CN102675366A - 2-烷氧基-6-氨基苯基二烷基膦及其合成和应用 - Google Patents
2-烷氧基-6-氨基苯基二烷基膦及其合成和应用 Download PDFInfo
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- CN102675366A CN102675366A CN2012101462206A CN201210146220A CN102675366A CN 102675366 A CN102675366 A CN 102675366A CN 2012101462206 A CN2012101462206 A CN 2012101462206A CN 201210146220 A CN201210146220 A CN 201210146220A CN 102675366 A CN102675366 A CN 102675366A
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- aminophenyl
- arh
- dialkyl phosphine
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- 238000003786 synthesis reaction Methods 0.000 title description 5
- 230000015572 biosynthetic process Effects 0.000 title description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 58
- 238000006243 chemical reaction Methods 0.000 claims abstract description 55
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 29
- 150000002576 ketones Chemical class 0.000 claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 238000010168 coupling process Methods 0.000 claims abstract description 6
- 238000005859 coupling reaction Methods 0.000 claims abstract description 5
- 230000008878 coupling Effects 0.000 claims abstract description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 126
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 69
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 64
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 61
- -1 sulfydryl Chemical group 0.000 claims description 36
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 24
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 14
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 13
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 13
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 12
- 229940093916 potassium phosphate Drugs 0.000 claims description 12
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 12
- 235000011009 potassium phosphates Nutrition 0.000 claims description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 claims description 5
- 229910052744 lithium Inorganic materials 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- WTAPZWXVSZMMDG-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WTAPZWXVSZMMDG-UHFFFAOYSA-N 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
- TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical compound Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 150000008422 chlorobenzenes Chemical class 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 36
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000003446 ligand Substances 0.000 abstract description 3
- 238000010189 synthetic method Methods 0.000 abstract 2
- 230000003213 activating effect Effects 0.000 abstract 1
- 150000001500 aryl chlorides Chemical class 0.000 abstract 1
- 230000000087 stabilizing effect Effects 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000007788 liquid Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000007787 solid Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- PFIADAMVCJPXSF-UHFFFAOYSA-N chloroneb Chemical compound COC1=CC(Cl)=C(OC)C=C1Cl PFIADAMVCJPXSF-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 5
- NPDACUSDTOMAMK-UHFFFAOYSA-N 4-Chlorotoluene Chemical compound CC1=CC=C(Cl)C=C1 NPDACUSDTOMAMK-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- NPUUWZQAVJYUTO-UHFFFAOYSA-N anisole;propan-2-one Chemical compound CC(C)=O.COC1=CC=CC=C1 NPUUWZQAVJYUTO-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
- FIENFAYQIMPCTI-UHFFFAOYSA-N 1,5-bis(4-methoxyphenyl)-2,4-diphenylpentan-3-one Chemical class C1(=CC=CC=C1)C(CC1=CC=C(C=C1)OC)C(=O)C(CC1=CC=C(C=C1)OC)C1=CC=CC=C1 FIENFAYQIMPCTI-UHFFFAOYSA-N 0.000 description 2
- VXEYCRTYRCTRCO-UHFFFAOYSA-N C1(=C(C=CC=C1)C(CC1=CC=C(C=C1)OC)C(=O)C(CC1=CC=C(C=C1)OC)C1=C(C=CC=C1)C)C Chemical compound C1(=C(C=CC=C1)C(CC1=CC=C(C=C1)OC)C(=O)C(CC1=CC=C(C=C1)OC)C1=C(C=CC=C1)C)C VXEYCRTYRCTRCO-UHFFFAOYSA-N 0.000 description 2
- GGCAOXPQBZLRIA-UHFFFAOYSA-N C1(=CC=CC=C1)C(CC1=CC(=CC=C1)N(C)C)C(=O)C(CC1=CC(=CC=C1)N(C)C)C1=CC=CC=C1 Chemical compound C1(=CC=CC=C1)C(CC1=CC(=CC=C1)N(C)C)C(=O)C(CC1=CC(=CC=C1)N(C)C)C1=CC=CC=C1 GGCAOXPQBZLRIA-UHFFFAOYSA-N 0.000 description 2
- VQAYVUJLTNCVFT-UHFFFAOYSA-N C1(=CC=CC=C1)C(CC1=CC(=CC=C1)OC)C(=O)C(CC1=CC(=CC=C1)OC)C1=CC=CC=C1 Chemical compound C1(=CC=CC=C1)C(CC1=CC(=CC=C1)OC)C(=O)C(CC1=CC(=CC=C1)OC)C1=CC=CC=C1 VQAYVUJLTNCVFT-UHFFFAOYSA-N 0.000 description 2
- WZLQGMKARRCAMX-UHFFFAOYSA-N C1(=CC=CC=C1)C(CC1=CC=C(C=C1)C)C(=O)C(CC1=CC=C(C=C1)C)C1=CC=CC=C1 Chemical compound C1(=CC=CC=C1)C(CC1=CC=C(C=C1)C)C(=O)C(CC1=CC=C(C=C1)C)C1=CC=CC=C1 WZLQGMKARRCAMX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- ANWCXEDEGDPSNU-UHFFFAOYSA-N fluorobenzene;propan-2-one Chemical compound CC(C)=O.FC1=CC=CC=C1 ANWCXEDEGDPSNU-UHFFFAOYSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000004714 phosphonium salts Chemical class 0.000 description 2
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 description 2
- 150000003613 toluenes Chemical class 0.000 description 2
- VMHYWKBKHMYRNF-UHFFFAOYSA-N (2-chlorophenyl)-phenylmethanone Chemical compound ClC1=CC=CC=C1C(=O)C1=CC=CC=C1 VMHYWKBKHMYRNF-UHFFFAOYSA-N 0.000 description 1
- HKFLWLGSDNGYNN-UHFFFAOYSA-N 1-butyl-2-chlorobenzene Chemical group CCCCC1=CC=CC=C1Cl HKFLWLGSDNGYNN-UHFFFAOYSA-N 0.000 description 1
- QGRPVMLBTFGQDQ-UHFFFAOYSA-N 1-chloro-2-methoxybenzene Chemical compound COC1=CC=CC=C1Cl QGRPVMLBTFGQDQ-UHFFFAOYSA-N 0.000 description 1
- QQLIGMASAVJVON-UHFFFAOYSA-N 1-naphthalen-1-ylethanone Chemical compound C1=CC=C2C(C(=O)C)=CC=CC2=C1 QQLIGMASAVJVON-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- XSAYZAUNJMRRIR-UHFFFAOYSA-N 2-acetylnaphthalene Chemical compound C1=CC=CC2=CC(C(=O)C)=CC=C21 XSAYZAUNJMRRIR-UHFFFAOYSA-N 0.000 description 1
- VDXLAYAQGYCQEO-UHFFFAOYSA-N 2-chloro-1,3-dimethylbenzene Chemical group CC1=CC=CC(C)=C1Cl VDXLAYAQGYCQEO-UHFFFAOYSA-N 0.000 description 1
- YOMBUJAFGMOIGS-UHFFFAOYSA-N 2-fluoro-1-phenylethanone Chemical compound FCC(=O)C1=CC=CC=C1 YOMBUJAFGMOIGS-UHFFFAOYSA-N 0.000 description 1
- GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- URBHJJGWUIXBFJ-UHFFFAOYSA-N [C].[Cl] Chemical compound [C].[Cl] URBHJJGWUIXBFJ-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical group [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000002896 organic halogen compounds Chemical class 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- NRNHJIRMWBDTJE-UHFFFAOYSA-N pentan-3-one;toluene Chemical compound CCC(=O)CC.CC1=CC=CC=C1 NRNHJIRMWBDTJE-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- C07F9/59—Hydrogenated 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
- B01J31/18—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
- B01J31/189—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 containing both nitrogen and phosphorus as complexing atoms, including e.g. phosphino moieties, in one at least bidentate or bridging ligand
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5022—Aromatic phosphines (P-C aromatic 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
- 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
-
- 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
- B01J2531/824—Palladium
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
本发明涉及2-烷氧基-6-氨基苯基二烷基膦及其合成方法和在钯催化的芳基氯化物与酮的偶联反应中的应用。本发明的2-烷氧基-6-氨基苯基二烷基膦，在反应体系中与钯催化剂进行配位，可以高选择性的激活惰性碳-氯键，并与体系中的酮的α-位发生反应得到对应的偶联化合物。本发明简洁一步合成在空气中能稳定存在的2-烷氧基-6-氨基苯基二烷基膦，与其他已知的用于碳-氯键活化的配体的合成方法相比，本发明的合成方法路线短，操作简单。
Description
技术领域
本发明涉及一种2-烷氧基-6-氨基苯基二烷基膦，简洁一步合成的方法，以及其在钯催化的芳基氯化物与酮的偶联反应中的应用。具体的讲就是合成在空气中能稳定存在的2-烷氧基-6-氨基苯基二烷基膦，利用其在反应体系内与钯催化剂进行配位进而高选择性的激活惰性碳-氯键并与体系中的酮发生偶联的方法。
背景技术
有机卤化物是有机合成中的重要砌块。然而在以往的应用中，人们往往是利用昂贵但活性相对较高的有机溴化物和碘化物来进行偶联反应构建目标分子(Chem. Rev. 1994, 94, 1047)。目前，虽然已经有一些芳基氯化物与酮的偶联反应的报道(Acc. Chem. Res.2003, 36, 234; Angew. Chem. Int. Ed.2010, 49, 676; Chem. Rev.2010, 110, 1082.)，但是依然存在着如下问题：
1、绝大多数的催化体系配体结构复杂、合成不便因此导致了高成本。
2、在不少催化体系中，无法对含有乙酰基的酮类进行高选择性单芳基化反应。
3、对于丙酮的芳基化反应研究较少，许多吸电子取代的芳基氯化物并不能利用前人的方法引入到丙酮羰基的α-位。
本发明旨在公开一种新型有机膦配体，并解决该领域当前存在的问题。
发明内容
本发明是针对现有技术的不足之处，提供一类新型的有机膦盐——2-烷氧基-6-氨基苯基二烷基膦及其制备方法以及上述有机膦与钯催化的高选择性的实现芳基氯化物与酮的偶联方法。
本发明的具体技术方案如下：
一种2-烷氧基-6-氨基苯基二烷基膦， 2-烷氧基-6-氨基苯基二烷基膦的结构式如下：
结构式中，R1，R2为：异丙基、环戊基、叔丁基、环己基、金刚烷基；R3为烷基、芳基，R4， R5为烷基、芳基；R6为取代的烷基、烷氧基、芳基、胺基、巯基、羰基、腈基，取代基的位置不固定，数量为0-3。
本发明所述的2-烷氧基-6-氨基苯基二烷基膦的制备方法，以三氯化磷，烷基氯化镁，取代烷氧基苯胺和正丁基锂为原料，用取代烷氧基苯胺与丁基锂在四氢呋喃中得到对应的锂试剂与烷基氯化镁和三氯化磷生成的二烷基氯化膦反应，生成芳基二烷基膦，通过重结晶得到对应的2-烷氧基-6-氨基苯基二烷基膦。
2-烷氧基-6-氨基苯基二烷基膦是通过下述步骤获得：
1）用取代烷氧基苯胺与丁基锂在有机溶剂正己烷中80 oC反应2~15小时得到对应的锂试剂；
2）将上述的锂试剂与二烷基氯化膦R1R2PCl在-78 oC~80 oC下反应2~10小时，生成2-烷氧基-6-氨基苯基二烷基膦；所述的二烷基氯化膦和取代烷氧基苯胺基锂的摩尔比为0.8~1.2：1；
上述的R1、R2、R3、R4、R5和R6如权利要求1所述。
本发明所述的2-烷氧基-6-氨基苯基二烷基膦经过重结晶纯化。
典型的反应式如下：
反应式中，R1，R2为：异丙基、叔丁基、环戊基、环己基、金刚烷基；R3为烷基、芳基，R4, R5为烷基、芳基；R6为烷基、烷氧基、芳基、氨基、巯基、羰基、腈基，数量为0-3。
本发明所述的2-烷氧基-6-氨基苯基二烷基膦用于芳基氯化物与酮的偶联反应反应制备偶联化合物，在惰性气体保护条件下、80~120 °C和有机溶剂中，碱、钯、2-烷氧基-6-氨基苯基二烷基膦、酮和芳基氯化物反应0.6~50小时得到对应的偶联产物；碱，钯，2-烷氧基-6-氨基苯基二烷基膦，酮，芳基氯化物当量比为1.0~4.0：0.01~0.05：0.015~0.075：1.0~4.0：1.0；有机溶剂为甲苯、苯、二甲苯、二氧六环或丙酮；碱为碳酸钾、磷酸钾、碳酸铯、叔丁醇钠、叔丁醇钾或氟化铯；钯为醋酸钯、氯化钯、二亚苄基丙酮钯、肉桂基氯化钯或烯丙基氯化钯；2-烷氧基-6-氨基苯基二烷基膦如权利要求1所述；芳基氯化物是R7取代的氯苯；酮为R8COCH2R9；R7为邻、间、对位取代的烷基、胺基或烷氧基；R8为各种取代的芳基、烷基及杂环基；R9为氢、各种取代的芳基、烷基及杂环基。
典型的芳基氯化物与酮的偶联方法可以采用如下反应式表示：
R7为邻、间、对位取代的烷基、氨基或烷氧基；R8为各种取代的芳基、烷基及杂环基；R9为氢、各种取代的芳基、烷基及杂环基；所述的有机溶剂为甲苯、苯、二甲苯、二氧六环、丙酮；所述的碱为碳酸钾、磷酸钾、碳酸铯、叔丁醇钠、叔丁醇钾或氟化铯；所述的钯为醋酸钯、氯化钯、二亚苄基丙酮钯、肉桂基氯化钯、烯丙基氯化钯；有机膦盐为2-烷氧基-6-氨基苯基二烷基膦。
本发明的有益效果如下：
本发明的2-烷氧基-6-氨基苯基二烷基膦与钯催化剂进行配位可以高选择性的激活惰性碳-氯键，并与体系中的酮的α-位发生偶联反应，得到对应的产物。与其他已知的用于这种反应的配体的合成方法相比，本发明的合成方法路线短，操作简单，这无疑具有很高的研究意义及实用价值。
本发明涉及一类新型有机膦的合成以及其在芳基氯化物与酮的偶联反应中的应用。具体说是合成空气中能稳定存在的2-烷氧基-6-氨基苯基二烷基膦，利用其与钯催化剂进行配位，从而对sp2碳-氯键进行高选择性激活，并与体系中的酮的α-位发生偶联反应。
本发明简洁一步合成了空气中能稳定存在的2-烷氧基-6-氨基苯基二烷基膦，发展了一种高效制备可用于惰性碳-氯键活化反应的新型有机膦化合物（2-烷氧基-6-氨基苯基二烷基膦）以及在芳基氯化物与酮的偶联反应中的应用，与其他已知的用于碳-氯键活化的配体的合成方法相比，本发明的合成方法路线短，操作简单。
具体实施方式
以下实施例有助于理解本发明，但不限于本发明的内容。
实施例1 . 2-甲氧基-6-哌啶基苯基二环己基膦
在氮气保护下，向2 mL 2-甲氧基-6-哌啶基苯(385.1 mg, 2 mmol)的正己烷溶液中滴加正丁基锂的正己烷溶液(0.83 mL, 2.5 M, 2 mmol)，滴毕80 oC油浴加热回流3小时。待反应体系冷却至室温后，向其中加入4 mL Cy2PCl (232.7 mg, 1 mmol)的THF溶液，室温搅拌13小时并用10 mL水淬灭。混合物用50 mL×2的乙酸乙酯萃取，20 mL饱和食盐水洗涤，无水硫酸钠干燥。硅胶柱层析(PE/EA/Et3N = 100/1/1)得产物2-甲氧基-6-哌啶基苯基二环己基膦 300.4 mg，产率77%。固体。
m.p.: 100.6-101.2 oC (methanol); 1H NMR (300 MHz, CDCl3) δ 7.28-7.15 (m, 1H, ArH), 6.75-6.65 (m, 1H, ArH), 6.60-6.50 (m, 1H, ArH), 3.78 (s, 3H, CH3), 2.98-2.89 (m, 4H, 2×CH2), 2.40-2.20 (m, 2H, 2×CH), 2.00-1.83 (m, 2H, CH2), 1.83-1.49 (m, 12H, 6×CH2), 1.49-1.07 (m, 10H, CH2), 1.07-0.88 (m, 2H, CH2); 13C NMR (75 MHz, CDCl3) δ 163.3 (d, J = 2.6 Hz), 162.4 (d, J = 18.7 Hz), 130.2, 120.5 (d, J = 27.4 Hz), 113.1 (d, J = 3.2 Hz), 106.0, 55.04, 54.96, 34.8 (d, J = 13.7 Hz), 32.5 (d, J = 24.2 Hz), 30.5 (d, J = 9.7 Hz), 27.4 (d, J = 7.1 Hz), 27.1 (d, J = 13.5 Hz), 26.5, 25.9, 24.3; 31P NMR (121 MHz, CDCl3) δ -3.74; IR (KBr) ν (cm-1) 2932, 2911, 2845, 2806, 1578, 1568, 1455, 1423, 1380, 1253, 1231, 1217, 1113, 1084, 1027, 1003; MS (70 eV, EI) m/z (%): 388 (M++1, 5.04), 387 (M+, 20.03), 222 (100); Anal. Calcd. for C24H38NOP: C, 74.38; H, 9.88; N, 3.61. Found: C, 74.06; H, 9.96; N, 3.70.
实施例2 . 2-甲氧基-6-(N’-甲基-N’-苯基氨基)苯基二环己基膦
在氮气保护下，向溶有2-甲氧基-6-(N’-甲基-N’-苯基氨基)苯 (9.5482 g，45 mmol)的45 mL干燥的正己烷溶液中滴入正丁基锂的正己烷溶液(18.8 mL，2.5 M，45 mmol)。滴毕后80 oC油浴加热2小时备用。
-40oC下，向氮气保护的溶有三氯化磷(2.61 mL，30 mmol)的100 mL干燥四氢呋喃溶液中滴入环己基氯化镁乙醚溶液(75 mL，0.88 M，66 mmol)，滴毕后室温下搅拌7小时。将上步合成的2-甲氧基-6-(N’-甲基-N’-苯基氨基)苯基锂溶液一次性倒入其中，并保持80 oC油浴加热搅拌12小时。反应体系冷却后用100 mL水淬灭。加入100 mL二氯甲烷、20 mL 5%的稀盐酸，分液，水层用2×100 mL的二氯甲烷萃取，有机层合并后用100 mL饱和碳酸氢钠溶液洗涤，无水硫酸钠干燥。利用甲醇/乙酸乙酯体系重结晶得到最终产物2-甲氧基-6-(N’-甲基-N’-苯基氨基)苯基二环己基膦6.3588 g，产率52%。白色固体。
m. p.: 169.1-170.4 oC (methanol/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.36 (t, J = 8.0 Hz, 1H, ArH), 7.20-7.10 (m, 2H, ArH), 6.82-6.76 (m, 2H, ArH), 6.71-6.65 (m, 1H, ArH), 6.54 (d, J = 8.1 Hz, 2H, ArH), 3.87 (s, 3H, OCH3), 3.22 (s, 3H, NCH3), 2.41-2.26 (m, 2H, 2×CH), 1.91-1.55 (m, 8H, 4×CH2), 1.40-0.86 (m, 12H, 6×CH2); 13C NMR (75 MHz, CDCl3) δ 163.8 (d, J = 3.3 Hz), 156.7 (d, J = 23.8 Hz), 149.8, 131.6, 128.4, 125.3 (d, J = 26.9 Hz), 121.8 (d, J = 3.9 Hz), 116.2, 113.3, 108.5, 55.3, 41.0 (d, J = 7.4 Hz), 35.0 (d, J = 12.0 Hz), 32.9 (d, J = 25.0 Hz), 30.9 (d, J = 8.1 Hz), 27.6 (d, J = 8.1 Hz), 27.1 (d, J = 14.2 Hz), 26.3; 31P NMR (121 MHz, CDCl3) δ -3.77; IR (KBr) ν (cm-1) 2914, 2846, 1601, 1582, 1499, 1472, 1455, 1439, 1347, 1247, 1185, 1106, 1079, 1055; MS (70 eV, EI) m/z (%): 410 (M++1, 2.02), 409 (M+, 9.31), 245 (100); Anal. Calcd. for C26H36NOP: C, 76.25; H, 8.86; N, 3.42. Found: C, 76.02; H, 8.88; N, 3.55.
实施例3. 1-苯基-2-(对甲氧苯基)-1-丙酮
在氮气保护下，向反应器中依次加入醋酸钯(6.7 mg, 0.030 mmol), 2-烷氧基-6-氨基苯基二烷基膦 (18.3 mg, 0.045 mmol), 叔丁醇钠 (115.4 mg, 1.2 mmol), 对氯苯甲醚(142.1 mg, 1.0 mmol)及1.5 mL无水甲苯，室温下搅拌约2 min。随后向体系中加入苯丙酮(160.9 mg, 1.2 mmol)及另外1.5 mL无水甲苯。反应器加热到110 oC并保持17.5小时。随后冷却，加入10 mL乙醚淬灭。混合物转移至分液漏斗中，并用10 mL乙醚、10 mL 5%的稀盐酸洗涤反应器。分液，水层用乙醚(10 mL×2)萃取，有机层合并后用20 mL饱和食盐水洗涤，无水硫酸钠干燥。过滤、浓缩后快速柱层析得到产物1-苯基-2-(对甲氧苯基)-1-丙酮209.3 mg，产率87%。液体。
1H NMR (300 MHz, CDCl3) δ 8.00-7.92 (m, 2H, ArH), 7.52-7.43 (m, 1H, ArH), 7.42-7.35 (m, 2H, ArH), 7.24-7.18 (m, 2H, ArH), 6.86-6.80 (m, 2H, ArH), 4.65 (q, J = 6.9 Hz, 1H, CH), 3.75 (s, 3H, OCH3), 1.52 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 200.5, 158.4, 136.5, 133.4, 132.6, 128.73, 128.69, 138.4, 114.3, 55.1, 46.9, 19.5; IR (neat) ν (cm-1) 3061, 2972, 2931, 2836, 1682, 1609, 1596, 1511, 1448, 1302, 1248, 1221, 1178, 1034, 1002; MS (70 eV, EI) m/z (%): 240 (M+, 4.46), 135 (100).
实施例3. 1-苯基-2-(间甲氧苯基)-1-丙酮
操作方法同实验实施例3。3-氯苯甲醚 (143.4 mg, 1.0 mmol)，苯丙酮 (160.6 mg, 1.2 mmol)，醋酸钯(6.6 mg, 0.029 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，叔丁醇钠(115.0 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(间甲氧苯基)-1-丙酮212.6 mg，产率88%。液体。
1H NMR (300 MHz, CDCl3) δ 8.02-7.96 (m, 2H, ArH), 7.46-7.39 (m, 1H, ArH), 7.38-7.30 (m, 2H, ArH), 7.21 (t, J = 8.0 Hz, 1H, ArH), 6.94-6.88 (m, 2H, ArH), 6.77-6.72 (m, 1H, ArH), 4.69 (q, J = 6.9 Hz, 1H, CH), 3.71 (s, 3H, OCH3), 1.56 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 199.8, 159.8, 142.8, 136.2, 132.5, 129.7, 128.5, 128.2, 119.9, 113.3, 111.8, 54.8, 47.6, 19.2; IR (neat) ν (cm-1) 3059, 2973, 2932, 2835, 1682, 1598, 1486, 1455, 1372, 1312, 1263, 1215, 1181, 1149, 1045, 1002; MS (70 eV, EI) m/z (%): 241 (M++1, 2.10), 240 (M+, 11.90), 105 (100).
实施例3 . 1-苯基-2-(间甲苯基)-1-丙酮
操作方法同实验实施例3。3-氯甲苯 (126.6 mg, 1.0 mmol)，苯丙酮 (161.1 mg, 1.2 mmol)，醋酸钯(6.6 mg, 0.029 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，叔丁醇钠(115.4 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(间甲苯基)-1-丙酮190.0 mg，产率85%。液体。
1H NMR (300 MHz, CDCl3) δ 8.10-7.94 (m, 2H, ArH), 7.52-7.44 (m, 1H, ArH), 7.44-7.35 (m, 2H, ArH), 7.25-7.18 (m, 1H, ArH), 7.17-7.10 (m, 2H, ArH), 7.07-7.02 (m, 1H, ArH), 4.69 (q, J = 6.8 Hz, 1H, CH), 2.33 (s, 3H, ArCH3), 1.57 (d, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 200.2, 141.3, 138.5, 136.4, 132.6, 128.73, 128.66, 128.3, 128.2, 127.6, 124.8, 47.7, 21.3, 19.4; IR (neat) ν (cm-1) 3058, 3025, 2975, 2930, 2870, 1682, 1605, 1596, 1583, 1488, 1448, 1372, 1338, 1238, 1208, 1181, 1158, 1075, 1002; MS (70 eV, EI) m/z (%): 224 (M+, 4.20), 105 (100).
实施例4 . 1-(对甲氧苯基)-2-(对甲氧苯基)-1-丙酮
操作方法同实验实施例3。4-氯苯甲醚(142.7 mg, 1.0 mmol)，对甲氧基苯丙酮 (195.8 mg, 1.2 mmol)，醋酸钯(6.6 mg, 0.029 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.2 mg, 0.045 mmol)，叔丁醇钠(115.9 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(对甲氧苯基)-2-(对甲氧苯基)-1-丙酮272.1 mg，产率100%。液体。
1H NMR (300 MHz, CDCl3) δ 7.99-7.92 (m, 2H, ArH), 7.24-7.18 (m, 2H, ArH), 6.87-6.79 (m, 4H, ArH), 4.61 (q, J = 6.9 Hz, 1H, CH), 3.76 (s, 3H, OCH3), 3.71 (s, 3H, OCH3), 1.50 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 198.9, 163.0, 158.2, 133.8, 130.8, 129.2, 128.5, 114.1, 113.5, 55.1, 54.9, 46.3, 19.4; IR (neat) ν (cm-1) 2969, 2932, 2837, 1668, 1600, 1574, 1514, 1455, 1419, 1371, 1303, 1258, 1169, 1114, 1032; MS (70 eV, EI) m/z (%): 270 (M+, 4.28), 135 (100).
实施例5 . 1-(对甲苯基)-2-苯基-1-丙酮
操作方法同实验实施例3。氯苯 (111.0 mg, 0.99 mmol)，对甲苯丙酮 (177.8 mg, 1.2 mmol)，醋酸钯(6.7 mg, 0.030 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，叔丁醇钠(115.8 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(对甲苯基)-2-苯基-1-丙酮216.5 mg (经1H NMR分析，有11.9%对甲苯丙酮)，产率90%。液体。
1H NMR (300 MHz, CDCl3) δ 7.87-7.80 (m, 2H, ArH), 7.30-7.20 (m, 4H, ArH), 7.20-7.08 (m, 3H, ArH), 4.64 (q, J = 7.0 Hz, 1H, CH), 2.27 (s, 3H, ArCH3), 1.50 (d, J = 7.0 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 199.7, 143.3, 141.6, 133.7, 129.0, 128.74, 128.72, 127.5, 126.6, 47.5, 21.3, 19.3; IR (neat) ν (cm-1) 3061, 3028, 2975, 2930, 2870, 1682, 1606, 1570, 1492, 1452, 1408, 1372, 1332, 1304, 1253, 1225, 1210, 1177, 1008; MS (70 eV, EI) m/z (%): 224 (M+, 0.64), 119 (100).
实施例6 1-苯基-2-(邻甲氧苯基)-1-丙酮
操作方法同实验实施例3。2-氯苯甲醚 (144.1 mg, 1.0 mmol)，苯丙酮 (161.3 mg, 1.2 mmol)，醋酸钯(6.7 mg, 0.030 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，叔丁醇钠(115.5 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(邻甲氧苯基)-1-丙酮198.8 mg，产率80%。液体。
1H NMR (300 MHz, CDCl3) δ 8.04-7.98 (m, 2H, ArH), 7.50-7.42 (m, 1H, ArH), 7.41-7.33 (m, 2H, ArH), 7.24-7.13 (m, 2H, ArH), 6.92-6.86 (m, 2H, ArH), 5.13 (q, J = 6.9 Hz, 1H, CH), 3.87 (s, 3H, OCH3), 1.51 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 201.2, 155.6, 136.4, 132.4, 130.0, 128.4, 128.2, 127.9, 120.9, 110.7, 55.3, 40.2, 17.5; IR (neat) ν (cm-1) 3063, 2974, 2933, 2871, 2837, 1682, 1597, 1584, 1493, 1449, 1371, 1326, 1291, 1245, 1222, 1182, 1113, 1061, 1050, 1028, 1002; MS (70 eV, EI) m/z (%): 241 (M++1, 1.81), 240 (M+, 9.60), 135 (100).
实施例7 . 1-(对氟苯基)-2-(对甲氧苯基)-1-丙酮
操作方法同实验实施例3。4-氯苯甲醚 (142.8 mg, 1.0 mmol)，对氟苯丙酮(183.5 mg, 1.2 mmol)，醋酸钯(6.7 mg, 0.030 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.3 mg, 0.045 mmol)，叔丁醇钠(115.6 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(对氟苯基)-2-(对甲氧苯基)-1-丙酮206.7 mg，产率80%。液体。
1H NMR (300 MHz, CDCl3) δ 8.01-7.93 (m, 2H, ArH), 7.22-7.15 (m, 2H, ArH), 7.14-6.99 (m, 2H, ArH), 6.87-6.80 (m, 2H, ArH), 4.59 (q, J = 7.0 Hz, 1H, CH), 3.74 (s, 3H, OCH3), 1.50 (d, J = 7.0 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 198.8, 165.3 (d, J = 252.7 Hz), 158.5, 133.3, 132.8 (d, J = 2.6 Hz), 131.3 (d, J = 8.6 Hz), 128.6, 115.4 (d, J = 21.2 Hz), 114.4, 55.1, 47.0, 19.4; 19F NMR (282 MHz, CDCl3) δ -105.7; IR (neat) ν (cm-1) 3071, 2974, 2932, 2869, 2837, 1682, 1598, 1514, 1505, 1455, 1409, 1372, 1336, 1302, 1247, 1180, 1157, 1114, 1101, 1035, 1006; MS (70 eV, EI) m/z (%): 259 (M++1, 1.10), 258 (M+, 6.27), 135 (100); HRMS calcd for C16H15O2F (M+): 258.1056. Found: 258.1057.
实施例8 . 1-(邻氟苯基)-2-(对甲氧苯基)-1-丙酮
操作方法同实验实施例3。4-氯苯甲醚(142.3 mg, 1.0 mmol)，邻氟苯丙酮(304.2 mg, 2.0 mmol)，醋酸钯(6.8 mg, 0.030 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，叔丁醇钠(192.7 mg, 2.0 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(邻氟苯基)-2-(对甲氧苯基)-1-丙酮134.7 mg，产率52%。液体。
1H NMR (300 MHz, CDCl3) δ 7.76-7.68 (m, 1H, ArH), 7.44-7.34 (m, 1H, ArH), 7.20-7.08 (m, 3H, ArH), 7.07-6.98 (m, 1H, ArH), 6.83-6.77 (m, 2H, ArH), 4.57 (q, J = 6.9 Hz, 1H, CH), 3.73 (s, 3H, OCH3), 1.52 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 199.8 (d, J = 3.8 Hz), 160.7 (d, J = 251.9 Hz), 158.5, 133.8 (d, J = 8.8 Hz), 132.3, 130.9 (d, J = 2.8 Hz), 129.1, 126.0 (d, J = 12.8 Hz), 124.2 (d, J = 3.9 Hz), 116.4 (d, J = 23.7 Hz), 114.0, 55.0, 50.9 (d, J = 5.9 Hz), 18.8; 19F NMR (282 MHz, CDCl3) δ -100.1; IR (neat) ν (cm-1) 3069, 3034, 2974, 2933, 2871, 2836, 1682, 1609, 1582, 1513, 1480, 1451, 1422, 1373, 1324, 1303, 1274, 1254, 1211, 1179, 1153, 1105, 1034, 1005; MS (70 eV, EI) m/z (%): 259 (M++1, 0.99), 258 (M+, 5.49), 135 (100); HRMS calcd for C16H15O2F (M+): 258.1056. Found: 258.1057.
实施例9 . 1-苯基-2-(间N,N-二甲基氨基苯基)-1-丙酮
操作方法同实验实施例3。3-(N,N-二甲基氨基)氯苯(155.9 mg, 1.0 mmol)，苯丙酮(160.9 mg, 1.2 mmol)，醋酸钯(6.7 mg, 0.030 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，叔丁醇钠(116.1 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(间N,N-二甲基氨基苯基)-1-丙酮200.7 mg，产率79%。液体。
11H NMR (300 MHz, CDCl3) δ 8.03-7.97 (m, 2H, ArH), 7.52-7.44 (m, 1H, ArH), 7.43-7.35 (m, 2H, ArH), 7.20-7.11 (m, 1H, ArH), 6.65-6.55 (m, 3H, ArH), 4.19 (s, 2H, CH2), 2.87 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 197.7, 150.6, 136.4, 135.1, 132.8, 129.1, 128.5, 128.4, 117.4, 113.1, 110.9, 45.9, 40.3; IR (neat) ν (cm-1) 3056, 2891, 2804, 1679, 1601, 1579, 1501, 1447, 1354, 1330, 1276, 1205, 1180, 1155, 1062; MS (70 eV, EI) m/z (%): 240 (M++1, 10.27), 239 (M+, 54.99), 105 (100); HRMS calcd for C16H17NO (M+): 239.1310. Found: 239.1309.
实施例10 . 1-对甲氧苯基-2-(对氟苯基)-1-丙酮
操作方法同实验实施例3。对氟氯苯 (130.2 mg, 1.0 mmol)，对甲氧基苯丙酮(198.4 mg, 1.2 mmol)，醋酸钯(11.1 mg, 0.050 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (30.8 mg, 0.075 mmol)，叔丁醇钠(115.0 mg, 1.2 mmol)及3 mL干燥甲苯，110 oC下反应得到1-对甲氧苯基-2-(对氟苯基)-1-丙酮252.8 mg (经1H NMR分析，有19%对甲氧基苯丙酮)，产率85%。固体。
m.p.: 83.3-84.0 oC (正己烷/乙酸乙酯); 1H NMR (300 MHz, CDCl3) δ 7.98-7.89 (m, 2H, ArH), 7.29-7.20 (m, 2H, ArH), 7.00-6.81 (m, 4H, ArH), 4.64 (q, J = 6.9 Hz, 1H, CH), 3.76 (s, 3H, OCH3), 1.49 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 198.5, 163.1, 159.9, 137.4 (d, J = 2.9 Hz), 130.8, 129.0 (d, J = 8.6 Hz), 128.9, 115.5 (d, J = 21.0 Hz), 113.5, 55.2, 46.3, 19.4; 19F NMR (282 MHz, CDCl3) δ -115.9; IR (KBr) ν (cm-1) 3072, 2975, 2934, 2840, 1674, 1600, 1574, 1510, 1456, 1419, 1373, 1338, 1311, 1258, 1225, 1171, 1114, 1030; MS (70 eV, EI) m/z (%): 258 (M+, 0.32), 135 (100); Anal. Calcd. for C16H15FO2: C, 74.40; H, 5.85. Found: C, 74.23; H, 5.82.
实施例11. 1-苯基-2-(对甲氧苯基)-1-乙酮
操作方法同实验实施例3。对氯苯甲醚(142.2 mg, 1.0 mmol)，苯乙酮 (302.1 mg, 2.5 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，三水磷酸钾(664.0 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(对甲氧苯基)-1-乙酮177.3 mg，产率79%。固体。
m.p.: 94.1-94.4 oC (正己烷); 1H NMR (300 MHz, CDCl3) δ 8.07-8.00 (m, 2H, ArH), 7.60-7.51 (m, 1H, ArH), 7.51-7.42 (m, 2H, ArH), 7.25-7.17 (m, 2H, ArH), 6.92-6.86 (m, 2H, ArH), 4.24 (s, 2H, CH2), 3.78 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3) δ 197.8, 158.3, 136.4, 132.9, 130.3, 128.45, 128.41, 126.3, 113.9, 55.0, 44.4; IR (KBr) ν (cm-1) 3056, 2998, 2954, 2934, 2905, 2835, 1691, 1612, 1596, 1579, 1514, 1463, 1447, 1411, 1335, 1301, 1245, 1218, 1204, 1178, 1107, 1035; MS (70 eV, EI) m/z (%): 227 (M++1, 3.58), 226 (M+, 21.25), 121 (100).
实施例12 . 1-苯基-2-(对甲苯基)-1-乙酮
操作方法同实验实施例3。对氯甲苯(125.6 mg, 1.0 mmol)，苯乙酮(300.1 mg, 2.5 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.3 mg, 0.045 mmol)，三水磷酸钾(665.8 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(对甲苯基)-1-乙酮140.5 mg，产率67% (petroleum ether/ethyl acetate = 20/1后正己烷重结晶)。固体。
m.p.: 95.8-96.1 oC(正己烷); 1H NMR (300 MHz, CDCl3) δ 8.07-8.00 (m, 2H, ArH), 7.62-7.53 (m, 1H, ArH), 7.52-7.43 (m, 2H, ArH), 7.22-7.13 (m, 4H, ArH), 4.27 (s, 2H, CH2), 2.35 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 197.7, 136.5, 136.3, 133.0, 131.3, 129.3, 129.2, 128.5, 45.0, 21.0; IR (KBr) ν (cm-1) 3051, 3024, 2896, 1686, 1592, 1578, 1515, 1448, 1406, 1335, 1221, 1209, 1197, 1181; MS (70 eV, EI) m/z (%): 211 (M++1, 0.65), 210 (M+, 3.47), 105 (100).
实施例13 . 1-苯基-2-(间甲氧苯基)-1-乙酮
操作方法同实验实施例3。间氯苯甲醚 (142.7 mg, 1.0 mmol)，苯乙酮(299.9 mg, 2.5 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.5 mg, 0.045 mmol)，三水磷酸钾(663.9 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(间甲氧苯基)-1-乙酮189.0 mg，产率84%。液体。
1H NMR (300 MHz, CDCl3) δ 8.02-7.96 (m, 2H, ArH), 7.55-7.47 (m, 1H, ArH), 7.46-7.38 (m, 2H, ArH), 7.21 (t, J = 7.8 Hz, 1H, ArH), 6.87-6.73 (m, 3H, ArH), 4.22 (s, 2H, CH2), 3.73 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3) δ 197.3, 159.6, 136.3, 135.9, 133.0, 129.5, 128.47, 128.45, 121.6, 115.0, 112.2, 55.0, 45.4; IR (neat) ν (cm-1) 3058, 3002, 2938, 2835, 1682, 1597, 1490, 1448, 1317, 1263, 1211, 1153, 1050, 1020, 1001; MS (70 eV, EI) m/z (%): 227 (M++1, 2.28), 226 (M+, 12.78), 105 (100).
实施例14 . 1-(2’-萘基)-2-(间甲氧苯基)-1-乙酮
操作方法同实验实施例3。间氯苯甲醚 (143.3 mg, 1.0 mmol)，2-萘乙酮 (426.3 mg, 2.5 mmol)，肉桂基氯化钯(7.9 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.5 mg, 0.045 mmol)，三水磷酸钾(665.3 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(2’-萘基)-2-(间甲氧苯基)-1-乙酮222.0 mg，产率80%。固体。
m.p.: 67.3-68.4 oC (正己烷/乙酸乙酯); 1H NMR (300 MHz, CDCl3) δ 8.49 (s, 1H, ArH), 8.05-7.99 (m, 1H, ArH), 7.92-7.86 (m, 1H, ArH), 7.85-7.77 (m, 2H, ArH), 7.59-7.45 (m, 2H, ArH), 7.21 (t, J = 7.8 Hz, 1H, ArH), 6.91-6.82 (m, 2H, ArH), 6.80-6.73 (m, 1H, ArH), 4.32 (s, 2H, CH2), 3.72 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3) δ 197.3, 159.6, 136.0, 135.4, 133.7, 132.3, 130.3, 129.5, 129.4, 128.4, 128.3, 127.6, 126.6, 124.1, 121.7, 115.0, 112.2, 55.0, 45.4; IR (KBr) ν (cm-1) 3056, 2937, 2835, 1677, 1625, 1597, 1584, 1561, 1490, 1467, 1437, 1383, 1352, 1265, 1152, 1123, 1048; MS (70 eV, EI) m/z (%): 277 (M++1, 2.13), 276 (M+, 9.94), 155 (100); Anal. Calcd. for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.65; H, 5.81.
实施例15 . 1-(1’-萘基)-2-(间甲氧苯基)-1-乙酮
操作方法同实验实施例3。对氯苯甲醚 (142.8 mg, 1.0 mmol)，1-萘乙酮(424.4 mg, 2.5 mmol)，肉桂基氯化钯(7.4 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.3 mg, 0.045 mmol)，三水磷酸钾(665.2 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(1’-萘基)-2-(间甲氧苯基)-1-乙酮215.1 mg，产率78%。固体。
m.p.: 74.7-75.4 oC (正己烷/乙酸乙酯); 1H NMR (300 MHz, CDCl3) δ 8.56 (d, J = 8.4 Hz, 1H, ArH), 7.91-7.84 (m, 2H, ArH), 7.82-7.75 (m, 1H, ArH), 7.53-7.36 (m, 3H, ArH), 7.20-7.12 (m, 2H, ArH), 6.86-6.77 (m, 2H, ArH), 4.23 (s, 2H, CH2), 3.67 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3) δ 201.7, 158.3, 135.3, 133.7, 132.5, 130.4, 130.2, 128.2, 127.74, 127.68, 126.31, 126.26, 125.6, 124.1, 113.9, 55.0, 47.8; IR (KBr) ν (cm-1) 3053, 3033, 3002, 2953, 2938, 2909, 2833, 1685, 1611, 1512, 1467, 1311, 1302, 1243, 1214, 1182, 1169, 1104, 1088, 1034; MS (70 eV, EI) m/z (%): 277 (M++1, 1.24), 276 (M+, 6.24), 155 (100).
实施例16 . 1-(间甲苯基)-2-(对甲氧苯基)-1-乙酮
操作方法同实验实施例3。对氯苯甲醚(141.7 mg, 1.0 mmol)，间甲苯乙酮(336.2 mg, 2.5 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，三水磷酸钾(664.9 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(间甲苯基)-2-(对甲氧苯基)-1-乙酮176.4 mg，产率74%。固体。
m.p.: 56.7-57.8 oC (n-hexane); 1H NMR (300 MHz, CDCl3) δ 7.82-7.75 (m, 2H, ArH), 7.36-7.27 (m, 2H, ArH), 7.20-7.10 (m, 2H, ArH), 6.88-6.79 (m, 2H, ArH), 4.18 (s, 2H, CH2), 3.73 (s, 3H, OCH3), 2.37 (s, 3H, ArCH3); 13C NMR (75 MHz, CDCl3) δ 198.0, 158.3, 138.2, 136.4, 133.7, 130.3, 128.9, 128.3, 126.4, 125.7, 113.9, 55.0, 44.4, 21.2; IR (KBr) ν (cm-1) 3034, 2999, 2933, 2835, 1694, 1682, 1614, 1585, 1515, 1463, 1301, 1282, 1246, 1178, 1156, 1107, 1035, 1000; MS (70 eV, EI) m/z (%): 241 (M++1, 1.89), 240 (M+, 10.02), 119 (100); Anal. Calcd. for C16H16O2: C, 79.97; H, 6.71. Found: C, 79.71; H, 6.69.
实施例17 . 1-(对氟苯基)-2-(间甲氧苯基)-1-乙酮
操作方法同实验实施例3。间氯苯甲醚 (143.7 mg, 1.0 mmol)，对氟苯乙酮(347.2 mg, 2.5 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.4 mg, 0.045 mmol)，三水磷酸钾(664.2 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-(对氟苯基)-2-(间甲氧苯基)-1-乙酮185.5 mg，产率75%。液体。
1H NMR (300 MHz, CDCl3) δ 8.05-7.98 (m, 2H, ArH), 7.27-7.18 (m, 1H, ArH), 7.12-7.04 (m, 2H, ArH), 6.86-6.75 (m, 3H, ArH), 4.20 (s, 2H, CH2), 3.75 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3) δ 195.8, 167.2, 163.9, 159.7, 135.7, 132.8, 132.7, 131.2, 131.1, 129.6, 121.6, 115.7, 115.4, 115.0, 112.2, 55.0, 45.4; 19F NMR (282 MHz, CDCl3) δ -104.9; IR (neat) ν (cm-1) 3072, 3002, 2940, 2836, 1682, 1597, 1506, 1491, 1455, 1437, 1331, 1264, 1232, 1157, 1099, 1050, 1002; MS (70 eV, EI) m/z (%): 245 (M++1, 3.27), 244 (M+, 17.36), 123 (100).
实施例18 . 1-苯基-2-(间二甲氨基苯基)-1-乙酮
操作方法同实验实施例3。3-(N,N-二甲基氨基)氯苯(156.6 mg, 1.0 mmol)，苯乙酮(299.6 mg, 2.5 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.5 mg, 0.045 mmol)，三水磷酸钾(666.4 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(间二甲氨基苯基)-1-乙酮183.9 mg，产率76%。液体。
1H NMR (300 MHz, CDCl3) δ 8.03-7.97 (m, 2H, ArH), 7.52-7.44 (m, 1H, ArH), 7.43-7.35 (m, 2H, ArH), 7.20-7.11 (m, 1H, ArH), 6.65-6.55 (m, 3H, ArH), 4.19 (s, 2H, CH2), 2.87 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 197.7, 150.6, 136.4, 135.1, 132.8, 129.1, 128.5, 128.4, 117.4, 113.1, 110.9, 45.9, 40.3; IR (neat) ν (cm-1) 3056, 2891, 2804, 1679, 1601, 1579, 1501, 1447, 1354, 1330, 1276, 1205, 1180, 1155, 1062; MS (70 eV, EI) m/z (%): 240 (M++1, 10.27), 239 (M+, 54.99), 105 (100); HRMS calcd for C16H17NO (M+): 239.1310. Found: 239.1309.
实施例19 . 1-苯基-2-(2’-甲基喹啉-7’-基)-1-乙酮
操作方法同实验实施例3。7-氯-2-甲基喹啉 (177.3 mg, 1.0 mmol)，苯乙酮(301.1 mg, 2.5 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (18.5 mg, 0.045 mmol)，三水磷酸钾(664.4 mg, 2.5 mmol)及3 mL干燥甲苯，110 oC下反应得到1-苯基-2-(2’-甲基喹啉-7’-基)-1-乙酮200.4 mg，产率77%。固体。
m.p.: 70.4-71.6 oC (正己烷/乙酸乙酯); 1H NMR (300 MHz, CDCl3) δ 8.06-8.00 (m, 2H, ArH), 7.99-7.88 (m, 2H, ArH), 7.72-7.65 (m, 1H, ArH), 7.55-7.47 (m, 1H, ArH), 7.46-7.35 (m, 3H, ArH), 7.22-7.15 (m, 1H, ArH), 4.45 (s, 2H, CH2), 2.70 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 197.0, 159.0, 147.7, 136.1, 136.0, 135.7, 133.1, 128.8, 128.5, 127.6, 127.1, 125.1, 121.7, 45.6, 25.2; IR (KBr) ν (cm-1) 3055, 2920, 2849, 1687, 1625, 1599, 1509, 1448, 1417, 1328, 1306, 1281, 1209, 1182, 1123; MS (70 eV, EI) m/z (%): 262 (M++1, 3.65), 261 (M+, 16.62), 105 (100); Anal. Calcd. for C18H15NO: C, 82.73; H, 5.79; N, 5.36. Found: C, 82.34; H, 5.91; N, 5.27.
实施例20 . 1-对甲氧苯基-2-丙酮
操作方法同实验实施例3。对氯苯甲醚 (143.2 mg, 1.0 mmol)，肉桂基氯化钯(7.9 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.5 mg, 0.060 mmol)，碳酸铯(651.0 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-对甲氧苯基-2-丙酮137.9 mg，产率84%。液体。
1H NMR (300 MHz, CDCl3) δ 7.15-7.07 (m, 2H, ArH), 6.92-6.82 (m, 2H, ArH), 3.79 (s, 3H, OCH3), 3.63 (s, 2H, CH2), 2.13 (s, 3H, COCH3); 13C NMR (75 MHz, CDCl3) δ 206.8, 158.5, 130.3, 126.1, 114.0, 55.1, 50.0, 29.0; IR (neat) ν (cm-1) 3002, 2957, 2935, 2911, 2837, 1713, 1612, 1584, 1514, 1464, 1442, 1423, 1356, 1301, 1249, 1179, 1158, 1109, 1034; MS (70 eV, EI) m/z (%): 165 (M++1, 2.58), 164 (M+, 23.60), 121 (100).
实施例21 . 1-(2’,6’-二甲苯基)-2-丙酮
操作方法同实验实施例3。2-氯间二甲苯(142.4 mg, 1.0 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.4 mg, 0.060 mmol)，碳酸铯(651.9 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(2’,6’-二甲苯基)-2-丙酮138.4 mg，产率84%。液体。
1H NMR (300 MHz, CDCl3) δ 7.15-7.03 (m, 3H, ArH), 3.79 (s, 2H, CH2), 2.27 (s, 6H, 2×ArCH3), 2.17 (s, 3H, COCH3); 13C NMR (75 MHz, CDCl3) δ 206.2, 136.7, 132.1, 128.1, 126.9, 45.0, 29.2, 20.2; IR (neat) ν (cm-1) 3021, 2922, 2867, 1715, 1589, 1470, 1446, 1415, 1379, 1357, 1317, 1223, 1158, 1095, 1053, 1031; MS (70 eV, EI) m/z (%): 163 (M++1, 3.30), 162 (M+, 27.85), 119 (100); HRMS calcd for C11H14O (M+): 162.1045. Found: 162.1046.
实施例22 . 1-(对甲苯基)-2-丙酮
操作方法同实验实施例3。对氯甲苯(127.0 mg, 1.0 mmol)，肉桂基氯化钯(7.9 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.3 mg, 0.060 mmol)，碳酸铯(652.2 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(对甲苯基)-2-丙酮100.5 mg，产率68%。液体。
1H NMR (300 MHz, CDCl3) δ 7.19-7.05 (m, 4H, ArH), 3.66 (s, 2H, CH2), 2.34 (s, 3H, ArCH3), 2.15 (s, 3H, COCH3); 13C NMR (75 MHz, CDCl3) δ 206.7, 136.6, 131.1, 129.4, 129.2, 50.6, 29.1, 21.0; IR (neat) ν (cm-1) 3023, 3004, 2922, 2857, 1714, 1615, 1514, 1417, 1356, 1229, 1158, 1040, 1023; MS (70 eV, EI) m/z (%): 149 (M++1, 3.90), 148 (M+, 31.26), 105 (100).
实施例23 . 1-(邻甲氧苯基)-2-丙酮
操作方法同实验实施例3。邻氯苯甲醚 (127.0 mg, 1.0 mmol)，肉桂基氯化钯(7.9 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.5 mg, 0.060 mmol)，碳酸铯(653.0 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(邻甲氧苯基)-2-丙酮147.7 mg，产率89%。液体。
1H NMR (300 MHz, CDCl3) δ 7.29-7.22 (m, 1H, ArH), 7.14-7.09 (m, 1H, ArH), 6.94-6.84 (m, 2H, ArH), 3.79 (s, 3H, OCH3), 3.66 (s, 2H, CH2), 2.12 (s, 3H, COCH3); 13C NMR (75 MHz, CDCl3) δ 206.9, 157.2, 131.0, 128.4, 123.5, 120.5, 110.3, 55.2, 45.4, 29.1; IR (neat) ν (cm-1) 3003, 2941, 2905, 2837, 1713, 1602, 1589, 1496, 1464, 1439, 1356, 1322, 1290, 1247, 1176, 1160, 1115, 1050, 1030; MS (70 eV, EI) m/z (%): 165 (M++1, 6.45), 164 (M+, 50.19), 91 (100).
实施例24 . 1-(对叔丁苯基)-2-丙酮
操作方法同实验实施例3。对叔丁基氯苯(167.4 mg, 0.99 mmol)，肉桂基氯化钯(7.9 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.5 mg, 0.060 mmol)，碳酸铯(652.3 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(对叔丁苯基)-2-丙酮155.3 mg，产率82%。液体。
1H NMR (300 MHz, CDCl3) δ 7.40-7.35 (m, 2H, ArH), 7.18-7.12 (m, 2H, ArH), 3.68 (s, 2H, CH2), 2.17 (s, 3H, COCH3), 1.33 (s, 9H, 3×CH3); 13C NMR (75 MHz, CDCl3) δ 206.9, 149.8, 131.0, 128.9, 125.6, 50.4, 34.4, 31.2, 29.2; IR (neat) ν (cm-1) 3027, 2962, 2905, 2869, 1713, 1514, 1463, 1416, 1394, 1357, 1326, 1269, 1229, 1203, 1158, 1110, 1020; MS (70 eV, EI) m/z (%): 191 (M++1, 4.99), 190 (M+, 30.84), 147 (100).
实施例25 . 1-(间二甲氨基苯基)-2-丙酮
操作方法同实验实施例3。间二甲氨基氯苯(156.0 mg, 0.99 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.6 mg, 0.060 mmol)，碳酸铯(653.2 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(间二甲氨基苯基)-2-丙酮122.2 mg，产率69%。液体。
1H NMR (300 MHz, CDCl3) δ 7.21 (t, J = 7.8 Hz, 1H, ArH), 6.69-6.62 (m, 1H, ArH), 6.61-6.53 (m, 2H, ArH), 3.64 (s, 2H, CH2), 2.95 (s, 6H, N(CH3)2), 2.15 (s, 3H, COCH3); 13C NMR (75 MHz, CDCl3) δ 207.0, 150.7, 135.0, 129.3, 117.4, 113.1, 111.1, 51.6, 40.4, 28.9; IR (neat) ν (cm-1) 3033, 2916, 2805, 1712, 1603, 1580, 1504, 1440, 1354, 1271, 1229, 1178, 1156, 1062; MS (70 eV, EI) m/z (%): 178 (M++1, 9.69), 177 (M+, 73.88), 134 (100).
实施例26 . 1-(2’-甲基喹啉-7’-基)-2-丙酮
操作方法同实验实施例3。2-甲基-7-氯喹啉(177.7 mg, 1.0 mmol)，肉桂基氯化钯(7.9 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.5 mg, 0.060 mmol)，碳酸铯(652.2 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(2’-甲基喹啉-7’-基)-2-丙酮162.0 mg，产率81%。固体。
m.p.: 68.7-69.6 oC(正己烷/乙酸乙酯); 1H NMR (300 MHz, CDCl3) δ 8.06-7.99 (m, 1H, ArH), 7.86 (s, 1H, ArH), 7.77-7.71 (m, 1H, ArH), 7.38-7.24 (m, 2H, ArH), 3.89 (s, 2H, CH2), 2.74 (s, 3H, ArCH3), 2.20 (s, 3H, COCH3); 13C NMR (75 MHz, CDCl3) δ 205.8, 159.3, 147.8, 135.8, 135.7, 128.9, 127.8, 127.1, 125.3, 121.9, 51.1, 29.3, 25.3; IR (KBr) ν (cm-1) 3050, 3001, 2921, 2853, 1713, 1626, 1606, 1545, 1510, 1420, 1357, 1304, 1222, 1159; MS (70 eV, EI) m/z (%): 200 (M++1, 2.64), 199 (M+, 17.92), 157 (100); Anal. Calcd. for C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found: C, 78.42; H, 6.61; N, 6.95.
实施例27 . 1-(1’-萘基)-2-丙酮
操作方法同实验实施例3。1-氯代萘(162.1 mg, 1.0 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.5 mg, 0.060 mmol)，碳酸铯(651.9 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(1’-萘基)-2-丙酮178.2 mg，产率97%。液体。
1H NMR (300 MHz, CDCl3) δ 7.96-7.87 (m, 2H, ArH), 7.87-7.80 (m, 1H, ArH), 7.60-7.44 (m, 3H, ArH), 7.42-7.37 (m, 1H, ArH), 4.12 (s, 2H, CH2), 2.13 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 206.7, 133.7, 132.0, 130.9, 128.6, 128.0, 127.8, 126.3, 125.7, 125.4, 123.6, 48.9, 28.8; IR (neat) ν (cm-1) 3046, 3006, 2918, 1712, 1596, 1510, 1417, 1398, 1356, 1320, 1229, 1163, 1021; MS (70 eV, EI) m/z (%): 185 (M++1, 3.44), 184 (M+, 23.34), 141 (100).
实施例28 . 1-(对苯甲酰基苯基)-2-丙酮
操作方法同实验实施例3。对苯甲酰基氯苯(216.3 mg, 1.0 mmol)，肉桂基氯化钯(7.8 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.5 mg, 0.060 mmol)，碳酸铯(651.5 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(对苯甲酰基苯基)-2-丙酮195.2 mg，产率82%。液体。
1H NMR (300 MHz, CDCl3) δ 7.83-7.75 (m, 4H, ArH), 7.62-7.54 (m, 1H, ArH), 7.52-7.43 (m, 2H, ArH), 7.35-7.28 (m, 2H, ArH), 3.81 (s, 2H, CH2), 2.22 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 205.1, 196.1, 138.8, 137.4, 136.1, 132.3, 130.3, 129.8, 129.3, 128.1, 50.5, 29.5; IR (neat) ν (cm-1) 3059, 3003, 2917, 1715, 1660, 1651, 1606, 1579, 1447, 1416, 1358, 1317, 1278, 1227, 1178, 1159, 1113, 1075, 1020, 1001; MS (70 eV, EI) m/z (%): 239 (M++1, 0.98), 238 (M+, 5.45), 196 (100).
实施例29 . 1-(对腈基苯基)-2-丙酮
操作方法同实验实施例3。对氯苯甲腈(137.6 mg, 1.0 mmol)，肉桂基氯化钯(7.9 mg, 0.015 mmol)，2-烷氧基-6-氨基苯基二烷基膦 (24.5 mg, 0.060 mmol)，碳酸铯(651.9 mg, 2.0 mmol)及4 mL丙酮，90 oC下反应得到1-(对腈基苯基)-2-丙酮127.6 mg，产率80%。固体。
m.p.: 79.8-80.1 oC (正己烷/乙酸乙酯); 1H NMR (300 MHz, CDCl3) δ 7.66-7.60 (m, 2H, ArH), 7.34-7.27 (m, 2H, ArH), 3.81 (s, 2H, CH2), 2.23 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 204.3, 139.3, 132.3, 130.3, 118.6, 111.0, 50.3, 29.8; IR (KBr) ν (cm-1) 3060, 3006, 2954, 2893, 2225, 1708, 1608, 1420, 1504, 1407, 1356, 1334, 1313, 1212, 1163, 1019; MS (70 eV, EI) m/z (%): 160 (M++1, 1.05), 159 (M+, 9.09), 43 (100).
Claims (8)
1.一种2-烷氧基-6-氨基苯基二烷基膦，其特征是：所述的2-烷氧基-6-氨基苯基二烷基膦的结构式如下：
结构式中，R1，R2为：异丙基、环戊基、叔丁基、环己基、金刚烷基；R3为烷基、芳基，R4， R5为烷基、芳基；R6为取代的烷基、烷氧基、芳基、胺基、巯基、羰基、腈基，取代基的位置不固定，数量为0-3。
2.一种如权利要求1所述的2-烷氧基-6-氨基苯基二烷基膦的制备方法，其特征是通过下述步骤获得：
用取代烷氧基苯胺与丁基锂在有机溶剂正己烷中80 oC反应2~15小时得到对应的锂试剂；
将上述的锂试剂与二烷基氯化膦R1R2PCl在-78 oC~80 oC下反应2~10小时，生成2-烷氧基-6-氨基苯基二烷基膦；所述的二烷基氯化膦和取代烷氧基苯胺基锂的摩尔比为0.8~1.2：1；
上述的R1、R2、R3、R4、R5和R6如权利要求1所述。
3.如权利要求2所述的2-烷氧基-6-氨基苯基二烷基膦的制备方法，其特征是所述的2-烷氧基-6-氨基苯基二烷基膦经过重结晶纯化。
4.一种如权利要求1所述的2-烷氧基-6-氨基苯基二烷基膦用于芳基氯化物与酮的偶联反应反应制备偶联化合物。
5.根据权利要求4所述的2-烷氧基-6-氨基苯基二烷基膦用于芳基氯化物与酮的偶联反应反应制备偶联化合物的制备方法，其特征是：在惰性气体保护条件下、80~120 °C和有机溶剂中，碱、钯、2-烷氧基-6-氨基苯基二烷基膦、酮和芳基氯化物反应0.6~50小时得到对应的偶联产物。
6.根据权利要求5所述的制备方法，其特征是：所述的碱，钯，2-烷氧基-6-氨基苯基二烷基膦，酮，芳基氯化物当量比为1.0~4.0：0.01~0.05：0.015~0.075：1.0~4.0：1.0。
7.根据权利要求5所述的制备方法，其特征是：所述的有机溶剂为甲苯、苯、二甲苯、二氧六环或丙酮；所述的碱为碳酸钾、磷酸钾、碳酸铯、叔丁醇钠、叔丁醇钾或氟化铯；所述的钯为醋酸钯、氯化钯、二亚苄基丙酮钯、肉桂基氯化钯或烯丙基氯化钯；2-烷氧基-6-氨基苯基二烷基膦如权利要求1所述。
8.根据权利要求5所述的制备方法，其特征是：所述的芳基氯化物是R7取代的氯苯；酮为R8COCH2R9；R7为邻、间、对位取代的烷基、胺基或烷氧基；R8为各种取代的芳基、烷基及杂环基；R9为氢、各种取代的芳基、烷基及杂环基。
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| CN105237568A (zh) * | 2015-10-19 | 2016-01-13 | 盘锦格林凯默科技有限公司 | 二叔丁基-4-二甲氨基苯基膦和双(二叔丁基-4-二甲氨基苯基膦)氯化钯的制备方法 |
| CN110105179A (zh) * | 2019-05-24 | 2019-08-09 | 浙江大学 | 一种钯/咪唑盐催化硝基芳烃和硼酸化合物偶联合成芳香族化合物的方法 |
| CN110105179B (zh) * | 2019-05-24 | 2022-04-29 | 浙江大学 | 一种钯/咪唑盐催化硝基芳烃和硼酸化合物偶联合成芳香族化合物的方法 |
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| US20140309422A1 (en) | 2014-10-16 |
| CN102675366B (zh) | 2015-09-30 |
| US9243011B2 (en) | 2016-01-26 |
| WO2013166770A1 (zh) | 2013-11-14 |
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