CN106905224A - Synthesis method of N-aryl substituted indeno [1,2-b ] indole compound - Google Patents
Synthesis method of N-aryl substituted indeno [1,2-b ] indole compound Download PDFInfo
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- CN106905224A CN106905224A CN201510971646.9A CN201510971646A CN106905224A CN 106905224 A CN106905224 A CN 106905224A CN 201510971646 A CN201510971646 A CN 201510971646A CN 106905224 A CN106905224 A CN 106905224A
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- indeno
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- -1 indeno [1,2-b ] indole compound Chemical class 0.000 title claims abstract description 41
- 238000001308 synthesis method Methods 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 70
- 238000006243 chemical reaction Methods 0.000 claims abstract description 58
- 238000010189 synthetic method Methods 0.000 claims abstract description 26
- 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 18
- 239000003054 catalyst Substances 0.000 claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 150000007530 organic bases Chemical class 0.000 claims abstract description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 25
- 230000015572 biosynthetic process Effects 0.000 claims description 18
- 238000003786 synthesis reaction Methods 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- MJFCDPLEATUOPF-UHFFFAOYSA-L dichloronickel;triphenylphosphane Chemical compound Cl[Ni]Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MJFCDPLEATUOPF-UHFFFAOYSA-L 0.000 claims description 5
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 5
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 claims description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical group [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- SHWZFQPXYGHRKT-FDGPNNRMSA-N (z)-4-hydroxypent-3-en-2-one;nickel Chemical compound [Ni].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O SHWZFQPXYGHRKT-FDGPNNRMSA-N 0.000 claims 1
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 239000000758 substrate Substances 0.000 abstract description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract 2
- 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 abstract 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 25
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 22
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 239000007789 gas Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 238000010898 silica gel chromatography Methods 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 238000013019 agitation Methods 0.000 description 12
- 230000008859 change Effects 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000012968 metallocene catalyst Substances 0.000 description 11
- 229910052759 nickel Inorganic materials 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 241000254173 Coleoptera Species 0.000 description 10
- 241000165940 Houjia Species 0.000 description 10
- 238000005660 chlorination reaction Methods 0.000 description 10
- DOZCTPAUYJQGBD-UHFFFAOYSA-N indeno[1,2-b]indole Chemical class C1=CC=C2C=C3C4=CC=CC=C4N=C3C2=C1 DOZCTPAUYJQGBD-UHFFFAOYSA-N 0.000 description 9
- 238000006116 polymerization reaction Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 6
- 238000011161 development Methods 0.000 description 5
- 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 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000012805 post-processing Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 241000950577 Antilla Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003426 co-catalyst Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 2
- 229920001684 low density polyethylene Polymers 0.000 description 2
- 239000004702 low-density polyethylene Substances 0.000 description 2
- 239000000463 material Substances 0.000 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 description 2
- ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+2].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 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003613 toluenes Chemical class 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 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
- YOTZCYVPIUXGKB-UHFFFAOYSA-N 1-methyl-2H-indeno[1,2-g]indole Chemical compound CN1CC=c2ccc3=c4ccccc4=Cc3c12 YOTZCYVPIUXGKB-UHFFFAOYSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 238000006418 Brown reaction Methods 0.000 description 1
- GPPQBEUFCHAZTC-UHFFFAOYSA-N C(c1ccccc1-1)c(c2c3cccc2)c-1[n]3-c1ccccc1 Chemical compound C(c1ccccc1-1)c(c2c3cccc2)c-1[n]3-c1ccccc1 GPPQBEUFCHAZTC-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical class CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 229910052775 Thulium Inorganic materials 0.000 description 1
- 229910010068 TiCl2 Inorganic materials 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 239000011954 Ziegler–Natta catalyst Substances 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- BEOKBUHJDGJDKO-UHFFFAOYSA-N [Cl].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound [Cl].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 BEOKBUHJDGJDKO-UHFFFAOYSA-N 0.000 description 1
- GMXBZGFAIZQTBK-UHFFFAOYSA-L [Ni](Cl)Cl.C1(=CC=CC=C1)P Chemical compound [Ni](Cl)Cl.C1(=CC=CC=C1)P GMXBZGFAIZQTBK-UHFFFAOYSA-L 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 229910052735 hafnium Inorganic materials 0.000 description 1
- VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000007172 homogeneous catalysis Methods 0.000 description 1
- RXXXUIOZOITBII-UHFFFAOYSA-N indeno[1,2-g]indole Chemical class C1=C2C=CC=CC2=C2C1=C1N=CC=C1C=C2 RXXXUIOZOITBII-UHFFFAOYSA-N 0.000 description 1
- 125000003454 indenyl group Chemical class C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229920001580 isotactic polymer Polymers 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
- DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses an N-aryl substituted indeno [1,2-b ]]The synthesis method of the indole compound comprises the following steps: (1) reacting the compound II with organic base in an organic solvent to generate a compound III; (2) in an organic solvent, in the presence of a catalyst, a compound III reacts with a compound IV to obtain N-aryl substituted indeno [1,2-b]An indole compound I; wherein, the structural formulas of the compounds I, II, III and IV are shown in the specification
Description
Technical field
The present invention relates to a kind of synthetic method of C-N couplings, a kind of N- aryl is related more particularly to and has taken
For the synthetic method of indeno [1,2-b] Benzazole compounds, belong to organic chemical synthesis field.
Background technology
Metallocene catalyst is usually have transition metal (such as titanium, zirconium, hafnium) or thulium
The compound constituted as part with least one cyclopentadiene or cyclopentadiene derivant, in recent years
Good development is obtained.Although Ziegler-Natta catalyst is the pillar of polyolefin manufacturing industry,
It is that single active center (metallocene and non-metallocene) catalyst but represents following industrial development direction.
Metallocene catalyst has the advantages, Zao Shang such as single active center, the controllable, high catalytic activity of three-dimensional selection
The fifties in century, metallocene was begun to as the research of olefin polymerization catalysis, Breslow and Natta
Independently of one another the polymerization of alkene has been carried out using metallocene as catalyst.The eighties, use aluminium methyl
Oxygen alkane (MAO) occurs in that breakthrough progress as co-catalyst, metallocene catalysis activity.
Kaminsky and Sinn et al. activate Cp with MAO first2TiCl2Make vinyl polymerization, activity is very high,
And can make propylene polymerization produce random polypropylene [H.Sinn,
W.Kaminsky,Adv.Organomet.Chem.,1980,18,99；H.Sinn,W.Kaminsky,H.J.Vollm
er,R.Woldt.Angew.Chem.Imt.Ed.Eng,.1980,19,390].The mid-80 Ewen and
Kaninsky reports what is constituted with the metallocene catalyst of chiral solid rigid and MAO co-catalysts respectively
Catalyst system and catalyzing can synthesize polypropylene [J.A.Ewen.J.Am.Chem.Soc., 1984,106,6355 of high isotactic；
W.Kaminsky,K.Kulper,H.H.Brintzinger,F.R.W.P.Wild.Angew.Chem.Int.Ed.Eng.,
1985,24,507], this great new neck for finding to open homogeneous catalysis system energy synthesing isotactic polymer
Domain, also for excellent basis has been established in the continuation development of metallocene catalyst.
The structures shape of the metallocene catalyst part performance of catalyst and the structure of olefinic polymerization product and
Performance, therefore, the design and synthesis to metallocene catalyst ligand structure turn into new metallocene catalyst
The core of development.United States Patent (USP) US6440889 reports N- methyl indenoindole with zirconium chloride formation
Metallocene catalyst is used for olefinic polymerization with activity higher, and this part mainly applies iodomethane and indenes
Diindyl synthesizes in the presence of potassium tert-butoxide and obtains, and the method is mainly used in N- alkyl substituted compounds
Thing.Similar Chinese patent CN101472960 also reports gap bridge indenoindolyl transition metal complex
Thing has prepared low density polyethylene (LDPE) in the presence of alkylaluminoxane.However, for N- aryl indenes
Diindyl is also rarely reported for the metallocene catalyst of part, and the introducing of aryl substituent is poly- in alkene to it
Play a part of also to elaborate in conjunction, do not have one mainly due to the preparation for this kind of compound
Individual effective method.Calculated through theory, N- aryl replaces indeno [1,2-b] indoles class formation as important
Cyclopentadienyl group, can be widely used in system as the critically important part of metallocene catalyst
Standby metallocene calalyst for polymerization of olefine, obtains the olefinic polymerization product of novel structure.
Just because of such important function and application potential of N- aryl substitution indenoindole compounds,
The high-efficiency synthesis method of such compound is developed, will be to metallocene catalyst development and pharmaceutical synthesis neck
Domain produces certain influence.Nifant etc. [Russian chemical Bulletin, 50 (8), 1439-1445,2001]
Once report 2- indones and hexichol hydrazine hydrochloride reacted can obtain N- phenyl indeno [1,2-b] Yin in ethanol
Diindyl, yield 41%, the method suitable substrates narrow range (only one example) and yield is relatively low, tool
Precursor reactant sees below formula：
Jon c.Antilla etc. once reported the synthetic route of N- (hetero) aryl indoles, indoles and fragrant bromoalkane with
CuI is catalyst, and chirality 1,2- cyclohexanediamine or N, N- dimethyl-ethylenediamine can be in high yield as part
Obtain a series of N- aryl-indole compounds [Jon c.Antilla, Artis Klapars, Stephen
L.Buchwald J.Am.Chem.Soc.124(39),11684-11688].But for N- aryl indenos Yin
The synthesis of diindyl class compound is but rarely reported.
The content of the invention
It is a primary object of the present invention to provide a kind of N- aryl substitution indeno [1,2-b] benzazolyl compounds
Synthetic method, to overcome such compound synthesis method in the prior art to lack, and method applicability is narrower
Defect.
The object of the present invention is achieved like this, and a kind of N- aryl replaces indeno [1,2-b] benzazolyl compounds
Synthetic method, the method is specially：
(1) in organic solvent, by compound ii and organic base reacting generating compound III；
(2) in organic solvent, in the presence of catalyst, compound III is made to occur with compounds Ⅳ anti-
Should, obtain N- aryl substitution indeno [1,2-b] benzazolyl compounds I；
Wherein, chemical compounds I, II, III, IV structural formula are
Wherein, R1, R2, R3, R4, R5It is independently selected from hydrogen, C1~C6Alkyl, C1~C6Alkoxy,
Halogen and trifluoromethyl constitute the one kind in group, and X is Br or I, preferably Br；
Wherein, R6, R7, R8, R9, R10, R11, R12, R13It is independently selected from hydrogen, C1~C6Alkyl,
C1~C6Alkoxy and halogen constitute the one kind in group.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
The C1~C6It with 1~6 alkyl of carbon atom, for example, can be methyl, ethyl, positive third that alkyl refers to
Base, isopropyl, normal-butyl, sec-butyl, isobutyl group, the tert-butyl group, n-pentyl, n-pentyl, just oneself
Base, isohesyl etc..
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
Organic solvent is preferably tetrahydrofuran in the step (1), and ether and dioxane are constituted in group
One kind, more preferably ether.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
Step (1) organic base is preferably n-BuLi, and tert-butyl lithium and lithium diisopropylamine are constituted
One kind in group.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
The catalyst is preferably palladium (Pd (OAc)2), tetrakis triphenylphosphine palladium (Pd (PPh3)4)、
Palladium acetylacetonate (Pd (acac)2), nickel chloride (NiCl2), nickel acetylacetonate (Ni (acac)2) and three
Phenylphosphine nickel chloride (NiCl2(PPh3)2) constitute one kind in group, more preferably triphenyl
Phosphine nickel chloride.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
Step (2) organic solvent is preferably toluene, dioxane, tetrahydrofuran, ether, N, N- bis-
NMF, acetonitrile and 1-METHYLPYRROLIDONE constitute the one kind in group, more preferably
Toluene.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
The compound ii is preferably 1 with the mol ratio of organic base:1.0~1.1.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
The compounds Ⅳ is preferably 1 with the mol ratio of catalyst:0.05~0.08.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
The mol ratio of the compound III and compounds Ⅳ is preferably 1:1.05~1.3.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
Preferably, the step (1) is specially in organic solvent, and compound ii and organic base are reacted
Generation compound III, then naturally cools to room temperature by reaction system, and reaction dissolvent is drained with vavuum pump,
Compound III is obtained, and its anhydrous and oxygen-free is preserved, treat that lower step is used.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
In the step (1), reaction temperature is preferably 0~5 DEG C, and the reaction time is preferably 3~5 hours.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
In the step (2), reaction temperature is preferably 80~120 DEG C, and it is small that the reaction time is preferably 10~16
When.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
The step (1) and (2) are all reacted under inert gas shielding, and the inert gas can be
Nitrogen or argon gas.
N- aryl of the present invention replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, wherein,
R in the compounds Ⅳ1, R2, R3, R4, R5It is independently selected from hydrogen, C1~C6Alkyl, C1~C6Alcoxyl
Base, halogen and trifluoromethyl constitute the one kind in group, and R1, R2, R3, R4And R5In at least
There are two for hydrogen.
Beneficial effects of the present invention：
The present invention is raw material using indeno [1,2-b] indoles and fragrant alkyl halide, with triphenylphosphine nickel chloride etc.
It is the catalyst a series of target product of having obtained in high yield, this method reaction condition is gentle, raw material letter
Singly it is easy to get, selected reaction condition strong applicability, suitable major part substrate raw material is first to N- aryl
Replace systematically discussing for indeno [1,2-b] Benzazole compounds synthetic method.
Specific embodiment
Embodiments of the invention are elaborated below：The present embodiment is with technical solution of the present invention as preceding
Put and implemented, give detailed implementation method and process, but protection scope of the present invention is not limited to
Following embodiments, the experimental technique of unreceipted actual conditions in the following example, generally according to conventional strip
Part.
Organic solvent：
In the present invention, do not have strict limitation to the consumption of organic solvent, those skilled in the art can be according to
According to being easy to reaction to carry out and control, and it is easy to the amount of post processing to be selected, it is also possible to according to conventional skill
Art means are reasonably determined.
Material rate：
In the present invention, considered critical is had no to organic base, is typically defined to n-BuLi, tert-butyl lithium and
Lithium diisopropylamine constitutes the one kind in group；Considered critical is also had no to catalyst, is generally defined
It is palladium (Pd (OAc)2), tetrakis triphenylphosphine palladium (Pd (PPh3)4), palladium acetylacetonate
(Pd(acac)2), nickel chloride (NiCl2), nickel acetylacetonate (Ni (acac)2) and triphenylphosphine chlorination
Nickel (NiCl2(PPh3)2) constitute one kind in group, more preferably triphenylphosphine nickel chloride；
Ratio to reaction raw materials also has no considered critical, is typically defined to the mol ratio of compound ii and organic base
It is 1:1.0~1.1, if the ratio is more than 1:1.0, then organic base deficiency compound ii can be caused not complete into salt
Entirely, if the ratio is less than 1:1.1, then organic alkali number increases can cause unnecessary waste.Compounds Ⅳ
It is 1 with the mol ratio of catalyst:0.05~0.08, if catalyst amount is less, reaction effect is bad,
Yield is undesirable, and some unknown side reactions can be produced if catalytic amount is excessive.Compound III and chemical combination
The mol ratio of thing IV is 1:1.05~1.3, if compounds Ⅳ amount deficiency can cause the yield to reduce, if consumption mistake
Can at most be made troubles to post processing.
Synthetic method：
In synthetic method of the present invention, step (1) is specially in organic solvent, and compound ii is being had
Compound III is generated in the presence of machine alkali, reaction system is then naturally cooled into room temperature, use vacuum pumping
Dry reaction solvent, obtains compound III, and its anhydrous and oxygen-free is preserved, and treats that lower step is used；
In synthetic method of the present invention, the post-processing operation after step (2) reaction terminates is as follows：Will reaction
System cools to room temperature, is washed through silica plug, obtains dark brown reaction solution, and three are washed with ethyl acetate
Organic phase vacuum distillation that is secondary, will obtaining, obtains residue, and crude product then is crossed into 200~300 purposes
Silica gel column chromatography, is isolated and purified, the mixed solution with dichloromethane and petroleum ether as eluent, its
Middle dichloromethane is 1 with the volume ratio of petroleum ether:15~5, so as to obtain neat compounds I.
Technical solution of the present invention is described in detail with reference to specific embodiment.
The invention provides the novel method for synthesizing that one kind synthesis N- aryl replaces indeno [1,2-b] indoles,
Its lithium salts for preparing indeno [1,2-b] indoles by the selection of alkali first, then by suitable catalysis
The investigation of the combined systems such as agent, organic solvent, it is achieved thereby that N- aryl indeno [1,2-b] indoles
Compound is efficiently synthesized, and the method is easy and effective, with quite varied market popularization value.
Experimental technique described in following embodiments, unless otherwise specified, is conventional method；The reagent
And material, unless otherwise specified, commercially obtain.
Synthesized by the method for Grandini first and obtain indeno [1,2-b] indoles, specific synthetic method is shown in ginseng
Document Organometallics is examined, 23 (3), 344-360,2004, reaction equation is as follows.
Embodiment 1：
Concrete operations are as follows：Weigh two mouthfuls of flasks that 20g 1- indones (150mmol) are added to 250mL
In, 200mL isopropanols are subsequently adding, mixture is slowly stirred to solid and is completely dissolved.Then it is slow
22 grams of 1,1- hexichol hydrazine hydrochloride (150mmol) are added, rear reactant mixture is added and is continued in room temperature
Lower stirring 50 minutes, is then heated slowly to backflow with oil bath, and mixture stops adding after flowing back 5 hours
Heat, is cooled to room temperature, has a small amount of solid to separate out.
After reaction terminates, 50mL saturated sodium bicarbonate solutions are configured, be slowly added into the above-mentioned solution of gained
In, continuing stirring has a large amount of solids to separate out, filtering, and sodium bicarbonate solution, water washing filter are then used respectively
Cake, dry 30 grams of dark green solids, recrystallizes the said goods and obtains 20 grams of indenos with absolute ethyl alcohol
[1,2-b] indoles (yield：65%) (be positioned over glove box in standby).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)
δ:8.23 (brs, 1H), 7.62 (d, J=7.6Hz, 2H), 7.52 (d, J=7.6Hz, 1H), 7.35-7.30 (m, 2H), 7.23-
7.12 (m, 3H), 7.09 (t, J=7.2Hz, 1H), 3.67 (s, 2H).
Embodiment 2：
4.1g compound iis (20mmol) are weighed, is positioned in dry two mouthfuls of flasks, vacuumize logical nitrogen
Gas shielded, adds 50mL newly to steam ether, obtains blackish green solution, cools to -40 DEG C and is slowly added to 9mL
N-butyllithium solution (2.4M, M represent mol/L), continues to stir 4 hours, obtains blackish green suspended
Liquid, oil pump takes ether solvent away, obtains 5.6g pale solids, is compound III.It is positioned over glove box
To treat that lower step is used.
Embodiment 3：
0.47g compound iis (2mmol) are weighed, is positioned in dry two mouthfuls of flasks, vacuumize logical nitrogen
Gas shielded, adds 10mL newly to steam ether, obtains blackish green solution, cools to -40 DEG C and is slowly added to 1mL
Tert .-butyllithium solution (2.4M), continues to stir 5 hours, obtains blackish green suspension, and oil pump takes second away
Ether solvents, obtain 0.40g compound IIIs.
Embodiment 4：
0.5g compound iis (2mmol) are weighed, is positioned in dry two mouthfuls of flasks, vacuumize logical nitrogen
Protection, adds 10mL newly to steam tetrahydrofuran, obtains blackish green solution, cools to -40 DEG C and is slowly added to 1
ML tert .-butyllithium solutions (2.4M), continue to stir 6 hours, obtain bottle green suspension, and oil pump is taken away
Ether solvent, obtains 0.47 compound III.
Embodiment 5：
0.53g compound iis (2mmol) are weighed, is positioned in dry two mouthfuls of flasks, vacuumize logical nitrogen
Gas shielded, adds 10mL newly to steam tetrahydrofuran, obtains blackish green solution, cools to -30 DEG C and is slowly added to 1
ML n-butyllithium solutions (2.4M), continue to stir 6 hours, obtain blackish green suspension, and oil pump is taken away
Tetrahydrofuran solvent, obtains 0.54g compound IIIs.
Embodiment 6
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.05 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 10 hours to 90 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 261 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 93%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.68 (d, J=8.0Hz, 1H), 7.58-7.54 (m, 4H),
7.48 (t, J=3.2Hz, 1H), 7.39 (d, J=6.4Hz, 1H), 7.18-7.16 (m, 4H), 7.07 (d, J=7.2Hz, 1H),
3.79(s,2H)。
Embodiment 7
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.08 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 10 hours to 90 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 251 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 85%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.68 (d, J=8.0Hz, 1H), 7.56 (d, J=7.6,1H), 7.53-
7.49 (m, 3H), 7.45 (t, J=7.2Hz, 1H), 7.39 (d, J=6.4Hz, 1H), 7.18-7.16 (m, 3H),
7.07 (d, J=7.2Hz, 1H), 3.82 (s, 2H), 1.52 (s, 3H).
Embodiment 8
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.08 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 2 hours at room temperature, Ran Houjia
Heat continues to react 10 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 200 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 67.8%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)
δ:7.73 (d, J=8.0Hz, 2H), 7.59 (d, J=7.6,1H), 7.49 (d, J=6.4Hz, 1H), 7.48-7.39 (m, 3H),
7.45 (t, J=7.2Hz, 1H), 7.39 (d, J=6.4Hz, 2H), 7.07 (d, J=7.2Hz, 2H), 3.83 (s, 2H),
1.54(s,3H)。
Embodiment 9
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.08 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 2 hours at room temperature, Ran Houjia
Heat continues to react 10 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 245 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 83%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)
δ:7.73 (d, J=8.0Hz, 2H), 7.59 (d, J=7.6,1H), 7.49 (d, J=6.4Hz, 1H), 7.48-7.39 (m, 3H),
7.45 (t, J=7.2Hz, 1H), 7.39 (d, J=6.4Hz, 2H), 7.07 (d, J=7.2Hz, 2H), 3.83 (s, 2H),
1.54(s,3H)。
Embodiment 10
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.05 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 14 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 263 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 78%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.70 (d, J=8.0Hz, 1H), 7.54 (d, J=7.6,1H), 7.53-
7.49 (m, 3H), 7.48 (t, J=7.2Hz, 1H), 7.39 (d, J=6.4Hz, 1H), 7.18-7.14 (m, 3H),
7.10 (d, J=7.2Hz, 1H), 3.80 (s, 2H), 1.50 (s, 9H).
Embodiment 11
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.05 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 14 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 310 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 91%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.70 (d, J=8.0Hz, 1H), 7.54 (d, J=7.6,1H), 7.53-
7.49 (m, 3H), 7.48 (t, J=7.2Hz, 1H), 7.39 (d, J=6.4Hz, 1H), 7.18-7.14 (m, 3H),
7.10 (d, J=7.2Hz, 1H), 3.80 (s, 2H), 1.50 (s, 9H).
Embodiment 12
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.05 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.3 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 10 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 276 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 79%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.70 (d, J=8.0Hz, 1H), 7.53-7.49 (m, 3H), 7.48-
7.46 (m, 2H), 7.39 (d, J=7.2Hz, 1H), 7.18-7.14 (m, 4H), 3.75 (s, 2H).
Embodiment 13
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.05 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 10 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 304 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 87%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.70 (d, J=8.0Hz, 1H), 7.53-7.49 (m, 3H), 7.48-
7.46 (m, 2H), 7.39 (d, J=7.2Hz, 1H), 7.18-7.14 (m, 4H), 3.75 (s, 2H).
Embodiment 14
Device has in 100 milliliters of there-necked flasks of magnetic agitation, adds 0.07 mM of triphenylphosphine chlorine
Change nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 10 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 211 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 65.3%).
1H-NMR(400MHz,CDCl3)δ:7.73 (d, J=8.0Hz, 2H), 7.59 (d, J=7.6,1H), 7.49 (d,
J=6.4Hz, 1H), 7.48-7.39 (m, 1H), 7.45 (t, J=7.2Hz, 1H), 7.39 (d, J=6.4Hz, 2H), 7.07 (d,
J=7.2Hz, 2H), 3.87 (s, 2H), 2.09 (s, 3H), 1.55 (s, 3H), 1.40 (s, 3H).
Embodiment 15
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.07 mM of triphenylphosphine chlorination
Nickel, 1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters without water beetle
Benzene, 1.2 mMs of above formula compounds Ⅳ is added with syringe, is stirred 1 hour at room temperature, Ran Houjia
Heat continues to react 12 hours to 110 DEG C, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 255 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 75.7%).
1H-NMR(400MHz,CDCl3)δ:7.70 (d, J=8.0Hz, 1H), 7.54 (d, J=7.6,1H), 7.53-
7.49 (m, 3H), 7.48 (t, J=7.2Hz, 1H), 7.39 (d, J=6.4Hz, 1H), 7.18-7.14 (m, 3H), 7.10 (d,
J=7.2Hz, 2H), 3.82 (s, 2H), 2.45 (t, J=2.4Hz, 2H), 1.94-1.80 (m, 2H), 1.44-1.34 (m,
2H), 0.95 (t, J=2.4Hz, 3H)
Embodiment 16
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, the nickel acetylacetonate of 0.06 mM of addition,
1.0 mMs of above formula compound IIIs, vacuumize and change N2Gas 3 times, adds 15 milliliters of dry toluenes, uses
Syringe adds 1.2 mMs of above formula compounds Ⅳ, stirs 1 hour at room temperature, is then heated to
100 DEG C are continued to react 10 hours, stop reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 205 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 73%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.68 (d, J=8.0Hz, 1H), 7.58-7.54 (m, 4H),
7.48 (t, J=3.2Hz, 1H), 7.39 (d, J=6.4Hz, 1H), 7.18-7.16 (m, 4H), 7.07 (d, J=7.2Hz, 1H),
3.79(s,2H)。
Embodiment 17
It is equipped with 100 milliliters of there-necked flasks of magnetic agitation, adds 0.06 mM of nickel chloride, 1.0 millis
Mole above formula compound III, vacuumizes and changes N2Gas 3 times, adds 15 milliliters of dry toluenes, uses syringe
Add 1.2 mMs of above formula compounds Ⅳ, stir 1 hour at room temperature, be then heated to 100 DEG C after
Continuous reaction 10 hours, stops reaction.
After reaction terminates, reaction system is naturally cooled into room temperature, washed through silica plug, obtain deep brown
Colour response liquid, is washed with ethyl acetate, and organic phase merges.Organic phase is dried with anhydrous magnesium sulfate, mistake
Filter, concentration, silica gel column chromatography separates the (mesh of silica gel 200-300；Petroleum ether/dichloromethane=15:1,
V/v), 154 milligrams of products are obtained, i.e., above-mentioned formula chemical compounds I (yield 55%).
Nuclear magnetic data：
1H-NMR(400MHz,CDCl3)δ:7.68 (d, J=8.0Hz, 1H), 7.58-7.54 (m, 4H),
7.48 (t, J=3.2Hz, 1H), 7.39 (d, J=6.4Hz, 1H), 7.18-7.16 (m, 4H), 7.07 (d, J=7.2Hz, 1H),
3.79(s,2H)。
Beneficial effects of the present invention：
The present invention is raw material using indeno [1,2-b] indoles and fragrant alkyl halide, with triphenylphosphine nickel chloride etc.
It is the catalyst a series of target product of having obtained in high yield, this method reaction condition is gentle, raw material letter
Singly it is easy to get, selected reaction condition strong applicability, suitable major part substrate raw material is first to N- aryl
Replace systematically discussing for indeno [1,2-b] Benzazole compounds synthetic method.
Certainly, the present invention can also have other various embodiments, without departing substantially from spiritual and its essence of the invention
In the case of, those of ordinary skill in the art can make various corresponding changes and deformation according to the present invention,
But these corresponding changes and deformation should all belong to the protection domain of the claims in the present invention.
Claims (13)
1. a kind of N- aryl replaces the synthetic method of indeno [1,2-b] benzazolyl compounds, it is characterised in that
The method is specially：
(1) in organic solvent, by compound ii and organic base reacting generating compound III；
(2) in organic solvent, in the presence of catalyst, compound III is made to occur with compounds Ⅳ anti-
Should, obtain N- aryl substitution indeno [1,2-b] benzazolyl compounds I；
Wherein, chemical compounds I, II, III, IV structural formula are
Wherein, R1, R2, R3, R4, R5It is independently selected from hydrogen, C1~C6Alkyl, C1~C6Alkoxy,
Halogen and trifluoromethyl constitute the one kind in group, and X is Br or I；
Wherein, R6, R7, R8, R9, R10, R11, R12, R13It is independently selected from hydrogen, C1~C6Alkyl,
C1~C6Alkoxy and halogen constitute the one kind in group.
2. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that organic solvent is tetrahydrofuran, ether and dioxane in the step (1)
One kind in constituted group.
3. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that step (1) organic base is n-BuLi, tert-butyl lithium and diisopropyl
Lithium amide constitutes the one kind in group.
4. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that the catalyst be palladium, tetrakis triphenylphosphine palladium, palladium acetylacetonate,
Nickel chloride, nickel acetylacetonate and triphenylphosphine nickel chloride constitute the one kind in group.
5. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that step (2) organic solvent be toluene, dioxane, tetrahydrofuran,
Ether, N,N-dimethylformamide, acetonitrile and 1-METHYLPYRROLIDONE constitute the one kind in group.
6. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that the compound ii is 1 with the mol ratio of organic base:1.0~1.1.
7. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that the compounds Ⅳ is 1 with the mol ratio of catalyst:0.05~0.08.
8. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that the mol ratio of the compound III and compounds Ⅳ is 1:1.05~1.3.
9. N- aryl according to claim 1 replaces the synthesis side of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that the step (1) be specially in organic solvent, by compound ii with it is organic
Alkali reacting generating compound III, then naturally cools to room temperature by reaction system, and reaction is drained with vavuum pump
Solvent, obtains compound III, and its anhydrous and oxygen-free is preserved, and treats that lower step is used.
10. N- aryl according to claim 1 replaces the synthesis of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that in the step (1), reaction temperature is 0~5 DEG C, and the reaction time is
3~5 hours.
11. N- aryl according to claim 1 replace the synthesis of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that in the step (2), reaction temperature is 80~120 DEG C, and the reaction time is
10~16 hours.
12. N- aryl according to claim 1 replace the synthesis of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that the step (1) and (2) are all reacted under inert gas shielding.
13. N- aryl according to claim 1 replace the synthesis of indeno [1,2-b] benzazolyl compounds
Method, it is characterised in that R in the compounds Ⅳ1, R2, R3, R4, R5Be independently selected from hydrogen,
C1~C6Alkyl, C1~C6Alkoxy, halogen and trifluoromethyl constitute the one kind in group, and R1,
R2, R3, R4And R5In at least two be hydrogen.
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Non-Patent Citations (2)
| Title |
|---|
| CHEN CHEN .ET AL,: "Arylation of Diarylamines Catalyzed by Ni(II)-PPh3 System", 《ORGANIC LETTERS》 * |
| LI, XIN-LE, ET AL: ""Nickel-catalyzed triarylamine synthesis: synthetic and mechanistic aspects"", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 * |
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