CN110818586B - 环戊二酰胺类配体、合成方法、在合成芳胺衍生物的偶联反应中的用途、及催化体系 - Google Patents
环戊二酰胺类配体、合成方法、在合成芳胺衍生物的偶联反应中的用途、及催化体系 Download PDFInfo
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- CN110818586B CN110818586B CN201910952195.2A CN201910952195A CN110818586B CN 110818586 B CN110818586 B CN 110818586B CN 201910952195 A CN201910952195 A CN 201910952195A CN 110818586 B CN110818586 B CN 110818586B
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- 239000003446 ligand Substances 0.000 title claims abstract description 54
- 238000005859 coupling reaction Methods 0.000 title claims abstract description 35
- 150000004982 aromatic amines Chemical class 0.000 title claims abstract description 13
- 230000003197 catalytic effect Effects 0.000 title claims abstract description 13
- BYGAVIIEJSUUHA-UHFFFAOYSA-N cyclopentane-1,1-dicarboxamide Chemical compound NC(=O)C1(C(N)=O)CCCC1 BYGAVIIEJSUUHA-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 9
- 238000001308 synthesis method Methods 0.000 title description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 37
- 239000010949 copper Substances 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 17
- 229910052802 copper Inorganic materials 0.000 claims description 17
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 15
- 229910021529 ammonia Inorganic materials 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000001502 aryl halides Chemical class 0.000 claims description 11
- 239000003054 catalyst Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- -1 amino, hydroxyl Chemical group 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 235000019270 ammonium chloride Nutrition 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 239000011630 iodine Substances 0.000 claims description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000005245 nitryl group Chemical group [N+](=O)([O-])* 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 235000011181 potassium carbonates Nutrition 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 4
- 239000001099 ammonium carbonate Substances 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- LYNLJRWPCQRLBT-UHFFFAOYSA-N 1-carbamoylcyclopentane-1-carboxylic acid Chemical compound NC(=O)C1(C(O)=O)CCCC1 LYNLJRWPCQRLBT-UHFFFAOYSA-N 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 3
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 3
- 229910002531 CuTe Inorganic materials 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 claims description 3
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 3
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 3
- PDZKZMQQDCHTNF-UHFFFAOYSA-M copper(1+);thiocyanate Chemical compound [Cu+].[S-]C#N PDZKZMQQDCHTNF-UHFFFAOYSA-M 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims description 3
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 235000017550 sodium carbonate Nutrition 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- XRLDSWLMHUQECH-UHFFFAOYSA-N cyclopentanecarboxamide Chemical compound NC(=O)C1CCCC1 XRLDSWLMHUQECH-UHFFFAOYSA-N 0.000 claims 3
- 150000001875 compounds Chemical class 0.000 claims 1
- XYMVZPOXZCDCNP-UHFFFAOYSA-N sulfamoyl cyanide Chemical compound NS(=O)(=O)C#N XYMVZPOXZCDCNP-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 13
- 238000010189 synthetic method Methods 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 125000000623 heterocyclic group Chemical group 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 150000001500 aryl chlorides Chemical class 0.000 description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 150000001499 aryl bromides Chemical class 0.000 description 8
- 125000000753 cycloalkyl group Chemical group 0.000 description 8
- 150000001503 aryl iodides Chemical class 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- 229910052759 nickel Inorganic materials 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 125000003003 spiro group Chemical group 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 229910052723 transition metal Inorganic materials 0.000 description 4
- 150000003624 transition metals Chemical class 0.000 description 4
- UDHAWRUAECEBHC-UHFFFAOYSA-N 1-iodo-4-methylbenzene Chemical compound CC1=CC=C(I)C=C1 UDHAWRUAECEBHC-UHFFFAOYSA-N 0.000 description 3
- WNRGWPVJGDABME-UHFFFAOYSA-N 3,5-Dimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1 WNRGWPVJGDABME-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000001448 anilines Chemical class 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 150000008424 iodobenzenes Chemical class 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 3
- OSTMCQXLMNDQGL-UHFFFAOYSA-N 1-azanylidyne-n-nitromethanesulfonamide Chemical compound [O-][N+](=O)NS(=O)(=O)C#N OSTMCQXLMNDQGL-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 2
- 235000019838 diammonium phosphate Nutrition 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JHFNJRVFKOQALR-UHFFFAOYSA-N 1-prop-2-enylpyrrole Chemical compound C=CCN1C=CC=C1 JHFNJRVFKOQALR-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- UKYGKNHLXAIOQN-UHFFFAOYSA-N 6-methylidenecyclohexa-2,4-dien-1-ol Chemical compound OC1C=CC=CC1=C UKYGKNHLXAIOQN-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 125000006416 CBr Chemical group BrC* 0.000 description 1
- 241000345998 Calamus manan Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KURZCZMGELAPSV-UHFFFAOYSA-N [Br].[I] Chemical group [Br].[I] KURZCZMGELAPSV-UHFFFAOYSA-N 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000004768 bromobenzenes Chemical class 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
- 239000006227 byproduct Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000008422 chlorobenzenes Chemical class 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- YYLFLXVROAGUFH-UHFFFAOYSA-N cyclopentane-1,1-dicarbonyl chloride Chemical compound ClC(=O)C1(C(Cl)=O)CCCC1 YYLFLXVROAGUFH-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical group [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- RCCYSVYHULFYHE-UHFFFAOYSA-N pentanediamide Chemical compound NC(=O)CCCC(N)=O RCCYSVYHULFYHE-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000012950 rattan cane Nutrition 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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Abstract
本发明公开了具有通式I的环戊二酰胺类配体、合成方法、在合成芳胺衍生物的偶联反应中的用途、及催化体系,所述的式I环戊二酰胺类化合物可以用作铜催化芳基卤代物合成芳胺衍生物的偶联反应中的配体,催化芳基卤与氨胺源形成C‑N键的偶联反应。在温和反应条件下以高收率得到芳胺衍生物,且配体结构简单,制备方便,用量少。
Description
技术领域
本发明涉及环戊二酰胺类配体、合成方法、在合成芳胺衍生物的偶联反应中的用途、及催化体系。
背景技术
传统的生成C-N,C-C,C-O,C-S键的方法一般为亲核取代,但芳环上的取代较为困难,一般需要高温高压下进行。而过渡金属催化的芳基卤代物与合适的亲核试剂如有机胺、活泼亚甲基、苯酚、醇、苯硫酚等发生相应的偶联反应则更为高效、温和地形成C-N,C-C,C-O,C-S键。
通常,芳基碘、芳基溴的反应活性较高,过渡金属与之氧化加成容易进行,在钯、铜、镍等过渡金属的催化下,在低于100℃温度下,能较好的实现相应的偶联反应。
和溴(碘)代芳烃相比,氯代芳烃便宜易得,更具有工业化意义;然而C-C1键键能高,过渡金属与之氧化加成就很难发生,反应不如溴代物和碘代物高效,常常需要使用高沸点、高粘度的溶剂。钯和镍催化的芳基氯代物的C-N偶联反应已有相关报道,Hartwig小组在2005年使用具有二茂铁结构的大位阻麟配体,顺利完成了芳环和芳杂环氯代物与一级胺的偶联反应,该体系中催化剂和配体的当量甚至可以降低到十万分之一的摩尔当量,对于个别芳杂环底物在室温条件下就可以完成此类反应,充分显示了该催化体系的高效;此外,该反应对于苯环上的取代基团也有着很好的兼容性。
Buchwald小组在2011年发现利用不同的麟配体,可以使氯代芳烃分别和一级胺、二级胺发生偶联,该体系对于底物具有很广的兼容性,除了一般脂肪胺,带有杂环的芳香胺也能顺利发生偶联。
虽然金属钯和镍在催化的氯代芳烃的氨基化反应中有着很高的效率,但是在大规模应用上存在一些问题:
1、体系中需要加入大位阻、结构较复杂的滕配体或氮杂卡宾配体来促进反应,这些配体在合成上较为繁琐,条件较为严苛;
2、钯催化剂的价格昂贵,且零价镍所需的反应操作相当苛刻,这在一定程度上限制了其应用。相比而言,铜催化剂廉价、稳定、易得,所使用的配体结构简单,可以明显避免这些缺陷。然而目前所报道的铜催化的偶联反应底物大多局限在碘代物和溴代物。
2008年,Sukbok Chang小组利用氨水和氯化铵作为氨源,在室温下利用L-proline实现了芳基碘和氨水或氯化铵的偶联反应,氨水和氯化铵作为胺源都能以较好的收率得到偶联产物,然而该方法仅用于芳基碘化物,并不涉及到更为普遍的芳基氯和芳基溴的底物。(Kim J,Chang S.Chemical Communications,2008,39(26):3052-3054.)
Xia,N;Tailler,M等利用2,4-戊二酮为配体,实现了芳基溴和氨水的C-N偶联,该体系的缺点主要是会产生C-C偶联的副产物,降低了反应的经济性。(Xia,N;Taillefer,M.Angew.Chem.Int.Ed.2009,48,337-339)
发明内容
发明目的:本发明目的是提供一种能够高效、温和促进铜催化的芳基氯、溴、碘与胺源进行偶联反应的配体、催化体系。
本发明适合用于铜催化芳基卤代物合成芳胺衍生物的偶联反应的环戊二酰胺配体,通过该类配体与铜试剂、碱、溶剂组成的合适催化体系,可以用于芳基卤代物的铜催化偶联反应,特别是能够有效促进室温下芳基碘与氨水的偶联,生成芳胺衍生物,合成众多有用的含取代基的苯胺衍生物,含取代基的杂环衍生物。
本发明另一目的是提供所述配体的合成方法。
本发明最后一目的是提供所述配体在合成芳胺衍生物的偶联反应中的用途。
技术方案:本发明具有通式I的环戊二酰胺类配体:
其中,
R1为未取代或R1-1取代的C6-C20芳基、未取代或R1-2取代的杂芳基、未取代或R1-3取代的C7-C25烷基-C6-C20芳基、未取代或R1-4取代的C1-C6烷基-杂芳基、未取代或R1-5取代的C3-C20环烷基、未取代或R1-6取代的杂环基;
所述杂芳基的杂原子选自N、O和S中的一种或多种,杂原子数为1-6个的3~20元杂环基;
所述环烷基或杂环基可以为单环、多环、螺环或桥环结构;
所述R1-1、R1-2、R1-3、R1-4、R1-5、R1-6分别选自卤素、硝基、羟基、氨基、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基、C6-C10的芳基或C6-C10的芳基-氧基;
R2为未取代或R2-1取代的C6-C20芳基、未取代或R2-2取代的杂芳基、未取代或R2-3取代的C7-C25烷基-C6-C20芳基、未取代或R2-4取代的C1-C6烷基-杂芳基、未取代或R2-5取代的C3-C20环烷基、未取代或R2-6取代的杂环基;
所述杂芳基的杂原子选自N、O和S中的一种或多种,杂原子数为1-6个的3~20元杂环基;
所述环烷基或杂环基可以为单环、多环、螺环或桥环结构;
所述R2-1、R2-2、R2-3、R2-4、R2-5、R2-6分别选自卤素、硝基、羟基、氨基、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基、C6-C10的芳基或C6-C10的芳基-氧基。
进一步地,当所述R1为未取代或R1-1取代的C6-C20芳基时,所述的R1-1的个数为一个或多个,当存在多个R1-1时,所述的R1-1可相同或不同;
R1为未取代或R1-1取代的C6-C20芳基时,所述的C6-10的芳基为苯基;
当R1-1为C1-C6烷基时,所述的C1-C6烷基为C1-C3烷基;
当R1-1为C1-C6烷氧基时,所述的C1-C6烷氧基为C1-C3烷氧基;
当R1-1为卤素时,所述的卤素为氟、氯、溴或碘;
当R2-1为C6-C10的芳基时,所述的C6-C10的芳基为苯基;
所述的R2为未取代或R2-1取代的C6-C20芳基、未取代时,所述的R2-1的个数为一个或多个,当存在多个R2-1时,所述的R2-1可相同或不同;
R2为未取代或R2-1取代的C6-C20芳基时,所述的C6-10的芳基为苯基;
当R2-1为C1-C6烷基时,所述的C1-C6烷基为C1-C3烷基;
当R2-1为C1-C6烷氧基时,所述的C1-C6烷氧基为C1-C3烷氧基;
当R2-1为卤素时,所述的卤素为氟、氯、溴或碘;
当R2-1为C6-C10的芳基时,所述的C6-C10的芳基为苯基。
进一步地,所述的R1-1取代的C6-C20芳基为如下任一种:
进一步地,所述的R2-1取代的C6-C20芳基为如下任一种:
进一步地,具有通式I的环戊二酰胺类配体,为如下任一种:
应理解,由于C-Br和C-I键的键能小于C-Cl键,在同等条件下,芳基溴代物、芳基碘代物的偶联反应相较于芳基氯代物而言更易发生。因此,上述配体除了,以用于芳基碘代物的偶联反应之外,也可以用于本领域常规的芳基溴代物、芳基氯代物的偶联反应。
所述的具有通式I的环戊二酰胺类配体的合成方法,其特征在于:
方法(i)包括步骤:
方法(ii)包括步骤:
所述的具有通式I的环戊二酰胺类配体在合成芳胺衍生物的偶联反应中的用途。
进一步地,在铜催化芳基卤代物合成芳胺衍生物的偶联反应如下:
在惰性溶剂中,用与氨源反应,得到其中,氨源选自液氨、氨气、氨水、氯化铵、硫酸铵、碳酸铵、磷酸氢胺;Y选自Cl、Br、I;Ar选自未取代或R3-1取代的C6-C20芳基、未取代或R3-2取代的杂芳基;杂芳基中的杂原子选自N、O和S中的一种或多种,杂原子数为1-6个的3~20元的杂芳基;
R3-1-R3-2独立选自卤素、硝基、氰基、磺酰胺基、氨基、羟基、C1-C6的烷基、C1-C6卤代基、C1-C6烷氧基、C1-C6芳基、C3-C6环烷基、杂芳基、杂环烷基、卤代C1-C6烷基、-NR3-1- 1R3-1-2、-(C=O)NR3-1-3R3-1-4或-NR3-1-5(C=O)R3-1-6或-(C=O)R3-1-7;
R3-1-1-R3-1-7独立选自氢、C1-C6的烷基、C1-C6烷氧基、C1-C6卤代基。
最为优选的铜催化芳基卤代物的偶联反应如下所示:
1.环戊二酰胺配体促进的铜催化的芳基碘与氨源的偶联反应
其中各基团的定义如上文中所述,Ar选自R3-1取代的C6-C20芳基、未取代或R3-2取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-6个的3~20元”的杂芳基、未取代;
R3-1-R3-2独立选自卤素、硝基、氰基、磺酰胺基、氨基、羟基、C1-C6的烷基、C1-C6卤代基、C1-C6烷氧基、C1-C6芳基、C3-C6环烷基、杂芳基、杂环烷基、卤代C1-C6烷基、-NR3-1- 1R3-1-2、-(C=O)NR3-1-3R3-1-4或-NR3-1-5(C=O)R3-1-6或-(C=O)R3-1-7;
R3-1-1-R3-1-7独立选自氢、C1-C6的烷基、C1-C6烷氧基、C1-C6卤代基;
所述的氨源选自:氨气、氨水、氯化铵、碳酸铵、碳酸氢铵、硫酸铵、硝酸铵、磷酸铵、磷酸氢二铵、叠氮化钠,优选氨气、氨水、氯化铵和磷酸氢二铵。
铜催化剂可以为CuI、CuBr、CuC1、CuTe、Cu(OAc)2、CuSO4、Cu2O、CuBr2、CuCl2、CuO、CuSCN、CuCN、Cu(acac)2,优选CuI。
配体为L(Ligand)可以为上文中所述的任意一种,优选L-1、L-2、L-5、L-6。
碱可以为碳酸钾、碳酸艳、磷酸钾、碳酸钠、碳酸氢钠、碳酸氢钾,优选碳酸绝、磷酸钾,最优选碳酸铯。
溶剂可以为DMSO、DMF、DMA、NMP、乙腈、叔丁醇、异丙醇、THF、1,4-二氧六环,优选DMSO、DMF,最优选DMSO。
反应温度在20-40℃,优选30-40℃。
2.环戊二酰胺配体促进的铜催化的芳基溴与氨源的偶联反应
3.环戊二酰胺配体促进的铜催化的芳基氯与氨源的偶联反应
进一步地,所述配体与芳基卤代物的摩尔比为1~10∶100;所述配体与铜催化剂的摩尔比为1~5∶1。
一种芳基偶联反应的催化体系,包括:铜催化剂、配体、碱或其水合物、有机溶剂;
所述铜催化剂选自CuI、CuBr、CuCl、CuTe、Cu(Oac)2、CuSO4、Cu2O、CuBr2、CuCl2、CuO,CuSCN,CuCN或Cu(acac)2中的一种或几种的组合;碱选自碳酸钾、碳酸艳、磷酸钾、碳酸氢钠、碳酸氢钾、碳酸钠、氢氧化锂、氢氧化钠、四丁基氢氧化铵中的一种或几种的组合;有机溶剂选自DMSO、DMF、DMA、NMP或PEG中的一种或几种的组合。
相关术语解释如下:
术语“卤素”指氟、氯、溴、碘。
术语“卤代”指基团上的一个或多个氢原子被卤素所取代。
术语“烷基”指直链或支链烷基。当烷基前具有碳原子数限定(如C1-C6)时,指所述的烷基含有1-6个碳原子,例如甲基、乙基、丙基、异丙基、丁基、异丁基、仲丁基、叔丁基、或类似基团。
术语“环烷基”指具有饱和的或部分饱和的单元,二环或三环(并环、桥环或螺环)环系。所述的环烷基可以具有3-20个碳原子。当某个环烷基前具有碳原子数限定(如C3-C20)时,指所述的环烷基含有3-20个碳原子,例如环丙基、环丁基、环戊基、环庚基、或类似基团。所述的环烷基可以是单环、多环、螺环或桥环形式。
如本文所用,术语“烷氧基”指通过氧原子相连的烷基(例如,-O-烷基,其中烷基如上所述),例如(但并不限于)甲氧基、乙氧基、丙氧基、异丙氧基、丁氧基、异丁氧基、仲丁氧基、叔丁氧基、或类似基团。当烷氧基前具有碳原子数限定(如C1-C6)时,指所述的环烷基含有1-6个碳原子。
术语“芳基”指单环,二环或稠环的芳香族碳氢基团,所述的芳基可以是取代或未取代的。当一个芳基前具有碳原子数限定(如C6-C20)时,指所述的芳基含有6-20个碳原子。
芳基的例子例如(但并不限于):苯基、联苯基、萘基、或类似基团(其中的每个碳原子均可以被任意取代)。术语“杂芳基”指单环,二环或稠环的芳香族基团,所述基团包括至少一个选自N、O或S的杂原子。所述的杂芳基可以是3-至20-元的,具有1-5个各自独立地选自N、O或S的杂原子的芳香环基。杂芳基的例子例如(但并不限于):吡啶、嘧啶、吡咯、唑、吲噪、呋喃、苯并呋喃、噻吩,或类似基团。
术语“杂环基”指单环或稠环的饱和或部分饱和取代基,所述基团包括至少一个相同或不同的选自N、O或S的杂原子。所述的杂环基可以是3-至20-元的,具有1-5个各自独立地选自N、O或S的杂原子的杂环基。杂环基的例子例如(但并不限于):氮杂环基、氧杂环基、硫杂环基、氮氧杂环基等。
术语“酯基”指具有“烷基-COO-”结构的基团,其中,烷基定义如上所述。
术语“酰基”指具有“烷基-COO-”结构的基团,其中,烷基定义如上所述。
术语“酰胺基”指具有“烷基NHC(O)-”或者“芳基NHC(O)-”结构的基团,其中,烷基、芳基定义如上所述。
“配体”除非特别说明,本文中所提到的配体指用于铜催化的芳基卤代物偶联反应中的配体。
有益效果:本发明提供了一类能够高效率地进行铜催化的芳基卤代物与氨源的偶联反应的催化体系,所述的催化体系能够使芳基碘在室温条件下进行的芳基碘代物的氨化,在80℃催化芳基溴的氨化,120℃催化芳基氯的氨化,且底物兼容性好,催化体系适用范围广;相较于现有技术中的芳基氯代物偶联反应方法,本发明的方法采用成本较低的铜催化剂体系,且配体结构简单,制备方便,用量少,反应经济;本发明的催化体系所使用的原料芳基氯代物与其他芳基卤代物相比,原料成本低,来源广泛,具有很好的大规模应用前景。
具体实施方式
实施例1、配体的合成(以L1为例)
将3,5-二甲氧基苯胺(10mmol)和三乙胺(11mmol)溶于40ml四氢呋喃,3,5-二甲氧基苯胺的浓度为0.2mol/L。冰水浴冷却,搅拌,再滴加环戊二酰氯(11mmol),体系变浑浊,产生三乙胺盐酸盐。滴加完毕后撤除冰水浴,自然恢复室温,继续搅拌1-2小时,TCL检测3,5-二甲氧基苯胺完全消耗,可停止搅拌进行后处理。
用滤纸对反应液减压抽滤,滤除三乙胺盐酸盐,滤饼再用少量四氢呋喃冲洗(不可用乙酸乙酯冲洗,否则三乙胺盐酸盐会溶解)。滤液减压浓缩后,对残余物进行硅胶柱层析纯化,洗脱剂为石油醚∶乙酸乙酯=3∶1,得白色固体4.10g,产率96%。
1H NMR(300MHz,Chloroform-d)δ7.85(s,1H),7.26(s,1H),6.74(d,J=2.3Hz,2H),6.24(s,1H),3.77(s,6H),2.37(t,J=7.1Hz,2H),2.06-1.66(m,3H).
13C NMR(300MHz,Chloroform-d)δ173.11,162.39,139.94,101.63,95.07,63.17,55.70,35.48,24.49.HRMS(ESI)calcd.for C23H28N2O6(M+H):429.1947,Found:429.1945.
其他配体合成如实施例1:
实施例2、对甲基碘苯与氨水的偶联反应合成对甲基苯胺
在10mL封管中加入碘化亚铜(0.1mol),配体(0.2mmol),碳酸铯(1.0mmol),对甲基碘苯,抽真空置换氩气3次,再加入1ml DMSO,和氨水900ul(28%),反应在30℃均匀搅拌24小时,反应完成后,加入水和乙酸乙酯,分液,水相用乙酸乙酯萃取2次,合并有机相,用无水硫酸钠干燥,浓缩后柱层析(石油醚∶乙酸乙酯=10∶1),得到产物对甲基苯胺100mg,产率93%。1HNMR(DMSO-d6):δ6.83(d,J=8.0Hz,2H),6.48(d,J=7.6Hz,2H),4.76(br,2H,NH),2.12(s,3H);13CNMR(DMSO-d6):δ146.4,129.8,124.9,114.8,20.6;HRMS(ESI)calcd.forC7H9N(M+H)+:107.0745,Found:107.0746.
实施例3、对甲基碘苯与氨水偶联反应合成对甲基苯胺
如实施例2,采用不同的环戊二酰胺配体,所得结果列与下表。
配体编号 | 产率(%) | 配体编号 | 产率 |
L1 | 93% | L4 | 82% |
L2 | 80% | L5 | 83% |
L3 | 85% | L9 | 81% |
实施例4、各种取代的碘苯与氨水的偶联反应合成相应的苯胺衍生物
在10mL封管中加入碘化亚铜(0.1mmol),配体L-1(0.2mmol),碳酸铯(2.0mmol),取代的碘苯(1.0mmol),抽真空置换氩气3次,加入氨水(12mmol)和1mL DMSO,反应在30℃下均匀搅拌24h,冷却后加入水和乙酸乙酯,分液,水相用乙酸乙酯萃取2次,合并有机相,用无水硫酸钠干燥,浓缩后柱层析,得产品苯胺衍生物。
本实施例使用不同取代的碘苯,不同取代的溴苯,不同取代的氯苯,与氨水进行偶联,所得结果列与下表。
Claims (10)
1.一种具有通式I的环戊二酰胺类配体:
其中,
R1为R1-1取代的C6-C20芳基、未取代或R1-2取代的杂芳基、未取代或R1-3取代的C7-C25烷基-C6-C20芳基、未取代或R1-4取代的C1-C6烷基-杂芳基;
所述杂芳基是杂原子选自N、O和S中的一种或多种,杂原子数为1-6个的3~20元杂芳基;
所述R1-1、R1-2、R1-3、R1-4、R1-5、R1-6分别选自卤素、硝基、氨基、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基、C6-C10的芳基或C6-C10的芳基-氧基;
R2为R2-1取代的C6-C20芳基、未取代或R2-2取代的杂芳基、未取代或R2-3取代的C7-C25烷基-C6-C20芳基、未取代或R2-4取代的C1-C6烷基-杂芳基;
所述杂芳基是杂原子选自N、O和S中的一种或多种,杂原子数为1-6个的3~20元杂芳基;
所述R2-1、R2-2、R2-3、R2-4、R2-5、R2-6分别选自卤素、硝基、氨基、C1-C6烷基、卤代C1-C6烷基、C1-C6烷氧基、C6-C10的芳基或C6-C10的芳基-氧基。
2.根据权利要求1所述的具有通式I的环戊二酰胺类配体,其特征在于:R1-1的个数为一个或多个,当存在多个R1-1时,所述的R1-1可相同或不同;
R1为R1-1取代的苯基;
R1-1为C1-C3烷基;
R1-1为C1-C3烷氧基;
R1-1为氟、氯、溴或碘;
R2-1的个数为一个或多个,当存在多个R2-1时,所述的R2-1可相同或不同;
R2-1为苯基、C1-C3烷基、C1-C3烷氧基、氟、氯、溴或碘;
R2为R2-1取代的苯基。
7.权利要求1所述的具有通式I的环戊二酰胺类配体在合成芳胺衍生物的偶联反应中的用途。
8.权利要求7所述的用途,其特征在于:在铜催化芳基卤代物合成芳胺衍生物的偶联反应如下:
在惰性溶剂中,用与氨源反应,得到其中,氨源选自液氨、氨气、氨水、氯化铵、硫酸铵、碳酸铵、磷酸氢胺;Y选自Cl、Br、I;Ar选自未取代或R3-1取代的C6-C20芳基、未取代或R3-2取代的杂芳基;所述杂芳基是杂原子选自N、O和S中的一种或多种,杂原子数为1-6个的3~20元的杂芳基;[Cu]选自CuI、CuCl、CuBr、CuCN;Ligand选自权利要求1-6中任一项所述的具有通式I的环戊二酰胺类配体;base选自碳酸钾、碳酸铯、碳酸钠、碳酸氢钠、氢氧化钠、氢氧化钾;solvent选自N,N-二甲基亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、四氢呋喃、1,4-二氧六环、甲苯、N-甲基吡咯烷酮;temp选自25~80℃;
R3-1、R3-2分别选自卤素、硝基、氰基、磺酰胺基、氨基、羟基、C1-C6的烷基、C1-C6卤代基、C1-C6烷氧基、C1-C6芳基、C3-C6环烷基、卤代C1-C6烷基、-NR3-1-1R3-1-2、-(C=O)NR3-1-3R3-1-4或-NR3-1-5(C=O)R3-1-6或-(C=O)R3-1-7;
R3-1-1、R3-1-2、R3-1-3、R3-1-4、R3-1-5、R3-1-6、R3-1-7分别选自氢、C1-C6的烷基、C1-C6烷氧基、C1-C6卤代基。
9.权利要求7所述的用途,其特征在于:所述配体与芳基卤代物的摩尔比为1~10∶100;所述配体与铜催化剂的摩尔比为1~5∶1。
10.一种芳基偶联反应的催化体系,其特征在于,包括:铜催化剂、权利要求1所述的配体、碱或碱的水合物和有机溶剂;
所述铜催化剂选自CuI、CuBr、CuCl、CuTe、Cu(Oac)2、CuSO4、Cu2O、CuBr2、CuCl2、CuO,CuSCN,CuCN或Cu(acac)2中的一种或几种的组合;碱选自碳酸钾、碳酸艳、磷酸钾、碳酸氢钠、碳酸氢钾、碳酸钠、氢氧化锂、氢氧化钠、四丁基氢氧化铵中的一种或几种的组合;有机溶剂选自DMSO、DMF、DMA、NMP或PEG中的一种或几种的组合。
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