmaceutical, the training south intermediate of PNB or PNZ protection, the characteristics such as in course of reaction, have reactant and the product molecular volume is larger, and hydrogenolysis temperature and hydrogenolysis temperature are low.Therefore, on kinetics, reactant and product have larger diffusional resistance, wish improves the Atom economy of reaction, require reduce reactant and the product diffusional resistance in palladium carbon catalyst surface and duct, for reactant or product provide a favourable condition at the mass transfer of palladium carbon catalyst inner surface, in the selection of active carbon, should choose the higher active carbon of the larger and mesoporous volume weight in aperture.
On the other hand, angle from reactive metal Pd, because the macromolecular reaction thing is difficult to diffuse to the darker surface, duct of palladium carbon catalyst granule interior and reacts, therefore, be in the Pd active component on darker surface, duct, catalyst granules inside, in real reaction, can not play a role and the engineering noise that becomes, for improving the catalytic efficiency of precious metals pd atom, obviously, active component Pd mainly is distributed near the outer surface and aperture of active carbon.In addition, with regard to single Pd crystallite, size is less, and the Pd atomicity that its outer surface exposes is also just more, and for debenzylation class protecting group, the activity of catalyst and metal Pd particle diameter are linear.Therefore, answer the size of reduce Pd crystallite.
In existing palladium carbon catalyst preparation method, there is complicated process of preparation, absorbent charcoal carrier micropore proportion is too high, the crystal grain diameter of active component Pd is excessive and Pd crystallite distributed depth causes the activity of catalyst, selectively not high excessively deeply.Some other physics, chemical property, it is wide that for example the particle diameter of absorbent charcoal carrier is too small or particle diameter distributes, so that the strainability of catalyst is poor.
Summary of the invention
The object of the invention is to overcome above-mentioned the deficiencies in the prior art, particularly low for existing catalyst activity and selectivity, the shortcoming that filterability is poor provides a kind of preparation method of the efficient palladium carbon catalyst be used to training the synthetic usefulness of southern class antibiotic.The activated carbon particle size distribution of this catalyst is suitable, specific area is high and mesoporous volume weight high, and near the outer surface and aperture of charcoal carrier, the activity of catalyst, selective height and filterability are good with ultra tiny distributions for active component Pd.
The present invention is achieved by the following technical solutions:
1, at first selects to have the high filtration that absorbent charcoal carrier that appropriate particle size and particle diameter distribute is realized catalyst;
2, then select to have the higher active carbon of the larger and mesoporous proportion in aperture, reduce the diffusional resistance of reactant or product, improve catalyst activity and selectivity;
3, the improvement by the preparation method, introduce the complexing agents such as natrium citricum, play the effect of Pd compound complexing agent and the agent of Pd protecting atom, on the one hand, increase later on the diameter of Pd presoma by complexing, the Pd presoma mainly is distributed in adsorption process near the outer surface and aperture of active carbon, on the other hand, in the reduction process of Pd presoma, protection Pd crystallite is difficult for growing up, make Pd with ultra tiny distributions at activated carbon surface, improve the effective rate of utilization of Pd atom, guarantee that catalyst has high activity;
4, adopt the absorption of segmentation room temperature, make metal Pd fully with ultra tiny distributions at activated carbon surface;
5, use the active carbon with following physical chemistry technical indicator: BET specific area 1100 m
2/ g, pore volume 1.58ml/g, average pore radius 2.0 nm, ash content 0.9%, pH are 6.
Preparation method provided by the invention, step is as follows:
(1) in the mixed serum of active carbon and ionized water, adsorbs in advance the complexing agents such as natrium citricum;
(2) preparation palladium salting liquid is added drop-wise in the slurries that step (1) obtains, and the palladium load capacity is 5%～10%;
(3) segmentation absorption palladium salting liquid, first step pH is controlled between 4～5, and second step pH is controlled between 9～10;
(4) slurries that step (3) obtained reduce with hydrazine hydrate, formaldehyde, hydrogen etc., namely obtain palladium carbon catalyst.
Described complexing agent refers to the salts such as natrium citricum, sodium acetate.
Described palladium salt refers to the mixed solution that water-soluble chlorination palladium and natrium citricum, sodium acetate etc. form.
Describedly before the reduction operation, second step pH is controlled between 9～10, the one, the hydrolysis of the water soluble compound of Pd is generated insoluble Pd (OH)
2Or PdOH
2O can prevent migration and the grain growth of Pd in the follow-up reduction process, the 2nd, with not fully the palladium presoma of absorption load on the active carbon in the mode of deposition sedimentation, guarantee the fully absorption of Pd presoma.
Key of the present invention has added complexing agent when being the preparation of Pd solution, complexing agent can produce stronger interaction and generate a kind of complex compound with Pd, complexing agent also can play the effect of stablizing the Pd pH value of solution when configuration Pd solution simultaneously, so can reduce the redox potential of Pd, when Pd loads on the active carbon, the Pd ion just can not reduced by Surface Groups of Active Carbons, thereby the Pd ion can be distributed in the surface of active carbon very uniformly.
Catalyst provided by the invention can be used for the southern deprotection of protection (Metro, imines and Bi A) training is converted into (Metro, imines and Bi A) training south.
The active testing of catalyst of the present invention:
The activity of the catalyst at first deprotection reaction of the L-Phe by benzyloxycarbonyl group protection is tested (reaction equation is seen following).
In 500 ml autoclaves, add successively benzyloxycarbonyl group-L-Phe 5 g, Pd/C catalyst 100 mg, ethanol 150 ml, deionized water 150 ml, speed of agitator 500 r/min are respectively in logical nitrogen and the hydrogen exchange still behind air and the nitrogen three times, keep Hydrogen Vapor Pressure 0.3 MPa, 30 ℃ of lower reaction 1.5 h.After reaction finished, negate was answered rear filtrate to carry out HPLC and is analyzed the quantitative L-Phe yield of area external standard method.The L-Phe yield is higher, and catalyst activity is better.The model reaction formula of taking off benzyloxycarbonyl group is as follows:
In 100 ml stainless steel autoclaves; add successively protection Meropenem 1.4 g, Pd/C catalyst 140 mg, oxolane 35 ml; deionized water 28 ml; 2,6-lutidines, 0.6 g is respectively in logical nitrogen and the hydrogen exchange still behind air and the nitrogen three times; keep Hydrogen Vapor Pressure 1.8 MPa; 45 ℃ of temperature controls, mixing speed 500 r/min carried out hydrogenation 1 hour.After reaction finished, negate was answered rear filtrate to carry out HPLC and is analyzed the quantitative Meropenem trihydrate yield of area external standard method.
The specific embodiment
The preparation method of the palladium carbon catalyst of the synthetic usefulness of the southern class antibiotic of training of the present invention, lead compound take the inferior palladium acid of chlorine and salt thereof as active component palladium, take powdered activated carbon as carrier, add natrium citricum or sodium acetate in the Pd maceration extract, then the segmentation of Pd maceration extract is adsorbed on the active carbon, obtain palladium carbon catalyst through the wet-chemical reduction, concrete steps are as follows:
(1) in the mixed serum of active carbon and ionized water, adsorbs in advance natrium citricum or sodium acetate complexing agent;
(2) preparation palladium salting liquid is added drop-wise in the slurries that step (1) obtains, and the palladium load capacity is 5%～10%;
(3) segmentation absorption palladium salting liquid, first step pH is controlled between 4～5, and second step pH is controlled between 9～10;
(4) slurries that step (3) obtained reduce with hydrazine hydrate, formaldehyde or hydrogen, namely obtain palladium carbon catalyst.
Described palladium salting liquid refers to the mixed solution that water-soluble chlorination palladium and natrium citricum or sodium acetate form.
The reduction of slurries is under liquid phase environment in the described step (4), is lower than to carry out under 100 ℃ the temperature.
Described catalyst is:
1) catalyst B ET specific area is 800～1200 m
2/ g, average grain diameter is 20～35 μ m, average pore radius 〉=1.5 nm;
2) weight content of metal Pd is 5%～10% in the catalyst;
3) load on palladium metal on the absorbent charcoal carrier, metallic particles is evenly distributed, crystallite dimension≤5 nm.
The lead compound of the employed palladium of catalyst is the inferior palladium acid of palladium bichloride, chlorine or sodium chloropalladite.
The employed active carbon of catalyst is that surface area is greater than 1000 m
2/ g, pore volume are greater than 1.0 ml/g, and average pore radius is greater than 1.5 nm, and particle mean size is 200～300 purpose wood activated charcoals.
Below in conjunction with the specific embodiment the present invention is described in further detail.
Embodiments of the invention are as follows:
Embodiment 1:1) take by weighing 180 g(dry weight basis) active carbon, add 5 L reactors, add water 0.9 L, stir 2 h;
2) take by weighing 33.2 g PdCl
2, add 20 ml concentrated hydrochloric acids and 1 L deionized water, be heated to the boiling dissolving, be cooled to room temperature;
3) with step) the 2 palladium salting liquids that obtain at the uniform velocity are added drop-wise in the active carbon slurries, dripping off rear is 4.5 with mass fraction 10% NaOH adjusting slurries pH, and then stirring and adsorbing 5 h drip mass fraction 10% NaOH and adjust the pH value, keep the pH value between 9-10, stir deposition and continue absorption 16 h;
4) under 80 ℃, add 70 ml formaldehyde, keep pH 9～10, reduce 4 h;
5) cooling, hold over night is filtered, and it is neutral to filtrate to spend ion-cleaning, gets the 10%Pd/C catalyst, moisture content 58.6%.
Embodiment 2:1) take by weighing 180 g(dry weight basis) active carbon and 13.5 g natrium citricums, add 5 L reactors, add water 0.9 L, stir 2 h;
2) take by weighing 33.2 gPdCl
2, add 20 ml concentrated hydrochloric acids and 1 L deionized water, be heated to the boiling dissolving, add 20 g natrium citricums, heated again 10 minutes, do not make the solution bumping, be cooled to room temperature;
3) with step 2) the palladium salting liquid that obtains at the uniform velocity is added drop-wise in the active carbon slurries, and dripping off rear is 4.6 with slurries pH, and then stirring and adsorbing 5 h drip mass fraction 10% NaOH and adjust pH value, keep pH value between 9-10, stir the deposition continuation and adsorb 16 h;
4) under 80 ℃, add 70 ml formaldehyde, keep pH 9～10, recovery times 4 h;
5) cooling, hold over night is filtered, and it is neutral to filtrate to spend ion-cleaning, gets the 10%Pd/C catalyst, moisture content 57.4%.
Embodiment 3:1) take by weighing 186 g(dry weight basis) active carbon and 14.0 g sodium acetates, add 5 L reactors, add water 900 mL, stir 2 h;
2) take by weighing 23.3 g PdCl
2, adding 14 ml concentrated hydrochloric acids and 1.4L deionized water, the ebuillition of heated dissolving adds 14 g sodium acetates, heats 10 minutes again, does not make the solution bumping, is cooled to room temperature;
3) with step 2) the palladium salting liquid that obtains at the uniform velocity is added drop-wise in the active carbon slurries, and dripping off rear is 4.2 with slurries pH, and then stirring and adsorbing 4 h drip mass fraction 10% NaOH and adjust pH value, keep pH value between 9-10, stir to deposit to adsorb 16 h;
4) regulate pH 9 ~ 10, hydrogen reducing times 6 h under the room temperature;
5) cooling, hold over night is filtered, and it is neutral to filtrate to spend ion-cleaning, gets the 7%Pd/C catalyst, moisture content 58.0%.
Embodiment 4:1) claim 190 g(dry weight basis) active carbon and 14.25 g sodium acetates, add 5 L reactors, add water 1 L, stir 2 h;
2) take by weighing the inferior palladium acid of 45.4 g chlorine, add the 1L deionized water and dilute, the ebuillition of heated dissolving adds 10 g sodium acetates, heats 10 minutes again, does not make the solution bumping, is cooled to room temperature;
3) with step 2) the palladium salting liquid that obtains at the uniform velocity is added drop-wise in the active carbon slurries, and dripping off rear slurry PH is 4.0, and then stirring and adsorbing 4 h drip mass fraction 10% NaOH and adjust pH value, keep pH value between 9-10, stir to deposit to adsorb 16 h;
4) under 80 ℃, add 100 ml hydrazine hydrates, keep pH 9 ~ 10, recovery times 2 h;
5) cooling, hold over night is filtered, and it is neutral to filtrate to spend ion-cleaning, gets the 5%Pd/C catalyst, moisture content 56.2%.
Embodiment 5:1) claim 190 g(dry weight basis) active carbon and 14.25 g natrium citricums, add 5 L reactors, add water 1 L, stir 2 h;
2) take by weighing the inferior palladium acid of 45.4 g chlorine, add 1 L deionized water and dilute, the ebuillition of heated dissolving adds 10 g natrium citricums, heats 10 minutes again, does not make the solution bumping, is cooled to room temperature;
3) with step 2) the palladium salting liquid that obtains at the uniform velocity is added drop-wise in the active carbon slurries, and dripping off rear slurry PH is 4.0, and then stirring and adsorbing 4 h drip mass fraction 10%NaOH and adjust pH value, keep pH value between 9-10, stir to deposit to adsorb 16 h;
4) under 80 ℃, add 70 ml formaldehyde, keep pH 9～10, recovery time 4h;
5) cooling, hold over night is filtered, and it is neutral to filtrate to spend ion-cleaning, gets the 5%Pd/C catalyst, moisture content 57.5%.
The catalyst characteristic feature performance table table 1 of each embodiment preparation.
Table 1
PSD: particle size distribution, PSD=[D (90)-D (10)]/D (50)
Filtering velocity condition determination: 5g catalyst, filtrate 150 ml, suction pressure :-0.06MPa.
Claims (6)
1. train the preparation method that southern class antibiotic synthesizes the palladium carbon catalyst of usefulness for one kind, it is characterized in that: the lead compound take the inferior palladium acid of chlorine and salt thereof as active component palladium, take powdered activated carbon as carrier, add natrium citricum or sodium acetate in the Pd maceration extract, then the segmentation of Pd maceration extract is adsorbed on the active carbon, obtain palladium carbon catalyst through the wet-chemical reduction, concrete steps are as follows:
(1) in the mixed serum of active carbon and ionized water, adsorbs in advance natrium citricum or sodium acetate complexing agent;
(2) preparation palladium salting liquid is added drop-wise in the slurries that step (1) obtains, and the palladium load capacity is 5%～10%;
(3) segmentation absorption palladium salting liquid, first step pH is controlled between 4～5, and second step pH is controlled between 9～10;
(4) slurries that step (3) obtained reduce with hydrazine hydrate, formaldehyde or hydrogen, namely obtain palladium carbon catalyst.
2. the preparation method of described palladium carbon catalyst according to claim 1 is characterized in that described palladium salting liquid refers to the mixed solution that water-soluble chlorination palladium and natrium citricum or sodium acetate form.
3. the preparation method of described palladium carbon catalyst according to claim 1, it is characterized in that: the reduction of slurries is under liquid phase environment in the described step (4), is lower than to carry out under 100 ℃ the temperature.
4. the preparation method of described palladium carbon catalyst according to claim 1 is characterized in that described catalyst is:
1) catalyst B ET specific area is 800～1200 m
2/ g, average grain diameter is 20～35 μ m, average pore radius 〉=1.5 nm;
2) weight content of metal Pd is 5%～10% in the catalyst;
3) load on palladium metal on the absorbent charcoal carrier, metallic particles is evenly distributed, crystallite dimension≤5 nm.
5. the preparation method of described palladium carbon catalyst according to claim 1, the lead compound that it is characterized in that the employed palladium of catalyst is the inferior palladium acid of palladium bichloride, chlorine or sodium chloropalladite.
6. the preparation method of described palladium carbon catalyst according to claim 1 is characterized in that the employed active carbon of catalyst is that surface area is greater than 1000 m
2/ g, pore volume are greater than 1.0 ml/g, and average pore radius is greater than 1.5 nm, and particle mean size is 200～300 purpose wood activated charcoals.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106179332A (en) * | 2015-05-07 | 2016-12-07 | 中国石油化工股份有限公司 | A kind of catalyst preparing 4-ADPA and preparation method |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4476242A (en) * | 1981-10-29 | 1984-10-09 | Standard Oil Company (Indiana) | Process for preparing palladium on carbon catalysts for purification of crude terephthalic acid |
| CN101637724A (en) * | 2008-07-29 | 2010-02-03 | 中国石油化工股份有限公司 | Method for preparing high-activity palladium/carbon catalyst |
| CN102397787A (en) * | 2010-09-14 | 2012-04-04 | 中国石油化工股份有限公司 | Method and device for preparing palladium-carbon catalyst |
| CN102658133A (en) * | 2012-05-09 | 2012-09-12 | 杭州凯大催化金属材料有限公司 | Method for preparing active carbon carrying precious metal catalyst |
-
2012
- 2012-12-07 CN CN2012105213217A patent/CN103041805A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4476242A (en) * | 1981-10-29 | 1984-10-09 | Standard Oil Company (Indiana) | Process for preparing palladium on carbon catalysts for purification of crude terephthalic acid |
| CN101637724A (en) * | 2008-07-29 | 2010-02-03 | 中国石油化工股份有限公司 | Method for preparing high-activity palladium/carbon catalyst |
| CN102397787A (en) * | 2010-09-14 | 2012-04-04 | 中国石油化工股份有限公司 | Method and device for preparing palladium-carbon catalyst |
| CN102658133A (en) * | 2012-05-09 | 2012-09-12 | 杭州凯大催化金属材料有限公司 | Method for preparing active carbon carrying precious metal catalyst |
Non-Patent Citations (2)
| Title |
|---|
| 戴云生等: "催化氢解脱苄基Pd/Ｃ催化剂的研究和应用", 《工业催化》 * |
| 黄伟等: "Pd/C催化剂研究进展", 《工业催化》 * |
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| WO2018062632A1 (en) * | 2016-09-29 | 2018-04-05 | 희성금속 주식회사 | Method for producing palladium/carbon catalyst capable of increasing production |
| CN107999063B (en) * | 2016-11-01 | 2020-03-31 | 中国石油化工股份有限公司 | Catalyst for producing 1, 4-diacetoxybutane from butadiene |
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