CN116174039A - 一类创新性卤过氧化物酶仿生催化剂的合成及其应用 - Google Patents
一类创新性卤过氧化物酶仿生催化剂的合成及其应用 Download PDFInfo
- Publication number
- CN116174039A CN116174039A CN202211061182.4A CN202211061182A CN116174039A CN 116174039 A CN116174039 A CN 116174039A CN 202211061182 A CN202211061182 A CN 202211061182A CN 116174039 A CN116174039 A CN 116174039A
- Authority
- CN
- China
- Prior art keywords
- reaction
- haloperoxidase
- organic
- catalyst
- nmr
- 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.)
- Pending
Links
- 239000003054 catalyst Substances 0.000 title claims abstract description 39
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 17
- 230000003592 biomimetic effect Effects 0.000 title claims abstract description 16
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 69
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 23
- 230000003647 oxidation Effects 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 21
- 230000001590 oxidative effect Effects 0.000 claims abstract description 12
- 150000004698 iron complex Chemical class 0.000 claims abstract description 11
- 239000011664 nicotinic acid Substances 0.000 claims abstract description 10
- 239000013110 organic ligand Substances 0.000 claims abstract description 8
- 239000007800 oxidant agent Substances 0.000 claims abstract description 8
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229960003531 phenolsulfonphthalein Drugs 0.000 claims abstract description 6
- 230000009920 chelation Effects 0.000 claims abstract description 5
- 150000003568 thioethers Chemical class 0.000 claims abstract description 4
- 238000005893 bromination reaction Methods 0.000 claims abstract description 3
- 230000031709 bromination Effects 0.000 claims abstract 2
- 239000006227 byproduct Substances 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 238000005658 halogenation reaction Methods 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 150000004889 1,3-dithianes Chemical class 0.000 claims description 5
- 150000002475 indoles Chemical class 0.000 claims description 5
- -1 sulfoxide compound Chemical class 0.000 claims description 5
- 230000026030 halogenation Effects 0.000 claims description 4
- 239000002815 homogeneous catalyst Substances 0.000 claims description 4
- 230000008707 rearrangement Effects 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000007363 ring formation reaction Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 230000006315 carbonylation Effects 0.000 claims 2
- 238000005810 carbonylation reaction Methods 0.000 claims 2
- 239000012467 final product Substances 0.000 claims 1
- 230000007935 neutral effect Effects 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 238000010791 quenching Methods 0.000 claims 1
- 230000000171 quenching effect Effects 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 abstract description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052794 bromium Inorganic materials 0.000 abstract description 3
- 238000007036 catalytic synthesis reaction Methods 0.000 abstract description 3
- 238000010276 construction Methods 0.000 abstract description 3
- 238000006685 Achmatowicz rearrangement reaction Methods 0.000 abstract description 2
- 238000010511 deprotection reaction Methods 0.000 abstract description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 abstract description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 abstract description 2
- 150000003555 thioacetals Chemical class 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 17
- 238000012512 characterization method Methods 0.000 description 16
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 15
- 239000008346 aqueous phase Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- FYELSNVLZVIGTI-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1CC)CC(=O)N1CC2=C(CC1)NN=N2 FYELSNVLZVIGTI-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 229910014265 BrCl Inorganic materials 0.000 description 1
- 108010073997 Bromide peroxidase Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011942 biocatalyst Substances 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000002957 persistent organic pollutant Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000005837 radical ions Chemical class 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
Classifications
-
- 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
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
-
- 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
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/518—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of sulfur-containing compounds to >C = O groups
-
- 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
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
-
- 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
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/567—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with sulfur as the only hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/02—1,2-Thiazines; Hydrogenated 1,2-thiazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
- C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
- C07D327/04—Five-membered rings
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/02—Iron compounds
- C07F15/025—Iron compounds without a metal-carbon linkage
-
- 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
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Indole Compounds (AREA)
- Catalysts (AREA)
Abstract
本发明提供了一种基于Fenton反应的创新性卤过氧化物酶仿生催化剂的合成及其应用的绿色方法,属于绿色有机化学领域。该方法以FeBr3/FeBr2螯合含有不同取代基的2,2′:6′,2″‑三联吡啶有机配体的铁配合物卤过氧化物酶作为催化剂,H2O2作唯一氧化剂,H2O作为副产物,廉价易得的水合溴化镁作溴源,在中性、室温条件下,短时间内完成多类有机分子的合成,如酚红溴代、硫缩醛脱保护、吲哚氧化、硫醚氧化、Achmatowicz重排等。本发明首次将Fenton反应应用于卤过氧化物酶仿生体系的构建,在HO·选择性氧化的基础上进一步改善催化效率低的问题。具有催化活性高、稳定性好、反应条件温和、合成路线短的特点,是非常绿色、环保、高效、应用范围广的催化合成方法,具有良好的应用前景。
Description
技术领域
本发明属于绿色化学和有机合成技术领域,具体涉及一种以FeBr3螯合以2,2′:6′,2″-三联吡啶为母核的有机配体的铁配合物卤过氧化物酶仿生催化剂,基于Fenton反应高效催化合成一大类有机分子的的绿色方法。
背景技术
卤化反应是一类极其重要的有机合成反应,传统卤化反应因存在使用有毒有害试剂、反应缺乏选择性等问题而有待改进,如使用传统溴化试剂(如Br2、BrCl、NBS等)制备溴代物时存在环境污染、操作不友好、溴原子利用率低等问题。酶催化卤化反应的突出优势在于常温常压下,可使用来源温和的卤素进行高效的催化反应,但酶活性不稳定、价格昂贵、不易获得、放大困难、需要大量缓冲溶液。卤过氧化物酶法是极为绿色的Br-原位氧化方法,该酶以H2O2为绿色氧化剂,通过酶活性中心催化卤化各种生物合成前体。开发绿色、安全、高效的Br-原位氧化策略用于一大类有机分子的合成意义深远。
HO·作为一种强氧化自由基可以实现Br-氧化成Br+,而HO·是芬顿(Fenton)反应产生的活性氧化物质,可以在Fe2+/Fe3+的催化下由H2O2分解产生。因此,将Fenton反应应用于卤过氧化物酶仿生体系的构建,实现Br-原位氧化,产生的Br+除用于溴化反应外,还可参与一系列有机分子的氧化和重排反应(如羟基氧化、硫缩醛脱保护、吲哚氧化、硫醚和硫醇氧化、Achmatowicz重排等)。这与目前普遍依赖的血红素依赖型卤过氧化物酶形成高价Fe=O复合物和钒依赖型卤过氧化物酶形成钒过氧活性中间体氧化Br-的策略截然不同。
目前Fenton反应主要围绕污染物降解展开,产生的强氧化自由基HO·能够降解有机污染物成环境无害的小分子(如二氧化碳和水),然而在有机合成中存在过度氧化、产物复杂、产率低等缺陷,且Fenton金属极易形成“铁泥”沉淀导致催化效率较低。开发一种基于Fenton反应的全新卤过氧化物酶仿生催化体系,高效选择性催化合成一大类有机分子具有深远意义。
综上所述,本研究通过引入特定有机配体(如2,2′:6′,2″-三联吡啶),与FeBr3/FeBr2络合,制备含Fe-Br键的配位络合物,形成一种卤过氧化物酶仿生体系,用于高效催化合成一大类有机分子。该铁配合物的溴过氧化物酶活性通过苯酚红到溴酚蓝的氧化进行了评价,并合成了由HOBr启动的分子内S=N环合的特异性荧光探针,用于检测HOBr的生成。Fenton金属(Fe)催化H2O2分解产生的强氧化自由基HO·可以通过“紧密自由基-离子对相互作用”被邻近的Br-(Fe-Br)及时捕获生成温和氧化剂Br+,避免过量HO·无选择性氧化引发的副反应。同时作为一种均相催化剂,有机配体增加了Fenton催化剂及催化中间态在有机相中的溶解度,避免催化活性中心(Fe2+/3+)形成“铁泥”沉淀从反应体系析出,从而有利于提高催化剂转化数和催化效率,以解决Fenton反应在有机合成中存在氧化选择性较差和催化效率低的问题。本研究中的卤过氧化物酶仿生催化剂模拟天然存在的卤过氧化物酶,对应用于催化卤化各种生物合成前体及重要有机化合物的绿色高效合成具有深远意义。
因此,开发一种绿色、高效、普遍适用的创新性卤过氧化物酶仿生催化剂,应用于天然生物合成前体及一大类重要有机分子的合成意义深远。
发明内容
本发明的目的是,开发一类基于Fenton反应的创新性卤过氧化物酶仿生催化剂,高效催化合成多种有机分子的绿色通用方法,该方法简单高效、绿色环保、易于操作、应用范围广。
本发明采用的技术方案为:
在中性、室温条件下,以FeBr3/FeBr2螯合含有不同取代基的2,2′:6′,2″-三联吡啶有机配体的铁配合物卤过氧化物酶作为催化剂,H2O2作唯一氧化剂,廉价易得的水合溴化镁作溴源,短时间内完成多类有机分子的合成。如有机分子的卤化反应、将1,3-二噻烷衍生物转化为羰基化合物、亚砜类化合物的制备、硫氮双键的环合、吲哚类衍生物的氧化重排、Achmatowicz重排等。
所述反应所用催化剂为卤过氧化物酶仿生催化剂,催化剂与原料有机分子的摩尔比为0.01-0.2∶1,所述催化剂的结构如式I所示:
其中R1、R2、R3可为氢原子、羧基、叔丁基、甲氧基、苯基、溴苯基、卤原子等常见基团。
所述反应所用氧化剂为过氧化氢,过氧化氢与原料有机分子的摩尔比为1-4∶1。
所述反应所用溶剂可为乙醇、乙腈、四氢呋喃等,及其与水不同比例的混合溶剂。
所述反应底物为具有不同官能团的有机硫化物、含氮有机硫化物、1,3-二噻烷衍生物、取代苯类化合物、糠醇、吲哚类衍生物,苯酚红等,所述反应底物的结构如式II-VIII所示:
其中R、R1、R2、R3、R4可为氢原子、烷基、烯基、炔基、芳基、酯基、脂环烃等不同官能团或呋喃、吡啶、噻吩、吡咯以及其他杂环等不同取代基,也可为常用的保护基团如Ac、TBS、THP、Bn、Boc和TIPS等。
所述反应的较佳反应时间为15min,反应温度为室温。
所述反应的处理方法为,反应结束后用Na2S2O3溶液淬灭,采用有机溶剂(如乙酸乙酯、二氯甲烷)萃取。收集有机相,无水硫酸钠干燥,过滤,浓缩,即可得产物。
本发明的有益效果:
本发明与现有技术相比具有以下优点和效果:
本发明首次将Fenton反应应用于卤过氧化物酶仿生体系的构建,实现了铁配合物卤过氧化物酶仿生催化剂的简单合成,以H2O2作唯一氧化剂,在中性、室温条件下应用于一大类有机分子的高效合成,该铁配合物的溴过氧化物酶活性通过苯酚红到溴酚蓝的氧化进行了评价。本发明通过引入有机配体形成一种均相催化剂,增加了Fenton催化剂及催化中间态在有机相中的溶解度,避免催化活性中心(Fe2+/3+)形成“铁泥”沉淀从反应体系析出,从而有利于提高催化剂转化数和催化效率,以解决Fenton反应在有机合成中存在氧化选择性较差和催化效率低的问题。与现有的有机分子卤化氧化方法相比,该方法具有成本低、反应快、产率高、底物适用范围广、反应条件温和、路线简单、容易操作、对环境友好等特点,具有良好的应用前景。
附图说明
图1和图2是实施例1的1H-NMR及13C-NMR谱图
图3是实施例2的1H-NMR谱图
图4和图5是实施例3的1H-NMR及13C-NMR谱图
图6和图7是实施例4的1H-NMR及13C-NMR谱图
图8和图9是实施例5的1H-NMR及13C-NMR谱图
图10和图11是实施例6的1H-NMR及13C-NMR谱图
图12和图13是实施例7的1H-NMR及13C-NMR谱图
图14和图15是实施例8的1H-NMR及13C-NMR谱图
图16和图17是实施例9的1H-NMR及13C-NMR谱图
图18和图19是实施例10的1H-NMR及13C-NMR谱图
图20和图21是实施例11的1H-NMR及13C-NMR谱图
图22和图23是实施例12的1H-NMR及13C-NMR谱图
图24和图25是实施例13的1H-NMR及13C-NMR谱图
图26和图27是实施例14的1H-NMR及13C-NMR谱图
图28和图29是实施例15的1H-NMR及13C-NMR谱图
图30和图31是实施例16的1H-NMR及13C-NMR谱图
具体实施方式
下面用具体实施方案详述本发明,但本发明的保护范围不仅限于此。
以下实施例中的1H-NMR及13C-NMR谱均在室温条件下测定,记录在400MHz光谱仪上,1H为400MHz,13C为100MHz,光谱仪来自布鲁克公司。
实施例1
1a(10mmol,2.33g)、FeBr3(11mmol,3.25g)、ACN 50ml依次加入100ml圆底烧瓶中,搅拌1h,反应完成后旋蒸减少体积,加入乙酸乙酯,抽滤,即可得目标产物1b(产率:98%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ9.37-9.20(m,2H),8.89-8.78(m,3H),8.00(t,J=7.7Hz,2H),7.22-7.08(m,4H).13C NMR(100MHz,CDCl3)δ159.62,157.56,152.65,138.81,138.13,127.64,124.04,123.93.
实施例2
将MgBr2·6H2O(98mmol,19.81g),ACN/H2O(3/1)28ml加入100ml圆底烧瓶中,加入2a(2.8mmol,1g)和卤过氧化物酶仿生催化剂1b(0.56mmol,0.30g),室温搅拌15min后,加入H2O2水溶液(30wt%,84mmol,8.43ml),在室温下搅拌反应15min。反应完成后旋蒸去除溶剂,柱层析纯化得目标产物2b(产率:70%)。该化合物的表征数据如下:1H NMR(400MHz,DMSO-d6)δ7.93(d,J=7.7Hz,1H),7.78-7.41(m,6H),7.14(s,1H).HRMS(ESI+)(m/z)calcd.forC19H11Br4O5S[M+H]+670.7014;found 670.7026.
实施例3
将MgBr2·6H2O(2.5mmol,0.51g),EtOH/H2O(3/1)25ml加入100ml圆底烧瓶中,加入3a(5mmol,1.08g)搅拌均匀,向混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物3b(产率:75%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ:7.96(d,J=8.0Hz,1H),7.89(dd,J=7.9,1.5Hz,1H),7.60-7.55(m,1H),7.42-7.40(m,2H),7.32-7.27(m,1H),7.22(dd,J=8.1,1.4Hz,1H),6.99-6.94(m,1H),2.33(s,3H).13C-NMR(100MHz,CDCl3)δ:148.6,132.5,131.8,130.4,127.5,125.8,124.7,124.5,124.2,123.5,120.8,119.7,32.0.
实施例4
将MgBr2·6H2O(2.5mmol,0.51g),EtOH/H2O(3/1)25ml加入100ml圆底烧瓶中,加入4a(5mmol,1.15g)搅拌均匀,向混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物4b(产率:70%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ:7.92(d,J=8.0Hz,1H),7.78(d,J=8.0Hz,1H),7.58-7.53(m,1H),7.41-7.34(m,2H),7.03(s,1H),6.80(d,J=8.0Hz,1H),2.34(s,3H),2.32(s,3H).13C-NMR(100MHz,CDCl3)δ:148.7,140.7,132.6,131.7,127.1,125.9,124.4,124.3,124.0,123.1,121.0,118.2,32.1,21.5.
实施例5
5a(5mmol,0.62g)、THF 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用乙酸乙酯(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物5b(产率:97%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ:7.65-7.62(m,2H),7.52-7.49(m,3H),2.70(s,3H).13C-NMR(100MHz,CDCl3)δ:145.8,131.0,129.4,123.5,44.0.
实施例6
6a(5mmol,0.69g)、THF 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用乙酸乙酯(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物6b(产率:85%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ:7.53(d,J=8.2Hz,2H),7.32(d,J=7.8Hz,2H),2.68(s,3H),2.40(s,3H).13C-NMR(100MHz,CDCl3)δ:142.5,141.5,130.0,123.6,44.0,21.4.
实施例7
7a(5mmol,0.49g)、THF/H2O(3/1)25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g,H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用乙酸乙酯(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物7b(产率:70%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ6.95(dd,J=10.4,3.0Hz,1H),6.16(d,J=10.4Hz,1H),5.63(d,J=3.0Hz,1H),4.57(d,J=16.9Hz,1H),4.13(d,J=16.9Hz,1H).13C NMR(100MHz,CDCl3)δ194.75,145.93,128.04,88.35,66.74.
实施例8
将8a(5mmol,0.66g)、THF/H2O(3/1)25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物8b(产率:60%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ9.28(s,1H),7.24-7.17(m,2H),7.03(td,J=7.6,2.5Hz,1H),6.94(dd,J=8.4,2.3Hz,1H),3.51-3.43(m,1H),1.50(d,J=7.7Hz,3H).13C NMR(100MHz,CDCl3)δ181.91,141.47,131.37,128.00,123.84,122.45,110.02,41.26,15.33.
实施例9
将9a(5mmol,0.99g)、ACN 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入铁配合物卤过氧化物酶催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物9b(产率:65%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ7.30(dd,J=8.7,7.4Hz,2H),7.00-6.91(m,3H),4.10-4.07(m,2H),3.98-3.95(m,2H),2.19-2.13(m,1H).13C NMR(100MHz,CDCl3)δ158.40,129.34,120.94,114.36,68.88,61.29.
实施例10
将10a(5mmol,1.05g)、ACN 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物10b(产率:75%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ7.99-7.93(m,2H),7.59-7.53(m,1H),7.46(t,J=7.6Hz,2H),2.60(s,3H).13C NMR(100MHz,CDCl3)δ198.28,137.26,133.23,128.69,128.43,26.73.
实施例11
将11a(4mmol,1.10g)、THF/H2O(3/1)20ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.4mmol,0.21g),H2O2水溶液(30wt%,8mmol,0.80ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,40mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物11b(产率:87%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ7.84-7.79(m,2H),7.62-7.58(m,2H),2.58(s,3H).13C NMR(100MHz,CDCl3)δ197.14,135.97,132.03,129.97,128.44,26.67.
实施例12
将12a(5mmol,1.25g)、ACN 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物12b(产率:80%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ10.40(s,1H),7.86(d,J=8.7Hz,1H),7.47(s,1H),7.37(d,J=7.3Hz,1H).13C NMR(100MHz,CDCl3)δ188.64,141.23,138.66,131.05,130.58,130.44,128.09.
实施例13
将13a(5mmol,1.37g)、ACN 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入卤过氧化物酶仿生催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物13b(产率:85%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ8.39(s,1H),8.01(d,J=9.4Hz,1H),7.83(d,J=9.0Hz,1H),7.75(d,J=8.6Hz,1H),7.19(d,J=9.1Hz,1H),7.14(s,1H),3.93(s,3H),3.10(q,J=7.3Hz,2H),1.27(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3)δ200.66,159.73,137.27,132.42,131.18,129.48,127.95,127.16,124.74,119.75,105.80,55.50,31.77,8.58.
实施例14
将14a(5mmol,1.26g)、ACN 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入铁配合物卤过氧化物酶催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物14b(产率:80%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ9.96(s,1H),7.77(d,J=8.2Hz,2H),7.32(d,J=7.8Hz,2H),2.43(s,3H).13C NMR(100MHz,CDCl3)δ192.11,145.66,134.32,129.96,129.82,21.99.
实施例15
将15a(5mmol,1.57g)、EtOH 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入铁配合物卤过氧化物酶催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物15b(产率:70%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ11.48(s,1H),8.95(d,J=9.0Hz,2H),8.62(s,1H),8.01(d,J=8.3Hz,2H),7.66(t,J=7.9Hz,2H),7.52(t,J=7.6Hz,2H).13C NMR(100MHz,CDCl3)δ193.08,135.32,132.20,131.13,129.38,129.21,125.77,124.75,123.62.
实施例16
将16a(5mmol,1.83g)、ACN 25ml依次加入100ml圆底烧瓶中,搅拌均匀,向二者混合物中依次加入铁配合物卤过氧化物酶催化剂1b(0.5mmol,0.26g),H2O2水溶液(30wt%,10mmol,1.00ml),在室温下搅拌反应15min。反应完成后用Na2S2O3溶液(0.1M,50mL)淬灭反应,水相用二氯甲烷(2x50mL)萃取,合并有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物16b(产率:65%)。该化合物的表征数据如下:1H NMR(400MHz,CDCl3)δ9.87(s,1H),7.83(d,J=8.9Hz,2H),6.99(d,J=8.8Hz,2H),3.88(s,3H).13C NMR(100MHz,CDCl3)δ190.92,164.72,132.09,130.08,114.42,55.69.
Claims (9)
1.一类基于Fenton反应的创新性卤过氧化物酶仿生催化剂的合成及其应用,其特征在于,所述方法包括:在中性、室温条件下,以多种有机分子为底物,FeBr3/FeBr2螯合以2,2′:6′,2″-三联吡啶为母核的有机配体的卤过氧化物酶作为均相催化剂,H2O2作唯一氧化剂,短时间内完成苯酚红的溴化、1,3-二噻烷衍生物羰基化、亚砜类化合物的制备、硫氮双键的环合、吲哚类衍生物的氧化重排、糠醇氧化反应等多类有机分子的合成。
2.根据权利要求1所述的方法,其特征在于:反应底物为具有不同官能团的有机硫化物、含氮有机硫化物、糠醇、1,3-二噻烷衍生物、吲哚类衍生物、苯酚红等,适用底物范围广泛。
3.根据权利要求1所述的方法,其特征在于:以FeBr3/FeBr2螯合以2,2′:6′,2″-三联吡啶为母核的有机配体的铁配合物卤过氧化物酶作为均相催化剂,催化剂与原料有机分子的摩尔比为0.01-0.2∶1。
4.根据权利要求1所述的方法,其特征在于:所用氧化剂为H2O2,H2O作为副产物,H2O2与原料有机分子的摩尔比为1-4∶1。
5.根据权利要求1所述的方法,其特征在于:反应于溶剂中进行,所用溶剂可为乙醇、乙腈、四氢呋喃等,及其与水不同比例的混合溶剂,原料有机分子与溶剂用量的比例为1mmol/5-16ml。
6.根据权利要求1所述的方法,其特征在于:反应温度为室温。
7.根据权利要求1所述的方法,其特征在于:较佳反应时间为15min。
8.根据权利要求1所述的方法,其特征在于:具体操作时,将原料有机分子加入适量溶剂中搅拌均匀,然后加入卤过氧化物酶仿生催化剂、H2O2水溶液,反应混合物在室温下搅拌反应15min,完成有机分子的卤化、1,3-二噻烷衍生物羰基化、亚砜类化合物的制备、硫氮双键环合、吲哚类衍生物的氧化重排、糠醇氧化等反应。
9.根据权利要求1所述的方法,其特征在于:所述反应的处理方法为,反应完成后用稀释的Na2S2O3溶液淬灭,用有机溶剂如二氯甲烷、乙酸乙酯萃取,收集有机相,无水硫酸钠干燥,过滤,减压浓缩,即可得产物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211061182.4A CN116174039A (zh) | 2022-09-01 | 2022-09-01 | 一类创新性卤过氧化物酶仿生催化剂的合成及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211061182.4A CN116174039A (zh) | 2022-09-01 | 2022-09-01 | 一类创新性卤过氧化物酶仿生催化剂的合成及其应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116174039A true CN116174039A (zh) | 2023-05-30 |
Family
ID=86451135
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211061182.4A Pending CN116174039A (zh) | 2022-09-01 | 2022-09-01 | 一类创新性卤过氧化物酶仿生催化剂的合成及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116174039A (zh) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104854150A (zh) * | 2012-04-27 | 2015-08-19 | 阿尔比马尔公司 | 活化剂组合物、其制备及其在催化剂中的用途 |
CN107847921A (zh) * | 2015-07-14 | 2018-03-27 | 国立大学法人九州大学 | 氢化硅烷化反应催化剂 |
CN114057545A (zh) * | 2021-12-07 | 2022-02-18 | 北京中医药大学 | 一种催化四氢吡喃醚脱保护为羟基化合物的绿色方法 |
CN114890879A (zh) * | 2022-03-02 | 2022-08-12 | 北京中医药大学 | 一种β-二羰基化合物的单溴代方法 |
-
2022
- 2022-09-01 CN CN202211061182.4A patent/CN116174039A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104854150A (zh) * | 2012-04-27 | 2015-08-19 | 阿尔比马尔公司 | 活化剂组合物、其制备及其在催化剂中的用途 |
CN107847921A (zh) * | 2015-07-14 | 2018-03-27 | 国立大学法人九州大学 | 氢化硅烷化反应催化剂 |
CN114057545A (zh) * | 2021-12-07 | 2022-02-18 | 北京中医药大学 | 一种催化四氢吡喃醚脱保护为羟基化合物的绿色方法 |
CN114890879A (zh) * | 2022-03-02 | 2022-08-12 | 北京中医药大学 | 一种β-二羰基化合物的单溴代方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN112778257A (zh) | 一种将糠醇氧化为二氢吡喃酮类衍生物的绿色方法 | |
CN110483460B (zh) | 一种3-硒代香豆素类化合物的制备方法 | |
CN113549062B (zh) | 一种金鸡纳碱衍生的大位阻手性季铵盐相转移催化剂及其合成方法 | |
CN105949168B (zh) | 一种合成异色酮类化合物的方法 | |
CN112961116B (zh) | 一种2-芳基甲酰基苯并恶唑化合物的合成方法 | |
CN111072555B (zh) | 制备杂环砜类有机化合物的方法 | |
CN116174039A (zh) | 一类创新性卤过氧化物酶仿生催化剂的合成及其应用 | |
CN112442008A (zh) | 一种温度调控单质硫与活泼内炔制备1,4-二噻烯和噻吩类化合物的方法及其转化反应 | |
CN114573512B (zh) | 一种合成c2-二氟烷基苯并咪唑衍生物的方法 | |
CN114989063A (zh) | 一种β-卤代吡咯类化合物的合成方法 | |
CN114133322A (zh) | 一种催化二硫缩醛/酮脱保护为羰基化合物的绿色方法 | |
CN107353245A (zh) | 一种喹啉类化合物的合成方法 | |
CN113651788A (zh) | 一种3-胺烷基色酮化合物及其制备方法 | |
CN110229096B (zh) | 一种2,6-吡啶二羧酸的制备方法 | |
CN114716361A (zh) | 一种合成手性螺环茚酮-吡咯类化合物的方法 | |
CN111087402B (zh) | 一种不对称合成ETP类天然产物epicoccin G生物碱的方法 | |
JP2003146978A (ja) | シス−β構造を有するサレンコバルト錯体を用いる光学活性なラクトン化合物の製造方法 | |
CN111808041B (zh) | 一种对二氟烷基的芳基噁唑烷酮类化合物及其制备方法 | |
CN113956139B (zh) | 一种将四氢噻唑类衍生物转化为羰基化合物的绿色方法 | |
CN113929565B (zh) | 一种催化1,3-氧硫杂环戊/己烷脱保护的绿色合成方法 | |
CN115304465B (zh) | 一种将1,3-二噻烷衍生物转化为羰基化合物的绿色方法 | |
CN113429323B (zh) | 一种磺酰基取代苯乙烯型轴手性类化合物的制备方法 | |
CN114213370B (zh) | 一种光诱导nhpi酯脱羧偶联合成烷基化富电子杂环芳烃方法 | |
Xiao et al. | Novel α-ketoesters from β-diketones via a vanadium-mediated tandem transformation under an oxygen atmosphere | |
CN114573431A (zh) | 一种制备α,α-二溴代酮的绿色方法 |
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 |