CN111484472B - 烷基腈类化合物的制备方法 - Google Patents
烷基腈类化合物的制备方法 Download PDFInfo
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- CN111484472B CN111484472B CN201910081372.4A CN201910081372A CN111484472B CN 111484472 B CN111484472 B CN 111484472B CN 201910081372 A CN201910081372 A CN 201910081372A CN 111484472 B CN111484472 B CN 111484472B
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- unsubstituted
- substituted
- aryl
- alkyl
- nickel
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- 238000004519 manufacturing process Methods 0.000 title description 3
- 150000001336 alkenes Chemical class 0.000 claims abstract description 62
- -1 alkyl nitrile compound Chemical class 0.000 claims abstract description 58
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 41
- 239000003054 catalyst Substances 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 25
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 11
- 238000007333 cyanation reaction Methods 0.000 claims abstract description 11
- 238000006722 reduction reaction Methods 0.000 claims abstract description 11
- 229940125904 compound 1 Drugs 0.000 claims abstract description 9
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000009471 action Effects 0.000 claims abstract description 5
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 5
- 230000001681 protective effect Effects 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 132
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 78
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 73
- 150000001875 compounds Chemical class 0.000 claims description 68
- 239000003446 ligand Substances 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 125000005842 heteroatom Chemical group 0.000 claims description 40
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- 229910052759 nickel Inorganic materials 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 30
- 150000002816 nickel compounds Chemical class 0.000 claims description 28
- 150000002815 nickel Chemical class 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 239000011701 zinc Substances 0.000 claims description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 239000003638 chemical reducing agent Substances 0.000 claims description 12
- 229910052786 argon Inorganic materials 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 150000002825 nitriles Chemical class 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 238000006467 substitution reaction Methods 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- 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 8
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound 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 claims description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000003849 aromatic solvent Substances 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 150000008282 halocarbons Chemical class 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical group [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 claims description 4
- 150000003462 sulfoxides Chemical class 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-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
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims description 3
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical group [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 2
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 claims description 2
- 125000006017 1-propenyl group Chemical group 0.000 claims description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- JCUYKJIVFPLSFL-UHFFFAOYSA-N P.C1=CC=CC=2OC3=CC=CC=C3CC12 Chemical compound P.C1=CC=CC=2OC3=CC=CC=C3CC12 JCUYKJIVFPLSFL-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- WXMZPPIDLJRXNK-UHFFFAOYSA-N butyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(CCCC)C1=CC=CC=C1 WXMZPPIDLJRXNK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000008367 deionised water Substances 0.000 claims description 2
- 229910021641 deionized water Inorganic materials 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
- AAXGWYDSLJUQLN-UHFFFAOYSA-N diphenyl(propyl)phosphane Chemical compound C=1C=CC=CC=1P(CCC)C1=CC=CC=C1 AAXGWYDSLJUQLN-UHFFFAOYSA-N 0.000 claims description 2
- WUOIAOOSKMHJOV-UHFFFAOYSA-N ethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(CC)C1=CC=CC=C1 WUOIAOOSKMHJOV-UHFFFAOYSA-N 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 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
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052754 neon Inorganic materials 0.000 claims description 2
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001400 nonyl group Chemical group [H]C([*])([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])[H] 0.000 claims description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 2
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 3
- 239000011630 iodine Substances 0.000 claims 3
- 229910052740 iodine Inorganic materials 0.000 claims 3
- 125000001033 ether group Chemical group 0.000 claims 2
- 239000013078 crystal Substances 0.000 claims 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 238000005669 hydrocyanation reaction Methods 0.000 abstract description 32
- 239000000758 substrate Substances 0.000 abstract description 9
- 125000000524 functional group Chemical group 0.000 abstract description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 183
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 179
- 238000006243 chemical reaction Methods 0.000 description 86
- 239000000047 product Substances 0.000 description 63
- 239000003208 petroleum Substances 0.000 description 50
- 238000010898 silica gel chromatography Methods 0.000 description 45
- 239000007788 liquid Substances 0.000 description 41
- 230000035484 reaction time Effects 0.000 description 36
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 21
- 239000003480 eluent Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000010828 elution Methods 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 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 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229940100603 hydrogen cyanide Drugs 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- HKQYGTCOTHHOMP-UHFFFAOYSA-N formononetin Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC=C2C1=O HKQYGTCOTHHOMP-UHFFFAOYSA-N 0.000 description 8
- 230000005311 nuclear magnetism Effects 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 7
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 6
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 5
- 239000002841 Lewis acid Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
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- NLEUXPOVZGDKJI-UHFFFAOYSA-N nickel(2+);dicyanide Chemical compound [Ni+2].N#[C-].N#[C-] NLEUXPOVZGDKJI-UHFFFAOYSA-N 0.000 description 1
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- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
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- 241000894007 species Species 0.000 description 1
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- 238000011105 stabilization Methods 0.000 description 1
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- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- KTQKOGBTMNDCFG-UHFFFAOYSA-N tert-butyl(diphenyl)silicon Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)C1=CC=CC=C1 KTQKOGBTMNDCFG-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
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- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
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Abstract
本发明公开了一种烷基腈类化合物的制备方法。具体地,该制备方法包括以下步骤:有机溶剂中,在保护气体存在下,在催化剂的作用下,将如式I所示的烯烃和氰基化试剂及水进行如下所示的还原反应,即可;所述的烷基腈类化合物1为化合物II和/或化合物III。本发明的制备方法条件温和,可以更为安全、高效地实现烯烃的氢氰化,且具有良好的底物普适性和官能团兼容性。
Description
技术领域
本发明涉及一种烷基腈类化合物的制备方法。
背景技术
腈类化合物广泛分布于医药、农药、功能材料以及具有生物活性的分子中。如乙腈作为分子量最小的腈类化合物常被用作有机反应的溶剂。丙烯腈常用作高聚物的单体,在合成纤维、树脂、橡胶等高分子材料中具有重要的地位。含卤素的芳基腈如溴苯腈和碘苯腈常被用作杀虫剂。微生物和植物中产生的蓖麻碱也含有氰基官能团。许多腈及其衍生物被发现具有很高的药物活性,例如抗炎、消炎、镇痛药布洛芬和奈普森即为对应苄腈的衍生物,含氰基的西药维格列汀、沙格列汀是调节血糖的药物。
腈类化合物是有机合成中重要的合成中间体,它们很容易转化成其它有用的官能化合物如醛、酮、羧酸、酯、胺以及酰胺等化合物,在过渡金属的活化作用下,C-CN发生断裂继而可以作为亲电试剂发生偶联反应或与炔烃发生碳氰化反应等。鉴于腈类化合物的重要价值,发展简洁、高效、环境友好的氰基化反应方法来合成腈类化合物的研究显得尤为必要。
过渡金属催化的烯烃的氢-氰化反应是合成烷基腈的重要方法之一,如以下文献均有记载:
(a)T.V.Rajanbabu,2011.Hydrocyanation of Alkenes and Alkynes.OrganicReactions.Volume 75,chapter 1,pp.1-74;
(b)L.Bini,C.Müller,D.Vogt,ChemCatChem 2010,2,590-608.
(c)A.L.Casalnuovo,T.V.Rajanbabu,Transition-metal catalyzed alkene andalkyne hydrocyanations.In Transition Metals for Organic Synthesis:BuildingBlocks and Fine Chemicals;M.Beller,C.Bolm,Eds.;Wiley-VCH,2008;Chapter 2.5,andreferences therein;
(d)M.Beller,J.Seayad,A.Tillack,H.Jiao,Angew.Chem.,Int.Ed.2004,43,3368-3398and references therein.
(e)C.A.Tolman,R.J.McKinney,W.C.Seidel,J.D.Druliner,W.R.Stevens,Adv.Catal.1985,33,1-46and references therein.
上述文献中报道的反应是由烯烃在过渡金属如Ni,Pd或Co催化下与剧毒的氰化氢或能够生成氰化氢的底物如丙酮氰醇或三甲基氰基硅反应生成氰基化产物,剧毒的氰化物限制了该反应的发展。文献中对于烯烃尤其是非活化烯烃的氢-氰化反应相对有限。
目前烯烃的氢-氰化反应研究主要集中于镍催化的烯烃同氰化氢或丙酮氰醇的研究,其中发展最为成熟的是1,3-丁二烯的氢氰化反应。以镍为催化剂可实现1,3-丁二烯的两次氢氰化反应合成尼龙66前体己二腈,该反应由Tolman等人在20世纪70年代初于杜邦公司开发。其年产量达100万吨,该方法相比丁二烯氯化氰化法降低成本15%,节能45%,具有路线短、节能环保、低成本等优势。该工艺如今已非常成熟,但被国外公司垄断,大大限制了我国尼龙66的工业生产。此外,文献报道中芳基烯烃的氢氰化反应也相对容易控制其区域选择性,由于芳基的稳定作用,反应更倾向于生成支链状的腈类化合物如II式。近年来,科学家们不断发展新颖的配体来调控烯烃氢氰化反应的区域选择性和对映选择性,得到了一些较好的结果。如以下文献中所记载:
(f)P.W.N.M.van Leeuwen,in Homogeneous Catalysis:Understanding of theArt,Kluwer Academic Publishers,Dordrecht,The Netherlands,2004,p.229.;
在该反应中,尤其值得一提的是在镍作用下2M3BN向3PN的异构化和3PN在路易斯酸和镍作用下向4PN的异构化。其反应历程如下:在镍催化剂的作用下丁二烯发生第一次氢氰化反应,生成了两种氰化产物,其中2-甲基-3-丁腈(2M3BN)可发生异构化反应转化为目标产物反式-3-戊烯腈(3PN),其后,路易斯酸(例如AlCl3、ZnCl2、BPh3等)促进了反式-3-戊烯腈(3PN)发生烯烃异构化反应得到4-戊烯腈(4PN),生成的末端烯腈再发生一次反马氏加成的氢氰化反应即可顺利得到己二腈(ADN)。
除了1,3-丁二烯,芳基烯烃的氢氰化反应也是科学家的研究重点,尤其是在不对称化学中,该反应得到了较多关注。Tolman等人首次报道了镍催化苯乙烯的氢氰化反应的研究。以Ni[P(O-o-tolyl)3]3为催化剂时反应更倾向遵循马氏加成规则。这一显著的区域选择性可能是因为镍中间体与芳环的相互作用或η3-苄基镍中间体更加稳定。体系中加入路易斯酸BPh3,反应按照反马氏加成规则进行所生成的直链状的腈会增多至33%。他们认为是路易斯酸与氰基配位后增大了镍中心的位阻所致。在后来的文献中,不断有新型配体被人们开发并用于烯烃的氢氰化反应中,其中手性双膦配体尤其发展迅速。双亚磷酸酯类型、联萘酚衍生的双亚磷酸酯、Xantphos类型、Xantphos和Thixantphos为基本骨架的次磷酸酯类的配体等均可应用于烯烃的氢氰化反应中。例如以下文献中的报道:
2000年,Chan小组以Ni(cod)2为催化剂,以手性的双亚磷酸酯为双膦配体催化丙酮氰醇对烯烃的氢氰化反应。作者通过对比实验发现,反应温度提高至100℃时,反应的转化率提升,若配体的用量提高至镍的7倍,反应可以基本转化完全,且表现出较好的区域选择性,但反应的ee值不太受影响。虽然ee值仍处于中等水平,但仍超过了过去的报道。作者认为,过量的配体有利于平衡向生成活性催化物种移动。
(g)M.Yan,Q.-Y.Xu,A.S.C.Chan,Tetrahedron:Asymmetry 2000,11,845–849
2008年Breit小组设计利用氢键作用将两种膦配体自组装得到双齿配体,期望将该类配体应用于镍催化的氢氰化反应中,实验结果显示,这种自组装的配体确实可以与金属镍发生配位作用,并且可成功催化芳基烯烃或者1,3-丁二烯类化合物的氢氰化反应,这是首次关于此类配体与镍(0)具有配位性能的报道。令人惊喜的是,这类配体还可以以高区域选择性得到支链产物。
(h)M,de Greef,B,Breit,Angew.Chem.Int.Ed.2009,48,551-554.
2013年,Schmalz小组发现MeOH和TMSCN的组合可原位生成HCN参与反应。以手性的亚磷酸酯L*为配体,在室温下即可以高效地将多种烯烃转化为手性腈类化合物。该反应不仅对于芳基末端烯烃具有良好的普适性,芳基和烷基取代的非末端烯烃在此条件下也具有良好的反应性能。
在所有的烯烃氢氰化反应中,非活化烯烃参与反应的难度较大。Taylor等人首先报道了零价镍催化非活化烯烃的氢氰化反应。通过筛选,作者发现AlCl3作为添加剂时反应较为高效,并且其可以促使反应更多的生成反马氏加成产物,即链状的腈。如上表所示,烯烃另一侧的取代的位阻对反应的区域选择性有着显著的影响,当其取代基从位阻较小的取代基如甲基变为位阻较大的取代基如异丙基和叔丁基时,选择性大幅提高,几乎仅有链状腈生成。1-己烯在该路易斯酸的促进下也可以较好的区域选择性得到庚腈。
(j)B.W.Taylor,H.E.Swift,J.Catal.1972,26,254-260.
2016年Koji Nemoto等人首次以锌还原稳定的二价镍得到零价镍来催化烯烃的氢-氰化反应。不仅芳基烯烃可以顺利发生氢-氰化反应,而且未活化的烷基烯烃在该催化体系下也能顺利转化为腈类化合物。该反应主要使用了比HCN更加稳定的液体丙酮氰醇现场生成HCN和烯烃发生加成反应,但丙酮氰醇的剧毒性不可忽视。更加遗憾的是,各类芳基烯烃以及烷基烯烃在此条件下均没有良好的区域选择性。
(k)Nemoto,K.;Nagafuchi,T.;Tominaga,K.;Sato,K.Tetrahedron Lett.2016,57,3199.
由于氰化氢是剧毒且易挥发的液体(bp27℃),在碱的存在下还有可能发生***性的聚合反应,在实验室及工业生产中极具危险性,因此发展安全、高效的氢-氰化反应特别是具有高区域和立体选择性的氢-氰化反应显得尤为迫切和需要。
最近Morandi等人报道了利用转移氢-氰化的策略可以实现无氰化氢参与的烯烃的氢-氰化反应。他们以镍络合物作为催化剂,通过烷基腈的C-CN键断裂以及β-H消除反应现场生成H-Ni-CN物质,进而与烯烃发生***和还原消除反应得到氢-氰化产物。
(l)X.Fang,P.Yu,B.Morandi,Science,2016,351,832-836.
以上报道的反应,虽然在镍催化的烯烃氢氰化反应的区域选择性和对映选择性方面取得了一些进展,反应中仍会使用到剧毒且易挥发的氰化氢,并且反应在底物普适性、官能团兼容性以及非活化的烷基烯烃的氢氰化反应的效率和选择性方面仍有待提高和突破。
因此,一种安全、高效、底物适应性广的腈类化合物的制备方法仍是本领域亟需发展的方法。
发明内容
本发明所要解决的技术问题是克服现有的镍催化的烯烃氢氰化反应中使用的氰基化试剂氰化氢剧毒且易挥发,底物普适性、官能团兼容性差,并且非活化的烷基烯烃的氢氰化反应的效率和选择性较差的缺陷,而提供了一种烷基腈类化合物的制备方法。本发明的制备方法条件温和,可以更为安全、高效地实现烯烃的氢氰化,且具有良好的底物普适性和官能团兼容性。
本发明通过以下技术方案解决上述技术问题。
本发明提供了一种烷基腈类化合物1的制备方法,其包括以下步骤:有机溶剂中,在保护气体存在下,在催化剂的作用下,将如式I所示的烯烃和氰基化试剂及水进行如下所示的还原反应,即可;所述的烷基腈类化合物1为化合物II和/或化合物III;
所述氰基化试剂为***、***、氰化镍和氰化锌中的一种或多种;
所述的催化剂包括镍类化合物和膦配体;所述的镍类化合物为0价镍、一价镍盐和二价镍盐中的一种或多种;当所述的镍类化合物包含二价镍盐时,所述的催化剂还包括还原剂;
其中,R1为未取代或R1-1取代的C6-14芳基、未取代或R1-2取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、未取代或R1-3取代的C1-10烷基、未取代或R1-4取代的C2-10烯基、未取代或R1-5取代的C3-8环烷基、未取代或R1-6取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基、
R1-1为-OH、-NH2、-CN、CF3、卤素、C1-10烷基、C1-10烷氧基、C6-14芳基、或、未取代或R1 -1-1取代的“杂原子选自N、O、S和B中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基;
R1-3为-OH、-CHO、OR1-3-1、/>未取代或R1-3-4取代的C6-14芳基(所述的C6-14芳基例如C6-10芳基,再例如苯基或萘基)、未取代或R1-3-5取代的C3-6环烷基(所述的C3-6环烷基例如环丙基、环戊基或环己基);
R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为C1-10烷基(例如C1-4烷基,再例如甲基、乙基、丙基、异丙基、正丁基、仲丁基、异丁基、叔丁基)、C1-10烷氧基(例如C1-4烷氧基,再例如甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、仲丁氧基、异丁氧基、叔丁氧基)、或者、未取代或R1-2-1取代的C6-14芳基(C6-14芳基例如C6-10芳基,再例如苯基);R1-2-1为-OH、-NH2、-CN、CF3、卤素、C1-4烷基(例如甲基、乙基、丙基或异丙基)或C1-4烷氧基(例如甲氧基、乙氧基、丙氧基或异丙氧基);
R1-5、R1-6和R1-3-5独立地为=O(即,碳原子上的两个偕氢被基团O取代)、C1-4烷基(例如甲基、乙基、丙基、异丙基)或C1-4烷氧基(例如甲氧基、乙氧基、丙氧基、异丙氧基);
R1-10独立地为H、-OH、-NH2、-CN、CF3、卤素、C1-4烷基(例如甲基、乙基、丙基、异丙基)或C1-4烷氧基(例如甲氧基、乙氧基、丙氧基、异丙氧基);m为0、1、2、3或4;
R1-3-1为氧保护基团{例如叔丁基二苯基甲硅烷基(TBDPS)或叔丁基二甲基硅基(TBS)}。
本发明中,所述的“取代”的个数可为一个或多个,例如1、2、3或4个;当存在多个“取代”时,所述的“取代”相同或不同。
本发明中,当R1-1为卤素时,所述的卤素较佳地为氟、氯、溴或碘,更佳地为氟。
本发明中,当R1-2-1为卤素时,所述的卤素较佳地为氟、氯、溴或碘,更佳地为氟。
本发明中,当R1-10为卤素时,所述的卤素较佳地为氟、氯、溴或碘,更佳地为氟。
本发明中,当R1为未取代或R1-1取代的C6-14芳基时,所述的C6-14芳基可为C6-10芳基,例如苯基或萘基。
本发明中,当R1为未取代或R1-3取代的C1-10烷基时,所述的C1-10烷基可为甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、正戊基、正己基、正庚基、正辛基、正壬基或正癸基(例如甲基、乙基、丙基、辛基或壬基)。
本发明中,当R1为未取代或R1-4取代的C2-10烯基时,所述的C2-10烯基可为C2-6烯基(例如乙烯基、1-丙烯基、2-丙烯基、1-丁烯基、2-丁烯基或丁二烯,再例如乙烯基)。
本发明中,当R1为未取代或R1-5取代的C3-8环烷基时,所述的C3-8环烷基可为C3-6环烷基(例如环丙基、环戊基或环己基)。
本发明中,当R1-1为C1-10烷基时,所述的C1-10烷基可为C1-4烷基(例如甲基、乙基、丙基、异丙基、正丁基、仲丁基、异丁基或叔丁基,再例如甲基或异丁基)。
本发明中,当R1-1为C1-10烷氧基时,所述的C1-10烷氧基可为C1-4烷氧基(例如甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、仲丁氧基、异丁氧基或叔丁氧基,再例如甲氧基)。
本发明中,当R1-1为C6-14芳基时,所述的C6-14芳基可为C6-10芳基(例如苯基)。
本发明某一方案中,当R1为未取代或R1-1取代的C6-14芳基、未取代或R1-2取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、未取代或R1-4取代的C2-10烯基、除了R1为其他基团如前任一方案所述时,所述的化合物1为化合物II。
本发明某一方案中,当R1为未取代或R1-3取代的C1-10烷基、未取代或R1-5取代的C3-8环烷基、未取代或R1-6取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基、其中,R1-3为-CHO、未取代或R1-3-5取代的C3-6环烷基、OTBS、或者、未取代或R14取代的C6-14芳基,其他基团如前任一方案所述时,所述的化合物1为化合物III。
本发明某一方案中,R1为R1-1取代的C6-14芳基、未取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、或者、其中,所述的未取代的5~20元杂芳基为咔唑基;R1-1为C1-10烷氧基或C6-14芳基,其他基团如前任一方案所述。
本发明某一方案中,R1为未取代或R1-1取代的C6-14芳基、未取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、未取代或R1-3取代的C1-10烷基、未取代或R1-5取代的C3-8环烷基、未取代或R1-6取代的“杂原子选自N、O和S,杂原子数为1-4个”的3~10元杂环烷基、或者、其中,所述的未取代的5~20元杂芳基为吲哚基;R1-1为-NH2、C1-10烷氧基、未取代或R1-1-1取代的“杂原子选自N、O、S和B中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基;R1-3为-OH、-CHO、/>OR1-3-1、/>R1-3-4取代的C6-14芳基、未取代或R1-3-5取代的C3-6环烷基;其他基团如前任一方案所述。
本发明某一方案中,R1为未取代或R1-1取代的C6-14芳基、或者、未取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基;其中,所述的未取代的5~20元杂芳基为咔唑基;R1-1独立地为-OH或CF3;其他基团如前任一方案所述。
本发明一实施方案中,所述的如式I所示的烯烃,可选自如下任一结构:
本发明一实施方案中,所述的如式I所示的烯烃,还可选自如下任一结构:
本发明一实施方案中,所述的如式I所示的烯烃,还可选自如下任一结构:
本发明中,所述氰基化试剂较佳地为氰化锌。
本发明中,所述有机溶剂可为本领域该类反应常规的有机溶剂,较佳地为芳香类溶剂(例如苯、甲苯和二甲苯中的一种或多种)、醚类溶剂{例如***、1,4-二氧六环和四氢呋喃(THF)中的一种或多种}、卤代烃类溶剂{例如二氯甲烷(DCM)、二氯乙烷(DCE)和氯仿中的一种或多种}、腈类溶剂(例如乙腈)、酰胺类溶剂{例如N,N-二甲基甲酰胺(DMF)和/或甲基磷酰胺}和亚砜类溶剂{例如二甲基亚砜(DMSO)}中的一种或多种;更佳地为醚类溶剂和/或腈类溶剂。
本发明中,所述保护气体可为本领域该类反应常用的保护气体,较佳地为氮气、氦气、氩气和氖气中的一种或多种;更佳地为氮气。
本发明中,所述的膦配体可为本领域该类反应常用的膦配体,较佳地为三苯基膦(PPh3)、三苯基亚磷酸酯(P(OPh)3)、三丁基膦(PBu3)、三环己基膦(PCy3)、二甲基苯基膦(PMe2Ph)、二苯基甲基膦(PMePh2)、双二苯基膦甲烷(dppm)、1,2-双(二苯膦)乙烷(dppe)、1,3-双(二苯基膦)丙烷(dppp)、1,4-双(二苯基膦)丁烷(dppb)、1,1’-双(二苯基膦)二茂铁(dppf)、双(2-二苯基磷苯基)醚(DPEphos)、9,9-二甲基-4,5-双二苯基膦氧杂蒽(Xantphos)和4,5-二(二叔丁基膦)-9,9-二甲基氧杂蒽(tBu-Xantphos)中的一种或多种;更佳地为1,3-双(二苯基膦)丙烷、1,1’-双(二苯基膦)二茂铁和9,9-二甲基-4,5-双二苯基膦氧杂蒽中的一种或多种。
本发明中,所述的0价镍可为Ni(cod)2(cod:1,5-环辛二烯)。
本发明中,所述的一价镍盐可为NiCl。
本发明中,所述的二价镍盐可为Ni(acac)2(acac:二乙酰丙酮)、NiCl2、NiCl2(DME)(DME:乙二醇二甲醚)、NiBr2(DME)、NiI2和Ni(ClO4)2中的一种或多种,较佳地为NiCl2和/或Ni(ClO4)2。
本发明中,所述的催化剂中,所述的镍类化合物和所述的膦配体可为本领域常规的存在形式,例如所述的镍类化合物和所述的膦配体为独立的化合物,或者,所述镍类化合物中的部分或全部、与、所述的膦配体中的部分或全部为络合物;所述的络合物例如0价镍与膦配体的络合物、一价镍盐与膦配体的络合物、和、二价镍盐与膦配体的络合物中的一种或多种。
本发明中,当所述镍类化合物中的部分或全部、与、所述的膦配体中的部分或全部为络合物时,其中,所述的0价镍与膦配体的络合物可为Ni(PPh3)4;所述的一价镍盐与膦配体的络合物可为NiCl(dppf);所述的二价镍盐与配体的络合物可为NiCl2(PPh3)4、NiCl2(dppf)、NiBr2(PPh3)2、NiCl2(PCy3)3、NiCl2(dppp)和NiCl2(dppe)的一种或多种。
本发明中,所述的催化剂中,较佳地,所述的镍类化合物和所述的膦配体为独立的化合物。
本发明中,所述的还原剂较佳地为Zn、Mn和Al中的一种或多种,更佳地为Zn。
本发明的某一方案中,所述的催化剂较佳地为二价镍盐、膦配体和Zn;所述的二价镍盐为NiCl2和/或Ni(ClO4)2,所述的膦配体为1,1’-双(二苯基膦)二茂铁和/或9,9-二甲基-4,5-双二苯基膦氧杂蒽膦配体。
本发明中,所述的镍类化合物和所述的水可为本领域常规的组合形式,例如所述的镍类化合物和所述的水为独立的化合物,或者,所述的镍类化合物中的部分或全部、与、所述的水中的部分或全部形成结晶水合物;所述的结晶水合物例如0价镍与水形成的结晶水合物、和/或、二价镍盐与水形成的结晶水合物。
本发明中,所述的水可为本领域常规使用的水,此处不做特别限定,只要不影响反应即可,例如去离子水。
本发明中,当所述的镍类化合物中的部分或全部、与、所述的水中的部分或全部形成结晶水合物时,其中,所述的二价镍盐与水形成的结晶水合物可为NiCl2·6H2O、NiI2·6H2O、Ni(acac)2·2H2O和Ni(ClO4)2·6H2O中的一种或多种,较佳地为NiCl2·6H2O和/或Ni(ClO4)2·6H2O。
本发明中,当所述的催化剂还包括还原剂时,所述的如式I所示的烯烃与所述的还原剂的摩尔比可为1:0.01~10,较佳地为1:0.2~1。
本发明中,所述如式I所示的烯烃与所述镍类化合物的摩尔比可为1:0.01~1,较佳地为1:0.03~0.06,例如1:0.05。
本发明中,所述镍类化合物与所述膦配体的摩尔比可为1:1~10,较佳地为1:1.1~2,更佳地为1:1.1~1.4,例如1:1.2。
本发明中,所述如式I所示的烯烃与所述氰基化试剂的摩尔比可为1:0.1~10,较佳地为1:0.5~0.8,例如1:0.6,1:0.8。
本发明中,所述如式I所示的烯烃在所述有机溶剂中的摩尔浓度可为0.01~1mmol/mL,较佳地为0.1~0.4mmol/mL,例如0.2mmol/mL。
本发明中,所述如式I所示的烯烃与水摩尔比可为1:1~10,较佳地为1:1~6,例如1:1.3、1:2.3或1:(529/90)。
本发明中,所述还原反应的温度可为本领域常规,例如20~100℃,较佳地为50~80℃。
本发明中,当所述的膦配体为1,3-双(二苯基膦)丙烷时,所述的还原反应中还可加入N,N-二甲基吡啶(DMAP)作为添加剂;所述的如式I所示的烯烃与所述的N,N-二甲基吡啶的摩尔比可为1:0.1~3,较佳地为1:0.8~1.2,例如1:1。
本发明中,所述还原反应的进程可以采用本领域常规的监测方法(例如TLC、HPLC或NMR)进行监测,一般以如式I所示的烯烃消失或不再反应时为反应终点,反应时间较佳地为0.1~200小时,更佳地为3~24小时,例如3.5小时、4小时、6小时、8小时、12小时或24小时。
本发明中,所述的还原反应结束后,较佳地,还可进一步包括后处理步骤。所述的后处理的条件和操作与本领域该类反应常规的后处理的条件和操作相同,其包括以下步骤:反应结束后,过滤,除去溶剂,分离提纯即可。所述过滤的条件和操作同本领域该类反应常规的条件和操作。所述除去溶剂的条件和操作可为本领域常规的条件和操作,例如减压浓缩。所述分离提纯的条件和操作可为本领域常规的条件和操作,例如柱层析分离,所述柱层析分离的洗脱剂较佳地为烷烃类溶剂(例如石油醚)与酯类溶剂(例如乙酸乙酯)的混合溶剂,所述的烷烃类溶剂与所述的酯类溶剂的体积比较佳地为100:1~0:1,更佳地为50:1~0:1。
本发明还提供了一种如式I-1所示的烯烃化合物,其结构如下所示:
除特别说明外,本发明所用试剂和原料均市售可得。
在不违背本领域常识的基础上,上述各优选条件,可任意组合,即得本发明各较佳实例。
本发明的积极进步效果在于:本发明提供的制备方法,以廉价易得的镍类化合物作为催化剂,安全、温和、高效地实现烯烃与氰基化试剂的反应,制备得到烷基腈类化合物。本发明的制备方法避免了传统合成方法中毒性较大的氰化氢或丙酮氰醇的使用,制得的烷基腈类具有良好的收率和立体选择性,在官能团兼容性和底物普适性方面也得到了很大提升。此外,本发明的制备方法使用水作为氢源,具有绿色、经济的优点。
具体实施方式
下面通过实施例的方式进一步说明本发明,但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法,按照常规方法和条件,或按照商品说明书选择。
制备实施例1
氩气保护下,甲基三苯基溴化膦(2.14g,6mmol)溶于干燥的四氢呋喃(10ml)中,向其中加入KOtBu(785.5mg,7mmol)。反应液在室温下搅拌30分钟后冷却至-78℃。向其中滴加3,5-二甲氧基苯甲醛(830.9mg,5mmol)的四氢呋喃(5mL)溶液,加毕后反应恢复室温继续搅拌12h。加入2mL甲醇淬灭反应,反应液浓缩,硅胶柱层析纯化。洗脱剂:石油醚/乙酸乙酯=10:1,产物为无色液体811mg,收率99%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ3.79(s,6H),5.24(d,J=10.8Hz,1H),5.72(dd,J=17.6,0.8Hz,1H),6.38(t,J=2.4Hz,1H),6.56(d,J=2.4Hz,2H),6.64(dd,J=17.6,10.8Hz,1H).13C NMR(100M,CDCl3):δ55.23,99.97,104.20,114.27,136.78,139.53,160.83.
制备实施例2
氩气保护下,甲基三苯基溴化膦(1.7861g,5mmol)溶于干燥的四氢呋喃(25mL)并冷却至0℃,向其中加入nBuLi(2mL,2.5M in hexane,5mmol)并在此温度下继续搅拌2h。继续向其中加入苯并噻吩-2-甲醛(811.1mg,5mmol)的四氢呋喃溶液(4mL)。反应液恢复室温继续搅拌4h后用加水淬灭。***萃取后用水和饱和NaCl洗涤,无水Na2SO4干燥,过滤浓缩,硅胶柱层析纯化。洗脱剂:石油醚/乙酸乙酯=10:1,产物为白色固体665mg,收率83%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ5.28(d,J=10.8Hz,1H),5.65(d,J=17.2Hz,1H),6.89(dd,J=17.2,10.8Hz,1H),7.13(s,1H),7.25-7.31(m,2H),7.65-7.67(m,1H),7.73-7.75(m,1H).13C NMR(100M,CDCl3):δ115.89,122.21,123.03,124.35,124.72,130.53,138.77,139.94,143.03.
制备实施例3
氩气保护下,刺芒柄花素(2.68g,10mmol)和三乙胺(2.02g,20mmol)溶于二氯甲烷(50mL)中,冷却至0℃后向其中加入Tf2O(3.10g,11mmol),加完后恢复室温反应2h。用饱和NH4Cl淬灭反应,二氯甲烷萃取。有机相合并后用无水Na2SO4干燥,过滤浓缩后柱层析纯化,洗脱剂:石油醚/二氯甲烷=1:2,得到中间体三氟甲磺酰基保护的刺芒柄花素,产物为白色固体2.76g,收率69%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ3.84(s,3H),6.97(d,J=8.8Hz,2H),7.33(dd,J=8.8,2.4Hz,1H),7.45(d,J=2.0Hz,1H),7.49(d,J=8.8Hz,2H),8.01(s,1H),8.40(d,J=8.8Hz,1H).13C NMR(100M,CDCl3):δ55.26,111.39,114.04,118.47,118.63(q,1JC-F=321.3Hz),123.08,124.14,125.62,129.12,130.00,152.02,152.80,156.27,159.86,175.11.19F NMR(400M,CDCl3):δ-72.61.
氩气保护下,取三氟甲磺酰基保护的刺芒柄花素(1.2010g,3mmol),Pd(PPh3)2Cl2(210.6mg,0.3mmol)和LiCl(127.2mg,3mol)溶于DMF(18mL)中,向其中滴加三丁基乙烯基锡(1.0464g,3.3mmol)。加完后置于90℃油浴中加入反应4h.反应完成后,将反应液冷却至室温,用***稀释,再用1M HCl溶液,饱和NaHCO3溶液以及饱和NaCl溶液洗涤,合并的水相再用***萃取一次。合并有机相,无水Na2SO4洗涤,过滤浓缩,硅胶柱层析纯化。洗脱剂:石油醚/二氯甲烷/乙酸乙酯=6:1:1,得到目标产物为白色固体637.7mg,收率为76%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ3.83(s,3H),5.48(d,J=11.2Hz,1H),5.94(d,J=17.6,Hz,1H),6.79(dd,J=17.6,11.2Hz,1H),6.96-6.98(m,1H),7.41(s,1H),7.46-7.52(m,3H),7.96(s,1H),8.24(d,J=8.4Hz,1H).13C NMR(100M,CDCl3):δ55.26,113.91,115.37,117.81,122.83,123.62,124.03,124.97,126.49,130.02,135.32,142.89,152.49,156.44,159.55,176.06.IR(neat):3092,3076,3040,3011,2972,2930,2838,1624,1609,1557,1513,1439,1407,1358,1291,1253,1233,1176,1106,1024,985,927,901,886,878,830,821,802,791,767,717cm-1.HRMS(ESI)计算值C18H15O3[M+H]+:279.1016,实测值279.1007。
制备实施例4
氩气保护下,雌酚酮(2.70g,10mmol)和三乙胺(2.02g,20mmol)溶于二氯甲烷(50mL)中,冷却至0℃后向其中加入Tf2O(3.10g,11mmol),加完后恢复室温反应3h。用饱和NH4Cl淬灭反应,二氯甲烷萃取。有机相合并后用无水Na2SO4干燥,过滤浓缩后柱层析纯化,洗脱剂:石油醚/乙酸乙酯=5:1,得到中间体三氟甲磺酰基保护的雌酚酮,产物为白色固体3.56g,收率89%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ0.92(s,3H),1.44-1.70(m,6H),1.96-2.20(m,4H),2.27-2.35(m,1H),2.38-2.43(m,1H),2.52(dd,J=18.6,8.8Hz,1H),2.93-2.96(m,2H),6.99-7.00(m,1H),7.04(dd,J=8.6,2.4Hz,1H),7.35(d,J=8.4Hz,1H).13C NMR(100M,CDCl3):δ13.68,21.46,25.58,25.98,29.28,31.39,35.70,37.65,44.00,47.75,50.28,118.19,118.66(1JC-F=320.5Hz),121.13,127.11,139.24,140.22,147.51,220.30.19F NMR(400M,CDCl3):-73.03.
氩气保护下,取三氟甲磺酰基保护的雌酚酮(1.2073g,3mmol),Pd(PPh3)2Cl2(210.6mg,0.3mmol)和LiCl(127.2mg,3mol)溶于DMF(18mL)中,向其中滴加三丁基乙烯基锡(1.0464g,3.3mmol)。加完后置于90℃油浴中加入反应4h.反应完成后,将反应液冷却至室温,用***稀释,再用1M HCl溶液,饱和NaHCO3溶液以及饱和NaCl溶液洗涤,合并的水相再用***萃取一次。合并有机相,无水Na2SO4洗涤,过滤浓缩,硅胶柱层析纯化。洗脱剂:二氯甲烷,得到目标产物为白色固体650.0mg,收率为77%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ0.90(s,3H),1.38-1.67(m,6H),1.94-2.18(m,4H),2.25-2.31(m,1H),2.39-2.44(m,1H),2.50(dd,J=18.8,8.4Hz,1H),2.89-2.93(m,2H),5.19(d,J=11.2Hz,1H),5.70(d,J=17.6Hz,1H),6.66(dd,J=17.6,10.8Hz,1H),7.14(s,1H),7.19-7.26(m,2H).13C NMR(100M,CDCl3):δ13.77,21.51,25.63,26.41,29.31,31.50,35.78,38.06,44.35,47.90,50.39,113.11,123.52,125.47,126.80,135.10,136.48,139.44.
制备实施例5
氩气保护下,苯丙醛(1.34g,10mmol)溶于四氢呋喃(20mL)中,冷却至0℃,向其中滴加乙烯基溴化镁(12mL,1M in THF,12mmol),加毕后恢复室温反应3h。用饱和NH4Cl溶液淬灭反应,乙酸乙酯萃取。有机相合并用水和饱和NaCl洗涤。无水Na2SO4.干燥,过滤浓缩,硅胶柱层析,洗脱剂:石油醚/乙酸乙酯=10:1,产物为无色液体1.34g,收率83%,1H NMR纯度大于98%。1H NMR(400MHz,CDCl3):δ1.76(s,1H),1.82-1.87(m,2H),2.64-2.78(m,2H),4.12(q,J=6.4Hz,1H),5.13(d,J=10.4Hz,1H),5.23(d,J=17.2Hz,1H),5.89(ddd,J=17.2,10.4,6.4Hz,1H),7.16-7.23(m,3H),7.28(t,J=7.2Hz,2H);13C NMR(100MHz,CDCl3):δ31.56,38.44,72.40,114.89,125.80,128.34,128.41,140.94,141.82.
制备实施例6
空气中,5-苯基戊-1-烯-3-醇(486.7mg,3mmol)溶于二氯甲烷中(20mL),向其加入咪唑(408.5mg,6mmol)和叔丁基二甲基氯硅烷(678.2mg,4.5mmol)。加完后室温反应2h。反应液硅藻土过滤,二氯甲烷洗涤。滤液浓缩后硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=50:1,产物为无色液体722.1mg,收率87%,1H NMR纯度大于98%。1H NMR(400MHz,CDCl3):δ0.08(s,3H),0.10(s,3H),0.96(s,9H),1.78-1.92(m,2H),2.62-2.76(m,2H),4.17-4.22(m,1H),5.10(dd,J=10.4,1.2Hz,1H),5.21(dd,J=17.4,1.2Hz,1H),5.84-5.92(m,1H),7.19-7.22(m,3H),7.29-7.32(m,2H);13C NMR(100MHz,CDCl3):δ-4.82,-4.33,18.25,25.89,31.45,39.81,73.33,113.95,125.65,128.30,128.37,141.43,142.46.
实施例1化合物(1a)
在充满氮气氛围的手套箱中,向8.0mL的反应瓶中依次加入NiCl2·6H2O(0.025mmol,5.9mg),Xantphos(0.03mmol,17.4mg),Zn(0.1mmol,6.5mg),Zn(CN)2(0.3mmol,35.2mg),对甲基苯乙烯(0.5mmol,59.1mg)和1,4-二氧六环(2.5mL),然后将反应瓶盖紧盖子移出手套箱外并用注射器加入水(50μL),然后放入预先加热至80℃的油浴中反应,4小时后停止反应,待反应液冷至室温后,硅胶过滤,乙酸乙酯洗涤,滤液浓缩,直接硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=100:1至50:1洗脱,产物为无色油状液体67.5mg,收率93%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.62(d,J=7.2Hz,3H),2.35(s,3H),3.86(q,J=7.2Hz,1H),7.18(d,J=8.0Hz,2H),7.25(d,J=8.4Hz,2H).13C NMR(100M,CDCl3):δ20.98,21.44,30.80,121.73,126.52,129.71,134.05,137.78.
实施例2化合物(1b)
实施例2的操作技术采用实施例1的操作,仅使用烯烃原料有所不同。
采用实施例1方案,以苯乙烯为原料,硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=50:1洗脱,产物为无色油状液体57.4mg,收率88%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.62(d,J=7.2Hz,3H),3.89(q,J=7.2Hz,1H),7.29-7.40(m,5H).13C NMR(100M,CDCl3):δ21.34,31.09,121.51,126.58,127.92,129.02,136.96.
实施例3化合物(1c)和化合物(2c)
在充满氮气氛围的手套箱中,向8.0mL的反应瓶中依次加入NiCl2·6H2O(0.025mmol,5.9mg),dppf(0.03mmol,16.6mg),Zn(0.5mmol,32.7mg),Zn(CN)2(0.3mmol,35.2mg),邻甲基苯乙烯(0.5mmol,59.1mg)和1,4-二氧六环(2.5mL),然后将反应瓶盖紧盖子移出手套箱外并用注射器加入水(50μL),然后放入预先加热至80℃的油浴中反应,4小时后停止反应,待反应液冷至室温后,硅胶过滤,乙酸乙酯洗涤,滤液浓缩,直接硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=50:1至20:1梯度洗脱,产物1c为无色油状液体46.0mg,收率63%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.60(d,J=7.2Hz,3H),2.35(s,3H),4.03(q,J=7.2Hz,1H),7.17-7.27(m,3H),7.43-7.45(m,1H).13C NMR(100M,CDCl3):δ18.90,19.93,28.05,121.72,126.59,126.88,128.02,130.90,134.69,135.17。产物2c为无色油状液体7.0mg,收率为10%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ2.33(s,3H),2.58(t,J=7.6Hz,2H),2.98(t,J=7.6Hz,2H),7.15-7.20(m,4H).13C NMR(100M,CDCl3):δ17..97,19.14,28.84,119.19,126.45,127.33,128.67,130.61,135.74,136.18.
实施例4化合物(1d)
实施例4-21的实验技术均采用实施例1的操作技术,仅使用的烯烃原料有所不同,个别实施例中反应时间或分离方法可能会有所不同。
采用实施例1方案,以对异丁基苯乙烯为原料,反应时间为6小时,制备板层析纯化,展开剂:石油醚/乙酸乙酯=50:1洗脱,产物为无色油状液体70.0mg,收率75%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ0.90(d,J=6.8Hz,6H),1.62(d,J=7.6Hz,3H),1.80-1.90(m,1H),2.47(d,J=7.2Hz,2H),3.86(q,J=7.2Hz,1H),7.14(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H).13C NMR(100M,CDCl3):δ21.34,22.22,30.09,30.78,44.85,121.73,126.34,129.72,134.22,141.53.
实施例5化合物(1e)
采用实施例1方案,以对甲氧基苯乙烯为原料,反应时间为4小时,硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1洗脱,产物为无色油状液体73.9mg,收率92%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.60(d,J=7.6Hz,3H),3.80(s,3H),3.84(q,J=7.8Hz,1H),6.89-6.92(m,2H),7.25-7.27(m,2H).13C NMR(100M,CDCl3):δ21.39,30.31,55.22,114.36,121.79,127.72,128.98,159.18.
实施例6化合物(1f)
采用实施例1方案,以3,5-二甲氧基苯乙烯为原料,反应时间为4小时,硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1洗脱,产物为无色油状液体91.3mg,收率95%,1HNMR纯度大于98%。1H NMR(400M,CDCl3):δ1.62(d,J=7.2Hz,3H),3.79-3.84(m,7H),6.40(t,J=2.0Hz,1H),6.49(d,J=2.0Hz,2H).13C NMR(100M,CDCl3):δ21.12,31.19,55.24,99.52,104.75,121.35,139.12,161.14.IR(neat):2985,2941,2839,2242,1596,1457,1429,1349,1328,1296,1204,1152,1051,836,735,694cm-1.HRMS(ESI)计算值C11H14NO2[M+H]+:192.1019,实测值192.1017。
实施例7化合物(1g)
采用实施例1方案,以对羟基苯乙烯为原料,反应时间为4小时,硅胶柱层析纯化,洗脱剂:石油醚至石油醚/乙酸乙酯=5:1至3:1梯度洗脱,产物为无色油状液体63.7mg,收率87%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.59(d,J=7.6Hz,3H),3.84(q,J=7.2Hz,1H),6.59(s,1H),6.82-6.86(m,2H),7.17(d,J=8.8Hz,2H).13C NMR(100M,CDCl3):δ21.21,30.30,115.97,121.95,127.88,128.44,155.67.IR(neat):3344,3022,2988,2936,2254,1613,1591,1515,1441,1372,1356,1343,1274,1264,1216,1185,1175,1107,1083,1054,987,837,818,732cm-1.HRMS(EI)计算值C9H9NO[M]+:147.0684,实测值147.0679.
实施例8化合物(1h)
采用实施例1方案,对氨基苯乙烯为原料,反应时间为4小时,硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=1:1洗脱,产物为浅黄色油状液体64.7mg,收率89%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.56(d,J=7.2Hz,3H),3.72(s,2H),3.76(q,J=7.2Hz,1H),6.64(d,J=8.4Hz,2H),7.09(d,J=8.8Hz,2H).13C NMR(100M,CDCl3):δ21.25,30.19,115.20,122.10,126.39,127.46,146.18.IR(neat):3460,3369,3325,2983,2924,2853,2238,1623,1516,1452,1378,1285,1183,1130,1084,988,826cm-1.HRMS(ESI)计算值C9H11N2[M]+:147.0917,实测值147.0914。
实施例9化合物(1i)
采用实施例1方案,以对氟苯乙烯为原料,反应时间为4小时,硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=40:1至20:1梯度洗脱,产物为无色油状液体60.4mg,收率81%,1HNMR纯度大于98%。1H NMR(400M,CDCl3):δ1.63(d,J=7.2Hz,3H),3.90(q,J=7.2Hz,1H),7.05-7.09(m,2H),7.31-7.35(m,2H).13C NMR(100M,CDCl3):δ21.37,30.44,115.97(2JC-F=22.1Hz),121.34,128.35(3JC-F=8.4Hz),132.77(4JC-F=3.8Hz),162.22(1JC-F=247.3Hz).19F NMR(400M,CDCl3):δ-114.02~113.95(m).
实施例10化合物(1j)
采用实施例1方案,以对三氟甲基苯乙烯为底物,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1,产物为无色油状液体84.0mg,收率84%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.67(d,J=7.2Hz,3H),3.99(q,J=7.2Hz,1H),7.50(d,J=8.0Hz,2H),7.66(d,J=8.0Hz,2H).13C NMR(100M,CDCl3):δ21.13,31.01,120.72,123.75(q,1JC-F=272.4Hz),126.08(q,3JC-F=3.8Hz),127.15,130.35(q,2JC-F=32.9Hz),140.95(q,5JC-F=1.5Hz).19F NMR(400M,CDCl3):δ-62.76.
实施例11化合物(1k)
采用实施例1方案,以对氰基苯乙烯为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=10:1,产物为无色油状液体66.2mg,收率85%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.68(d,J=7.6Hz,3H),4.02(q,J=7.2Hz,1H),7.52(d,J=8.4Hz,2H),7.71(d,J=8.4Hz,2H).13C NMR(100M,CDCl3):δ20.93,31.11,112.01,118.01,120.26,127.52,132.81,142.00.
实施例12化合物(1l)
采用实施例1方案,以对位片哪醇硼酸酯取代的苯乙烯为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1至10:1,产物为白色固体98.8mg,收率77%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.34(s,12H),1.62(d,J=7.2Hz,3H),3.90(q,J=7.2Hz,1H),7.36(d,J=7.6Hz,2H),7.83(d,J=7.6Hz,2H).13C NMR(100M,CDCl3):δ21.29,24.72,31.23,83.82,121.24,125.91,135.47,139.88.IR(neat):2983,2920,2239,1614,1521,1454,1412,1398,1358,1333,1282,1267,1167,1138,1094,1021,963,856,833,675,656cm-1.HRMS(ESI)计算值C15H24O2N2 10B[M+NH4]+:274.1962,实测值274.1961.
实施例13化合物(1m)
采用实施例1方案,以4-乙烯基联苯为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=40:1至20:1,产物为白色固体98.3mg,收率95%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.63(d,J=7.2Hz,3H),3.90(q,J=7.2Hz,1H),7.32-7.44(m,5H),7.57(t,J=8.4Hz,4H).13C NMR(100M,CDCl3):δ21.26,30.76,121.47,126.93,127.03,127.48,127.67,128.74,135.89,140.07,140.88.
实施例14化合物(1n)
采用实施例1方案,以2-乙烯基萘为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=40:1至20:1,产物为白色固体82.4mg,收率91%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.66(d,J=7.2Hz,3H),3.99(q,J=7.2Hz,1H),7.37(dd,J=8.6,2.0Hz,1H),7.45-7.50(m,2H),7.79-7.83(m,4H).13C NMR(100M,CDCl3):δ21.22,31.20,121.50,124.26,125.41,126.33,126.57,127.57,127.70,128.98,132.60,133.14,134.19.
实施例15化合物(1o)
采用实施例1方案,以2-甲氧基-6-乙烯基萘为原料,反应时间为8小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1,产物为白色固体103.7mg,收率98%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.65(d,J=7.6Hz,3H),3.87(s,3H),3.95(q,J=7.2Hz,1H),7.09(d,J=2.0Hz,1H),7.15(dd,J=9.0,2.0Hz,1H),7.34(dd,J=8.4,1.2Hz,1H),7.67-7.72(m,3H).13C NMR(100M,CDCl3):δ21.19,30.98,55.12,105.49,119.37,121.65,124.75,125.18,127.72,128.57,129.12,131.85,133.83,157.90.
实施例16化合物(1p)
采用实施例1方案,以3-乙烯基吡啶为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=1:1,产物为无色液体54.6mg,收率83%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.68(d,J=7.2Hz,3H),3.98(q,J=7.2Hz,1H),7.34-7.37(m,1H),7.75(d,J=8.0Hz,1H),8.60-8.62(m,2H).13C NMR(100M,CDCl3):δ20.99,28.78,120.42,123.74,132.72,134.12,148.02,149.34.IR(neat):3037,2988,2941,2243,1577,1481,1455,1426,1301,1181,1129,1089,1043,1027,990,810,711cm-1.HRMS(ESI)计算值C8H9N2[M+H]+:133.0760,实测值133.0758.
实施例17化合物(1q)
采用实施例1方案,以3-乙烯基吲哚为原料,反应时间为8小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=10:1,产物为无色液体73.8mg,收率87%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.67(d,J=7.2Hz,3H),4.08(q,J=7.2Hz,1H),7.04(d,J=1.6Hz,1H),7.12-7.22(m,2H),7.31(d,J=8.0Hz,1H),7.62(d,J=8.0Hz,1H),8.28(s,1H).13C NMR(100M,CDCl3):δ19.39,22.66,111.36,111.62,118.17,119.86,121.66,121.98,122.50,124.94,136.33.IR(neat):3409,3063,2983,2943,2240,1618,1457,1421,1355,1339,1248,1225,1100,1032,1012,909,819,765,739cm-1.HRMS(EI)计算值C11H10N2[M]+:170.0844,实测值170.0842.
实施例18化合物(1r)
采用实施例1方案,以2-乙烯基苯并噻吩,反应时间为8小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1,产物为白色固体79.0mg,收率84%,1H NMR纯度大于98%。1HNMR(400M,CDCl3):δ1.73(d,J=7.2Hz,3H),4.16(q,J=7.2Hz,1H),7.27-7.36(m,3H),7.69-7.71(m,1H),7.76(d,J=7.6Hz,1H).13C NMR(100M,CDCl3):δ20.87,27.20,120.09,122.11,122.17,123.58,124.63,124.69,138.96,139.24,139.66.IR(neat):3056,2993,2983,2938,2925,2241,1459,1435,1376,1205,1156,1143,1129,1057,967,943,876,841,823,728,679,666cm-1.HRMS(EI)计算值C11H9NS[M]+:187.0456,实测值187.0459.
实施例19化合物(1s)
采用实施例1方案,以刺芒柄花素衍生的烯为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=3:1,产物为白色固体131.0mg,收率86%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.70(d,J=7.2Hz,3H),3.82(s,3H),4.05(q,J=7.2Hz,1H),6.96(d,J=8.8Hz,2H),7.37(d,J=8.4Hz,1H),7.49(d,J=8.8Hz,3H),7.99(s,1H),8.29(d,J=8.4Hz,1H).13C NMR(100M,CDCl3):δ20.99,31.04,55.16,113.83,116.18,120.41,123.54,123.84,125.04,127.38,129.89,142.81,152.51,156.09,159.54,175.66.IR(neat):3081,2961,2937,2909,2833,2246,1637,1624,1606,1574,1562,1511,1437,1371,1357 1289,1246,1229,1195,1178,1116,1107,1028,902,887,837,818,805,789,701cm- 1.HRMS(ESI)计算值C19H16NO3[M+H]+:306.1125,实测值306.1117.
实施例20化合物(1t)
采用实施例1方案,以雌酚酮衍生的烯烃为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=3:1,产物为浅黄色固体146.0mg,收率95%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ0.91(s,3H),1.40-1.67(m,9H),1.95-2.19(m,4H),2.26-2.31(m,1H),2.39-2.44(m,1H),2.50(dd,J=18.6,8.6Hz,1H),2.91-2.95(m,2H),3.84(q,J=7.2Hz,1H),7.10-7.13(m,2H),7.30(d,J=7.6Hz,1H).13C NMR(100M,CDCl3):δ13.62,21.20,21.23,21.35,25.46,26.13,29.12,29.15,30.50,30.52,31.33,35.62,37.78,44.02,47.71,50.21,121.57,123.85,125.94,127.03,134.29,134.31,137.26,139.47,220.51.IR(neat):3369,2927,2859,2239,1732,1498,1454,1404,1373,1243,1086,1050,1008,819cm-1.HRMS(ESI)计算值C21H25NO[M]+:307.1936,实测值307.1943.
实施例21化合物(1u)
采用实施例1方案,以4-苯基-1,3-丁二烯为底物,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=50:1,产物为无色液体63.0mg,收率80%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.49(d,J=6.8Hz,3H),3.45-3.52(m,1H),6.06(dd,J=15.8,6.4Hz,1H),6.71(d,J=16.0Hz,1H),7.24-7.38(m,5H).13C NMR(100M,CDCl3):δ18.95,28.27,120.81,124.23,126.45,128.17,128.63,132.41,135.60.
实施例22化合物(3a)
在充满氮气氛围的手套箱中,向8.0mL的反应瓶中依次加入NiCl2·6H2O(0.025mmol,5.9mg),dppf(0.03mmol,16.6mg),Zn(0.1mmol,6.5mg),Zn(CN)2(0.3mmol,35.2mg),N-乙烯基吡咯酮(0.5mmol,55.6mg)和乙腈(2.5mL),然后将反应瓶盖紧盖子移出手套箱外并用注射器加入水(18μL),然后放入预先加热至80℃的油浴中反应,12小时后停止反应,待反应液冷至室温后,硅胶过滤,乙酸乙酯洗涤,滤液浓缩,直接硅胶柱层析纯化,洗脱剂:乙酸乙酯洗脱,产物为无色油状液体55.4mg,收率80%,1H NMR纯度大于98%。1HNMR(400M,CDCl3):δ2.06-2.14(m,2H),2.41(t,J=8.0Hz,2H),2.64(t,J=6.4Hz,2H),3.55-3.59(m,4H).13C NMR(100M,CDCl3):δ16.39,17.98,30.43,38.82,47.87,117.96,175.44.
实施例23化合物(3b)
实施例23-27的操作技术与实施例22的操作几乎一致,仅使用不同的烯烃为原料。
采用实施例22方案,以N-乙烯基咔唑为原料,反应时间为12小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=5:1,产物为白色固体106.8mg,收率97%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ2.62(t,J=7.2Hz,2H),4.41(t,J=7.2Hz,2H),7.20-7.28(m,4H),7.41(t,J=7.6Hz,2H),8.03(d,J=7.6Hz,2H).13C NMR(100M,CDCl3):δ17.02,38.54,108.09,117.35,119.75,120.50,123.09,125.99,139.34.IR(neat):3045,2956,2930,2244,1593,1485,1459,1419,1383,1353,1333,1327,1261,1225,1198,1152,1123,1066,744,724cm-1.HRMS(EI)计算值C15H13N2[M]+:220.1000,实测值220.1005.
实施例24化合物(3c)
采用实施例22方案,以叔戊酸乙烯酯为原料,反应时间为12小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=10:1,产物为无色液体41.1mg,收率53%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.24(s,9H),2.72(t,J=6.4Hz,2H),4.27(t,J=6.4Hz,2H).13C NMR(100M,CDCl3):δ17.89,26.95,38.69,58.43,116.68,177.91.
实施例25化合物(3d)
采用实施例22方案,以苯基乙烯基砜为原料,反应时间为12小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=2:1,产物为白色固体84.0mg,收率86%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ2.81(t,J=7.6Hz,2H),3.41(t,J=7.6Hz,2H),7.62(t,J=7.6Hz,2H),7.72(t,J=7.6Hz,1H),7.93(d,J=7.6Hz,2H).13C NMR(100M,CDCl3):δ11.79,50.75,116.09,128.04,129.57,134.51,137.27.
实施例26化合物(3e)和(4e)
采用实施例22方案,以二甲基苯基乙烯基硅烷为原料,反应时间为12小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1,得到产物为3e及4e的混合物(3e:4e=16.7:1)为无色液体81.3mg,总收率86%。其中3e的核磁如下:1H NMR(400M,CDCl3):δ0.34(s,6H),1.11-1.15(m,2H),2.22-2.26(m,2H),7.35-7.38(m,3H),7.47-7.49(m,2H)13C NMR(100M,CDCl3):δ-3.67,11.77,11.95,121.02,127.95,129.41,133.76,136.46,17.02,38.54,108.09,117.35,119.75,120.50,123.09,125.99,139.34.另一异构体4e的部分核磁如下:Partial 1H NMR(400M,CDCl3):δ0.28(d,J=0.8Hz,6H),1.22(d,J=7.2Hz,3H),1.98(q,J=7.2Hz,1H),7.54-7.57(m,2H).Partial 13C NMR(400M,CDCl3):δ-5.69,-5.09,11.43,11.86,128.02,130.04,133.76.
实施例27化合物(3f)
采用实施例22方案,以烯丙基磷酸二乙酯为原料,反应时间为12小时。硅胶柱层析纯化,洗脱剂:乙酸乙酯,产物为无色液体86.9mg,收率85%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.34(t,J=7.2Hz,6H),1.85-2.03(m,4H),2.52(t,J=6.8Hz,2H),4.07-4.17(m,4H).13C NMR(100M,CDCl3):δ16.17(d,3JC-P=5.7Hz),17.46(d,2JC-P=15.4Hz),18.90(d,3JC-P=4.5Hz),24.20(d,1JC-P=142.6Hz),61.59(d,2JC-P=6.1Hz),118.63.31P NMR(400M,CDCl3):δ29.28.IR(neat):3458,2979,2927,2909,2244,1233,1163,1024,957,784,733cm-1.HRMS(ESI)计算值for C8H20N2O3P[M+NH4]+:223.1206,测量值223.1201.
实施例28化合物(5a)和化合物(6a)
在充满氮气氛围的手套箱中,向8.0mL的反应瓶中依次加入Ni(ClO4)2·6H2O(0.025mmol,9.1mg),dppp(0.03mmol,14.8mg),Zn(0.5mmol,32.7mg),Zn(CN)2(0.3mmol,35.2mg),DMAP(0.5mmol,61.1mg),2-烯丙基萘(0.5mmol,84.1mg)和乙腈(2.5mL),然后将反应瓶盖紧盖子移出手套箱外并用注射器加入水(18μL),然后放入预先加热至80℃的油浴中反应,24小时后停止反应,待反应液冷至室温后,硅胶过滤,乙酸乙酯洗涤,滤液浓缩,直接制备板层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1展开,产物5a为白色固体8.8mg,收率9%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.36(d,J=6.8Hz,3H),2.92-3.01(m,2H),3.09-3.14(m,1H),7.34(dd,J=8.6,1.6Hz,1H),7.46-7.49(m,2H),7.69(s,1H),7.80-7.83(m,3H).13C NMR(100M,CDCl3):δ17.62,27.42,40.11,122.54,125.88,126.27,126.93,127.65,127.84,128.46,132.52,133.40,134.27.产物6a为白色固体76.2mg,收率为78%。1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.94-2.01(m,2H),2.23(t,J=7.2Hz,2H),2.86(t,J=7.2Hz,2H),7.25(dd,J=8.2,1.6Hz,1H),7.39-7.46(m,2H),7.58(s,1H),7.75-7.79(m,3H).13C NMR(100M,CDCl3):δ16.16,26.55,34.27,119.40,125.40,126.05,126.66,127.31,127.50,128.20,132.06,133.37,137.02.
实施例29化合物(5b)和化合物(6b)
采用实施例28方案,4-烯丙基苯甲醚为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=20:1,产物为5b和6b的混合物70.6mg(6b:5b=8.3:1)为无色液体,总收率81%。其中6b的核磁如下:1H NMR(400M,CDCl3):δ1.89-1.96(m,2H),2.28(t,J=7.2Hz,2H),2.70(t,J=7.2Hz,2H),3.78(s,3H),8.40(d,J=8.4Hz,2H),7.09(d,J=8.4Hz,2H).13C NMR(100M,CDCl3):δ16.10,26.95,33.29,55.09,113.89,119.47,129.25,129.95,131.58,158.08.另一异构体5b的部分核磁如下:partial 1H NMR(400M,CDCl3):δ1.30(d,J=6.4Hz,3H),2.77-2.87(m,3H),3.78(s,3H),7.14(d,J=8.8Hz,2H),partial 13CNMR(400M,CDCl3):δ17.34,27.61,38.96,113.90.
实施例30化合物(5c)和化合物(6c)
采用实施例28方案,以4-苯基-1-丁烯为原料,反应时间为4小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1至20:1,产物5c为无色液体9.2mg,收率12%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.33(d,J=7.2Hz,3H),1.79-1.88(m,1H),1.91-2.01(m,1H),2.53-2.62(m,1H),2.71-2.79(m,1H),2.84-2.91(m,1H),7.19-7.26(m,3H),7.29-7.33(m,2H).13C NMR(100M,CDCl3):δ17.97,24.81,33.15,35.71,122.74,126.38,128.38,128.61,140.11.产物6c为无色液体64.3mg,收率81%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.62-1.69(m,2H),1.73-1.81(m,2H),2.31(t,J=7.2Hz,2H),2.64(t,J=7.2Hz,2H),7.15-7.21(m,3H),7.26-7.30(m,2H).13C NMR(100M,CDCl3):δ16.92,24.71,30.14,34.85,119.54,125.95,128.24,128.35,141.12.
实施例31化合物(5d)和化合物(6d)
采用实施例28方案,以1-癸烯为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=5:1,产物为5d和6d的混合物64.7mg(6b:5b=12.5:1)为无色液体,总收率77%。其中6d的核磁如下:1H NMR(400M,CDCl3):δ0.88(t,J=6.8Hz,3H),1.20-1.32(m,12H),1.41-1.46(m,2H),1.62-1.69(m,2H),2.33(t,J=7.2Hz,2H),3.64(t,J=6.4Hz,2H).13C NMR(100M,CDCl3):δ13.96,16.98,22.54,25.26,28.54,28.64,29.13,29.19,29.34,31.73,119.73.部分5d的核磁如下:partial 1H NMR(400M,CDCl3):δ0.88(t,J=6.8Hz,3H),2.55-2.64(m,1H),partial 13C NMR(400M,CDCl3):δ17.90,25.38,26.91,28.95,29.05,29.20,31.69,33.95.
实施例32化合物(5e)和化合物(6e)
采用实施例28方案,以叔丁基二苯基硅保护的4-丁烯-醇为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1,产物5e为无色液体11.5mg,收率7%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.06(s,9H),1.32(d,J=7.2Hz,3H),1.68-1.79(m,1H),1.81-1.89(m,1H),2.92-3.01(m,1H),3.73-3.85(m,2H),7.37-7.46(m,6H),7.64(m,4H).13C NMR(100M,CDCl3):δ17.76,19.18,21.94,26.79,36.70,60.53,122.91,127.75,127.76,129.78,129.80,133.15,133.35,135.45,135.51.IR(neat):3071,2931,2857,2239,1587,1472,1428,1388,1110,998,981,902,822,738,700,687cm-1.HRMS(ESI)calcd for C21H31N2OSi[M+NH4]+:355.2200,found 355.2196.产物6e为无色液体124.3mg,收率74%。1H NMR(400M,CDCl3):δ1.06(s,9H),1.64-1.71(m,2H),1.73-1.81(m,2H),2.30(t,J=7.2Hz,2H),3.69(t,J=6.0Hz,2H),7.35-7.43(m,6H),7.64-7.66(m,4H).13C NMR(100M,CDCl3):δ16.74,19.05,22.09,26.73,31.08,62.52,119.62,127.60,129.60,133.45,135.38.IR(neat):3071,3045,2931,2857,2244,1590,1472,1427,1385,1186,1109,1007,974,822,740,700,686cm-1.HRMS(ESI)calcd for C21H31N2OSi[M+NH4]+:355.2200,found 355.2199.
实施例33化合物(5f)和化合物(6f)
采用实施例28方案,以5-戊烯-1-醇为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=3:1,产物为5f和6f的混合物(6f:5f=9.1:1)为无色液体50.4mg,总收率89%。其中6f的核磁如下:1H NMR(400M,CDCl3):δ1.49-1.64(m,4H),1.67-1.74(m,2H),2.27(s,1H),2.38(t,J=7.2Hz,2H),3.64(t,J=6.4Hz,2H).13C NMR(100M,CDCl3):δ16.98,24.85,25.01,31.53,61.98,119.68.部分5f的核磁如下:partial 1H NMR(400M,CDCl3):δ1.34(d,J=7.2Hz,3H),2.64-2.73(m,1H),partial 13C NMR(400M,CDCl3):δ17.87,25.24,29.77,30.38,61.54.
实施例34化合物(5g)和化合物(6g)
采用实施例28方案,以N-烯丙基邻苯二甲酰亚胺为底物,反应时间为24小时。制备板层析纯化,洗脱剂:石油醚/乙酸乙酯=5:1,产物5g为白色固体18.2mg,收率17%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.40(d,J=6.8Hz,3H),3.19-3.28(m,1H),3.77(dd,J=13.8,6.8Hz,1H),4.02(dd,J=13.6,8.4Hz,1H),7.76-7.79(m,2H),7.87-7.91(m,2H).13CNMR(100M,CDCl3):δ15.54,25.23,40.09,120.37,123.68,131.59,134.40,167.69。产物6g为无色液体83.5mg,收率78%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ2.05-2.12(m,2H),2.45(t,J=7.2Hz,2H),3.82(t,J=6.4Hz,2H),7.73-7.77(m,2H),7.84-7.88(m,2H).13C NMR(100M,CDCl3):δ14.95,24.60,36.50,118.70,123.30,131.70,134.11,168.10.
实施例35化合物(6h)
采用实施例28方案,以戊烯酸乙酯为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=10:1至3:1,产物为无色液体57.5mg,收率74%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.26(t,J=7.2Hz,3H),1.68-1.82(m,4H),2.34-2.41(m,4H),4.14(q,J=7.2Hz,2H).13C NMR(100M,CDCl3):δ14.00,16.74,23.69,24.61,33.09,60.28,119.21,172.58.
实施例36化合物(6i)
采用实施例28方案,以1-十一碳烯醛为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=10:1,产物为无色液体57.1mg,收率58%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.26-1.30(m,10H),1.39-1.46(m,2H),1.59-1.69(m,4H),2.34(t,J=7.2Hz,2H),2.41-2.45(m,2H),9.76(s,1H).13C NMR(100M,CDCl3):δ16.96,21.88,25.20,28.47,28.56,28.95,29.05,29.09,29.11,43.73,119.74,202.80.
实施例37化合物(6j)
采用实施例28方案,以2-乙烯基环己酮为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=10:1至5:1,产物为无色液体56.4mg,收率68%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.32-1.46(m,2H),1.58-1.78(m,4H),1.82-1.92(m,2H),2.05-2.14(m,2H),2.28-2.42(m,5H).13C NMR(100M,CDCl3):δ17.17,23.08,24.81,27.77,28.60,33.97,41.90,49.75,119.50,212.26.
实施例38化合物(6k)
采用实施例28方案,以环己基乙烯为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1,产物为无色液体55.0mg,收率80%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ0.87-0.95(m,2H),1.09-1.30(m,3H),1.35-1.44(m,1H),1.55(q,J=7.2Hz,2H),1.65-1.74(m,5H),2.35(t,J=7.2Hz,2H).13C NMR(100M,CDCl3):δ14.49,25.81,26.17,32.36,32.42,36.43,119.96.
实施例39化合物(6l)
采用实施例28方案,以二甲基叔丁基硅基保护的烯丙醇为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=50:1,产物为无色液体120.7mg,收率80%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ0.12(d,J=2.0Hz,6H),0.95(s,9H),1.77-1.94(m,4H),2.43(t,J=7.2Hz,2H),2.66(t,J=8.4Hz,2H),3.85-3.90(m,1H),7.19-7.24(m,3H),7.30-7.34(m,2H).13C NMR(100M,CDCl3):δ-4.74,-4.44,12.97,17.92,25.73,31.19,32.10,38.52,69.70,119.85,125.86,128.15,128.39,141.64.IR(neat):3084,3060,3026,2952,2929,2857,2246,1603,1495,1469,1453,1362,1254,1092,993,834,774,746,698,663cm-1.HRMS(EI)计算值C18H29NOSi[M]+:303.2018,实测值303.2010.
实施例40化合物(6m)
采用实施例1方案,以2-乙烯基吡啶为原料,反应时间为24小时。硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=1:1,产物为无色液体60.4mg,收率91%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ2.84(t,J=7.2Hz,2H),3.11(t,J=7.2Hz,2H),7.17-7.23(m,2H),7.65(td,J=7.6,0.8Hz,1H),8.55(d,J=4.8Hz,1H).13C NMR(100M,CDCl3):δ16.37,33.09,119.27,121.98,122.90,136.55,149.36,156.97.
实施例41化合物(1a)
在250mL的schlenk管中依次加入NiCl2·6H2O(0.5mmol,118.8mg),Xantphos(0.6mmol,347.2mg),Zn(2mmol,130.8mg),Zn(CN)2(6mmol,704.5mg),抽换氩气三次后在氩气下加入1,4-二氧六环(50mL)、对甲基苯乙烯(10mmol,1.18g)和水(1mL),然后将反应管封好后置于预先加热至80℃的油浴中反应,6小时后停止反应,待反应液冷至室温后,硅胶过滤,乙酸乙酯洗涤,滤液浓缩后用20mL乙酸乙酯溶解并加入3mL 30%H2O2,于室温下搅拌10分钟。向反应体系中加入饱和的Na2S2O3淬灭反应,乙酸乙酯萃取,有机相用水洗,饱和NaCl洗涤,无水Na2SO4干燥,过滤浓缩,硅胶柱层析纯化,洗脱剂:石油醚/乙酸乙酯=30:1洗脱,产物为无色油状液体1.25g,收率86%,1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.62(d,J=7.2Hz,3H),2.35(s,3H),3.86(q,J=7.2Hz,1H),7.18(d,J=8.0Hz,2H),7.25(d,J=8.4Hz,2H).13C NMR(100M,CDCl3):δ20.98,21.44,30.80,121.73,126.52,129.71,134.05,137.78.
实施例42化合物(1a)
充满氮气的手套箱中,8mL样品瓶中依次加入Ni(cod)2(6.9mg,0.025mmol),9,9-二甲基-4,5-双二苯基膦氧杂蒽(17.4mg,0.03mmol),1,4-二氧六环(2.5mL),室温下搅拌10分钟,再依次向其中加入Zn(CN)2(35.2mg,0.3mmol),和4-甲基苯乙烯(59.1mg,0.5mmol)。盖好瓶盖移出手套箱,向其中加入水(50μL),置于预先加热到80℃油浴中反应4h。短硅胶柱过滤,乙酸乙酯洗涤,浓缩,硅胶柱层析,石油醚/乙酸乙酯=100:1到50:1洗脱,得到产物为无色液体65.3mg,收率90%。1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.62(d,J=7.2Hz,3H),2.35(s,3H),3.86(q,J=7.2Hz,1H),7.18(d,J=8.0Hz,2H),7.25(d,J=8.4Hz,2H).13C NMR(100M,CDCl3):δ20.98,21.44,30.80,121.73,126.52,129.71,134.05,137.78.
实施例43化合物(1a)
在充满氮气氛围的手套箱中,向4.0mL的反应瓶中依次加入NiCl(dppf)(0.015mmol,9.7mg),Zn(CN)2(21.1mg,0.18mmol),1,4-二氧六环(1.5mL),对甲基苯乙烯(0.3mmol,35.5mg),然后将反应瓶盖紧盖子移出手套箱外并用注射器加入水(30μL),然后放入预先加热至80℃的油浴中反应,8小时后停止反应,待反应液冷至室温后,硅胶过滤,乙酸乙酯洗涤,滤液浓缩,硅胶柱层析,石油醚/乙酸乙酯=50:1洗脱,得到产物为无色液体37.0mg,收率为85%。。1H NMR纯度大于98%。1H NMR(400M,CDCl3):δ1.62(d,J=7.2Hz,3H),2.35(s,3H),3.86(q,J=7.2Hz,1H),7.18(d,J=8.0Hz,2H),7.25(d,J=8.4Hz,2H).13C NMR(100M,CDCl3):δ20.98,21.44,30.80,121.73,126.52,129.71,134.05,137.78.
实施例44化合物(1a)
以1a的制备为例:除下列条件外,采用实施例1方案,不同的用水量条件下进行反应。
a在4mL小瓶中的0.3mmol规模。以均三甲苯为内标通过粗反应混合物的1H NMR测定产率。
实施例45化合物(1a)
以1a的制备为例:除下列条件外,采用实施例1方案,不同的镍催化剂条件下进行反应。
a在4mL小瓶中的0.3mmol规模。以均三甲苯为内标通过粗反应混合物的1H NMR测定产率。
实施例46化合物(1a)
以1a的制备为例:除下列条件外,采用实施例1方案,在不同的配体条件下进行反应。
a在4mL小瓶中的0.3mmol规模。以均三甲苯为内标通过粗反应混合物的1H NMR测定产率。
实施例47化合物(1a)
以1a的制备为例:除下列条件外,采用实施例1方案,在不同的溶剂条件下进行反应。
a在4mL小瓶中的0.3mmol规模。以均三甲苯为内标通过粗反应混合物的1H NMR测定产率。
实施例48化合物(1a)
以1a的制备为例:除下列条件外,采用实施例1方案,在不同的Zn(CN)2用量、不同的还原剂、以及不同的温度条件下进行反应。
a在4mL小瓶中的0.3mmol规模。以均三甲苯为内标通过粗反应混合物的1H NMR测定产率。
实施例49化合物(1a)
以1a的制备为例:除下列条件外,采用实施例1方案,使用单因素变量进行反应。
结果如下所示:控制实验
a在4mL小瓶中的0.3mmol规模。以均三甲苯为内标通过粗反应混合物的1H NMR测定产率。
对比实施例1化合物(1a)
在充满氮气氛围的手套箱中,向8.0mL的反应瓶中依次加入NiCl2·6H2O(0.025mmol,5.9mg),9,9-二甲基-4,5-双二苯基膦氧杂蒽(0.03mmol,17.4mg),Zn(0.1mmol,6.5mg),1,4-二氧六环(2.5mL),对甲基苯乙烯(0.5mmol,59.1mg)和TMSCN(99.2mg,1.0mmol),然后将反应瓶盖紧盖子移出手套箱外并用注射器加入水(50μL)和MeOH(32mg,1mmol),然后放入预先加热至80℃的油浴中反应,4小时后停止反应,待反应液冷至室温后,硅胶过滤,***洗涤,滤液浓缩,加入均三甲氧基苯为内标,测核磁收率,产物1a收率为0%,原料剩余83%。硅胶柱层析,正戊烷洗涤,回收原料63%。
Claims (12)
1.一种烷基腈类化合物1的制备方法,其特征在于,其包括以下步骤:有机溶剂中,在保护气体存在下,在催化剂的作用下,将如式I所示的烯烃和氰基化试剂及水进行如下所示的还原反应,即可;所述的烷基腈类化合物1为化合物II和/或化合物III;
所述氰基化试剂为氰化锌;
所述的催化剂包括镍类化合物和膦配体;所述的镍类化合物为0价镍、一价镍盐和二价镍盐中的一种或多种;当所述的镍类化合物包含二价镍盐时,所述的催化剂还包括还原剂;
所述的0价镍为Ni(cod)2;
所述的一价镍盐为NiCl;
所述的二价镍盐为Ni(acac)2、NiCl2、NiCl2(DME)、NiBr2(DME)、NiI2和Ni(ClO4)2中的一种或多种;
所述的还原剂为Zn、Mn和Al中的一种或多种;
其中,R1为未取代或R1-1取代的C6-14芳基、未取代或R1-2取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、未取代或R1-3取代的C1-10烷基、未取代或R1-4取代的C2-10烯基、未取代或R1-5取代的C3-8环烷基、未取代或R1-6取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基、或者、
R1-1为-OH、-NH2、-CN、CF3、卤素、C1-10烷基、C1-10烷氧基、C6-14芳基、或、未取代或R1-1-1取代的“杂原子选自N、O、S和B中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基;
R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为C1-10烷基、C1-10烷氧基、或者、未取代或R1-2-1取代的C6-14芳基;R1-2-1为-OH、-NH2、-CN、CF3、卤素、C1-4烷基或C1-4烷氧基;
R1-5、R1-6和R1-3-5独立地为=O、C1-4烷基或C1-4烷氧基;
R1-10独立地为H、-OH、-NH2、-CN、CF3、卤素、C1-4烷基或C1-4烷氧基;m为0、1、2、3或4;
R1-3-1为氧保护基团。
2.如权利要求1所述的制备方法,其特征在于,
所述的“取代”的个数为一个或多个;当存在多个“取代”时,所述的“取代”相同或不同;
和/或,当R1-1为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R1-2-1为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R1-10为卤素时,所述的卤素为氟、氯、溴或碘;
和/或,当R1为未取代或R1-1取代的C6-14芳基时,所述的C6-14芳基为C6-10芳基;
和/或,当R1为未取代或R1-2取代的5~20元杂芳基时,所述的5~20元杂芳基为5~13元杂芳基;
和/或,当R1为未取代或R1-3取代的C1-10烷基时,所述的C1-10烷基为甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、正戊基、正己基、正庚基、正辛基、正壬基或正癸基;
和/或,当R1为未取代或R1-4取代的C2-10烯基时,所述的C2-10烯基为C2-6烯基;
和/或,当R1为未取代或R1-5取代的C3-8环烷基时,所述的C3-8环烷基为C3-6环烷基;
和/或,当R1为未取代或R1-6取代的3~10元杂环烷基时,所述的3~10元杂环烷基为3~6元杂环烷基;
和/或,当R1-1为C1-10烷基时,所述的C1-10烷基为C1-4烷基;
和/或,当R1-1为C1-10烷氧基时,所述的C1-10烷氧基为C1-4烷氧基;
和/或,当R1-1为C6-14芳基时,所述的C6-14芳基为C6-10芳基;
和/或,当R1-1为未取代或R1-1-1取代的3~10元杂环烷基时,所述的3~10元杂环烷基为3~6元杂环烷基;
和/或,当R1-3为未取代或R1-3-4取代的C6-14芳基时,所述的C6-14芳基为C6-10芳基;
和/或,当R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为C1-10烷基时,所述的C1-10烷基为C1-4烷基;
和/或,当R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为C1-10烷氧基时,所述的C1-10烷氧基为C1-4烷氧基;
和/或,当R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为未取代或R1-2-1取代的C6-14芳基,所述的C6-14芳基为C6-10芳基。
3.如权利要求2所述的制备方法,其特征在于,
所述的“取代”的个数为1、2、3或4个;
和/或,当R1-1、R1-2-1和R1-10独立地为卤素时,所述的卤素为氟;
和/或,当R1为未取代或R1-1取代的C6-14芳基时,所述的C6-14芳基为苯基或萘基;
和/或,当R1为未取代或R1-2取代的5~20元杂芳基时,所述的5~20元杂芳基为吡啶基、吲哚基、苯并噻吩基或咔唑基;
和/或,当R1为未取代或R1-3取代的C1-10烷基时,所述的C1-10烷基为甲基、乙基、丙基、辛基或壬基;
和/或,当R1为未取代或R1-4取代的C2-10烯基时,所述的C2-10烯基为乙烯基、1-丙烯基、2-丙烯基、1-丁烯基、2-丁烯基或丁二烯;
和/或,当R1为未取代或R1-5取代的C3-8环烷基时,所述的C3-8环烷基为环丙基、环戊基或环己基;
和/或,当R1为未取代或R1-6取代的3~10元杂环烷基时,所述的3~10元杂环烷基为四氢呋喃基、吡咯烷基、哌啶基、哌嗪基或吗啉基;
和/或,当R1-1为C1-10烷基时,所述的C1-10烷基为甲基或异丁基;
和/或,当R1-1为C1-10烷氧基时,所述的C1-10烷氧基为甲氧基;
和/或,当R1-1为C6-14芳基时,所述的C6-14芳基为苯基;
和/或,当R1-3为未取代或R1-3-4取代的C6-14芳基时,所述的C6-14芳基为苯基或萘基;
和/或,当R1-3为未取代或R1-3-5取代的C3-6环烷基时,所述的C3-6环烷基为环丙基、环戊基或环己基;
和/或,当R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为C1-10烷基时,所述的C1-10烷基为甲基、乙基、丙基、异丙基、正丁基、仲丁基、异丁基、叔丁基;
和/或,当R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为C1-10烷氧基时,所述的C1-10烷氧基为甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、仲丁氧基、异丁氧基、叔丁氧基;
和/或,当R1-2、R1-4、R1-7、R1-8、R1-9a、R1-9b、R1-9c、R1-1-1、R1-3-2、R1-3-3a、R1-3-3b和R1-3-4独立地为未取代或R1-2-1取代的C6-14芳基时,所述的C6-14芳基为苯基;
和/或,当R1-2-1、R1-5、R1-6、R1-3-5和R1-10独立地为C1-4烷基时,所述的C1-4烷基为甲基、乙基、丙基或异丙基;
和/或,当R1-2-1、R1-5、R1-6、R1-3-5和R1-10独立地为C1-4烷氧基时,所述的C1-4烷氧基为甲氧基、乙氧基、丙氧基或异丙氧基;
和/或,R1-3-1为叔丁基二苯基甲硅烷基或叔丁基二甲基硅基。
5.如权利要求1~4中任一项所述的制备方法,其特征在于,当R1为未取代或R1-1取代的C6-14芳基、未取代或R1-2取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、未取代或R1-4取代的C2-10烯基、或者、除了R1为/>所述的化合物1为化合物II;
6.如权利要求1~4中任一项所述的制备方法,其特征在于,所述的R1的定义如下任一方案所述:
方案1:R1为R1-1取代的C6-14芳基、未取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、或者、其中,所述的未取代的5~20元杂芳基为咔唑基;R1-1独立地为C1-10烷氧基或C6-14芳基;
方案2:R1为未取代或R1-1取代的C6-14芳基、未取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基、未取代或R1-3取代的C1-10烷基、未取代或R1-5取代的C3-8环烷基、未取代或R1-6取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基、或者、/>其中,所述的未取代的5~20元杂芳基为吲哚基;R1-1为-NH2、C1-10烷氧基、未取代或R1-1-1取代的“杂原子选自N、O、S和B中的一种或多种,杂原子数为1-4个”的3~10元杂环烷基;R1-3为-OH、-CHO、/>OR1-3-1、/>R1-3-4取代的C6-14芳基、未取代或R1-3-5取代的C3-6环烷基;
方案3:R1为未取代或R1-1取代的C6-14芳基、或者、未取代的“杂原子选自N、O和S中的一种或多种,杂原子数为1-4个”的5~20元杂芳基;其中,所述的未取代的5~20元杂芳基为咔唑基;R1-1为-OH或CF3;
8.如权利要求1所述的制备方法,其特征在于,所述有机溶剂为芳香类溶剂、醚类溶剂、卤代烃类溶剂、腈类溶剂、酰胺类溶剂和亚砜类溶剂中的一种或多种;
和/或,所述保护气体为氮气、氦气、氩气和氖气中的一种或多种;
和/或,所述的膦配体为三苯基膦、三苯基亚磷酸酯、三丁基膦、三环己基膦(PCy3)、二甲基苯基膦、二苯基甲基膦、双二苯基膦甲烷、1,2-双(二苯膦)乙烷、1,3-双(二苯基膦)丙烷、1,4-双(二苯基膦)丁烷、1,1’-双(二苯基膦)二茂铁、双(2-二苯基磷苯基)醚、9,9-二甲基-4,5-双二苯基膦氧杂蒽和4,5-二(二叔丁基膦)-9,9-二甲基氧杂蒽中的一种或多种;
和/或,所述的催化剂中,所述的镍类化合物和所述的膦配体为独立的化合物,或者,所述镍类化合物中的部分或全部、与、所述的膦配体中的部分或全部为络合物;
和/或,所述的镍类化合物和所述的水为独立的化合物,或者,所述的镍类化合物中的部分或全部、与、所述的水中的部分或全部形成结晶水合物;
和/或,当所述的催化剂还包括还原剂时,所述的如式I所示的烯烃与所述的还原剂的摩尔比为1:0.01~10;
和/或,所述如式I所示的烯烃与所述镍类化合物的摩尔比为1:0.01~1;
和/或,所述镍类化合物与所述膦配体的摩尔比为1:1~10;
和/或,所述如式I所示的烯烃与所述氰基化试剂的摩尔比为1:0.1~10;
和/或,所述如式I所示的烯烃在所述有机溶剂中的摩尔浓度为0.01~1mmol/mL;
和/或,所述如式I所示的烯烃与水摩尔比为1:1~10;
和/或,所述还原反应的温度为20~100℃。
9.如权利要求8所述的制备方法,其特征在于,所述的有机溶剂为醚类溶剂和/或腈类溶剂;
和/或,当所述的有机溶剂为芳香类溶剂时,所述的芳香类溶剂为苯、甲苯和二甲苯中的一种或多种;
和/或,当所述的有机溶剂为醚类溶剂时,所述的醚类溶剂为***、1,4-二氧六环和四氢呋喃中的一种或多种;
和/或,当所述的有机溶剂为卤代烃类溶剂时,所述的卤代烃类溶剂为二氯甲烷、二氯乙烷和氯仿中的一种或多种;
和/或,当所述的有机溶剂为腈类溶剂时,所述的腈类溶剂为乙腈;
和/或,当所述的有机溶剂为酰胺类溶剂时,所述的酰胺类溶剂为N,N-二甲基甲酰胺和/或甲基磷酰胺;
和/或,当所述的有机溶剂为亚砜类溶剂时,所述的亚砜类溶剂为二甲基亚砜;
和/或,所述的保护气体为氮气;
和/或,所述的膦配体为1,3-双(二苯基膦)丙烷、1,1’-双(二苯基膦)二茂铁和9,9-二甲基-4,5-双二苯基膦氧杂蒽中的一种或多种;
和/或,所述的催化剂中,当所述镍类化合物中的部分或全部、与、所述的膦配体中的部分或全部为络合物时,所述的络合物为0价镍与膦配体的络合物、一价镍盐与膦配体的络合物、和、二价镍盐与膦配体的络合物中的一种或多种;
和/或,所述的还原剂为Zn;
和/或,当所述的镍类化合物中的部分或全部、与、所述的水中的部分或全部形成结晶水合物;所述的结晶水合物为0价镍与水形成的结晶水合物、和/或、二价镍盐与水形成的结晶水合物;
和/或,所述的水为去离子水;
和/或,当所述的催化剂还包括还原剂时,所述的如式I所示的烯烃与所述的还原剂的摩尔比为1:0.2~1;
和/或,所述如式I所示的烯烃与所述镍类化合物的摩尔比为1:0.03~0.06;
和/或,所述镍类化合物与所述膦配体的摩尔比为1:1.1~1.4;
和/或,所述如式I所示的烯烃与所述氰基化试剂的摩尔比为1:0.5~0.8;
和/或,所述如式I所示的烯烃在所述有机溶剂中的摩尔浓度为0.1~0.4mmol/mL;
和/或,所述如式I所示的烯烃与水摩尔比为1:1~6;
和/或,所述还原反应的温度为50~80℃;
和/或,当所述的膦配体为1,3-双(二苯基膦)丙烷时,所述的还原反应中加入N,N-二甲基吡啶作为添加剂;所述的如式I所示的烯烃与所述的N,N-二甲基吡啶的摩尔比为1:0.1~3。
10.如权利要求9所述的制备方法,其特征在于,
所述的催化剂中,当所述镍类化合物中的部分或全部、与、所述的膦配体中的部分或全部为络合物,所述的络合物为0价镍与膦配体的络合物时,所述的络合物为Ni(PPh3)4;
和/或,所述的催化剂中,当所述镍类化合物中的部分或全部、与、所述的膦配体中的部分或全部为络合物,所述的络合物为一价镍盐与膦配体的络合物时,所述的络合物为NiCl(dppf);
和/或,所述的催化剂中,当所述镍类化合物中的部分或全部、与、所述的膦配体中的部分或全部为络合物,所述的络合物为二价镍盐与膦配体的络合物时,所述的络合物为NiCl2(PPh3)4、NiCl2(dppf)、NiBr2(PPh3)2、NiCl2(PCy3)3、NiCl2(dppp)和NiCl2(dppe)的一种或多种;
和/或,所述的催化剂中,所述的镍类化合物和所述的膦配体为独立的化合物;
和/或,当所述的镍类化合物中的部分或全部、与、所述的水中的部分或全部形成结晶水合物,所述的结晶水合物为二价镍盐与水形成的结晶水合物时,所述的结晶水合物为NiCl2·6H2O、NiI2·6H2O、Ni(acac)2·2H2O和Ni(ClO4)2·6H2O中的一种或多种。
11.如权利要求10所述的制备方法,其特征在于,
当所述的镍类化合物中的部分或全部、与、所述的水中的部分或全部形成结晶水合物,所述的结晶水合物为二价镍盐与水形成的结晶水合物时,所述的结晶水合物为NiCl2·6H2O和/或Ni(ClO4)2·6H2O;
和/或,所述的催化剂为所述的催化剂为二价镍盐、膦配体和Zn;所述的二价镍盐为NiCl2和/或Ni(ClO4)2,所述的膦配体为1,1’-双(二苯基膦)二茂铁和/或9,9-二甲基-4,5-双二苯基膦氧杂蒽膦配体。
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CN114956929B (zh) * | 2022-05-13 | 2024-03-05 | 华中师范大学 | 一种手性腈类化合物的合成方法 |
CN116947695B (zh) * | 2023-09-19 | 2023-12-26 | 上海如鲲新材料股份有限公司 | 一种1,3,6-己烷三腈的制备方法和应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102351684A (zh) * | 2011-09-26 | 2012-02-15 | 常州市天华制药有限公司 | 2-苯基丙酸的制备方法 |
CN104292098A (zh) * | 2014-09-28 | 2015-01-21 | 威海迪嘉制药有限公司 | 一种2-苯基丙酸的制备方法 |
-
2019
- 2019-01-28 CN CN201910081372.4A patent/CN111484472B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102351684A (zh) * | 2011-09-26 | 2012-02-15 | 常州市天华制药有限公司 | 2-苯基丙酸的制备方法 |
CN104292098A (zh) * | 2014-09-28 | 2015-01-21 | 威海迪嘉制药有限公司 | 一种2-苯基丙酸的制备方法 |
Non-Patent Citations (3)
Title |
---|
Nickel(0)-TPPTS-Cyanide Complex in Water An Efficient and Flexible Catalyst for the Isomerisation of Olefinic Compounds at Room Temperature;E.G.Kuntz et al;《Oil & Gas Science and Technology》;20071231;第62卷(第6期);第781-785页 * |
Regio- and Stereoselective Chan-Lam-Evans Enol Esterification of Carboxylic Acids with Alkenylboroxines;Luuk Steemers et al;《Adv. Synth. Catal.》;20181108;第360卷(第21期);第4241-4245页 * |
手性中间体氢化阿托酸的合成新法;李仲新 等;《浙江化工》;20101231;第41卷(第2期);第11-14页 * |
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