CN101693202B - Hydrogenation reaction catalyst of pioglitazone hydrochloride key intermediate and hydrogenation reaction method - Google Patents
Hydrogenation reaction catalyst of pioglitazone hydrochloride key intermediate and hydrogenation reaction method Download PDFInfo
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- CN101693202B CN101693202B CN2009100757542A CN200910075754A CN101693202B CN 101693202 B CN101693202 B CN 101693202B CN 2009100757542 A CN2009100757542 A CN 2009100757542A CN 200910075754 A CN200910075754 A CN 200910075754A CN 101693202 B CN101693202 B CN 101693202B
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- 238000005984 hydrogenation reaction Methods 0.000 title claims abstract description 33
- 238000000034 method Methods 0.000 title claims abstract description 18
- GHUUBYQTCDQWRA-UHFFFAOYSA-N Pioglitazone hydrochloride Chemical compound Cl.N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 GHUUBYQTCDQWRA-UHFFFAOYSA-N 0.000 title abstract 2
- 239000007809 chemical reaction catalyst Substances 0.000 title abstract 2
- 229960002827 pioglitazone hydrochloride Drugs 0.000 title abstract 2
- 239000003054 catalyst Substances 0.000 claims abstract description 59
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 18
- 230000000694 effects Effects 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 6
- 229910052802 copper Inorganic materials 0.000 claims abstract description 5
- 229910052759 nickel Inorganic materials 0.000 claims abstract description 5
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 3
- 229910052804 chromium Inorganic materials 0.000 claims abstract description 3
- 239000002131 composite material Substances 0.000 claims abstract description 3
- 229910052742 iron Inorganic materials 0.000 claims abstract description 3
- 229910052725 zinc Inorganic materials 0.000 claims abstract 2
- 239000002904 solvent Substances 0.000 claims description 24
- 239000000376 reactant Substances 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 12
- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 10
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 6
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 150000001555 benzenes Chemical class 0.000 claims description 2
- 238000010790 dilution Methods 0.000 claims description 2
- 239000012895 dilution Substances 0.000 claims description 2
- 125000000532 dioxanyl group Chemical group 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 12
- 229910052788 barium Inorganic materials 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000010792 warming Methods 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000010949 copper Substances 0.000 description 5
- 239000011651 chromium Substances 0.000 description 4
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 102000004316 Oxidoreductases Human genes 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 238000000975 co-precipitation Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 238000004898 kneading Methods 0.000 description 3
- KBJMLQFLOWQJNF-UHFFFAOYSA-N nickel(ii) nitrate Chemical compound [Ni+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O KBJMLQFLOWQJNF-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- POAOYUHQDCAZBD-UHFFFAOYSA-N 2-butoxyethanol Chemical compound CCCCOCCO POAOYUHQDCAZBD-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- WRSVIZQEENMKOC-UHFFFAOYSA-N [B].[Co].[Co].[Co] Chemical compound [B].[Co].[Co].[Co] WRSVIZQEENMKOC-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910001429 cobalt ion Inorganic materials 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- JGUQDUKBUKFFRO-CIIODKQPSA-N dimethylglyoxime Chemical compound O/N=C(/C)\C(\C)=N\O JGUQDUKBUKFFRO-CIIODKQPSA-N 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- JBQYATWDVHIOAR-UHFFFAOYSA-N tellanylidenegermanium Chemical compound [Te]=[Ge] JBQYATWDVHIOAR-UHFFFAOYSA-N 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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- Catalysts (AREA)
Abstract
The invention discloses a hydrogenation reaction catalyst of a pioglitazone hydrochloride key intermediate and a hydrogenation reaction method. The key intermediate is 5-[4-[2-(5-ethyl-2-pyridyl) oxethyl] benzylidene]-2,4-thiazolidinedione; the catalyst takes AL2O3 as a carrier and comprises composite active components selected from one or several simple substances or the simple substances and the oxides thereof of Ni, Cu, Co, Zn, Fe, Cr, Ca and Ba, the mass content of each component is 1-20 percent of the total mass of the catalyst, and the mass content of the total active component is 10-40 percent of the total mass of the catalyst. The catalyst has simple and convenient preparation, low catalyst cost, stable activity and circular utilization. The hydrogenation reaction method has the characteristics of easy control of operation conditions, good catalyst property and high product yield.
Description
Technical field
The present invention relates to a kind of hydrogen addition technology of pyrrolidine hydrochloride row ketone key intermediate, especially a kind of pyrrolidine hydrochloride row ketone key intermediate 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, the catalyst for hydrogenation of 4-thiazolidinedione and process for selective hydrogenation thereof.
Background technology
PIOGITAZONE HYDROCHLORIDE is the thiazolidinediones insulin sensitizer of being developed jointly by Japan military field (Takeda) and U.S.'s gift Lay (Eli Lilly) company, and gone on the market in the U.S. by the FDA approval in July, 1999.Pioglitazone is a peroxidase paraphyte activated receptor gamma agonist, and its mechanism of action reduces insulin resistance, thereby reduces blood sugar for strengthening the sensitiveness of peripheral organization to insulin, is mainly used in the treatment of diabetes B.5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, the 4-thiazolidinedione is the key intermediate of PIOGITAZONE HYDROCHLORIDE, it promptly gets PIOGITAZONE HYDROCHLORIDE through hydrogenation, salify.5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, the structure of 4-thiazolidinedione is:
5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, the method for hydrotreating of 4-thiazolidinedione have following relevant report: US 4,812,570 report with 5% palladium carbon catalyst (consumption be reaction raw materials 50%) at 100 ℃, 50kg/cm
2Catalytic hydrogenation under the Hydrogen Vapor Pressure gets Pioglitazone, yield 63.8%, and its shortcoming is: palladium-carbon catalyst cost height, and reaction system pressure is bigger.WO 9,313, and 095 and WO2,004,000,810 have reported the CoCl with silica gel load
2Make catalyst, in the presence of dimethylglyoxime with the method for the two keys of sodium borohydride reduction, but can bring heavy metal cobalt ions and boride in the course of reaction, thereby reduce the quality of product, must adopt and make with extra care purification process and just can obtain product than good quality.Therefore, to 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, hydrogenation reaction research of 4-thiazolidinedione is necessary.
Summary of the invention
The technical problem to be solved in the present invention provides the pyrrolidine hydrochloride row ketone key intermediate catalyst for hydrogenation that a kind of cost is low, product quality is high.
The present invention also provides a kind of pyrrolidine hydrochloride row ketone key intermediate process for selective hydrogenation.
For solving the problems of the technologies described above, the technical scheme that catalyst of the present invention is taked is: this key intermediate is 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, the 4-thiazolidinedione, this catalyst is with Al
2O
3Be carrier, the composite reactive component constitutes,
Described active component be selected from nickel (Ni), copper (Cu), cobalt (Co), zinc (Zn), iron (Fe), chromium (Cr), calcium (Ca), the barium (Ba) one or more simple substance or; Simple substance and its oxide,
The mass content of each active component is 1%～20% of a catalyst gross mass, and the mass content of gross activity composition is 10%～40% of a catalyst gross mass.
The preferred Ni of the described active component of catalyst of the present invention, Ni/Cu or Ni/Cu/Fe.
Process for selective hydrogenation of the present invention is: this key intermediate is 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, the 4-thiazolidinedione, under the effect of catalyst of the present invention, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione solvent dilution, obtain reactant liquor, wherein solvent quality is the 70-95% of reactant liquor gross mass; Reactant liquor is 50～250 ℃ in temperature, hydrogenation reaction under Hydrogen Vapor Pressure 0.5～3.0MPa condition.
Reactant liquor is preferably 100～150 ℃ of temperature in the process for selective hydrogenation of the present invention, hydrogenation reaction under reaction pressure 0.8～1.3MPa condition.
Solvent described in the process for selective hydrogenation of the present invention is preferably dioxane, benzene series solvent or ether solvent, and solvent quality is 80～95% of a reactant liquor gross mass.
Adopt the beneficial effect that technique scheme produced to be: Preparation of Catalyst of the present invention is easy, and the catalyst cost is low, and is activity stabilized, can be recycled.
Process for selective hydrogenation of the present invention has operating condition and is easy to control, and catalyst performance is good, the characteristics that product yield is high.
The specific embodiment
This pyrrolidine hydrochloride row ketone key intermediate catalyst for hydrogenation adopts conventional method for preparing catalyst preparation, as preferred infusion process, coprecipitation and kneading extrusion method, improves the catalytic performance of catalyst by the compound action of active component and carrier.
The present invention is further detailed explanation below in conjunction with the specific embodiment.
Embodiment 1: the immersion process for preparing catalyst
The heating of 60g nickel nitrate is dissolved in the 100ml deionized water, adds 100g γ-Al
2O
3, stir, dipping spends the night, in 110 ℃ at drying box inner drying 20h, in 550 ℃ of roasting 5h in muffle furnace, promptly get this catalyst with hydrogen reductase 12 h under 400 ℃, 1.0MPa condition, consisting of of catalyst be nickeliferous 10.9%, contain Al
2O
390.1%.
Embodiment 2: coprecipitation prepares catalyst
50g nickel nitrate, 20g copper nitrate, 10g ferric nitrate are dissolved in the 500ml deionized water, add 100g Al
2O
3Powder stirs, and is heated to 80 ℃, and keeping temperature stabilization dropwise to splash into mass percent at 80 ℃ is 20% Na
2CO
3The aqueous solution leaves standstill, filters, washs to not containing Na to pH=7.5
+Ion, in 110 ℃ at drying box inner drying 20h, in 550 ℃ of roasting 5h in muffle furnace, promptly get this catalyst with hydrogen reductase 12 h under 400 ℃, 1.0MPa condition, consisting of of catalyst is nickeliferous 9.4%, cupric 4.9%, iron content 1.3%, contain Al
2O
384.4%.
Embodiment 3: kneading extrusion method prepares catalyst
50g nickel nitrate, the heating of 20g copper nitrate are dissolved in the 120ml deionized water, add 100g γ-Al
2O
3Powder, fully be ground to fully mix, extruded moulding, in 110 ℃ at drying box inner drying 20h, in 550 ℃ of roasting 5h in muffle furnace, promptly get this catalyst with hydrogen reductase 12 h under 400 ℃, 1.0MPa condition, consisting of of catalyst is nickeliferous 9.6%, cupric 5.0%, contain Al
2O
385.4%.
Embodiment 4-10: wherein embodiment 4-6 adopts traditional immersion process for preparing; Embodiment 7,8 adopts traditional kneading extrusion method preparation; Embodiment 9,10 adopts traditional coprecipitation preparation.The component and the weight content thereof of the catalyst that each embodiment obtains are as shown in table 1.
Table 1: the component of each catalyst and weight content thereof among the embodiment 4-10
| 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
| Ni(％) | 1.0 | / | / | / | 5.9 | 6.4 | / |
| NiO(％) | / | 13.9 | / | / | / | / | 15.1 |
| Cu(％) | / | 12.7 | / | 6.7 | 2.4 | / | / |
| CuO(％) | 7.4 | / | / | / | / | / | 2.4 |
| Co(％) | / | 7.2 | / | / | / | / | / |
| Co 2O 3(％) | / | / | / | 3.4 | / | / | / |
| Zn(％) | 6.1 | / | / | / | / | / | 1.8 |
| ZnO(％) | / | / | / | 5.6 | / | / | / |
| Fe(％) | / | / | 20.0 | / | 1.7 | 4.6 | / |
| Fe 2O 3(％) | / | / | / | / | / | 2.0 | / |
| Cr(％) | 4.8 | / | / | / | / | / | / |
| Cr 2O 3(％) | / | / | / | / | / | 3.8 | 3.9 |
| Ca(％) | / | 6.2 | / | / | / | / | / |
| CaO(％) | / | / | / | / | / | 6.3 | / |
| Ba(％) | / | / | / | 7.1 | / | / | / |
| BaO(％) | 3.5 | / | / | / | / | / | 4.6 |
| Al 2O 3(％) | 77.2 | 60.0 | 80.0 | 77.2 | 90.0 | 76.9 | 72.2 |
Embodiment 11: in dischargeable capacity is the catalyst 3.0g of the autoclave adding of 500ml by embodiment 1 preparation, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione 15.0g, solvent P-Dioxane 300ml (in the reactant liquor quality of solvent P-Dioxane be the reactant liquor gross mass 95%), nitrogen replacement 3 times, charging into hydrogen to pressure is 1.0MPa (1.01 * 10
6Pa), be warming up to 100 ℃, hydrogenation reaction 2h removes by filter catalyst, and filtrate concentrating separated out PIOGITAZONE HYDROCHLORIDE 10.0g.As calculated, the yield of present embodiment is 66.3%.
Embodiment 12: dischargeable capacity is that the autoclave of 500ml adds the catalyst 3.0g by embodiment 2 preparations, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione 15.0g, solvent dioxane 300ml, nitrogen replacement 3 times, charging into hydrogen to pressure is 1.0MPa, be warming up to 100 ℃, hydrogenation reaction 2h removes by filter catalyst, and filtrate concentrating separated out PIOGITAZONE HYDROCHLORIDE 11.8g.As calculated, the yield of present embodiment is 78.2%.
Embodiment 13: dischargeable capacity is that the autoclave of 500ml adds the catalyst 3.0g by embodiment 3 preparations, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione 15.0g, solvent dioxane 300ml, nitrogen replacement 3 times, charging into hydrogen to pressure is 1.0MPa, be warming up to 100 ℃, hydrogenation reaction 2h removes by filter catalyst, and filtrate concentrating separated out PIOGITAZONE HYDROCHLORIDE 10.8g.As calculated, the yield of present embodiment is 71.6%.
Embodiment 14: in dischargeable capacity is the catalyst 3.0g of the autoclave adding of 200ml by embodiment 4 preparations, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione 15.0g, solvent benzol 68ml (in the reactant liquor quality of solvent benzol be the reactant liquor gross mass 80%), nitrogen replacement 3 times, charging into hydrogen to pressure is 3.0MPa, be warming up to 50 ℃, hydrogenation reaction 2h removes by filter catalyst, and filtrate concentrating separated out PIOGITAZONE HYDROCHLORIDE 11.3g.As calculated, the yield of present embodiment is 75.3%.
Embodiment 15: in dischargeable capacity is the catalyst 3.0g of the autoclave adding of 100ml by embodiment 5 preparations, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione 15.0g, solvent toluene 40ml (in the reactant liquor quality of solvent toluene be the reactant liquor gross mass 70%), nitrogen replacement 3 times, charging into hydrogen to pressure is 0.8MPa, be warming up to 150 ℃, hydrogenation reaction 2h removes by filter catalyst, and filtrate concentrating separated out PIOGITAZONE HYDROCHLORIDE 10.4g.As calculated, the yield of present embodiment is 69.3%.
Embodiment 16: in dischargeable capacity is the catalyst 3.0g of the autoclave adding of 200ml by embodiment 6 preparations, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione 15.0g, solvent ethylene glycol mono-n-butyl ether 150ml (in the reactant liquor quality of solvent ethylene glycol mono-n-butyl ether be the reactant liquor gross mass 90%), nitrogen replacement 3 times, charging into hydrogen to pressure is 0.5MPa, be warming up to 250 ℃, hydrogenation reaction 2h, remove by filter catalyst, filtrate concentrating separated out PIOGITAZONE HYDROCHLORIDE 11.2g.As calculated, the yield of present embodiment is 74.7%.
Embodiment 17: in dischargeable capacity is the catalyst 3.0g of the autoclave adding of 200ml by embodiment 7 preparations, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione 15.0g, the single ether 90ml of solvent ethylene glycol (in the reactant liquor quality of the single ether of solvent ethylene glycol be the reactant liquor gross mass 84.8%), nitrogen replacement 3 times, charging into hydrogen to pressure is 0.5MPa, be warming up to 250 ℃, hydrogenation reaction 2h, remove by filter catalyst, filtrate concentrating separated out PIOGITAZONE HYDROCHLORIDE 10.6g.As calculated, the yield of present embodiment is 70.7%.
Embodiment 18: press the foregoing description 12 selected catalyst and reaction condition, reuse react afterwards the recovery catalyst at every turn, the number of times that can be recycled of catalyst is investigated, the results are shown in Table 2.
Table 2: catalyst recycle experimental result
| Cycle-index (inferior) | 1 | 2 | 3 | 4 | 5 |
| Product yield (%) | 78.2 | 75.6 | 75.2 | 73.1 | 69.8 |
As shown in Table 2, after this catalyst repeatedly recycled, product yield did not have obvious reduction, so this catalyst has characteristics activity stabilized, that can be recycled.
Claims (4)
1. pyrrolidine hydrochloride row ketone key intermediate process for selective hydrogenation, this key intermediate is 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2, the 4-thiazolidinedione, it is characterized in that: under the effect of catalyst, 5-[4-[2-(5-ethyl-2-pyridine radicals) ethyoxyl] benzylidene]-2,4-thiazolidinedione solvent dilution obtains reactant liquor, and wherein solvent quality is the 70-95% of reactant liquor gross mass; Reactant liquor is 50～250 ℃ in temperature, hydrogenation reaction under Hydrogen Vapor Pressure 0.5～3.0MPa condition; Described catalyst is with Al
2O
3Be carrier, the composite reactive component constitutes,
Described active component be selected among Ni, Cu, Co, Zn, Fe, Cr, Ca, the Ba one or more simple substance or; Simple substance and its oxide,
The mass content of each active component is 1%～20% of a catalyst gross mass, and the mass content of gross activity composition is 10%～40% of a catalyst gross mass.
2. pyrrolidine hydrochloride row ketone key intermediate process for selective hydrogenation according to claim 1 is characterized in that the preferred Ni of described active component, Ni/Cu or Ni/Cu/Fe.
3. pyrrolidine hydrochloride row ketone key intermediate process for selective hydrogenation according to claim 1 and 2 is characterized in that: reactant liquor is 100～150 ℃ of temperature, hydrogenation reaction under reaction pressure 0.8～1.3MPa condition.
4. pyrrolidine hydrochloride row ketone key intermediate process for selective hydrogenation according to claim 3, it is characterized in that: described solvent is dioxane, benzene series solvent or ether solvent, and solvent quality is 80～95% of a reactant liquor gross mass.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1124488A (en) * | 1993-05-25 | 1996-06-12 | 曼海姆泊灵格股份公司 | New thiazolidindiones and drugs containing them |
| CN1436596A (en) * | 2002-02-07 | 2003-08-20 | 中国石油化工股份有限公司 | Prepn process and application of catalyst for preparing lower C2-C4 alcohol |
-
2009
- 2009-10-21 CN CN2009100757542A patent/CN101693202B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1124488A (en) * | 1993-05-25 | 1996-06-12 | 曼海姆泊灵格股份公司 | New thiazolidindiones and drugs containing them |
| CN1436596A (en) * | 2002-02-07 | 2003-08-20 | 中国石油化工股份有限公司 | Prepn process and application of catalyst for preparing lower C2-C4 alcohol |
Non-Patent Citations (3)
| Title |
|---|
| Lifeng Zhang et al.."Ethanol steam reforming over Ni-Cu/Al2O3-MyOz (M=Si, La, Mg, and Zn) catalysts".《Journal of Natural Gas Chemistry》.2009,第18卷 |
| 白国义等."分子间醇的催化胺化反应的铜基催化剂的筛选与表征".《现代化工》.2006,第26卷(第3期), |
| 陈永东等."超高温焙烧的Ni/Al2O3对甲烷部分氧化反应的催化活性".《催化学报》.2008,第29卷(第5期), |
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