CN116444390A - 碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法 - Google Patents
碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 29
- -1 fluoroaryl biphenyl Chemical compound 0.000 title claims abstract description 24
- 235000010290 biphenyl Nutrition 0.000 title claims abstract description 21
- 238000005859 coupling reaction Methods 0.000 title claims abstract description 11
- 238000010168 coupling process Methods 0.000 title claims abstract description 10
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 230000008878 coupling Effects 0.000 title claims abstract description 9
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 title claims abstract description 9
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title abstract description 20
- 239000004305 biphenyl Substances 0.000 title abstract description 18
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 67
- 239000000654 additive Substances 0.000 claims abstract description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 230000000996 additive effect Effects 0.000 claims abstract description 31
- 238000005286 illumination Methods 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 12
- 239000011737 fluorine Substances 0.000 claims abstract description 12
- 239000012298 atmosphere Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000000460 chlorine Substances 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 229910052759 nickel Inorganic materials 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 239000003446 ligand Substances 0.000 claims description 12
- 239000007789 gas Substances 0.000 claims description 9
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
- 150000001491 aromatic compounds Chemical class 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 229930195733 hydrocarbon Natural products 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- 229910052725 zinc Inorganic materials 0.000 claims description 4
- 239000011701 zinc Substances 0.000 claims description 4
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims 1
- 230000004913 activation Effects 0.000 abstract description 8
- 239000000463 material Substances 0.000 abstract description 5
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- 239000003054 catalyst Substances 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 13
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Inorganic materials [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 11
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 238000012512 characterization method Methods 0.000 description 9
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 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 4
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005265 energy consumption Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- JRTIUDXYIUKIIE-KZUMESAESA-N (1z,5z)-cycloocta-1,5-diene;nickel Chemical compound [Ni].C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 JRTIUDXYIUKIIE-KZUMESAESA-N 0.000 description 2
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001500 aryl chlorides Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000001555 benzenes Chemical class 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000004407 fluoroaryl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- UMTMDKJVZSXFNJ-UHFFFAOYSA-N nickel;trihydrate Chemical compound O.O.O.[Ni] UMTMDKJVZSXFNJ-UHFFFAOYSA-N 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- WACNXHCZHTVBJM-UHFFFAOYSA-N 1,2,3,4,5-pentafluorobenzene Chemical compound FC1=CC(F)=C(F)C(F)=C1F WACNXHCZHTVBJM-UHFFFAOYSA-N 0.000 description 1
- FARSXMMESQDZMY-UHFFFAOYSA-N 4-chloro-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=C(Cl)C=C1 FARSXMMESQDZMY-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241001411320 Eriogonum inflatum Species 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 238000006464 oxidative addition reaction Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- 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
-
- 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
- B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
- B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
- C07C17/269—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions of only halogenated hydrocarbons
-
- 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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- 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
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- 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
- B01J2531/847—Nickel
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- Organic Chemistry (AREA)
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- Engineering & Computer Science (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了一种碳‑氟/碳‑氯偶联直接得到(多)氟芳基联苯的方法,其包括如下步骤:将(多)氟芳烃化合物和氯代芳烃化合物、添加剂、镍催化剂、还原剂和溶剂混合后,在惰性气体气氛和光照下进行反应;所述添加剂的结构式为LiX、NaX、MgX2、NR4X中的一种或几种的组合;其中X为氟、氯、溴、碘的一种或多种,R为烷基。本发明通过采用添加剂促进C‑F键的活化,在无导向基团的存在下可以高选择性的合成C‑H键邻位的(多)氟联苯类化合物,步骤简单,并且制备得到了具有单一结构的(多)氟芳基联苯,在精细化工、材料科学和制药领域都有较好的应用。
Description
技术领域
本发明涉及含氟联芳基化合物的制备技术领域,尤其涉及一种碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法。
背景技术
含氟化合物尤其是多氟联芳基化合物,广泛存在于许多药物分子(Diflunisal,Cevipabulin等)和材料中[参见:(a)Berger,R.,Resnati,G.,Metrangolo,P.,Weber,E.&Hulliger,J.Chem.Soc.Rev.2011,40,3496-3508.(b)Muller,K.,Faeh,C.&Diederich,F.Science,2007,317,1881-1886.]。目前,合成多氟联芳基化合物主要方法是将简单的多氟芳烃首先转化成含羧基,硼酸酯等化合物,然后通过suzuki偶联反应,同有机金属试剂或芳基溴或芳基碘在高温下得到。该方法的主要缺点是反应多氟苯需要预先活化,步骤比较繁杂。而且该反应需要使用碱以及高温,限制了底物的适用面,不能存在对有机金属试剂敏感的羰基、羟基等基团;反应也不适用于更廉价的芳基氯。利用廉价易得的多氟苯直接转化是一种非常理想的策略。目前策略主要是利用多氟芳烃的酸性C-H键活化而实现。但是此类反应受到底物电性影响非常大,底物中氟的数量通常要多于三个,限制了底物的种类。且当底物中存在多个C-H键时,产物通常不单一,产生的多个同分异构体非常不利于后续分离。此外,反应中依旧需要使用碱以及高温。C-F键选择性的断裂直接官能团化是合成多氟联苯非常理想的方法,但是由于C-F键的键能非常强,且多氟芳基上多个氟的控制选择性也非常难的,通常需要使用预先安装导向基团的手段,才能实现,且反应也通常需要使用到有机金属试剂,不利于大规模生产和应用。[参见:(a)Ahrens,T.,Kohlmann,J.,Ahrens,M.&Braun,T.Chem.Rev.2015,115,931-972(2015).(b)Das,A.&Chatani,N.ACS Catal.11,12915-12930(2021).]。
当前,直接使用廉价易得的氟苯和氯苯直接以高收率高选择性得到(多)氟联芳基化合物是非常理想的策略,但是这种方法由于C-F/C-Cl键的电性以及强键能等原因目前仍未能实现。
有鉴于此,特提出本发明。
发明内容
本发明的目的是提供一种碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法,其采用(多)氟芳烃化合物和氯代芳烃化合物为原料,以镍催化剂为催化剂,采用添加剂作为协同催化试剂,制备得到了具有单一结构的(多)氟芳基联苯,避免了现有技术中产物中多种同分异构体共存的问题,并且本发明所提供的方法操作简单,反应条件温和,可以一步合成(多)氟芳基联苯。
为了实现上述目的,本发明特采用以下技术方案:
本发明提供了一种碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法,其包括如下步骤:
将(多)氟芳烃化合物和氯代芳烃化合物、添加剂、镍催化剂、还原剂和溶剂混合后,在气体气氛和光照下进行反应;
所述添加剂的结构式为LiX、NaX、MgX2、NR4X中的一种或几种的组合;
其中X为氟、氯、溴、碘的一种或多种,R为烷基。
本发明通过采用添加剂,促进了C-F键的活化,在无导向基团的存在下即可高选择性的合成C-H键邻位的(多)氟联苯类化合物,提高氟苯的区域选择性,保证化合物的纯度,同时采用可见光光照代替传统加热的方法,可以提高产率,对底物的兼容性更好,而且采用可见光光照的耗能低于传统加热的耗能,更加的节能。
同时本发明中还采用了镍催化剂,镍是一种富电子的金属,镍的性质决定可以有丰富的氧化态,能够提供电子,有利于促进氧化加成,添加剂也是有利于促进氧化加成的,两者配合使用,可以更好的促进氧化加成反应的进行,
优选地,所述光照的波长为300-500nm,所述光照的功率为0-90W;
优选地,所述光照的波长为390nm,所述光照的功率为40W。
优选地,所述烷基为四丁基氯化铵,四丁基碘化胺,四丁基溴化胺中的一种;
优选地,所述添加剂的结构式为LiI。
本发明将添加剂选择为LiI是由于LiI和氟苯之间存在有静电吸引,可以形成锂键,削弱了碳氟键,有利于镍***C-F键中。此外,LiI在过渡态中会有一个协同作用,利于氟的离去。而不同位点的碳氟键活化的能垒由于过渡态结构的差异相差很多,因此具有很好的选择性。因此本发明通过采用添加剂可以在无引导基团的情况下实现C-F键的活化。
可见,上述过程中,添加剂的添加、光照以及催化剂的选择缺一不可,通过选择适宜的添加剂配合特定的催化剂,在光照条件下,提高了整个反应的区域选择性,制备得到了具有单一结构的(多)氟芳基联苯,避免了现有技术中各种结构的(多)氟芳基联苯均存在最终产物中,影响了后续实际应用的价值。并且本发明的操作方法较现有技术具有反应条件温和,操作简单,一步法即可合成(多)氟芳基联苯。
优选地,按摩尔分数计,混合时选择1-50.0份的(多)氟芳烃化合物、0.1-5.0份的氯代芳烃化合物和1-5.0份的添加剂、0.01-0.2份的镍催化剂;1.0-5.0份的还原剂。
优选地,按摩尔分数计,混合时添加有2.0份的(多)氟芳烃化合物,1.0份的氯代芳烃化合物,2.5份的添加剂,0.1份的镍催化剂,2.0份的还原剂。
优选地,所述(多)氟芳烃化合物为单氟芳烃或者多氟芳烃其中一种,其结构式选择为以下结构式中的一种:
其中,R为烷基、芳基、三氟甲基、羟基、酯基、磺酰基、氨基、氢的一种或多种;n为2-5中的任意一个整数。
优选地,所述氯代芳烃化合物选择为单氯芳烃和氯代杂芳烃的其中一种,其结构式的选择为以下结构式的其中一种:
其中,R为烷基、芳基、三氟甲基、羟基、酯基、磺酰基、氨基的一种或多种的组合;R1为烷基、氢的其中一种。
优选地,所述镍催化剂选择为以下结构式的一种:
其中,X为Br、I、Cl和F中的其中一种,R1为烷基、芳基、烷氧基、卤素、三氟甲基、酯基和氰基中的其中一种,R2为环辛二烯。
优选地,所述镍催化剂的制备方法包括如下步骤:
将镍与配体加入到溶剂中进行反应,即可制得目标产物;
所述镍选择为以下结构式的一种:Ni(COD)2、NiX2·DME、NiX2;
所述配体选择为以下结构式的一种:
优选地,本发明中制备镍催化剂的溶剂与制备(多)氟芳基联苯所用的溶剂为同一种溶剂,所述溶剂为四氢呋喃、1,4-二氧六环、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、乙腈、二甲基亚砜中的一种;
优选地,镍选择为Ni(COD)2,配体选择为溶剂选择为四氢呋喃,镍与配体以摩尔比为1:(1-3)的比例加入到溶剂中。
优选地,所述还原剂为锌、锰、镁的一种;
优选地,所述还原剂为锌;
优选地,所述气体气氛为惰性气体;
优选地,所述气体气氛为氮气;
优选地,所述反应的温度为0-70℃;
优选地,所述反应的温度为30℃。
在本发明的方案中,上述设计的所有的参数,不管是各个组分的选择、各个组分之间的摩尔比、光照的波长及功率、气体气氛、催化剂的选择和催化剂的组分及组分之间的摩尔比等都最好控制在本发明的范围之内的,不能过高也不能过低,例如当反应的温度过高时,虽然产率会有提升,但副产物会变多,并且不够经济。温度过低则反应难以发生,产率大大下降。气体氛围也需控制,空气下也可得到产物,但产率下降,催化剂容易失去活性。添加剂的用量也需要控制,当添加剂的用量过多时,产率会降低,氟苯自身偶联副反应变多;当添加剂用量过少时,氟苯转换不全,产率会降低。催化剂的用量也需要控制,当镍催化剂过少时,反应时间需要延长,不高效。当镍催化剂用量过多时,容易形成镍黑,产率会有所下降,经济效率不高。光照的波长需要控制,低于300nm的光照射,产率会有所降低,而且光的能量太高,对底物结构有一定的限制。但光的波长在500nm后,产率也会有所降低。光照的功率也需要控制,当功率过低时,反应速率会变低,效率不高。当光照功率过大时,浪费能源,而且也容易导致温度过高,副反应变多以及催化剂失去活性。
为了更加清楚地理解本发明的方案,通过具体的实例来对本发明的反应机理进行说明:将所述配体选择为4,4'-二叔丁基-2,2'-联吡啶,所述镍催化剂为选择为双-(1,5-环辛二烯)镍,将(多)氟芳烃化合物选择为多氟苯,将添加剂选择为碘化锂,将氯代芳烃化合物选择为芳基氯,将溶剂选择为四氢呋喃,将还原剂选择为锌粉,将灯光选择为390nm,当灯光功率选择为40W,其中,碘化锂可以促进C-F键的氧化加成,选择性也是在这一过程得到控制。光照可以促进镍的还原。反应机理如下图所示:
从上述图中那我们可以看出,首先零价镍催化剂和氟苯氧化加成为二价镍中间体2。我们认为这一步将是确定区域选择性的关键步骤,碘化锂同氟苯之间形成锂键,不仅促进C-F键的活化,还确定了区域选择性。中间体2在光照条件下成为激发态中间体3,随后被锌粉还原成为一价镍中间体4。中间体4随后同氯苯氧化加成得到中间体6,随后经过还原消除得到产物,并生成一价镍中间体8。后者在锌粉的还原下生成零价镍催化剂,并完成整个催化循环。
本发明与现有技术相比,至少有以下优异之处:
(1)本发明通过添加剂,促进了C-F键的活化,在无导向基团的存在下可以高选择性的合成之前很难实现的C-H键邻位的(多)氟联苯类化合物,得到的化合物为具有单一结构产物,避免了现有技术中多种结构产物共存的现象,方便后续的应用。
(2)本发明所提供的方法步骤简单,反应条件温和,同时采用可见光光照代替传统加热的方法,降低能耗。
(3)本发明通过使用廉价易得的氯苯代替昂贵的芳基硼酸或者难储存的金属试剂,降低了操作难度,可以高效的合成多种含氟芳基联苯。
附图说明
通过阅读下文优选实施方式的详细描述,各种其他的优点和益处对于本领域普通技术人员将变得清楚明了。附图仅用于示出优选实施方式的目的,而并不认为是对本发明的限制。而且在整个附图中,用相同的参考符号表示相同的部件。在附图中:
图1为本发明实施例1所提供的的核磁氢谱表征数据图;
图2为本发明实施例1所提供的的核磁氟谱表征数据图;
图3为本发明实施例1所提供的的核磁碳谱表征数据图。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述,但是本领域技术人员将会理解,下列实施例仅用于说明本发明,而不应视为限制本发明的范围。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。
实施例1
本发明提供了一种碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法,其包括如下步骤:
(1)镍催化剂的制备;
在充满氮气的气套箱中,向装有搅拌子的烧瓶中加入0.024mmol的4,4'-二叔丁基-2,2'-联吡啶,0.02mmol的双-(1,5-环辛二烯)镍,接着加入0.5mL的四氢呋喃,在室温下搅拌15min,得到0.02mmol的目标产物-镍催化剂。
(2)N,N-二甲基-4-(2,3,4,5-四氟苯基)苯甲酰胺的制备;
取用干净的烧瓶,在充满氮气的气套箱中,向烧瓶中依次加入0.2mmol 4-氯-N,N-二甲基苯甲酰胺,0.4mmol五氟苯,0.5mmol碘化锂,0.4mmol锌粉,0.5mL四氢呋喃,然后将步骤(1)所制备的镍催化剂加入烧瓶中,盖上瓶塞,转移出手套箱,在390nm、40W的紫光照射条件下,在30℃下搅拌12h,反应结束后使用饱和氯化铵和乙酸乙酯萃取三次。合并有机相,通过柱层析(200-300目)分离浓缩得到
在实验完成后,采用电子天平称量,得出目标产物的产率为73%,核磁和气相色谱显示,产物为氟苯C-H键邻位取代的单一结构,无其他区域选择性的副产物。其中图1为核磁氢谱表征数据图,图2为核磁氟谱表征数据图,图3为核磁碳谱表征数据图。
具体表征数据为:1HNMR(400MHz,Chloroform-d):δ7.52(s,4H),7.09–7.02(m,1H),3.13(s,3H),3.03(s,3H).19FNMR(376MHz,Chloroform-d):δ-139.15(ddd,J=21.1,12.5,2.6Hz),-143.45(ddd,J=20.5,12.5,3.4Hz),-154.78(td,J=20.0,2.6Hz),-156.22(td,J=20.5,3.4Hz).13CNMR(101MHz,Chloroform-d):δ170.8,147.1(dm,J=245.1Hz),144.9(dm,J=250.0Hz),141.2(dm,J=252.9Hz),140.0(dm,J=256.3Hz),136.7,134.2,128.8(d,J=2.4Hz),127.6,124.5–124.4(m),111.3(d,J=19.7Hz),39.5,35.4。
高分辨质谱的具体表征数据为:HRMS(ESI,m/z):Calculated for C15H12F4NO(M+H)+298.0850,found 298.0842。
实施例2-3
具体实施方式与实施例1一致,不同之处如下表1所示:
表1不同组分的摩尔比对产率的影响
实施例4-5
具体实施方式与实施例1一致,不同之处如下表2所示:
表2反应条件对产率的影响
实施例6-8
具体实施方式与实施例1一致,不同之处如下表3所示:
表3组分的不同对产率的影响
实施例9
具体实施方式与实施例1一致,唯一不同之处在于将添加剂选择为氯化镁和氯化锂按摩尔比为2:1混合而成,所得到的产率为45%,所得到的产物的结构式为
实施例10
具体实施方式与实施例1一致,唯一不同之处在于将所述添加剂的用量选择为0.05mmol,所得到的产率为15%,所得到的产物的结构式为
实施例11
具体实施方式与实施例1一致,唯一不同之处在于将添加剂用量选择为1.5mmol,所得到的产率为26%,所得到的产物的结构式为
实施例12
具体实施方式与实施例1一致,唯一不同之处在于将光照的波长选择为600nm,所得到的产率为29%,所得到的产物的结构式为
实施例13
具体实施方式与实施例1一致,唯一不同之处在于将光照的功率选择为200W,所得到的产率为35%,所得到的产物的结构式为
实施例14
具体实施方式与实施例1一致,唯一不同之处在于所述镍催化剂的是由Ni(COD)2和以摩尔比为5:1制备而成,所得到的产率为25%,所得到的产物的结构式为/>
实施例15
具体实施方式与实施例1一致,唯一不同之处在于所述镍催化剂选择为二氯化镍,所得到的产率为40%,所得到的产物的结构式为
实施例16
具体实施方式与实施例1一致,不同之处在于将步骤2中的(多)氟芳烃化合物选择为氯代芳烃化合物选择为/>添加剂的用量选择为0.2mmol,得到产物为/>产率为66%。
具体表征数据为:1H NMR(400MHz,Chloroform-d):δ8.18(q,J=1.6Hz,1H),8.11(dt,J=7.6,1.6Hz,1H),7.79–7.65(m,2H),7.61–7.45(m,5H),3.95(s,3H),3.14(s,3H),3.04(s,3H).19F NMR(376MHz,Chloroform-d):δ-56.10(t,J=24.2Hz),-114.95(qd,J=24.2,2.6Hz),-115.16(qd,J=24.3,2.6Hz).13C NMR(126MHz,Chloroform-d):δ170.9,166.5,156.1(d,J=262.7Hz),136.6,135.3(t,J=5.2Hz),134.6,133.8,133.4,133.4,130.9,130.1(d,J=2.2Hz),129.7,129.1,129.1,128.9,128.0,127.5,127.1,126.2(dd,J=14.9,4.4Hz),126.0(dd,J=14.6,4.5Hz),121.7(q,J=275.9Hz),52.4,39.8,35.4.HRMS(ESI,m/z):Calculated for C24H19F5NO3(M+H)+464.1280,found 464.1273.
实施例17
具体实施方式与实施例1一致,不同之处在于将步骤2中的(多)氟芳烃化合物选择为氯代芳烃化合物选择为/>添加剂的用量选择为0.4mmol,得到产物为/>产率为63%。
具体表征数据为:1HNMR(400MHz,Chloroform-d):δ7.96(dt,J=6.4,2.0Hz,1H),7.94–7.90(m,2H),7.86–7.81(m,1H),7.57(dd,J=8.0,1.6Hz,2H),3.94(s,3H),1.37(s,12H).19FNMR(376MHz,Chloroform-d):δ-135.32(d,J=20.4Hz),-135.99(d,J=20.5Hz).11BNMR(128MHz,Chloroform-d):δ31.45.13CNMR(101MHz,Chloroform-d):δ165.2,151.0(dd,J=257.0,12.6Hz),150.7(dd,J=249.3,13.6Hz),136.3,135.5,135.1,131.2(d,J=11.3Hz),128.2,128.2,127.1,126.4(d,J=16.5Hz),117.6,117.4,84.00,52.6,24.9.HRMS(APCI,m/z):Calculated for C20H22BF2O4(M+H)+375.1574,found 375.1577。
对比例1
具体实施方式与实施例1一致,唯一不同之处在于将配体选择为三苯基膦,所得到的产率为0%。
对比例2
具体实施方式与实施例1一致,唯一不同之处在于不使用添加剂,所得到的产率为0%。
对比例3
采用现有技术制备含(多)氟联芳基化合物,其反应方程式如下所示:
最后可知其区域选择性为C1:C3=55:45,产率为38%。
对比例4
采用现有技术制备含(多)氟联芳基化合物,其反应方程式如下所示:
最后可知其区域选择性为C3:C2=94:6,产率为67%。
从上述的实施例1-17和对比例1-4的结果可以看出在该反应中,难度最大的是区域选择性的调控和产率问题。
首先是针对实施例:将实施例2-17的数据与实施例1相比,在实施例10中,添加剂的用量过少,造成氟苯转换不全,导致产率降低,在实施例11中,添加剂的用量过多时,会造成偶联反应的发生,造成副反应增多,进而导致产率降低,在实施例12中,将波长选择为600nm,超过了本发明的最高波长500nm,这就造成光照对于本发明的反应失去了作用,导致产率降低,而实施例13中光照的功率达到了200W,这间接造成了反应温度的上升,降低了产率,实施例14中镍的用量远远大于配体的用量,这就造成了多余的镍在反应过程中容易失活,形成镍黑,不能起到催化效果。本发明的目的是提供一种碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法,其采用廉价的(多)氟芳烃化合物和氯代芳烃化合物为原料,以镍催化剂为催化剂,采用添加剂作为协同催化试剂,高效高选择性的制备各类结构专一的含氟联芳基化合物。多氟苯的直接C-F键转化中通常存在选择性问题,导致容易生成多种同分异构体,不利于后续的分离以及在药物、材料研究中的应用。本发明保证所制备的(多)氟芳基联苯只有单一取代的产物存在,降低了后续分离过程的难度。本方法条件温和,能适用于多种官能团,生成产物在精细化工、材料科学和制药领域都有较好的应用。
接着是针对于对比例而言,正如本发明中的实施例1和对比例3,后者使用了贵金属钯催化剂以及金属格式试剂,其区域选择性和产率都较差,且原料不易储存。相较于对比例3,本发明的催化剂选用廉价镍催化剂,以及商业丰富可得的氯苯为原料,可得到结构单一的产物,更有利于应用在复杂分子的修饰以及大量制备中。对比例4中,同样使用了贵金属钯催化剂,且反应温度在120℃。尽管能够以较高选择性得到C3-F键断裂产物,但是对于化学键键能最高的C1-F键,没法断裂形成相应产物。相较于对比例4,本发明采用紫光照射,在30℃就可以得到最难得到的结构C3选择性产物,其能源消耗大大降低,更加绿色和环保。对比例1中,使用了电子供体更强的三苯基膦配体,但是由于其中间体很难被还原,所以反应没法循环,也就不会制备出含氟联苯了。在对比例2中,没有使用添加剂,导致C-F键不能很好的被活化,所以无法得到含氟联苯。因此,只有严格按照本发明的方案进行制备,才可以低成本的制备出优异的高区域选择性的含(多)氟联苯。
通过实施例1-17和对比例1-4的比较可以看出:本发明所准备的(多)氟芳基联苯为单一结构产物,产物中并无同分异构体的存在,避免了在后续进行应用时需分离同分异构体的操作,同时,本发明的方法步骤简单,反应条件温和,按照本发明所公开的组分和方法才可以制备出单一结构的(多)氟芳基联苯。
本发明生产单一结构的(多)氟芳基联苯,避免了在产物中多个结构的(多)氟芳基联苯同时存在,也避免了再进一步制备药物或其他材料的后续应用中,还需要进一步分离为单一结构的麻烦。
最后,可以理解的是,以上实施方式仅仅是为了说明本发明的原理而采用的示例性实施方式,然而本发明并不局限于此。对于本领域普通技术人员而言,在不脱离本发明的原理和实质的情况下,可以做出各种变型和改进,这些变型和改进也视为本发明的保护范围。
Claims (10)
1.一种碳-氟/碳-氯偶联直接得到(多)氟芳基联苯的方法,其特征在于,包括如下步骤:
将(多)氟芳烃化合物和氯代芳烃化合物、添加剂、镍催化剂、还原剂和溶剂混合后,在气体气氛和光照下进行反应;
所述添加剂的结构式为LiX、NaX、MgX2、NR4X中的一种或几种的组合;
其中X为氟、氯、溴、碘的一种或多种,R为烷基。
2.根据权利要求1所述的方法,其特征在于,所述光照的波长为300-500nm,所述光照的功率为0-90W;
优选地,所述光照的波长为390nm,所述光照的功率为40W。
3.根据权利要求1所述的方法,其特征在于,所述烷基为四丁基氯化铵,四丁基碘化胺,四丁基溴化胺中的一种;
优选地,所述添加剂的结构式为LiI。
4.根据权利要求1所述的方法,其特征在于,按摩尔分数计,混合时选择1-50.0份的(多)氟芳烃化合物、1.0份的氯代芳烃化合物和1-5.0份的添加剂、0.01-0.2份的镍催化剂;1.0-5.0份的还原剂。
5.根据权利要求1所述的方法,其特征在于,按摩尔分数计,混合时添加有2.0份的(多)氟芳烃化合物,1.0份的氯代芳烃化合物,2.5份的添加剂,0.1份的镍催化剂,2.0份的还原剂。
6.根据权利要求1所述的方法,其特征在于,所述(多)氟芳烃化合物为单氟芳烃或者多氟芳烃其中一种,其结构式选择为以下结构式中的一种:
其中,R为烷基、芳基、三氟甲基、羟基、酯基、磺酰基、氨基、氢的一种或多种;n为2-5中的任意一个整数。
7.根据权利要求1所述的方法,其特征在于,所述氯代芳烃化合物选择为单氯芳烃和氯代杂芳烃的其中一种,其结构式的选择为以下结构式的其中一种:
其中,R为烷基、芳基、三氟甲基、羟基、酯基、磺酰基、氨基的一种或多种的组合,R1为烷基、氢的其中一种。
8.根据权利要求1所述的方法,其特征在于,所述镍催化剂选择为以下结构式的一种:
其中,X为Br、I、Cl和F中的其中一种,R1为烷基、芳基、烷氧基、卤素、三氟甲基、酯基和氰基中的其中一种,R2为环辛二烯。
9.根据权利要求8所述的方法,其特征在于,所述镍催化剂的制备方法包括如下步骤:
将镍与配体加入到溶剂中进行反应,即可制得目标产物;
所述镍选择为以下结构式的一种:Ni(COD)2、NiX2·DME、NiX2;
所述配体选择为以下结构式的一种:
所述溶剂为四氢呋喃、1,4-二氧六环、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、乙腈、二甲基亚砜中的一种;
优选地,镍选择为Ni(COD)2,配体选择为溶剂选择为四氢呋喃,镍与配体以摩尔比为1:(1-3)的比例加入到溶剂中。
10.根据权利要求1所述的方法,其特征在于,所述还原剂为锌、锰、镁的一种;
优选地,所述还原剂为锌;
优选地,所述气体气氛为惰性气体;
优选地,所述气体气氛为氮气;
优选地,所述反应的温度为0-70℃;
优选地,所述反应的温度为30℃。
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