CN110272357A - A kind of preparation method of alkenyl cyanides - Google Patents
A kind of preparation method of alkenyl cyanides Download PDFInfo
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- CN110272357A CN110272357A CN201810210712.4A CN201810210712A CN110272357A CN 110272357 A CN110272357 A CN 110272357A CN 201810210712 A CN201810210712 A CN 201810210712A CN 110272357 A CN110272357 A CN 110272357A
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- -1 alkenyl cyanides Chemical class 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 34
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 24
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 17
- 239000007868 Raney catalyst Substances 0.000 claims abstract description 14
- 229910000564 Raney nickel Inorganic materials 0.000 claims abstract description 14
- 239000000758 substrate Substances 0.000 claims abstract description 13
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 3
- 238000006722 reduction reaction Methods 0.000 claims abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 162
- 150000001875 compounds Chemical class 0.000 claims description 73
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 239000003446 ligand Substances 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 12
- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 claims description 12
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 7
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 claims description 7
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 5
- 239000007789 gas Substances 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical group [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 4
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 claims description 4
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 claims description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 claims description 4
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 claims description 3
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 claims description 2
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-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
- 229910021587 Nickel(II) fluoride Inorganic materials 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- XINWHKIKKFDJLM-UHFFFAOYSA-N butane;diphenylphosphane Chemical compound CCCC.C=1C=CC=CC=1PC1=CC=CC=C1.C=1C=CC=CC=1PC1=CC=CC=C1 XINWHKIKKFDJLM-UHFFFAOYSA-N 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 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 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- HASCQPSFPAKVEK-UHFFFAOYSA-N dimethyl(phenyl)phosphine Chemical compound CP(C)C1=CC=CC=C1 HASCQPSFPAKVEK-UHFFFAOYSA-N 0.000 claims description 2
- TWWJJVNUZQLCPD-UHFFFAOYSA-N diphenylphosphane;methane Chemical compound C.C=1C=CC=CC=1PC1=CC=CC=C1 TWWJJVNUZQLCPD-UHFFFAOYSA-N 0.000 claims description 2
- CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- UJNZOIKQAUQOCN-UHFFFAOYSA-N methyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C)C1=CC=CC=C1 UJNZOIKQAUQOCN-UHFFFAOYSA-N 0.000 claims description 2
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- NLEUXPOVZGDKJI-UHFFFAOYSA-N nickel(2+);dicyanide Chemical compound [Ni+2].N#[C-].N#[C-] NLEUXPOVZGDKJI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005561 phenanthryl group Chemical group 0.000 claims description 2
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 claims description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 2
- 150000003214 pyranose derivatives Chemical class 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 claims description 2
- BZLZKLMROPIZSR-UHFFFAOYSA-N triphenylsilicon Chemical compound C1=CC=CC=C1[Si](C=1C=CC=CC=1)C1=CC=CC=C1 BZLZKLMROPIZSR-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-UHFFFAOYSA-N 0.000 claims 1
- ZOAMZFNAPHWBEN-UHFFFAOYSA-N 2-$l^{1}-oxidanylpropane Chemical compound CC(C)[O] ZOAMZFNAPHWBEN-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- STCDDNDGEFVYKE-UHFFFAOYSA-N diphenylphosphane;propane Chemical compound CCC.C=1C=CC=CC=1PC1=CC=CC=C1.C=1C=CC=CC=1PC1=CC=CC=C1 STCDDNDGEFVYKE-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- QEKXARSPUFVXIX-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dibromide Chemical compound [Ni+2].[Br-].[Br-].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QEKXARSPUFVXIX-UHFFFAOYSA-L 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 9
- 229910052759 nickel Inorganic materials 0.000 abstract description 7
- 125000000524 functional group Chemical group 0.000 abstract description 6
- 230000001737 promoting effect Effects 0.000 abstract description 3
- 230000009471 action Effects 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 228
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 179
- 238000005160 1H NMR spectroscopy Methods 0.000 description 120
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 60
- 239000003480 eluent Substances 0.000 description 60
- 238000010898 silica gel chromatography Methods 0.000 description 60
- 239000007788 liquid Substances 0.000 description 26
- 239000003208 petroleum Substances 0.000 description 25
- 238000010828 elution Methods 0.000 description 21
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 13
- 239000007787 solid Substances 0.000 description 11
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 11
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 7
- 150000001336 alkenes Chemical class 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000010408 film Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000004575 stone Substances 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 238000005669 hydrocyanation reaction Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 231100000004 severe toxicity Toxicity 0.000 description 3
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-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
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 description 1
- FXDIAIYWNITYLJ-SXGWCWSVSA-N (3z)-3-(1h-indol-3-ylmethylidene)-2-benzofuran-1-one Chemical compound C12=CC=CC=C2C(=O)O\C1=C/C1=CNC2=CC=CC=C12 FXDIAIYWNITYLJ-SXGWCWSVSA-N 0.000 description 1
- XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 description 1
- JMBLSGAXSMOKPN-UHFFFAOYSA-N 2-methylnaphthalen-1-amine Chemical compound C1=CC=CC2=C(N)C(C)=CC=C21 JMBLSGAXSMOKPN-UHFFFAOYSA-N 0.000 description 1
- DHDHJYNTEFLIHY-UHFFFAOYSA-N 4,7-diphenyl-1,10-phenanthroline Chemical class C1=CC=CC=C1C1=CC=NC2=C1C=CC1=C(C=3C=CC=CC=3)C=CN=C21 DHDHJYNTEFLIHY-UHFFFAOYSA-N 0.000 description 1
- WQUHPLQCUQJSQW-VOTSOKGWSA-N 4-[(e)-2-phenylethenyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1\C=C\C1=CC=CC=C1 WQUHPLQCUQJSQW-VOTSOKGWSA-N 0.000 description 1
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910018502 Ni—H Inorganic materials 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical compound CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- BOHDZKSQXXJHBO-YRNVUSSQSA-N chembl3208829 Chemical compound C1=CC=CC2=NC(/C=N/O)=CC=C21 BOHDZKSQXXJHBO-YRNVUSSQSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- ZVDBUOGYYYNMQI-UHFFFAOYSA-N dodec-1-yne Chemical compound CCCCCCCCCCC#C ZVDBUOGYYYNMQI-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- BFSQJYRFLQUZKX-UHFFFAOYSA-L nickel(ii) iodide Chemical compound I[Ni]I BFSQJYRFLQUZKX-UHFFFAOYSA-L 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- UFITZXXHLWZPNO-UHFFFAOYSA-N perchloric acid;hexahydrate Chemical compound O.O.O.O.O.O.OCl(=O)(=O)=O UFITZXXHLWZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000000276 potassium ferrocyanide Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- GHUURDQYRGVEHX-UHFFFAOYSA-N prop-1-ynylbenzene Chemical group CC#CC1=CC=CC=C1 GHUURDQYRGVEHX-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
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- C07C253/08—Preparation of carboxylic acid nitriles by addition of hydrogen cyanide or salts thereof to unsaturated compounds
- C07C253/12—Preparation of carboxylic acid nitriles by addition of hydrogen cyanide or salts thereof to unsaturated compounds to compounds containing carbon-to-carbon triple bonds
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- C07C255/06—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms of an acyclic and unsaturated carbon skeleton
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- C07C255/33—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring with cyano groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
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- C07C255/34—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring with cyano groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by unsaturated carbon chains
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- C07C255/40—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by doubly-bound oxygen atoms
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- C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
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- C07D209/04—Indoles; Hydrogenated indoles
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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Abstract
The preparation method of the invention discloses a kind of alkenyl cyanides as shown in Formula II comprising following steps: in organic solvent, under gas shield, at a temperature of 20 DEG C -100 DEG C, in Raney nickel, reducing agent and H2Under the action of O, alkynes and cyanylation agent shown in formula I are subjected to reduction reaction as follows, the alkenyl cyanides as shown in Formula II are made.Preparation method of the invention is easy to operate, reaction condition is mild using cheap nickel as catalyst system, and functional group compatibility is good, wide application range of substrates, reaction efficiency and high income, therefore application with higher and promotional value.
Description
Technical field
The invention belongs to organic chemistry fileds, more particularly to a kind of preparation method of alkenyl cyanides.
Background technique
Cyano is the important functional group in organic synthesis, can carry out a variety of chemical conversioning reactions, can such as be converted into carboxylic
Acid, aldehyde, ketone, ester, amide, amine, tetrazolium and other nitrogen heterocyclics etc..Further, since highly polar, the strong electrophilic of cyano
Property and the features such as good metabolic stability one kind that cyano is become in pharmaceutical chemistry and materials chemistry research it is extremely important
Functional group；Therefore the cyanalation reaction that the cyano functional groupization reaction of research organic molecule is especially catalyzed, which is undoubtedly to synthesize, to be had
Project extremely important and with great challenge in chemical machine.
Hydrogen-cyanogenation of transition metal-catalyzed alkene or alkynes be synthesize alkenyl cyanogen or alkyl cyanide important method it
One, as following documents is on the books:
(a)T.V.Rajanbabu,2011.Hydrocyanation of Alkenes and Alkynes.Organic
Reactions.Volume 75,chapter 1,pp.1–74；
(b)A.L.Casalnuovo,T.V.Rajanbabu,Transition-metalcatalyzed alkene and
alkyne hydrocyanations.In Transition Metals for Organic Synthesis:Building
Blocks and Fine Chemicals；M.Beller,C.Bolm,Eds.；Wiley-VCH,2008；Chapter 2.5,and
references therein；
(c)M.Beller,J.Seayad,A.Tillack,H.Jiao,Angew.Chem.,Int.Ed.2004,43,
3368-3398and references therein.
Above-mentioned reaction reported in the literature is to be descended and severe toxicity by alkene or alkynes in transition metal such as Ni, Pd or Co catalysis
Hydrogen cyanide or the substrate such as cyanalation product of acetone cyanohydrin reaction generation that hydrogen cyanide can be generated, but hydrogen-cyaniding to alkynes
Repercussion study is very limited.
The hydrogen of alkynes-cyanogenation research at present focuses primarily upon the alkynes of nickel catalysis grinding with hydrogen cyanide or acetone cyanohydrin
Study carefully, but the regioselectivity of such reaction is poor, usually cannot get single hydrogen-cyaniding product.In addition, the substrate of reaction is general
Adaptive and functional group compatibility are poor, and the efficiency and yield of reaction are to be improved.As recorded in having in following documents:
(d)W.R.Jackson,C.G.Lovel,J.Chem.Soc.Chem.Commun.1982,1231-1232；
In the reaction, obtained hydrocyanation product yield is lower, and 2 and 3 mixing yield is about 5~51%, and should
Reaction cannot obtain single hydrocyanation product, and the ratio of products therefrom is about 2/3=9/1.
(e)W.R.Jackson,C.G.Lovel,Aust.J.Chem.1983,36,1975-1982；
(f)N.J.Fitzmaurice,W.R.Jackson,P.Perlmutter,J.Organomet.Chem.1985,
285,375-381.
Since hydrogen cyanide is severe toxicity and volatile liquid (bp27 DEG C), in the presence of base it is also possible to occurring explosive
Polymerization reaction, the great risk in laboratory and industrial production, therefore it is special to develop safe and efficient hydrogen-cyanogenation
It is that there is hydrogen-cyanogenation of high regio- and stereo-selectivity to seem especially urgent and needs.
Nearest Morandi etc. is reported on Science may be implemented no hydrogen cyanide ginseng using transfer hydrogen-cyaniding strategy
With alkene hydrogen-cyanogenation.They pass through the C-CN key fracture of alkyl nitrile and β-H using nickel complex as catalyst
Elimination reaction locally produces NC-Ni-H substance, and then insertion occurs and restores elimination reaction with alkene to obtain hydrogen-cyaniding product,
Also have the hydrogen-cyanogenation of several alkynes in this article, but be confined to interior alkynes (X.Fang, P.Yu, B.Morandi, Science,
2016,351,832-836).Its reaction is as follows:
Therefore this field needs a kind of preparation method of safe and efficient, substrate wide adaptability alkenyl cyanides.
Summary of the invention
The technical problem to be solved by the present invention is to overcome in the preparation method of alkenyl cyanogen in the prior art, usually using acute
Poison hydrogen cyanide as cyanogen source, and usually using valuableness catalyst, substrate narrow application range, severe reaction conditions, solid and
Regioselectivity difference and the defects such as efficiency and yield are low, and then provide a kind of preparation method of alkenyl cyanides.This
The preparation method of invention is easy to operate, reaction condition is mild using cheap nickel as catalyst system, and functional group compatibility is good, bottom
Object is applied widely, reaction efficiency and high income, therefore application with higher and promotional value.
The present invention is to solve technical problem by the following technical programs.
The preparation method of the present invention provides a kind of alkenyl cyanides as shown in Formula II comprising following steps:
In organic solvent, under gas shield, at a temperature of 20 DEG C -100 DEG C, in Raney nickel, reducing agent and H2It, will be as under the action of O
Alkynes and cyanylation agent shown in Formulas I carry out reduction reaction as follows, and the alkenyl cyanogen class chemical combination as shown in Formula II is made
Object；
Wherein, the cyanylation agent is selected from one of Cymag, potassium cyanide, nickel cyanide and zinc cyanide or a variety of；
The Raney nickel is selected from Ni (acac)2、Ni(cod)2、NiCl2·6H2O、NiCl2、NiBr2、NiBr2
(PPh3)2、NiCl2(dppf)、NiCl2(glyme)、NiBr2(DME)、NiF2And Ni (ClO4)26H2One of O or a variety of；
The reducing agent is manganese powder, zinc powder or iron powder；
R1And R2Independently be hydrogen, halogen, hydroxyl,C2-4Alkenyl, C1-10Alkane
Base, by one or more R3Substituted C1-10Alkyl is (when there are multiple R3When, the R3It is identical or different), C3-8Naphthenic base,
By one or more R4Substituted C3-8Naphthenic base is (when there are multiple R4When, the R4It is identical or different), C6-14Aryl, by one
A or multiple R5Substituted C6-14Aryl is (when there are multiple R5When, the R5It is identical or different), C2-14Heteroaryl, by R6Replace
C2-14Heteroaryl is (when there are multiple R6When, the R6It is identical or different),
R1aAnd R1bIt independently is hydrogen, C1-4Alkyl or C6-14Aryl；R1cAnd R1dIt independently is C1-4Alkyl, C1-4Alkoxy or C6-14Virtue
Base；
Each R3Independently be hydroxyl, halogen, cyano,C6-14Aryl, C2-4Alkenyl, C1-4Alkyl
Or C2-14Heteroaryl；R3aAnd R3bIt independently is hydrogen, C6-14Aryl orR3a1For C1-4Alkyl；R3cFor C1-4Alkoxy；
Each R4It independently is hydroxyl, halogen, cyano or C1-4Alkyl；
Each R5Independently be hydroxyl, halogen, cyano,C6-14Aryl, C2-4Alkene
Base, C2-4Alkynyl, C6-14The C that aryl replaces2-4Alkynyl, C1-4Alkyl, C1-4Alkoxy, halogenated C1-4Alkyl, C3-6Naphthenic base orR5aAnd R5bIndependently be H orR5a1For C1-4Alkyl or benzyl；R5cFor amino or
Sulfonic group；R5dFor C1-4Alkyl；
Each R6It independently is hydroxyl, halogen, cyano, C1-4Alkyl or C1-4Alkoxy；
R7、R8And R9It is each independently C6-14Aryl, C1-4Alkyl, C1-4Alkoxy or halogenated C1-4Alkyl；
The C2-14Hetero atom in heteroaryl is selected from O, N and S, and hetero atom number is 1-4, when hetero atom is multiple,
The hetero atom is identical or different.
In the present invention, R1a、R1b、R1c、R1d、R3、R3a1、R4、R5、R5a1、R5d、R6、R7、R8Or R9In, the C1-4Alkyl
It can be methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl or isobutyl group, preferably methyl or ethyl.
In the present invention, R1Or R2In, the C1-10Alkyl can be methyl, ethyl, n-propyl, isopropyl, normal-butyl, uncle
Butyl, isobutyl group, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or positive decyl.
In the present invention, R1c、R1d、R5、R6、R7、R8Or R9In, the C1-4Alkoxy can be methoxyl group, ethyoxyl, the third oxygen
Base, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.
In the present invention, R5、R7、R8Or R9In the C that is preferably replaced by one or more halogens1-4Alkyl, wherein halogen is excellent
Select F, Cl, Br or I；The C1-4Alkyl is as defined above described；Halogenated C of the present invention1-4Alkyl may be, for example ,-CF3。
In the present invention, R1、R2、R3、R4、R5Or R6In, the halogen be preferably F, Cl, Br or I (for example, F, Cl or
Br)。
In the present invention, R1、R2、R3Or R5Described in C2-4Alkenyl can be vinyl, 1- acrylic, 2- acrylic, 1- fourth
Alkenyl, 2- n-butene base, 3- n-butene base,Preferred vinyl.
In the present invention, R1Or R2In, the C3-8Naphthenic base can be C3-6Naphthenic base, preferably cyclopropyl, cyclobutyl, ring penta
Base or cyclohexyl.
In the present invention, R1、R2、R1a、R1b、R1c、R1d、R3、R3a、R3b、R5、R5a1、R5d、R7、R8Or R9In, the C6-14
Aryl can be phenyl, naphthalene, anthryl or phenanthryl, preferably phenyl.
In the present invention, R1、R2Or R3In, the C2-14Heteroaryl can for pyridyl group, thienyl, furyl, imidazole radicals,
Pyranose, pyrimidine radicals, indyl, carbazyl, thiazolyl, quinolyl, isoquinolyl, indolizine base, benzothienyl, benzo furan
It mutters base or benzothiazolyl, preferably pyridyl group.
In the present invention, describedIt can be trimethyl silicon substrate, triethyl group silicon substrate, fert-butyidimethylsilyl
Silicon substrate, triisopropylsilyl or triphenyl silicon substrate, preferably triisopropylsilyl.
In the present invention, the compound of formula I can beWherein, R3Defined as described above, n is between 1-16
Integer.
In the present invention, the compound of formula I can beWherein R5It is defined as described above.
In a preferred embodiment of the invention, R1And R2It independently is hydrogen, C1-10Alkyl, by one or more R3It takes
The C in generation1-10Alkyl (when there are multiple R3When, the R3It is identical or different), C3-8Naphthenic base, by one or more R4Replace
C3-8Naphthenic base is (when there are multiple R4When, the R4It is identical or different), C6-20Aryl, by one or more R5Replace
C6-20Aryl (when there are multiple R5When, the R5It is identical or different), C2-14Heteroaryl, Wherein, R1、R2、R3、R4、R5、R7、R8And R9It is defined as described above.
In a preferred embodiment of the invention, each R3It independently isHalogen,Cyano or C6-14
Aryl；R3aAnd R3bIt independently is hydrogen, C6-14Aryl orR3a1For C1-4Alkyl；R3cFor C1-4Alkoxy；Wherein R3、
R3a、R3b、R3cAnd R3a1It is defined as described above.
In a preferred embodiment of the invention, the R4For hydroxyl；Wherein R4It is defined as described above.
In a preferred embodiment of the invention, each R5It independently isC6-14Aryl, C2-4Alkenyl, C6-14Virtue
The C that base replaces2-4Alkynyl, C1-4Alkyl, C1-4Alkoxy, halogenated C1-4Alkyl orR5aAnd R5bSolely
On the spot for H orR5a1For C1-4Alkyl or benzyl；R5cFor amino or sulfonic group；R5dFor C1-4Alkyl；Wherein R5、R5a、
R5b、R5c、R5a1And R5dIt is defined as described above.
In a preferred embodiment of the invention, R7、R8And R9It is each independently C1-4Alkyl.
In a preferred embodiment of the invention, each R5Selected from halogen, C2-4Alkenyl, C1-4Alkyl, C1-4Alkoxy or
C6-14Aryl.
In a preferred embodiment of the invention, R1And R2It independently is C1-10Alkyl, by one or more R3Replace
C1-10Alkyl, C6-20Aryl, by one or more R5Substituted C6-20Aryl, C2-14Heteroaryl or by R6Replace
C2-14Heteroaryl；Wherein R1、R2、R3And R5It is defined as described above.
In a preferred embodiment of the invention, R1And R2One be H, another for halogen, hydroxyl,C2-4Alkenyl, C1-10Alkyl, by one or more R3Substituted C1-10Alkyl,
C3-8Naphthenic base, by one or more R4Substituted C3-8Naphthenic base, C6-20Aryl, by one or more R5Substituted C6-20's
Aryl, C2-14Heteroaryl, by R6Substituted C2-14Heteroaryl,Its
Middle R1、R2、R1a、R1b、R1cAnd R1dIt is defined as described above.
In a preferred embodiment of the invention, R1And R2It is identical.
In a preferred embodiment of the invention, R1And R2It independently is hydrogen, C1-10Alkyl, by one or more R3It takes
The C in generation1-10Alkyl (when there are multiple R3When, the R3It is identical or different), C3-8Naphthenic base, by one or more R4Replace
C3-8Naphthenic base is (when there are multiple R4When, the R4It is identical or different), C6-20Aryl, by one or more R5Replace
C6-20Aryl (when there are multiple R5When, the R5It is identical or different), C2-14Heteroaryl,
Each R3It independently isHalogen,Cyano or C6-14Aryl；R3aAnd R3bIndependently be hydrogen,
C6-14Aryl orR3a1For C1-4Alkyl；R3cFor C1-4Alkoxy；
The R4For hydroxyl；
Each R5It independently isC6-14Aryl, C2-4Alkenyl, C6-14The C that aryl replaces2-4Alkynyl, C1-4Alkyl,
C1-4Alkoxy, halogenated C1-4Alkyl orR5aAnd R5bIndependently be H orR5a1For
C1-4Alkyl or benzyl；R5cFor amino or sulfonic group；R5dFor C1-4Alkyl；
R7、R8And R9It is each independently C1-4Alkyl；
Wherein each substituent group is defined as described above.
In the present invention, the compound of formula I can be following any compound:
In preparation method of the invention, the cyanylation agent can be zinc cyanide.
In preparation method of the invention, the Raney nickel can be Ni (acac)2、NiCl2·6H2O、Ni(cod)2And
Ni(ClO4)2 6H2One of O or a variety of, preferably Ni (acac).
In preparation method of the invention, the reducing agent can be manganese powder or zinc powder.
In preparation method of the invention, the organic solvent is selected from benzene,toluene,xylene, ether, Isosorbide-5-Nitrae-dioxy six
Ring, tetrahydrofuran, methylene chloride, dichloroethanes, chloroform, acetonitrile, n,N-dimethylacetamide, methyl phosphamide and dimethyl are sub-
One of sulfone is a variety of；Preferably acetonitrile and/or tetrahydrofuran；
The preparation method of the alkenyl cyanides of the present invention as shown in Formula II, can also be in the presence of ligand
Reaction.
Ligand of the present invention can be this field such reaction conventional ligands, preferably bipyridyl (bipy), 4,4'-, bis- uncle
Two pyridine of butyl -2,2'- (dtbbpy), 2,9- dimethyl -1,10- phenanthroline (neocuproine, neocuproine), triphenyl
Phosphine (PPh3), 2,6- diisopropyl N-heterocyclic carbine (IPr), the double diphenylphosphine xanthenes of 9,9- dimethyl -4,5-
(xantphos), triethyl phosphine, tributylphosphine (TBUP), tricyclohexyl phosphine (TCHP), double diphenylphosphine methane (dppm), diformazan
Base Phenylphosphine (PMe2Ph), diphenyl methyl phosphine (PMePh2), bis- (diphenyl phosphine) ethane (dppe) of 1,2-, the bis- (diphenyl of 1,3-
Phosphine) propane (dppp), bis- (diphenylphosphine) butane (dppb) of 1,4-, 4,5- bis- (di-t-butyl phosphine) -9,9- xanthphos
(t) and one of 3- (dicyclohexyl phosphino-) -1- methyl -2- phenyl -1H- indoles (CM-phos) or more Bu-xantphos
Kind, more preferable bipyridyl (bipy), 4,4'- di-t-butyl -2,2'-, bis- pyridine (dtbbpy), 2,9- dimethyl -1,10- phenanthrene are coughed up
Quinoline (neocuproine, neocuproine), triphenylphosphine (PPh3), 2,6- diisopropyl N-heterocyclic carbine (IPr) and 9,9- bis-
The bis- diphenylphosphine xanthenes (xantphos) of methyl -4,5-, one of or it is a variety of, for example, 2,9- dimethyl -1,10- phenanthrene is coughed up
Quinoline (neocuproine, neocuproine) or the double diphenylphosphine xanthenes (xantphos) of 9,9- dimethyl -4,5-.
In preparation method of the invention, the molar ratio of the alkynes shown in formula I and the reducing agent can be 1:0.01
~1:10, preferably 1:0.1~1:1 are more preferably 1:0.2~1:0.5.
In preparation method of the invention, the molar ratio of the alkynes shown in formula I and the Raney nickel can be 1:
0.01~1:1, preferably 1:0.02~1:0.5 are more preferably 1:0.02~1:0.05.
In preparation method of the invention, the molar ratio of the Raney nickel and the ligand can be 1:1~1:10, preferably
It is more preferably 1:1.2 for 1:1~1:5.
In preparation method of the invention, when the Raney nickel includes the ligand, for example, NiCl2(dppf)、
Or NiBr2(PPh3)2When, the preparation reaction can not need that additional ligand is added.
In preparation method of the invention, the molar ratio of the alkynes and the cyanylation agent can be 1:0.1~1:10, compared with
It is goodly 1:0.5~1:2, is more preferably 1:0.6~1:1.2, for example, 1:0.8.
In preparation method of the invention, the molal volume ratio of the alkynes shown in formula I and the solvent can be
0.01mmol/mL~1mmol/mL, preferably 0.15mmol/mL~0.5mmol/mL.
In preparation method of the invention, the molal volume ratio of the alkynes and water shown in formula I can be 0.5mmol/mL
~1.5mmol/mL, preferably 1mmol/mL.
In preparation method of the invention, preferably 25 DEG C to 80 DEG C of the reaction temperature.
In preparation method of the invention, when reducing agent is zinc powder, Raney nickel can be NiCl2·6H2O, ligand can
For Xantphos, reaction temperature can be 80 DEG C.
In preparation method of the invention, the process answered can using in this field routine monitoring method (such as
TLC, HPLC or NMR) it is monitored, as reaction end when generally being disappeared using alkynes or no longer being reacted.
It is the reaction time that the reaction time can be conventional for such reaction of this field, excellent in preparation method of the invention
It selects 0.1 hour to 200 hours, further preferred 30 minutes to 24 hours.
In preparation method of the invention, the gas for protection can be the guarantor of the organic chemical reactions of this field routine
Protect gas, preferably one of nitrogen, helium, argon gas and neon or a variety of, preferably nitrogen.
In preparation method of the invention, the reaction may also include following post-processing step: after reaction, filtering,
Solvent is removed, pillar layer separation obtains target compound, and the pillar layer separation can be using the generic operation in this field
Conventional method.The mixed solvent of eluant, eluent preferred alkane solvents and esters solvent, the alkane solvents and the ester
The volume ratio of class solvent preferred 100:1~1:3, more preferable 50:1~3:1, for example, 30:1~10:1.Or eluant, eluent can be
Alkane solvents, esters solvent and halogenated alkanes solvents, volume ratio can be 5:1:1~1:1:1, preferably 2:1:1.Described
The preferred petroleum ether of alkane solvents, the esters solvent ethyl acetate, the preferred methylene chloride of the halogenated alkane.
In preparation method of the invention, the water can be water commonly used in the art, be not specially limited herein, only
Meet reaction to require, may be, for example, deionized water.
The present invention also provides a kind of alkenyl cyanides as shown in Formula II,
Wherein, R1And R2It is as defined above described in text.
In the present invention, the Formula II compound can beWherein, R3It is defined as described above, n 1-16
Between integer.
In the present invention, the Formula II compound can beWherein R5It is defined as described above.
In the present invention, the Formula II compound can be following any compound:
In the present invention, the Formula II compound can be a certain individual isomer of the compound, i.e.,.
In the present invention, the structure of the Formula II compound can be determined by its mono-crystalline structures.
On the basis of common knowledge of the art, above-mentioned each optimum condition, can any combination to get each preferable reality of the present invention
Example.
The reagents and materials used in the present invention are commercially available.
The positive effect of the present invention is that: preparation method provided by the invention uses Raney nickel cheap and easy to get
And ligand, can safely, mildly, efficiently realize reacting for alkynes and the lesser cyanylation agent of toxicity, alkenyl is prepared
Cyanides, avoiding the hydrogen cyanide in conventional method using severe toxicity is cyanylation agent.In addition, preparation method of the invention
Use water as hydrogen source, has the advantages that green, economy.
Preparation method of the invention is safe, simple to operation, mild, efficient, also has good functional group compatibility and bottom
Object universality etc. is specific, therefore application with higher and promotional value.
Detailed description of the invention
Fig. 1 is the mono-crystalline structures schematic diagram of the compounds of this invention 2q.
Specific embodiment
The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to the reality
It applies among a range.In the following examples, the experimental methods for specific conditions are not specified, according to conventional methods and conditions, or according to quotient
The selection of product specification.
1 compound of embodiment (1a)
In the glove box full of nitrogen atmosphere, Ni (acac) is sequentially added into the reaction flask of 8.0mL2
(0.025mmol,6.4mg),Mn(0.1mmol,5.5mg),Zn(CN)2(0.4mmol, 47.0mg), to methyl phenylacetylene
Then reaction flask is covered tightly outside lid removal glove box and is added with syringe by (0.5mmol, 58.1mg) and acetonitrile (2.5mL)
Water (0.5mL) will be put into the oil bath for be previously heated to 25 DEG C after the lid sealing completely of reaction flask with insulating tape and be reacted, and 24
Stop reaction after hour, after reaction solution is cooled to room temperature, 10% ammonium hydroxide is added and is quenched, ethyl acetate extraction, washing, saturation chlorine
Change sodium solution washing, anhydrous sodium sulfate is dried, filtered, is concentrated, direct silica gel column chromatography purifying, eluant, eluent: petroleum ether to petroleum
Ether/ethyl acetate=100:1 gradient elution, product be yellow oily liquid 59.1mg, yield 83%,1H NMR purity is greater than
98%.1H NMR(400MHz,CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz,
2H), 7.48 (d, J=8.0Hz, 2H)13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,
126.82,129.45,129.57,140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
2 compound of embodiment (1a)
In the embodiment of the present invention 2-6, technical solution is substantially the same manner as Example 1, the difference is that only ligand difference.
Using 1 scheme of embodiment, bipyridyl is ligand, silica gel column chromatography purifying, eluant, eluent: petroleum ether to petroleum ether/second
Acetoacetic ester=100:1 gradient elution, yield 82%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.37
(s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C NMR
(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,140.04.HRMS
(EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
3 compound of embodiment (1a)
Using 1 scheme of embodiment, 4,4'- di-t-butyl -2,2'-, bis- pyridine is ligand, silica gel column chromatography purifying, elution
Agent: petroleum ether to petrol ether/ethyl acetate=100:1 gradient elution, yield 74%,1H NMR purity is greater than 98%.1H NMR
(400MHz,CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J
=8.0Hz, 2H)13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,
129.57,140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
4 compound of embodiment (1a)
Using 1 scheme of embodiment, neocuproine is ligand, and silica gel column chromatography purifies, eluant, eluent: petroleum ether to petroleum ether/
Ethyl acetate=100:1 gradient elution, yield 88%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.37
(s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C NMR
(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,140.04.HRMS
(EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
5 compound of embodiment (1a)
Using 1 scheme of embodiment, triphenylphosphine is ligand, and silica gel column chromatography purifies, eluant, eluent: petroleum ether to petroleum ether/
Ethyl acetate=100:1 gradient elution, yield 72%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.37
(s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C NMR
(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,140.04.HRMS
(EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
6 compound of embodiment (1a)
Using 1 scheme of embodiment, 2,6- diisopropyl N-heterocyclic carbines are ligand, silica gel column chromatography purifying, eluant, eluent: stone
Oily ether is to petrol ether/ethyl acetate=100:1 gradient elution, yield 84%,1H NMR purity is greater than 98%.1H NMR
(400MHz,CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J
=8.0Hz, 2H)13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,
129.57,140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
7 compound of embodiment (1a)
In the embodiment of the present invention 7-8, technical solution is substantially the same manner as Example 1, the difference is that only catalyst not
Together.
Using 1 scheme of embodiment, cyclo-octadiene base nickel is catalyst, silica gel column chromatography purifying, eluant, eluent: petroleum ether to stone
Oily ether/ethyl acetate=100:1 gradient elution, yield 38%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):
δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C
NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,
140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
8 compound of embodiment (1a)
Using 1 scheme of embodiment, perchlorate hexahydrate's nickel is catalyst, silica gel column chromatography purifying, eluant, eluent: petroleum ether to stone
Oily ether/ethyl acetate=100:1 gradient elution, yield 67%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):
δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C
NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,
140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
9 compound of embodiment (1a)
In the embodiment of the present invention 9, technical solution is substantially the same manner as Example 1, the difference is that only organic solvent difference.
Using 1 scheme of embodiment, tetrahydrofuran is solvent, and silica gel column chromatography purifies, eluant, eluent: petroleum ether to petroleum ether/
Ethyl acetate=100:1 gradient elution, yield 83%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.37
(s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C NMR
(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,140.04.HRMS
(EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
10 compound of embodiment (1b)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are nothing
Color oily liquids 63.0mg, yield 79%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ3.83(s,3H),
5.96 (s, 1H), 6.19 (s, 1H), 6.92 (d, J=9.2Hz, 2H), 7.52 (d, J=8.4Hz, 2H)13C NMR(100MHz,
CDCl3): δ 55.29,114.21,117.88,122.10,124.80,125.51,127.01,160.75.H RMS (EI) calculated value
C10H9NO[M]+: 159.0684, measured value 159.0688.
11 compound of embodiment (1c)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=5:1, product are pale yellow
Color oily liquids 61.4mg, yield 85%,1H NMR purity is greater than 98%.1H NMR(400MHz,C6D6):δ3.02(br,2H),
5.39 (s, 1H), 5,56 (s, 1H), 6.25 (dd, J=1.6,8.0Hz, 1H), 6.60 (t, J=2.0Hz, 1H), 6.76 (dd, J
=0.8,8.0Hz, 1H), 6.89 (t, J=8.0Hz, 1H)13C NMR(100MHz,C6D6):δ112.10,115.18,
116.18,118.30,123.19,127.38,129.99,133.67,147.83.HRMS (ESI) calculated value C9H9N2[M+H]+:
145.0760 measured value 145.0759.
12 compound of embodiment (1d)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=5:1, product are white
Solid 115.0mg, yield 83%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ5.19(s,2H),5.99
(s, 1H), 6.22 (s, 1H), 7.06 (br, 1H), 7.33-7.37 (m, 5H), 7.44 (d, J=8.0Hz, 2H), 7.51 (d, J=
8.8Hz,2H).13C NMR(100MHz,CDCl3):δ67.14,117.73,118.53,121.97,126.48,126.59,
127.15,128.22,128.38,128.56,135.65,139.34,153.06.HRMS (EI) calculated value C17H14N2O2[M]+:
278.1055 measured value 278.1054.
13 compound of embodiment (1e)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are nothing
Color liquid 55.1mg, yield 77%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.44(s,3H),5.99
(s,1H),6.25(s,1H),7.22-7.32(m,4H).13C NMR(100MHz,CDCl3):δ19.99,117.84,123.13,
126.39,128.86,129.46,130.78,133.55,133.70,135.70.HRMS (EI) calculated value C10H9N[M]+:
143.0735 measured value 143.0731.
14 compound of embodiment (1f)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are shallow
Yellow liquid 65.6mg, yield 73%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.14(s,1H),
6.39 (s, 1H), 7.43-7.45 (m, 2H), 7.50-7.58 (m, 2H), 7.85-7.88 (m, 2H), 8.10 (d, J=8.4Hz,
1H).13C NMR(100MHz,CDCl3):δ118.32,122.08,124.11,125.15,126.43,126.90,127.06,
128.62,130.07,130.11,131.66,133.54,134.65.HRMS (ESI) calculated value C13H10N[M+H]+:
180.0808 measured value 180.0807.
15 compound of embodiment (1g)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are shallow
Yellow solid 58.3mg, yield 79%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.09(s,1H),
6.27(s,1H),7.09-7.13(m,2H),7.57-7.60(m,2H).13C NMR(100MHz,CDCl3): δ 116.04 (d, J=
22.0Hz), 117.47,121.77,127.63 (d, J=8.6Hz), 127.74 (d, J=1.9Hz), 128.47 (d, J=
3.3Hz), 163.48 (d, J=249.3Hz) .HRMS (EI) calculated value C9H6NF[M]+: 147.0484, measured value 147.0481.
16 compound of embodiment (1h)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are shallow
Yellow liquid 62.9mg, yield 77%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.12(s,1H),
6.32 (s, 1H), 7.39 (d, J=8.4Hz, 2H), 7.53 (d, J=8.8Hz, 2H)13C NMR(100MHz,CDCl3):δ
117.22,121.76,126.91,128.38,129.14,130.69,135.89.HRMS (EI) calculated value C9H6NCl[M]+:
163.0189 measured value 163.0185.
17 compound of embodiment (1i)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are shallow
Yellow liquid 74.4mg, yield 72%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.13(s,1H),
6.34 (s, 1H), 7.46 (d, J=8.8Hz, 2H), 7.55 (d, J=8.8Hz, 2H)13C NMR(100MHz,CDCl3):δ
117.16,121.88,124.17,127.15,128.47,131.15,132.12.HRMS (EI) calculated value C9H6NBr[M]+:
206.9684 measured value 206.9692.
18 compound of embodiment (1j)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are white
Color solid 50.6mg, yield 51%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.25(s,1H),6.46
(s,1H),7.68-7.74(m,4H).13C NMR(100MHz,CDCl3): δ 117.01,121.87,123.60 (q, J=
270.9Hz), 126.03 (q, J=3.7Hz), 126.12,130.27,131.76 (q, J=32.8Hz), 135.60 (q, J=
1.5Hz) .HRMS (EI) calculated value C10H6NF3[M]+: 197.0452, measured value 197.0451.
19 compound of embodiment (1k)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=1:3, product are white
Solid 46.3mg, yield 54%,1H NMR purity is greater than 98%.1H NMR(400MHz,DMSO-d6):δ6.47(s,1H),6.87
(s, 1H), 7.53 (br, 1H), 7.75 (d, J=8.4Hz, 2H), 7.98 (d, J=8.4Hz, 2H), 8.11 (br, 1H)13C NMR
(100MHz,DMSO-d6):δ117.63,120.49,125.52,128.37,132.53,134.47,135.33,
167.06.HRMS (EI) calculated value C10H8N2O[M]+: 172.0637, measured value 172.0641.
20 compound of embodiment (1l)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are shallow
Yellow solid 76.1mg, yield 74%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.07(s,1H),
6.32 (s, 1H), 7.36 (t, J=7.2Hz, 1H), 7.44 (t, J=7.6Hz, 2H), 7.56-7.65 (m, 6H)13C NMR
(100MHz,CDCl3):δ117.63,122.34,126.04,126.91,127.47,127.64,127.84,128.83,
131.03,139.63,142.52.HRMS (EI) calculated value C15H11N[M]+: 205.0891, measured value 205.0889.
21 compound of embodiment (1m)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are shallow
Yellow solid 58.3mg, yield 75%,1H NMR purity is greater than 98%.1H NMR(400MHz,C6D6): δ 5.08 (d, J=
10.4Hz, 1H), 5.34 (s, 1H), 5.48 (s, 1H), 5.56 (dd, J=0.8,17.4Hz, 1H), 6.41-6.48 (m, 1H),
7.04 (d, J=8.4Hz, 2H), 7.23 (d, J=8.4Hz, 2H)13C NMR(100MHz,C6D6):δ115.28,117.80,
122.58,126.13,126.95,127.09,132.06,136.14,139.18.HRMS (EI) calculated value C11H9N[M]+:
155.0735 measured value 155.0732.
22 compound of embodiment (1n)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are white
Color solid 77.8mg, yield 68%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.09(s,1H),6.31
(s, 1H), 7.34 (t, J=7.2Hz, 3H), 7.52-7.55 (m, 6H)13C NMR(100MHz,CDCl3):δ88.44,91.49,
117.33,122.14,122.61,124.85,125.55,128.33,128.57,131.56,131.68,131.99.HRMS
(EI) calculated value C17H11N[M]+: 229.0891, measured value 229.0888.
23 compound of embodiment (1o)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=3:1, product are white
Solid 25.7mg, yield 39%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.17(s,1H),6.37
(s, 1H), 7.30-7.33 (m, 1H), 7.81-7.84 (m, 1H), 8.59 (dd, J=1.6,4.6Hz, 1H), 8.80 (d, J=
2.0Hz,1H).13C NMR(100MHz,CDCl3):δ116.69,120.15,123.57,128.28,129.97,133.12,
146.83,150.77.HRMS (EI) calculated value C8H6N2[M]+: 130.0531, measured value 130.0529.
24 compound of embodiment (1p)
Using 1 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are nothing
Color liquid 14.5mg, yield 14%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ7.15-7.17(m,
2H),7.21-7.29(m,3H),7.36(s,6H).13C NMR(100MHz,CDCl3):δ114.27,120.13,128.50,
128.80,129.03,129.24,129.72,129.82,132.57,133.46,144.14.
25 compound of embodiment (2a)
In the glove box full of nitrogen atmosphere, Ni (acac) is sequentially added into the reaction flask of 8.0mL2
(0.025mmol,6.4mg),neocuproine(0.03mmol,6.2mg),Mn(0.25mmol,13.8mg),Zn(CN)2
Then reaction flask is covered tightly lid and moved by (0.4mmol, 47.0mg), 1- dodecyne (0.5mmol, 83.2mg) and acetonitrile (2.5mL)
Glove box is outer out and water (0.5mL) is added with syringe, will be put into advance after the lid sealing completely of reaction flask with insulating tape
It is heated to reacting in 50 DEG C of oil bath, stops reaction after 24 hours, after reaction solution is cooled to room temperature, water quenching is added and goes out, acetic acid second
Ester extraction, washing, saturated sodium chloride solution washing, anhydrous sodium sulfate are dried, filtered, are concentrated, and direct silica gel column chromatography purifying is washed
De- agent: petrol ether/ethyl acetate=100:1 gradient elution, product are colourless oil liquid 60.0mg, yield 62%,1H NMR
Purity is greater than 98%.1H NMR(400MHz,CDCl3): δ 0.88 (t, J=7.2Hz, 3H), 1.27-1.30 (m, 14H), 1.54-
1.57 (m, 2H), 2.25 (t, J=7.6Hz, 2H), 5.70 (s, 1H), 5.82 (s, 1H)13C NMR(100MHz,CDCl3):δ
14.04,22.61,27.48,28.54,29.15,29.23,29.41,29.48,31.82,34.57,118.70,123.35,
129.97.HRMS (EI) calculated value C13H22N[M-H]+: 192.1752, measured value 192.1757.
26 compound of embodiment (2b)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are
Colourless liquid 42.0mg, yield 61%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ0.88-0.91(m,
3H), 1.24-1.36 (m, 6H), 1.52-1.59 (m, 2H), 2.25 (t, J=8.0Hz, 2H), 5.71 (s, 1H), 5.83 (s,
1H).13C NMR(100MHz,CDCl3):δ13.93,22.41,27.42,28.18,31.31,34.54,118.70,123.32,
130.01.HRMS (EI) calculated value C9H14N[M-H]+: 136.1126, measured value 136.1130.
27 compound of embodiment (2c)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are
Colourless liquid 56.6mg, yield 79%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ3.54(s,2H),
5.68-5.69(m,1H),5.893-5.894(m,1H),7.20-7.22(m,2H),7.27-7.29(m,1H),7.32-7.36
(m,2H).13C NMR(100MHz,CDCl3):δ40.62,118.41,122.54,127.31,128.79,128.82,130.99,
135.47.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0730.
28 compound of embodiment (2d)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are
Colourless liquid 61.7mg, yield 78%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3): δ 2.54 (t, J=
8.0Hz, 2H), 2.86 (t, J=8.0Hz, 2H), 5.61 (s, 1H), 5.79 (s, 1H), 7.16-7.22 (m, 3H), 7.27-7.31
(m,2H).13C NMR(100MHz,CDCl3):δ33.69,36.30,118.39,122.16,126.34,128.31,128.44,
130.89,139.46.HRMS (EI) calculated value C11H11N[M]+: 157.0891, measured value 157.0894.
29 compound of embodiment (2e)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=30:1, product are nothing
Color liquid 56.1mg, yield 67%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.58-1.69(m,
4H), 2.29 (t, J=7.2Hz, 2H), 2.35 (t, J=7.2Hz, 2H), 3.68 (s, 3H), 5.74 (s, 1H), 5.86 (s, 1H)
.13C NMR(100MHz,CDCl3):δ23.67,26.78,33.38,34.11,51.43,118.38,122.59,130.42,
173.49.HRMS (ESI) calculated value C9H17N2O2[M+NH4]+: 185.1285, measured value 185.1283.
30 compound of embodiment (2f)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=5:1, product are nothing
Color liquid 50.3mg, yield 84%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.91-1.99(m,
2H),2.42-2.48(m,4H),5.86(s,1H),5.96(s,1H).13C NMR(100MHz,CDCl3):δ15.92,22.96,
(32.96,117.68,118.46,120.63,132.11.HRMS EI) calculated value C7H8N2[M]+: 120.0687, measured value
120.0684.
31 compound of embodiment (2g)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, product are
Colourless liquid 39.1mg, yield 60%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.01-2.08(m,
2H), 2.47 (t, J=7.2Hz, 2H), 3.58 (t, J=6.4Hz, 2H), 5.81 (s, 1H), 5.92 (s, 1H)13C NMR
(100MHz,CDCl3): δ 29.87,31.56,43.13,118.16,121.40,131.58.HRMS (EI) calculated value C6H8NCl
[M]+: 129.0345, measured value 129.0339.
32 compound of embodiment (2h)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=3:1, product are nothing
Color liquid 59.2mg, yield 85%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.39-1.45(m,
2H), 1.55-1.64 (m, 4H), 2.26-2.29 (m, 3H), 3.63 (t, J=6.8Hz, 2H), 5.74 (s, 1H), 5.85 (s,
1H).13C NMR(100MHz,CDCl3):δ24.63,27.17,32.00,34.35,62.19,118.55,122.86,
130.35.HRMS (ESI) calculated value C8H14NO[M+H]+: 140.1070, measured value 140.1070.
33 compound of embodiment (2i)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=5:1, product are nothing
Color liquid 54.1mg, yield 68%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ3.10(s,1H),5.22
(s,1H),5.98(s,1H),6.05(s,1H),7.34-7.40(m,5H).13C NMR(100MHz,CDCl3):δ73.95,
116.90,126.08,126.44,128.80,129.92,139.07.HRMS (EI) calculated value C10H9NO[M]+:159.0684,
Measured value 159.0678.
34 compound of embodiment (2j)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=5:1, product are nothing
Color liquid 76.9mg, yield 82%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.95-2.09(m,
2H),2.67-2.76(m,2H),2.78(s,1H),4.20(s,1H),5.95(s,1H),5.96(s,1H),7.18-7.20(m,
3H),7.26-7.30(m,2H).13C NMR(100MHz,CDCl3):δ31.13,36.91,71.25,116.95,126.08,
126.56,128.32,128.45,130.20,140.61.HRMS (EI) calculated value C12H13NO[M]+: 187.0997, measured value
187.0990.
35 compound of embodiment (2k)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=10:1, product are nothing
Color liquid 62.0mg, yield 82%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.26(s,1H),
1.62-1.78(m,9H),2.10(s,1H),5.95(s,1H),6.10(s,1H).13C NMR(100MHz,CDCl3):δ21.24,
(24.78,35.81,72.39,117.79,128.27,132.05.HRMS ESI) calculated value C9H17N2O[M+NH4]+:
169.1335 measured value 169.1333.
36 compound of embodiment (2l)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=10:1, product are shallow
Yellow liquid 43.7mg, yield 71%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.53(s,3H),
2.46 (s, 1H), 5.25 (d, J=10.8Hz, 1H), 5.38 (d, J=17.2Hz, 1H), 5.94-6.01 (m, 2H), 6.08 (s,
1H).13C NMR(100MHz,CDCl3):δ26.79,73.52,115.24,117.28,128.82,129.51,140.32.HRMS
(EI) calculated value C7H8NO[M-H]+: 122.0606, measured value 122.0600.
37 compound of embodiment (2m)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=30:1, product are shallow
Yellow liquid 43.1mg, yield 54%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ3.93(s,2H),
4.11 (s, 1H), 5.97-5.98 (m, 2H), 6.57 (d, J=8.4Hz, 2H), 6.76 (t, J=7.2Hz, 1H), 7.18 (t, J=
7.2Hz,2H).13C NMR(100MHz,CDCl3):δ46.38,112.88,117.64,118.46,120.97,129.30,
130.70,146.25.HRMS (ESI) calculated value C10H11N2[M+H]+: 159.0917, measured value 159.0915.
38 compound of embodiment (2n)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=3:1, product are nothing
Color liquid 63.0mg, yield 83%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.92(s,3H),4.50
(s, 2H), 5.86 (s, 1H), 5.99 (s, 1H), 7.26 (d, J=7.6Hz, 2H), 7.39-7.41 (m, 1H), 7.46 (t, J=
6.8Hz,2H).13C NMR(100MHz,CDCl3):δ22.35,51.15,117.35,119.18,127.82,128.39,
129.83,133.00,141.85,170.58.HRMS (ESI) calculated value C12H13N2O[M+H]+: 201.1022, measured value
201.1020.
39 compound of embodiment (2o)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are nothing
Color liquid 73.2mg, yield 80%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ4.77(s,2H),5.37
(s, 1H), 5.88 (s, 1H), 6.55 (d, J=2.4Hz, 1H), 7.02 (d, J=2.4Hz, 1H), 7.11-7.15 (m, 1H),
7.18-7.21 (m, 2H), 7.63 (d, J=7.6Hz, 1H)13C NMR(100MHz,CDCl3):δ48.11,102.94,
109.05,116.71,119.18,120.12,121.22,122.21,127.72,128.71,131.19,135.65.HRMS
(ESI) calculated value C12H11N2[M+H]+: 183.0917, measured value 183.0914.
40 compound of embodiment (2p)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, product are nothing
Color liquid 2.6mg, yield 2%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3): δ 1.12 (d, J=7.6Hz,
18H), 1.25-1.32 (m, 3H), 6.21 (d, J=2.4Hz, 1H), 6.77 (d, J=2.8Hz, 1H)13C NMR(100MHz,
CDCl3): δ 10.60,18.07,120.72,147.26.HRMS (EI) calculated value C12H23NSi[M]+: 209.1600, measured value
209.1593.
41 compound of embodiment (2q)
Using 25 scheme of embodiment, silica gel column chromatography is purified, eluant, eluent: petrol ether/ethyl acetate/methylene chloride=2:1:
1, product be white solid 135.6mg, yield 80%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ
0.88-0.93(m,1H),1.01-1.10(m,4H),1.20-1.27(m,4H),1.30-1.35(m,1H),1.42-1.50(m,
2H), 1.63-1.75 (m, 5H), 1.86 (d, J=12.0Hz, 1H), 2.00-2.05 (m, 2H), 2.12-2.18 (m, 1H),
2.27-2.45(m,4H),2.98(s,1H),5.72(s,1H),5.85(s,1H),6.09(s,1H).13C NMR(100MHz,
CDCl3):δ14.10,17.18,20.47,23.63,31.33,32.51,32.53,33.68,35.38,36.03,36.47,
38.40,47.09,48.89,53.10,84.53,118.43,123.68,129.82,130.63,171.19,199.65.HRMS
(ESI) calculated value C22H30NO2[M+H]+: 340.2271, measured value 340.2266.
The mono-crystalline structures of compound 2q are as shown in Figure 1.
42 compound of embodiment (2r)
Using 25 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=3:1, product are white
Color solid 165.6mg, yield 74%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.29(s,9H),
2.46 (br, 8H), 3.48 (s, 2H), 4.24 (s, 1H), 5.96 (s, 1H), 6.18 (s, 1H), 7.15 (t, J=7.6Hz, 1H),
7.20-7.26 (m, 4H), 7.30 (d, J=8.0Hz, 2H), 7.36 (d, J=7.6Hz, 2H), 7.46 (s, 4H)13C NMR
(100MHz,CDCl3):δ31.28,34.29,51.72,53.10,62.52,75.59,117.57,122.46,124.91,
125.78.127.05,127.31,127.78,128.35,128.46,128.85,130.78,134.76,141.88,144.98,
149.70.HRMS (EI) calculated value C31H35N3[M]+: 449.2831, measured value 449.2820.
43 compound of embodiment (3a)
In the glove box full of nitrogen atmosphere, NiCl is sequentially added into the reaction flask of 4.0mL2·6H2O
(0.009mmol,2.1mg),Xantphos(0.012mmol,6.9mg),Zn(0.06mmol,3.9mg),Zn(CN)2
(0.24mmol, 28.2mg), hexichol list alkynes (0.3mmol, 53.5mg) and acetonitrile (1.5mL), then cover tightly lid for reaction flask
It is outer and water (0.5mL) is added with syringe to remove glove box, with insulating tape will reaction flask lid sealing it is complete after be put into it is pre-
It is first heated to reacting in 80 DEG C of oil bath, stops reaction after 10 hours, after reaction solution is cooled to room temperature, water quenching is added and goes out, acetic acid
Ethyl ester extraction, washing, saturated sodium chloride solution washing, anhydrous sodium sulfate are dried, filtered, are concentrated, direct silica gel column chromatography purifying,
Eluant, eluent: petrol ether/ethyl acetate=100:1 gradient elution, product are colourless oil liquid, yield 95%,1H NMR purity
Greater than 98%.1H NMR(400MHz,CDCl3): δ 7.15 (d, J=7.6Hz, 2H), 7.21 (t, J=7.6Hz, 2H), 7.27 (t,
J=7.2Hz, 1H), 7.35-7.36 (m, 6H)13C NMR(100MHz,CDCl3):δ114.22,120.07,128.46,
128.75,128.98,129.20,129.68,129.78,132.54,133.41,144.08.IR(neat):3051,3029,
2205,1606,1574,1490,1445,1399,1184,1079,1019,927,893,771,760,726,690cm-1.HRMS
(ESI) calculated value C15H12N[M+H]+: 206.0964, measured value 206.0961.
44 compound of embodiment (3b)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, yield
93%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3): δ 2.30 (s, 3H), 2.36 (s, 3H), 7.02 (d, J=
8.0Hz, 2H), 7.07 (d, J=8.4Hz, 2H), 7.14 (d, J=8.4Hz, 2H), 7.23-7.28 (m, 3H)13C NMR
(100MHz,CDCl3):δ21.26,21.33,113.10,120.45,128.58,129.14,129.62,129.66,129.81,
(130.78,139.13,140.11,143.57.IR film): 3027,2921,2205,1606,1508,1448,1410,1379,
1322,1210,1184,1114,1040,1018,952,900,813,772,724,714cm-1.HRMS (ESI) calculated value
C17H16N[M+H]+: 234.1277, measured value 234.1276.
45 compound of embodiment (3c)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=30:1, yield
96%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ3.77(s,3H),3.82(s,3H),6.72-6.76
(m,2H),6.86-6.89(m,2H),7.12-7.15(m,2H),7.19(s,1H),7.30-7.33(m,2H).13C NMR
(100MHz,CDCl3):δ55.18,55.20,111.14,113.83,114.35,120.74,125.07,126.21,130.08,
(131.41,142.70,159.92,160.57.IR film): 2965,2937,2831,2202,1601,1568,1508,1462,
1442,1424,1293,1247,1173,1111,1024,905,829,804,735cm-1.HRMS (ESI) calculated value C17H16NO2
[M+H]+: 266.1176, measured value 266.1172.
46 compound of embodiment (3d)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=50:1, yield
93%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3): δ 2.23 (s, 3H), 2.38 (s, 3H), 6.66 (d, J=
7.6Hz,1H),6.81-6.85(m,1H),7.10-7.27(m,6H),7.59(s,1H).13C NMR(100MHz,CDCl3):δ
19.45,19.88,113.86,119.67,125.62,126.46,128.67,129.11,129.51,129.59,130.41,
(130.80,131.95,132.55,136.27,137.33,143.93.IR film): 3067,3023,2920,2210,1598,
1479,1458,1377,1288,1260,1230,1099,1020,905,765,754,729,720cm-1.HRMS (ESI) is calculated
Value C17H19N2[M+NH4]+: 251.1543, measured value 251.1542.
47 compound of embodiment (3e)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, yield
92%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ6.91-6.97(m,2H),7.04-7.09(m,2H),
7.13-7.17(m,2H),7.31(s,1H),7.33-7.38(m,2H).13C NMR(100MHz,CDCl3): δ 112.95 (d, J=
1.5Hz), 115.83 (d, J=22.0Hz), 116.34 (d, J=22.0Hz), 119.72,128.31 (d, J=3.8Hz),
129.37 (d, J=3.8Hz), 130.76 (d, J=8.4Hz), 131.72 (d, J=8.3Hz), 143.00,161.83 (d, J=
22.8Hz), 164.33 (d, J=25.0Hz) .IR (film): 3076,2232,2208,1599,1505,1408,1374,1297,
1228,1158,1101,1037,1014,901,831,787,731,717,684cm-1.HRMS (ESI) calculated value C15H13F2N2[M
+NH4]+: 259.1041, measured value 259.1042.
48 compound of embodiment (3f)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=100:1, yield
82%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ7.08-7.11(m,2H),7.21-7.24(m,2H),
7.29-7.35(m,5H).13C NMR(100MHz,CDCl3):δ113.69,119.38,128.95,129.43,130.12,
(130.62,130.86,131.53,135.53,136.02,143.12.IR film): 3042,2209,1902,1779,1610,
1589,1489,1399,1366,1310,1222,1177,1092,1012,897,822,763,722,689cm-1.HRMS(EI)
Calculated value C15H9NCl2[M]+: 273.0112, measured value 273.0119.
49 compound of embodiment (3g)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=10:1, yield
88%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ1.36-1.42(m,6H),4.34-4.42(m,4H),
7.22 (d, J=8.4Hz, 2H), 7.43-7.45 (m, 2H), 7.48 (s, 1H), 7.91-7.93 (m, 2H), 8.02-8.04 (m,
2H).13C NMR(100MHz,CDCl3):δ14.13,14.16,61.17,61.22,115.41,118.97,128.83,
129.46,129.65,130.17,131.34,131.43,136.34,137.15,144.03 165.47,165.50.IR is (thin
Film): 2992,2948,2204,1734,1716,1699,1607,1563,1405,1364,1283,1 269,1182,1125,
1100,1017,925,856,777,770,740,701cm-1.HRMS (ESI) calculated value C21H23N2O4[M+NH4]+:
367.1652 measured value 367.1648.
50 compound of embodiment (3h)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=10:1, yield
87%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ7.37-7.46(m,2H),7.54(s,1H),7.55-
7.64(m,2H),7.68(s,1H),7.82-7.85(m,1H),7.89-7.94(m,2H),9.88(s,1H),9.98(s,1H)
.13C NMR(100MHz,CDCl3):δ114.78,118.94,129.48,129.77,130.04,130.51,130.68,
131.04,133.04,133.84,134.44,134.82,136.62,137.08,143.68 190.96,190.98.IR is (thin
Film): 2848,2748,2216,1737,1596,1474,1381,1227,1155,1141,912,89 5,801,783,713,
693,684cm-1.HRMS (EI) calculated value C17H11NO2[M]+: 261.0790, measured value 261.0789.
51 compound of embodiment (3i)
Using 43 scheme of embodiment, silica gel column chromatography purifying, eluant, eluent: petrol ether/ethyl acetate=5:1, yield 65%
,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ7.19-7.22(m,1H),7.35-7.43(m,2H),7.48
(s, 1H), 7.73 (dt, J=2.0,7.6Hz, 1H), 8.46 (d, J=2.0Hz, 1H), 8.55 (dd, J=1.6,4.8Hz, 1H),
8.60 (d, J=2.4Hz, 1H), 8.65 (dd, J=1.6,4.8Hz, 1H)13C NMR(100MHz,CDCl3):δ113.36,
118.56,123.42,123.91,128.30,128.96,136.01,136.15,142.30,149.37,150.52,150.61,
150.85.IR (film): 3034,2912,2213,1611,1583,1567,1479,1411,1184,1127,1023,8 95,
853,810,753cm-1.HRMS (ESI) calculated value C13H10N3[M+H]+: 208.0869, measured value 208.0868.
Comparative example 1
Using 1 scheme of embodiment, 1,10- ferrosin is ligand, silica gel column chromatography purifying, eluant, eluent: petroleum ether to petroleum
Ether/ethyl acetate=100:1 gradient elution, yield 1%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ
2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C
NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,
140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 2
Using 1 scheme of embodiment, 4,7- diphenyl -1,10- phenanthrolines are ligand, silica gel column chromatography purifying, eluant, eluent: stone
Oily ether is to petrol ether/ethyl acetate=100:1 gradient elution, yield 7%,1H NMR purity is greater than 98%.1H NMR(400MHz,
CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz,
2H).13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,
140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 3
Using 1 scheme of embodiment, 2,9- dimethyl -4,7- biphenyl -1,10- phenanthrolenes are ligand, silica gel column chromatography
Purifying, eluant, eluent: petroleum ether to petrol ether/ethyl acetate=100:1 gradient elution, yield 27%,1H NMR purity is greater than
98%.1H NMR(400MHz,CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz,
2H), 7.48 (d, J=8.0Hz, 2H)13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,
126.82,129.45,129.57,140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 4
Using 1 scheme of embodiment, 1,1'- bis- (diphenylphosphine) ferrocene are ligand, and silica gel column chromatography purifies, eluant, eluent:
Petroleum ether is to petrol ether/ethyl acetate=100:1 gradient elution, yield 4%,1H NMR purity is greater than 98%.1H NMR
(400MHz,CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J
=8.0Hz, 2H)13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,
129.57,140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 5
Using 1 scheme of embodiment, the bis- diphenylphosphine xanthenes of 9,9- dimethyl -4,5- are ligand, and silica gel column chromatography purifies,
Eluant, eluent: petroleum ether to petrol ether/ethyl acetate=100:1 gradient elution, yield 20%,1H NMR purity is greater than 98%.1H
NMR(400MHz,CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48
(d, J=8.0Hz, 2H)13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,
129.45,129.57,140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 6
Using 1 scheme of embodiment, nickel iodide is catalyst, and silica gel column chromatography purifies, eluant, eluent: petroleum ether to petroleum ether/
Ethyl acetate=100:1 gradient elution, yield 18%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.37
(s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C NMR
(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,140.04.HRMS
(EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 7
Using 1 scheme of embodiment, diethylene glycol dimethyl ether nickelous bromide is catalyst, silica gel column chromatography purifying, eluant, eluent: stone
Oily ether is to petrol ether/ethyl acetate=100:1 gradient elution, yield 7%,1H NMR purity is greater than 98%.1H NMR(400MHz,
CDCl3): δ 2.37 (s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz,
2H).13C NMR(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,
140.04.HRMS (EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 8
Using 1 scheme of embodiment, reaction temperature is 0 DEG C, silica gel column chromatography purifying, eluant, eluent: petroleum ether to petroleum ether/second
Acetoacetic ester=100:1 gradient elution, yield 3%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.37(s,
3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C NMR
(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,140.04.HRMS
(EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 9
Using 1 scheme of embodiment, reaction temperature is 150 DEG C, silica gel column chromatography purifying, eluant, eluent: petroleum ether to petroleum ether/
Ethyl acetate=100:1 gradient elution, yield 14%,1H NMR purity is greater than 98%.1H NMR(400MHz,CDCl3):δ2.37
(s, 3H), 6.02 (s, 1H), 6.27 (s, 1H), 7.21 (d, J=8.0Hz, 2H), 7.48 (d, J=8.0Hz, 2H)13C NMR
(100MHz,CDCl3):δ21.14,117.79,122.63,125.49,126.82,129.45,129.57,140.04.HRMS
(EI) calculated value C10H9N[M]+: 143.0735, measured value 143.0734.
Comparative example 10
Using 1 scheme of embodiment, cyanylation agent is changed to potassium ferrocyanide, bearing reaction cannot occur substantially.
Comparative example 11
Using 1 scheme of embodiment, cyanylation agent is changed to tetramethyl cyanogen silane, bearing reaction cannot occur substantially.
Comparative example 12
Using 1 scheme of embodiment, cyanylation agent is changed to acetonitrile, bearing reaction cannot occur substantially.
Comparative example 13
Using 1 scheme of embodiment, cyanylation agent is changed to cuprous cyanide, bearing reaction cannot occur substantially.
Claims (10)
1. a kind of preparation method of the alkenyl cyanides as shown in Formula II, which is characterized in that the preparation method include with
Lower step: in organic solvent, under gas shield, at a temperature of 20 DEG C -100 DEG C, in Raney nickel, reducing agent and H2The effect of O
Under, alkynes and cyanylation agent shown in formula I are subjected to reduction reaction as follows, the alkenyl cyanogen as shown in Formula II is made
Class compound；
Wherein, the cyanylation agent is selected from one of Cymag, potassium cyanide, nickel cyanide and zinc cyanide or a variety of；
The Raney nickel is selected from Ni (acac)2、Ni(cod)2、NiCl2·6H2O、NiCl2、NiBr2、NiBr2(PPh3)2、
NiCl2(dppf)、NiCl2(glyme)、NiBr2(DME)、NiF2With Ni (ClO4)2 6H2One of O or a variety of；
The reducing agent is manganese powder, zinc powder or iron powder；
R1And R2Independently be hydrogen, halogen, hydroxyl,C2-4Alkenyl, C1-10Alkyl, quilt
One or more R3Substituted C1-10Alkyl, C3-8Naphthenic base, by one or more R4Substituted C3-8Naphthenic base, C6-14Aryl, quilt
One or more R5Substituted C6-14Aryl, C2-14Heteroaryl, by R6Substituted C2-14Heteroaryl,R1aAnd R1bIt independently is hydrogen, C1-4Alkyl or C6-14Aryl；R1cWith
R1dIt independently is C1-4Alkyl, C1-4Alkoxy or C6-14Aryl；
Each R3Independently be hydroxyl, halogen, cyano,C6-14Aryl, C2-4Alkenyl, C1-4Alkyl or
C2-14Heteroaryl；R3aAnd R3bIt independently is hydrogen, C6-14Aryl orR3a1For C1-4Alkyl；R3cFor C1-4Alkoxy；
Each R4It independently is hydroxyl, halogen, cyano or C1-4Alkyl；
Each R5Independently be hydroxyl, halogen, cyano,C6-14Aryl, C2-4Alkenyl,
C2-4Alkynyl, C6-14The C that aryl replaces2-4Alkynyl, C1-4Alkyl, C1-4Alkoxy, halogenated C1-4Alkyl, C3-6Naphthenic base orR5aAnd R5bIndependently be H orR5a1For C1-4Alkyl or benzyl；R5cFor amino or
Sulfonic group；R5dFor C1-4Alkyl；
Each R6It independently is hydroxyl, halogen, cyano, C1-4Alkyl or C1-4Alkoxy；
R7、R8And R9It is each independently C6-14Aryl, C1-4Alkyl, C1-4Alkoxy or halogenated C1-4Alkyl；
The C2-14Heteroaryl in hetero atom be selected from O, N and S, hetero atom number be 1-4, when hetero atom be it is multiple when, it is described
Hetero atom it is identical or different.
2. the preparation method of the alkenyl cyanides as described in claim 1 as shown in Formula II, which is characterized in that
When there are multiple R3When, the R3It is identical or different；
And/or when there are multiple R4When, the R4It is identical or different；
And/or when there are multiple R5When, the R5It is identical or different；
And/or when there are multiple R6When, the R6It is identical or different；
And/or R1a、R1b、R1c、R1d、R3、R3a1、R4、R5、R5a1、R5d、R6、R7、R8Or R9In, the C1-4Alkyl is methyl, second
Base, n-propyl, isopropyl, normal-butyl, tert-butyl or isobutyl group, preferably methyl or ethyl；
And/or R1Or R2In, the C1-10Alkyl be methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group,
N-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or positive decyl；
And/or R1c、R1d、R5、R6、R7、R8Or R9In, the C1-4Alkoxy is methoxyl group, ethyoxyl, propoxyl group, isopropyl oxygen
Base, n-butoxy, isobutoxy or tert-butoxy；
And/or R5、R7、R8Or R9In, the halogenated C1-4Alkyl is the C replaced by one or more halogens1-4Alkyl, wherein halogen
Element is F, Cl, Br or I；The wherein C1-4Alkyl is methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl or isobutyl
Base, preferably methyl or ethyl；The halogenated C1-4Alkyl preferably-CF3；
And/or R1、R2、R3、R4、R5Or R6In, the halogen is F, Cl, Br or I, preferably F, Cl or Br；
And/or R1、R2、R3Or R5In, the C2-4Alkenyl is vinyl, 1- acrylic, 2- acrylic, 1- cyclobutenyl, the positive fourth of 2-
Alkenyl, 3- n-butene base,Preferred vinyl；
And/or R1Or R2In, the C3-8Naphthenic base is C3-6Naphthenic base, preferably cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl；
And/or R1、R2、R1a、R1b、R1c、R1d、R3、R3a、R3b、R5、R5a1、R5d、R7、R8Or R9In, the C6-14Aryl be phenyl,
Naphthalene, anthryl or phenanthryl；It is preferred that phenyl；
And/or R1、R2Or R3In, the C2-14Heteroaryl is pyridyl group, thienyl, furyl, imidazole radicals, pyranose, pyrimidine
Base, indyl, carbazyl, thiazolyl, quinolyl, isoquinolyl, indolizine base, benzothienyl, benzofuranyl or benzo
Thiazolyl, preferably pyridyl group；
And/or it is describedFor trimethyl silicon substrate, triethyl group silicon substrate, t-Butyldimethylsilyl, three isopropyls
Base silicon substrate or triphenyl silicon substrate, preferably triisopropylsilyl；
And/or the compound of formula I isWherein, integer of the n between 1-16；
And/or the compound of formula I is
3. the preparation method of the alkenyl cyanides as described in claim 1 as shown in Formula II, which is characterized in that
R1And R2It independently is hydrogen, C1-10Alkyl, by one or more R3Substituted C1-10Alkyl, C3-8Naphthenic base, by one
Or multiple R4Substituted C3-8Naphthenic base, C6-20Aryl, by one or more R5Substituted C6-20Aryl, C2-14Heteroaryl,
Or
And/or each R3It independently isHalogen,Cyano or C6-14Aryl；R3aAnd R3bIndependently be hydrogen,
C6-14Aryl orR3a1For C1-4Alkyl；R3cFor C1-4Alkoxy；
And/or the R4For hydroxyl；
And/or each R5It independently isC6-14Aryl, C2-4Alkenyl, C6-14The C that aryl replaces2-4Alkynyl, C1-4Alkyl,
C1-4Alkoxy, halogenated C1-4Alkyl orR5aAnd R5bIndependently be H orR5a1For
C1-4Alkyl or benzyl；R5cFor amino or sulfonic group；R5dFor C1-4Alkyl；
And/or R7、R8And R9It is each independently C1-4Alkyl；
And/or each R5Selected from halogen, C2-4Alkenyl, C1-4Alkyl, C1-4Alkoxy or C6-14Aryl；
And/or R1And R2It is each independently C1-10Alkyl, by one or more R3Substituted C1-10Alkyl, C6-20Virtue
Base, by one or more R5Substituted C6-20Aryl, C2-14Heteroaryl or by R6Substituted C2-14Heteroaryl；
And/or R1And R2In, one be H, another for halogen, hydroxyl, C2-4Alkene
Base, C1-10Alkyl, by one or more R3Substituted C1-10Alkyl, C3-8Naphthenic base, by one or more R4Substituted C3-8
Naphthenic base, C6-20Aryl, by one or more R5Substituted C6-20Aryl, C2-14Heteroaryl, by R6Substituted C2-14's
Heteroaryl,
And/or R1And R2It is identical.
4. the preparation method of the alkenyl cyanides as described in claim 1 as shown in Formula II, which is characterized in that
R1And R2It independently is hydrogen, C1-10Alkyl, by one or more R3Substituted C1-10Alkyl, C3-8Naphthenic base, by one
Or multiple R4Substituted C3-8Naphthenic base, C6-20Aryl, by one or more R5Substituted C6-20Aryl, C2-14Heteroaryl,
Each R3It independently isHalogen,Cyano or C6-14Aryl；R3aAnd R3bIt independently is hydrogen, C6-14Aryl
OrR3a1For C1-4Alkyl；R3cFor C1-4Alkoxy；
The R4For hydroxyl；
Each R5It independently isC6-14Aryl, C2-4Alkenyl, C6-14The C that aryl replaces2-4Alkynyl, C1-4Alkyl, C1-4Alkane
Oxygroup, halogenated C1-4Alkyl orR5aAnd R5bIndependently be H orR5a1For C1-4Alkane
Base or benzyl；R5cFor amino or sulfonic group；R5dFor C1-4Alkyl；
R7、R8And R9It is each independently C1-4Alkyl.
5. the preparation method of the alkenyl cyanides according to any one of claims 1-4 as shown in Formula II, feature exist
In the compound shown in formula I is following any compound:
6. the preparation method of the alkenyl cyanides as described in claim 1 as shown in Formula II, which is characterized in that
The cyanylation agent is zinc cyanide；
And/or the Raney nickel is selected from Ni (acac)2、NiCl2·6H2O、Ni(cod)2And Ni (ClO4)26H2One in O
Kind is a variety of；Preferably Ni (acac)；
And/or the reducing agent is manganese powder or zinc powder；
And/or the organic solvent is selected from benzene,toluene,xylene, ether, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran, dichloromethane
One of alkane, dichloroethanes, chloroform, acetonitrile, n,N-dimethylacetamide, methyl phosphamide and dimethyl sulfoxide are a variety of；
Preferably acetonitrile and/or tetrahydrofuran；
And/or the molar ratio of the alkynes shown in formula I and the reducing agent is 1:0.01~1:10, preferably 1:0.1
~1:1 is more preferably 1:0.2~1:0.5；
And/or the molar ratio of the alkynes shown in formula I and the Raney nickel is 1:0.01~1:1, preferably 1:
0.02~1:0.5 is more preferably 1:0.02~1:0.05；
And/or the molar ratio of the Raney nickel and the ligand is 1:1~1:10, preferably 1:1~1:5, more preferably for
1:1.2；
And/or the molar ratio of the alkynes and the cyanylation agent is 1:0.1~1:10, preferably 1:0.5~1:2, more
It goodly is 1:0.6~1:1.2, for example, 1:0.8；
And/or the molal volume ratio of the alkynes shown in formula I and the solvent is 0.01mmol/mL~1mmol/mL, compared with
It goodly is 0.15mmol/mL~0.5mmol/mL；
And/or the molal volume ratio of the alkynes and water shown in formula I is 0.5mmol/mL~1.5mmol/mL, preferably
For 1mmol/mL；
And/or the reaction temperature is 25 DEG C to 80 DEG C.
7. the preparation method of the alkenyl cyanides as described in claim 1 as shown in Formula II, which is characterized in that described anti-
It should be carried out in the presence of ligand.
8. the preparation method of the alkenyl cyanides as claimed in claim 7 as shown in Formula II, which is characterized in that
The ligand is selected from bipyridyl, two pyridine of 4,4'- di-t-butyl -2,2'-, 2,9- dimethyl -1,10- phenanthroline, three
The double diphenylphosphine xanthenes of Phenylphosphine, 2,6- diisopropyl N-heterocyclic carbine, 9,9- dimethyl -4,5-, triethyl phosphine, tributyl
Bis- (diphenyl phosphine) ethane of phosphine, tricyclohexyl phosphine, double diphenylphosphine methane, dimethylphenylphosphine, diphenyl methyl phosphine, 1,2-, 1,
Bis- (diphenylphosphine) propane of 3-, bis- (diphenylphosphine) butane of 1,4-, (the di-t-butyl phosphine) -9,9- of 4,5- bis- xanthphos,
With one of 3- (dicyclohexyl phosphino-) -1- methyl -2- phenyl -1H- indoles or a variety of, preferably bipyridyl, the tertiary fourth of 4,4'- bis-
Two pyridine of base -2,2'-, 2,9- dimethyl -1,10- phenanthroline, triphenylphosphine, 2,6- diisopropyl N-heterocyclic carbine and 9,9-
One of bis- diphenylphosphine xanthenes of dimethyl -4,5- are a variety of, more preferable 2,9- dimethyl -1,10- phenanthroline or 9,9-
The double diphenylphosphine xanthenes of dimethyl -4,5-.
9. a kind of alkenyl cyanides as shown in Formula II,
Wherein, R1And R2Definition it is as described in claim 1.
10. the alkenyl cyanides as claimed in claim 9 as shown in Formula II, which is characterized in that
The Formula II compound isWherein, R3Definition it is as described in claim 1, n is whole between 1-16
Number；
And/or the Formula II compound isWherein, R5Definition it is as described in claim 1；
And/or the Formula II compound is following any compound:
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| W. ROY JACKSON，CRAIG G. LOVE1: "Nickel(0) Catalysed Additions of Hydrogen Cyanide to Alkynes:Stereochemistry, Mechanism, and Preparative Application", 《J. CHEM. SOC., CHEM. COMMUN.》 * |
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| CN113754597B (en) * | 2021-09-07 | 2024-07-16 | 凯美克(上海)医药科技有限公司 | Benzhydryl piperazine compound containing linear olefin and preparation method thereof |
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