CN114656501A - 2,2′-联吡啶骨架双膦配体及其制备方法、应用 - Google Patents
2,2′-联吡啶骨架双膦配体及其制备方法、应用 Download PDFInfo
- Publication number
- CN114656501A CN114656501A CN202210438026.9A CN202210438026A CN114656501A CN 114656501 A CN114656501 A CN 114656501A CN 202210438026 A CN202210438026 A CN 202210438026A CN 114656501 A CN114656501 A CN 114656501A
- Authority
- CN
- China
- Prior art keywords
- formula
- diphosphine ligand
- ligand
- compound
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000003446 ligand Substances 0.000 title abstract description 66
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 title abstract description 64
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 title abstract description 15
- 230000003197 catalytic effect Effects 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 20
- -1 phosphate compound Chemical class 0.000 claims description 3
- 102000004882 Lipase Human genes 0.000 claims 5
- 108090001060 Lipase Proteins 0.000 claims 5
- 239000004367 Lipase Substances 0.000 claims 5
- 235000019421 lipase Nutrition 0.000 claims 5
- 229910019142 PO4 Inorganic materials 0.000 claims 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims 2
- 239000010452 phosphate Substances 0.000 claims 2
- 102100021851 Calbindin Human genes 0.000 claims 1
- 101000898082 Homo sapiens Calbindin Proteins 0.000 claims 1
- 101001021643 Pseudozyma antarctica Lipase B Proteins 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 abstract description 38
- 239000010948 rhodium Substances 0.000 abstract description 33
- 229910052703 rhodium Inorganic materials 0.000 abstract description 26
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 abstract description 25
- 238000007037 hydroformylation reaction Methods 0.000 abstract description 24
- 230000015572 biosynthetic process Effects 0.000 abstract description 19
- 229910000073 phosphorus hydride Inorganic materials 0.000 abstract description 19
- 238000003786 synthesis reaction Methods 0.000 abstract description 16
- 239000002994 raw material Substances 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 238000010923 batch production Methods 0.000 abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 238000006467 substitution reaction Methods 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 150000001336 alkenes Chemical class 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 10
- 239000007789 gas Substances 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 238000006317 isomerization reaction Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- WJIBZZVTNMAURL-UHFFFAOYSA-N phosphane;rhodium Chemical compound P.[Rh] WJIBZZVTNMAURL-UHFFFAOYSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000542 sulfonic acid group Chemical group 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229910021604 Rhodium(III) chloride Inorganic materials 0.000 description 1
- SZKMTZNASRXXCE-UHFFFAOYSA-N [2-[2-(diphenylphosphanylmethyl)phenyl]phenyl]methyl-diphenylphosphane Chemical group C=1C=CC=C(C=2C(=CC=CC=2)CP(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1CP(C=1C=CC=CC=1)C1=CC=CC=C1 SZKMTZNASRXXCE-UHFFFAOYSA-N 0.000 description 1
- RHKGZYVYKXVQSD-MECAPONASA-N [Rh].[O+]#[C-].C\C(O)=C\C(C)=O.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound [Rh].[O+]#[C-].C\C(O)=C\C(C)=O.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RHKGZYVYKXVQSD-MECAPONASA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical group C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- GGRQQHADVSXBQN-FGSKAQBVSA-N carbon monoxide;(z)-4-hydroxypent-3-en-2-one;rhodium Chemical group [Rh].[O+]#[C-].[O+]#[C-].C\C(O)=C\C(C)=O GGRQQHADVSXBQN-FGSKAQBVSA-N 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- SONJTKJMTWTJCT-UHFFFAOYSA-K rhodium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Rh+3] SONJTKJMTWTJCT-UHFFFAOYSA-K 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2461—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as ring members in the condensed ring system or in a further ring
- B01J31/2471—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as ring members in the condensed ring system or in a further ring with more than one complexing phosphine-P atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/49—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide
- C07C45/50—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide by oxo-reactions
- C07C45/505—Asymmetric hydroformylation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/32—Addition reactions to C=C or C-C triple bonds
- B01J2231/321—Hydroformylation, metalformylation, carbonylation or hydroaminomethylation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
- B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/822—Rhodium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了2,2'‑联吡啶骨架双膦配体及其制备方法、应用,其中,双膦配体采用2,2'‑联吡啶骨架,在用于氢甲酰化反应时,与现有催化体系相比,不仅利用膦与铑配位发挥空间和电子效应,还利用骨架上N的配位能力,显著提高双膦配体与铑络合物的配位能力,改善铑的固有催化性能;此外,用于合成该双膦配体的原料易得、合成条件温和、合成步骤简单,有利于工业化批量生产,具有广泛的推广价值。
Description
技术领域
本发明涉及氢甲酰化反应催化剂领域,具体涉及2,2′-联吡啶骨架双膦配体及其制备方法、应用。
背景技术
氢甲酰化反应是指烯烃与合成气在过渡金属络合催化剂作用下反应生成醛的反应过程,其产生的醛及其衍生物被广泛地用作合成增塑剂、表面活性剂、溶剂和香料等的原料。目前,氢甲酰化反应已成为工业应用中最重要的化学反应之一。
膦配体在氢甲酰化反应的催化剂体系中发挥着重要作用,膦配体与铑金属配合物组成的催化剂对于氢甲酰化反应的反应性能有非常重要的影响,这使得类型各异的膦配体不断被开发出来用于制备氢甲酰化反应的催化剂。其中,适当刚性骨架取代的多齿膦配体制备的催化剂在氢甲酰化反应中表现出更优异的催化性能。
现有的多齿膦配体主要有联苯骨架取代的双齿膦配体BISBI,二苯甲酮骨架取代的双齿膦配体,联苯骨架取代的四齿膦配体等,这类多齿膦配体虽然能够利用膦、铑配位发挥空间和电子效应,但是,在与铑配位过程中膦配体两个苯环之间的旋转容易造成对铑的配位能力较低,降低催化体系的催化性能。
发明内容
本发明的一个目的在于提供2,2′-联吡啶骨架双膦配体,通过现有的多齿膦配体的骨架进行设计以改善膦配体与铑的配合,解决现有技术中多齿膦配体由于骨架中的两个苯环之间将产生旋转而造成的对铑的配位能力较低问题,进一步提高铑的固有催化性能。
本发明通过下述技术方案实现:
2,2′-联吡啶骨架双膦配体,该双膦配体的结构式如式I所示:
式I中,R1和R2各自独立地选自取代或未取代的以下基团:
所述取代是指被选自下组的一个或多个取代基所取代:卤素、磺酸基、C1~C6的烷基、 C1~C6的卤代烷基、C1~C6的烷氧基、C1~C6的烷酰基、C1~C6的酯基、腈基、C1~C6的磺酸基。
本技术方案中,双膦配体采用2,2′-联吡啶骨架,其在与铑络合物构成催化体系时,不仅可以通过P与铑络合物配位得到结构式如式III所示的化合物,还可以通过吡啶上的N与铑络合物配位形成结构式如式IV或式V所示的化合物。
因此,在配位过程中,两个吡啶环之间相对旋转后,双膦配体可以通过P或N与铑络合物配合,利用N的辅助配位能力显著地提高了铑的固有催化性能,进而提高了催化体系的催化性能,对于不同结构的烯烃的氢甲酰化反应,都能获得较好的反应活性和选择性。
式I中,基团R1和R2可以相同,也可以不同,优选地,基团R1和R2相同。R1和R2可独自地选自前述取代或未取代的基团。其中,所述取代可以是一取代、二取代、三取代、四取代、五取代、六取代、七取代或八取代,优选地,所述取代为一取代或二取代。在部分实施例中,R1和R2采用未被取代的基团。
本领域技术人员应当理解,具有式I所示结构式的化合物也应当包括该化合物的对映体、消旋体或非对映异构体。
本技术方案所提供的双膦配体采用2,2′-联吡啶骨架,在用于氢甲酰化反应时,与现有催化体系相比,不仅利用膦与铑配位发挥空间和电子效应,还利用骨架上N的配位能力,显著提高双膦配体与铑络合物的配位能力,改善铑的固有催化性能;此外,用于合成该双膦配体的原料易得、合成条件温和、合成步骤简单,有利于工业化批量生产,具有广泛的推广价值。
进一步地,所述R1和R2各自独立地选自取代或未取代的以下基团:
其中,Y为O、S、或CH2;
所述取代是指被选自下组的一个或多个取代基所取代:卤素、磺酸基、C1~C6的烷基、 C1~C6的卤代烷基、C1~C6的烷氧基。
进一步地,所述双膦配体具有以下任一种结构式:
本发明的另一个目的在于提供前述任一种2,2′-联吡啶骨架双膦配体的制备方法,该制备方法的原料易得、合成步骤简单、容易放大生产获得,具有很高的实用价值,并且,通过该方法制备得到的双膦配体具有很好的稳定性,更重要的是,该双膦配体能够利用吡啶上的N 进行辅助配位,显著地提高催化体系的催化性能。
具体地,该制备方法包括以下步骤:将结构式为式II的化合物与LiPR1R2或NaPR1R2在惰性气氛下反应得到式I的化合物;
其中,X为卤素。
本技术方案中,利用结构式II的化合物合成结构式I的化合物的合成路线为:
其中,结构式II的化合物可以按照文献[J]Journal of Organic Chemistry,2014,79,777-782 中报道的方法进行合成获得。
进一步地,向结构式II的化合物溶液中缓慢加入LiPR1R2溶液或NaPR1R2溶液并保持温度小于10℃,加完后升至室温反应直至反应结束。本技术方案中,将结构式II加入至有机溶剂中溶解得到结构式II的化合物溶液,将LiPR1R2或NaPR1R2加入至有机溶剂中溶解得到 LiPR1R2溶液或NaPR1R2溶液。之后,在低温下,优选为0~5℃下,将LiPR1R2溶液或NaPR1R2溶液滴加至结构式II的化合物溶液中,并在滴加完毕后升温至室温反应。反应完毕,经萃取、干燥、过滤、浓缩、纯化等后处理工序制得结构式I的化合物。
在部分实施例中,所述的有机溶剂为苯、甲苯、二甲苯、三甲苯、乙醚、四氢呋喃中的一种或多种。
在一个或多个实施例中,所述惰性气氛为氩气或氮气。
进一步地,LiPR1R2或NaPR1R2与式II的化合物的摩尔比为2:1~10:1。
本发明的又一个目的在于提供前述任一种2,2′-联吡啶骨架双膦配体的应用,所述双膦配体用于烯烃氢甲酰化或烯烃异构化氢甲酰化反应的催化体系。2,2′-联吡啶骨架双膦配体与铑络合物构成催化剂组合物,用于烯烃氢甲酰化或烯烃异构化氢甲酰化反应,以提高原料烯烃的转化率、成醛率、以及直链醛的选择性。优选地,用于C2~C18烯烃氢甲酰化或C4~C18烯烃异构化氢甲酰化反应。
在一个或多个实施例中,所述铑络合物为Rh(acac)(CO)2、Rh(acac)(CO)(PPh3)、HRh(CO)(PPh3)3、RhCl3、[Rh(cod)Cl]2、[Rh(CO)2Cl]2、Rh(acac)(C2H4)、[Rh(C2H4)2Cl]2中的至少一种;其中,acac为乙酰丙酮,cod为1,5-环辛二烯。
进一步地,所述应用包括以下步骤:原料烯烃、催化剂组合物和溶剂混合均匀后形成混合物,所述混合物与一氧化碳和氢气构成的合成气反应直至反应完成;所述催化剂组合物包括所述双膦配体和铑络合物。
在部分优选的实施例中,在反应釜中加入原料烯烃、催化剂组合物、溶剂后,充入合成气(CO:H2=1:1)置换反应釜数次后,充入合成气并加热升温反应,反应过程中保持反应釜内总压为0.2~4MPa、温度为60~120℃。
进一步地,所述催化剂组合物的膦铑比为2~40。优选地,催化剂组合物的膦铑比为2~20,进一步优选地,催化剂组合物的膦铑比为2~10。
本发明与现有技术相比,具有如下的优点和有益效果:
1、本发明的双膦配体采用2,2′-联吡啶骨架,在用于氢甲酰化反应时,与现有催化体系相比,不仅利用膦与铑配位发挥空间和电子效应,还利用骨架上N的配位能力,显著提高双膦配体与铑络合物的配位能力,改善铑的固有催化性能;
2、本发明用于合成该双膦配体的原料易得、合成条件温和、合成步骤简单,有利于工业化批量生产,具有广泛的推广价值;
3、本发明的2,2′-联吡啶骨架双膦配体与铑络合物构成催化剂组合物,用于烯烃氢甲酰化或烯烃异构化氢甲酰化反应,能够有效地提高原料烯烃的转化率、成醛率、以及直链醛的选择性。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚明白,下面结合实施例,对本发明作进一步的详细说明,本发明的示意性实施方式及其说明仅用于解释本发明,并不作为对本发明的限定。
本发明所有原料,对其来源没有特别限制,在市场上购买的或按照本领域技术人员熟知的常规方法即可制备。
本发明所有原料,对其纯度没有特别限制,本发明优选采用分析纯或化工领域常规的纯度要求。本发明所有原料,其牌号和简称均属于本领域常规牌号和简称,每个牌号和简称在其相关用途的领域内均是清楚明确的,本领域技术人员根据牌号、简称以及相应的用途,能够从市售中购买得到或者通过常规方法制备得到。
本发明对所述取代基的表达方式没有特别限制,均采用本领域技术人员熟知的表达方式,本领域技术人员基于常识,可根据其表达方式正确理解其含义。
【实施例1】
双膦配体1的制备:
在氩气氛下,向500mL三口瓶,加入结构式II的化合物(6.652g,19.45mmol)和无水四氢呋喃(200mL),其中X为Br取代;在0~5℃下,滴加LiPPh2(8.217g,42.8mmol)的四氢呋喃溶液(100mL),滴加完毕后,升至室温下反应4小时。
加入100mL蒸馏水,用二氯甲烷萃取(3×100mL),有机相用无水硫酸镁干燥后,过滤浓缩,残余物经柱层析纯化,得到8.8g双膦配体1,收率为82%。
核磁共振波谱法结构表征:31P NMR(162MHz,氘代氯仿)δ-13.33ppm。
【实施例2】
双膦配体2的制备:
在氩气氛下,向500mL三口瓶,加入结构式II的化合物(6.652g,19.45mmol)和无水四氢呋喃(200mL),其中X为Br取代;在0~5℃下,滴加LiP(p-CF3Ph)2(13.776g,42mmol) 的四氢呋喃溶液(100mL),滴加完毕后,升至室温下反应4小时。
加入100mL蒸馏水,用二氯甲烷萃取(3×100mL),有机相用无水硫酸镁干燥后,过滤浓缩,残余物经柱层析纯化,得到9.01g双膦配体2,收率为78%。
核磁共振波谱法结构表征:31P NMR(162MHz,氘代氯仿)δ-12.12ppm。
【实施例3】
双膦配体3的制备:
在氩气氛下,向500mL三口瓶,加入结构式II的化合物(6.652g,19.45mmol)和无水四氢呋喃(200mL),其中X为Br取代;在0~5℃下,滴加LiP(p-CH3Ph)2(6.8g,40mmol) 的四氢呋喃溶液(100mL),滴加完毕后,升至室温下反应4小时。
加入100mL蒸馏水,用二氯甲烷萃取(3×100mL),有机相用无水硫酸镁干燥后,过滤浓缩,残余物经柱层析纯化,得到9.11g双膦配体3,收率为77%。
核磁共振波谱法结构表征:31P NMR(162MHz,氘代氯仿)δ-14.53ppm。
【实施例4】
双膦配体4的制备
在氩气氛下,向500mL三口瓶,加入结构式II的化合物(6.652g,19.45mmol)和无水四氢呋喃(200mL),其中X为Br取代;在0~5℃下,滴加二吡咯膦锂(9.46g,42mmol) 的四氢呋喃溶液(100mL),滴加完毕后,升至室温下反应4小时。
加入100mL蒸馏水,用二氯甲烷萃取(3×100mL),有机相用无水硫酸镁干燥后,过滤浓缩,残余物经柱层析纯化,得到8.4g双膦配体4,收率为85%。
核磁共振波谱法结构表征:31P NMR(162MHz,氘代氯仿)δ78.21ppm。
【实施例5】
双膦配体5的制备
在氩气氛下,向500mL三口瓶,加入结构式II的化合物(6.652g,19.45mmol)和无水四氢呋喃(200mL),其中X为Br取代;在0~5℃下,滴加二吲哚膦锂(10.8g,40mmol) 的四氢呋喃溶液(100mL),滴加完毕后,升至室温下反应4小时。
加入100mL蒸馏水,用二氯甲烷萃取(3×100mL),有机相用无水硫酸镁干燥后,过滤浓缩,残余物经柱层析纯化,得到11.99g双膦配体5,收率为87%。
核磁共振波谱法结构表征:31P NMR(162MHz,氘代氯仿)δ73.81ppm。
【实施例6】
双膦配体6的制备
在氩气氛下,向500mL三口瓶,加入结构式II的化合物(6.652g,19.45mmol)和无水四氢呋喃(200mL),其中X为Br取代;在0~5℃下,滴加相应锂化合物(8.24g,40mmol) 的四氢呋喃溶液(100mL),滴加完毕后,升至室温下反应4小时。
加入100mL蒸馏水,用二氯甲烷萃取(3×100mL),有机相用无水硫酸镁干燥后,过滤浓缩,残余物经柱层析纯化,得到6.32g双膦配体6,收率为56%。
核磁共振波谱法结构表征:31P NMR(162MHz,氘代氯仿)δ-15.65ppm。
【实施例7】
双膦配体用于1-己烯的氢甲酰化反应
在50ml高压反应釜中,加入0.15mmol双膦配体,0.05mmol Rh(acac)(CO)2,50mmol1- 己烯,5ml甲苯,随后充入合成气(CO:H2=1:1)置换反应釜三次,再次充入合成气,保持反应釜内总压为2MPa,迅速升温至80℃并开始搅拌,反应2h后停止搅拌,并迅速冷却至室温,取出反应液分析。分析结果如表1所示:
表1
膦配体 | 转化率(%) | 成醛率(%) | 直链醛选择性(%) |
1 | 99 | 98 | 98 |
2 | 99 | 98 | 99 |
3 | 97 | 97 | 96 |
4 | 99 | 93 | 99 |
5 | 99 | 94 | 99 |
6 | 99 | 94 | 97 |
【实施例8】
双膦配体用于苯乙烯的氢甲酰化反应
在50ml高压反应釜中,加入0.15mmol双膦配体,0.05mmol Rh(acac)(CO)2,50mmol苯乙烯,5ml甲苯,随后充入合成气(CO:H2=1:1)置换反应釜三次,再次充入合成气,保持反应釜内总压为1MPa,迅速升温至100℃并开始搅拌,反应2h后停止搅拌,并迅速冷却至室温,取出反应液分析。分析结果如表2所示:
表2
【实施例9】
双膦配体用于降冰片二烯的氢甲酰化反应
在50ml高压反应釜中,加入0.15mmol双膦配体,0.05mmol Rh(acac)(CO)2,50mmol降冰片二烯,5ml甲苯,随后充入合成气(CO:H2=1:1)置换反应釜三次,再次充入合成气,保持反应釜内总压为3MPa,迅速升温至90℃并开始搅拌,反应4h后停止搅拌,并迅速冷却至室温,取出反应液分析。分析结果如表3所示:
表3
膦配体 | 转化率(%) | 成醛率(%) | 双醛选择性(%) |
1 | 99 | 99 | 92 |
2 | 99 | 99 | 95 |
3 | 99 | 99 | 90 |
4 | 99 | 99 | 97 |
5 | 99 | 99 | 98 |
6 | 99 | 99 | 91 |
通过表1~表3可以看出,包含了本发明的2,2′-联吡啶骨架双膦配体的催化剂体系在进行烯烃氢甲酰化反应时具有高转化率和成醛率。并且,利用氮的配位能力,改善铑的固有催化性能,对于不同结构的烯烃的氢甲酰化反应,都能获得较好的反应活性和选择性。
以上所述的具体实施方式,对本发明的目的、技术方案和有益效果进行了进一步详细说明,所应理解的是,以上所述仅为本发明的具体实施方式而已,并不用于限定本发明的保护范围,凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (2)
2.根据权利要求1所述的一类手性α-羟(酯)基磷酸酯类化合物,其特征在于:该化合物的制备方法步骤如下:
用脂肪酶催化体系与式I-1所示化合物进行催化转化反应,反应完毕得到式I-2所示化合物以及未反应的式I-1所示化合物;
所述脂肪酶催化体系由商业化脂肪酶CALB和乙酸乙烯酯溶液组成,脂肪酶与式I-1所示化合物的重量比为100mg∶100mg,在催化体系中,脂肪酶与所述乙酸乙烯酯溶液的用量比为100mg∶10mL;
反应温度为30~37℃,时间为16~432小时。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210438026.9A CN114656501B (zh) | 2022-04-25 | 2022-04-25 | 2,2′-联吡啶骨架双膦配体及其制备方法、应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210438026.9A CN114656501B (zh) | 2022-04-25 | 2022-04-25 | 2,2′-联吡啶骨架双膦配体及其制备方法、应用 |
Publications (3)
Publication Number | Publication Date |
---|---|
CN114656501A true CN114656501A (zh) | 2022-06-24 |
CN114656501A9 CN114656501A9 (zh) | 2022-07-22 |
CN114656501B CN114656501B (zh) | 2024-03-19 |
Family
ID=82036744
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210438026.9A Active CN114656501B (zh) | 2022-04-25 | 2022-04-25 | 2,2′-联吡啶骨架双膦配体及其制备方法、应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114656501B (zh) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103980317A (zh) * | 2014-05-28 | 2014-08-13 | 南开大学 | 联吡啶四齿配体钌络合物及其制备方法和应用 |
US20160107151A1 (en) * | 2013-03-04 | 2016-04-21 | National University Corporation Nagoya University | Ligand, metal complex containing ligand, and reaction using metal complex containing ligand |
WO2022078996A1 (en) * | 2020-10-13 | 2022-04-21 | Basf Se | Value chain return process for spent polyurethanes by hydrogenation |
-
2022
- 2022-04-25 CN CN202210438026.9A patent/CN114656501B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160107151A1 (en) * | 2013-03-04 | 2016-04-21 | National University Corporation Nagoya University | Ligand, metal complex containing ligand, and reaction using metal complex containing ligand |
CN103980317A (zh) * | 2014-05-28 | 2014-08-13 | 南开大学 | 联吡啶四齿配体钌络合物及其制备方法和应用 |
WO2022078996A1 (en) * | 2020-10-13 | 2022-04-21 | Basf Se | Value chain return process for spent polyurethanes by hydrogenation |
Non-Patent Citations (1)
Title |
---|
ZIESSEL, RAYMOND ET AL.: "A new family of aromatic polyimine chelates substituted with two diphenylphosphines", TETRAHEDRON LETTERS, vol. 30, no. 4, pages 463 - 466, XP055279844, DOI: 10.1016/S0040-4039(00)95229-8 * |
Also Published As
Publication number | Publication date |
---|---|
CN114656501B (zh) | 2024-03-19 |
CN114656501A9 (zh) | 2022-07-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Sollewijn Gelpke et al. | Synthesis of the Dibenzofuran‐Based Diphosphine Ligand BIFAP and Its Water‐Soluble Derivative BIFAPS and Their Use in Ruthenium‐Catalyzed Asymmetric Hydrogenation.[≠] | |
CN113583045B (zh) | 一种含双齿膦配体的催化剂组合物及其应用 | |
US6683208B2 (en) | Optically active diphosphines, preparation thereof according to a process for the resolution of the racemic mixture and use thereof | |
CN108002966B (zh) | 一种合成1,2-二芳基乙烷类化合物的方法 | |
CN114478362A (zh) | 一种手性吡啶醇衍生物的制备方法 | |
JP4223085B2 (ja) | トリシクロデカンジアルデヒドの製造方法 | |
CN113583046B (zh) | 双齿膦配体及其制备方法、应用 | |
CN114656501A (zh) | 2,2′-联吡啶骨架双膦配体及其制备方法、应用 | |
EP3438115B1 (en) | Ruthenium based complexes | |
US6521795B2 (en) | 6,6′-bis-(1-phosphanorbornadiene) diphosphines, their preparation and their uses | |
US6399834B1 (en) | Methods for producing chiral aldehydes | |
CN114478372A (zh) | 一种吡啶醇氮氧化物的不对称制备方法 | |
Fan et al. | Rhodium catalyzed asymmetric Pauson-Khand reaction using SDP ligands | |
CN114736239B (zh) | 一种双齿膦配体及其制备方法、应用 | |
Kanai et al. | Asymmetric cyclopropanation of chiral fumarates with gem-dihalides catalyzed by Co (0) or Ni (0) complexes and zinc | |
JP3919268B2 (ja) | ルテニウム−光学活性ホスフィン錯体、その製法およびこれを用いた光学活性4−メチル−2−オキセタノンの製造方法 | |
KR100915095B1 (ko) | 알파, 베타-알킨 에스터 화합물의 β-보론화 방법 | |
CN114874127B (zh) | 一种二氟羰基化吲哚酮类化合物的制备方法 | |
CN112479842B (zh) | 一种4-叔丁基苯丙醛的制备方法 | |
US7151070B2 (en) | Chiral catalyst, process for preparing the same and its use in the oxidate coupling of naphthols | |
CN115466288B (zh) | 一类基于手性双膦配体合成硒/硫类配体的方法 | |
CN112239456B (zh) | 一种取代2,3-二氢喹诺酮化合物的制备方法 | |
CN112538095B (zh) | 一种手性四齿配体、手性钌络合物,及制备(r)-(-)-1,3-丁二醇的方法 | |
CN109081785B (zh) | 一种含氟甘氨酸酯衍生物的合成方法 | |
CN117776958A (zh) | 一种芳烃羧酸间位烷基化产物及其合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CI02 | Correction of invention patent application | ||
CI02 | Correction of invention patent application |
Correction item: Claims Correct: Correct False: error Number: 25-02 Page: full text Volume: 38 |
|
GR01 | Patent grant | ||
GR01 | Patent grant |