CN105061436B - A kind of preparation method of polysubstituted condensed indole diindyl class compound - Google Patents
A kind of preparation method of polysubstituted condensed indole diindyl class compound Download PDFInfo
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- CN105061436B CN105061436B CN201510575211.2A CN201510575211A CN105061436B CN 105061436 B CN105061436 B CN 105061436B CN 201510575211 A CN201510575211 A CN 201510575211A CN 105061436 B CN105061436 B CN 105061436B
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- indoles
- silica gel
- phenyl
- cyanophenyls
- reaction
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 59
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title abstract description 28
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title abstract description 28
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims abstract description 18
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 88
- 239000000741 silica gel Substances 0.000 claims description 88
- 229910002027 silica gel Inorganic materials 0.000 claims description 88
- 150000002475 indoles Chemical class 0.000 claims description 62
- 238000006243 chemical reaction Methods 0.000 claims description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 52
- 239000012074 organic phase Substances 0.000 claims description 43
- 239000003208 petroleum Substances 0.000 claims description 42
- 239000002904 solvent Substances 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 25
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 22
- 229920006395 saturated elastomer Polymers 0.000 claims description 22
- 235000002639 sodium chloride Nutrition 0.000 claims description 22
- 239000007787 solid Substances 0.000 claims description 21
- ZEHBVFZOFKRVJW-UHFFFAOYSA-M [I+].[O-]S(=O)(=O)C(F)(F)F Chemical class [I+].[O-]S(=O)(=O)C(F)(F)F ZEHBVFZOFKRVJW-UHFFFAOYSA-M 0.000 claims description 20
- SBQIJPBUMNWUKN-UHFFFAOYSA-M diphenyliodanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C=1C=CC=CC=1[I+]C1=CC=CC=C1 SBQIJPBUMNWUKN-UHFFFAOYSA-M 0.000 claims description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- -1 carbomethoxy Chemical group 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- AIDLAEPHWROGFI-UHFFFAOYSA-N 2-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=C(C(O)=O)C=CC=C1C(O)=O AIDLAEPHWROGFI-UHFFFAOYSA-N 0.000 claims description 3
- PNWSHHILERSSLF-UHFFFAOYSA-N 4-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=C1C(O)=O PNWSHHILERSSLF-UHFFFAOYSA-N 0.000 claims description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- 239000012298 atmosphere Substances 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 claims description 3
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005810 2,5-xylyl group Chemical group [H]C1=C([H])C(=C(*)C([H])=C1C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(II) bromide Substances [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 241000255964 Pieridae Species 0.000 claims 2
- DZHAKMZHPZQEIN-UHFFFAOYSA-N [I].FC(F)F Chemical compound [I].FC(F)F DZHAKMZHPZQEIN-UHFFFAOYSA-N 0.000 claims 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract description 4
- 239000000047 product Substances 0.000 description 81
- 238000007789 sealing Methods 0.000 description 44
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 25
- 229910001873 dinitrogen Inorganic materials 0.000 description 23
- 239000003921 oil Substances 0.000 description 23
- 238000000926 separation method Methods 0.000 description 23
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 23
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 22
- 229910052710 silicon Inorganic materials 0.000 description 22
- 239000010703 silicon Substances 0.000 description 22
- 239000000499 gel Substances 0.000 description 21
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 20
- 239000003480 eluent Substances 0.000 description 19
- 238000005303 weighing Methods 0.000 description 16
- 238000000605 extraction Methods 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000000758 substrate Substances 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 229930013930 alkaloid Natural products 0.000 description 4
- 150000003797 alkaloid derivatives Chemical class 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000446 fuel Substances 0.000 description 3
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 238000006783 Fischer indole synthesis reaction Methods 0.000 description 2
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- UOZOCOQLYQNHII-UHFFFAOYSA-N 6-bromo-2-(6-bromo-3-hydroxy-1H-indol-2-yl)indol-3-one Chemical compound [O-]c1c([nH]c2cc(Br)ccc12)C1=[NH+]c2cc(Br)ccc2C1=O UOZOCOQLYQNHII-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- 241001465805 Nymphalidae Species 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Chemical compound C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000032770 biofilm formation Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229930005303 indole alkaloid Natural products 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 241000238565 lobster Species 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 229960005453 strychnine Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- ZVAPIIDBWWULJN-UHFFFAOYSA-N tyrian purple Natural products N1C2=CC(Br)=CC=C2C(=O)C1=C1C(=O)C2=CC=C(Br)C=C2N1 ZVAPIIDBWWULJN-UHFFFAOYSA-N 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of polysubstituted condensed indole diindyl class compound.It comprises the following steps：In the presence of a catalyst, compound shown in compound shown in Formula II and formula III is subjected to intramolecular cyclization reaction in organic solvent, obtains compound shown in Formulas I.The characteristics of preparation method of the present invention has economic, convenient, pervasive and green, can prepare the heterocyclic compound of high added value.
Description
Technical field
Field is catalyzed and synthesized the invention belongs to fine chemical product, and in particular to a kind of polysubstituted condensed indole diindyl class
The preparation method of compound.
Background technology
Indoles and its derivative are that a common class has pharmacological activity and the heterocyclic compound of bioactivity, and indoles
Skeleton is the important structural motif of a class, widely exists in natural products, dyestuff, material and various pharmaceutical chemistry intermediates,
In antibiotic, cancer therapy drug and inverase.For example, the Indomethacin of United States Merck company research and development in 1963
(Indometacin), it can as the important NSAIDs of a class (NSAID), can anti-inflammatory analgetic, treatment heating etc. disease
Disease；Extracted in Tai Er purples (Tyrian purple), a kind of point secret thing from conch it is oxidized after obtained dyestuff；From sea
The istain Alkaloid extracted in foreign biology lobster and human body is a kind of natural active compound, with antibacterial, reduction
Cholesterol, the pharmacological activity such as anticancer；It is isolated strychnia (Strychnine) from the fruit and bark of vomiting nut,
It is the heterocyclic compound that a class contains indoles skeleton, with good physiologically active, can effectively prevents the transport of amino acid.
Indole alkaloid, more than 1400 kinds, is maximum alkaloid family, such as vincaleukoblastinum, tryptamines ketone compounds in nature.
Due to its unique pharmacological activity, indoles and the like also turns into widely used in modern medicines exploitation and constructed
Unit.For example, alkaloid reserpine is used to treat central nervous system disease, such as anxiety disorder and phrenoblabia first
(Chen,R.-E.；Huang,J.Chem.Rev.2005,105,4671).Since 20 world sixties, it is various physiologically
Important, the alkaloid with indoles skeleton is emerged in multitude, and for treating various inflammation, hypertension and being used as calmness
Agent (" Pyrroles and Their Benzoderivatives:Synthesis and Applications”:Sundberg
R.J.in Comprehensive Heterocyclic Chemistry,Vol.4(Eds.:A.R.Katritzky,
C.W.Rees),Pergamon,Oxford,1984,313).Indole derivatives are also used as ceS signal molecules
(Intercellularsignal molecule) participate in bacterium a variety of physiological activities (such as drug resistance, plasmid stability, virulence with
And biofilm formation etc.) regulating and controlling effect, also participate in coordinating flora competition, be beneficial to human body intestinal canal flora balance and immune system
(Han,Y.et al.J.Appl.Microbio.2010,108,139).Indoles and its derivative are also used as a kind of fluorescence examination
Agent, due to its significant fluorescence change in displacement, so as to it is effective avoid uneven dyeing, photobleaching the problems such as
(Bottari,G.et al.Chem.Rev.2010,110,6768；Torre,G.；et al.Chem.Rev.2004,104,
3723).In addition, indole derivatives are also used as fuel, the microbiological fuel cell using indoles as fuel is obtained in recent years
Extensive development (Luo Yong, China Environmental Science, 2010,30,770).
The synthesis of indoles and its derivative can trace back to 19th-century, and most classical example is to report for 1883
Fischer indole synthesis.But, when containing hetero atom in substrate, the efficiency of Fischer indole synthesis is very low, when
During using asymmetrical carbonyls, reaction can generate two isomers.Therefore, this method is not wide to the applicability of substrate,
The Benzazole compounds rolled into a ball with specified substituent can only be synthesized, are unfavorable for the efficient structure of polycyclic Benzazole compounds,
Through the diversified demand of molecule in modern organic and pharmaceutical synthesis can not be met.In recent years, many chemists also develop
Serial of methods builds fused polycycle Benzazole compounds, for example, C-H alkylenes/molecule of the regioselectivity of palladium chtalyst
Intramolecular cyclization cascade reaction, has synthesized a series of indoles [1,2-a] quinoxaline derivant (Wang, L.et
al.Org.Lett.2012,14,740).Also build the polynary volution compound containing indoles skeleton, with Oxoindole or
Person's 3- alkenyls Oxoindole be raw material, occur under the catalysis of various transition metal a series of cyclizations (Pesciaioli,
F.et al.Chem.Eur.J.,2011,17,2842；Noole,A.et al.Chem.Eur.J.2012,18,14929；Dou,
X.-W.et al.Chem.Eur.J.,2012,18,8315).In recent years, the synthesis of indoles diindyl cyclics is caused
The concern of chemist, but the method for synthesis is fewer, such as with indole-2-carboxylic acid lipoid substance and stupid acetylene compound
Indoles diindyl ketone compounds (Robert, D.G.et can be generated under conditions of fluorine anion is as catalyst
al.Synlett 2009,12,2010；Rogness,D.C.et al.Tetrahedron Lett.2009,50,4003).Also
The cyclization life of intramolecular occurs under conditions of oxidant potassium persulfate for the N- imino group phenyl-indole class compounds of palladium chtalyst
Into indoles diindyl ketone compounds (Hazra, S.et al.RSC Adv., 2015,5,22480).But these synthetic methods
Also have the shortcomings that different, what is had will use the catalyst of fluo anion, produce the waste material containing halogen；Also using for having is expensive
Metal palladium catalyst and some strong basicities etc. are to the disagreeableness reagent of environment.Therefore, exploitation one is more convenient, efficient and green
Indoles diindyl class compound synthesis technology turn into people explore target.
The content of the invention
It is an object of the invention to provide a kind of preparation method of polysubstituted condensed indole diindyl class compound.
Preparation method provided by the present invention, comprises the following steps：In the presence of a catalyst, by compound shown in Formula II
(the i.e. aryl iodide trifluoro-methanyl sulfonate chemical combination of compound shown in (i.e. N- (2- cyanophenyls)-Benzazole compounds) and formula III
Thing) intramolecular cyclization reaction (activation of itrile group) is carried out in organic solvent, obtain (the 10- aryl imines of compound shown in Formulas I
Base-indoles simultaneously [1,2-a] indole derivatives).
In the Formulas I and formula III, R1Selected from electrophilic or electron donating group, specifically may be selected from hydrogen, methyl, isopropyl,
At least one of the tert-butyl group, fluorine, chlorine, bromine and carbomethoxy；R1Number be 1-5；R1In the remaining binding site of phenyl ring
At at least one.
In the Formulas I and Formula II, R2Selected from electrophilic or electron donating group, specifically may be selected from methyl, methoxyl group, fluorine,
At least one of chlorine, bromine and hydrogen；R2Number be 1-4；R2In the remaining binding site of phenyl ring at least one at.
In the formula III, Ar is aryl, specifically may be selected from phenyl, p-methylphenyl, to 2-methyl-2-phenylpropane base, 2,5- xylyls,
2,4,6- trimethylphenyls, p-fluorophenyl, p-bromophenyl, rubigan or to methyl formate phenyl；In the formula III, I bands are just
Electron ion, OTf is-OSO2CF3(trifluoromethanesulfonic acid root) electronegative ion, both are combined by ionic bond.
Compound described in the Formulas I specifically may be selected from 10- phenyl imines base-indoles simultaneously [1,2-a] indoles, 10- (4- methyl
Phenyl) imido grpup-indoles simultaneously [1,2-a] indoles, 10- (4- tert-butyl-phenyls) imido grpup-indoles simultaneously [1,2-a] indoles, 10-
(2,5- 3,5-dimethylphenyls) imido grpup-indoles simultaneously [1,2-a] indoles, imido grpup-indoles is simultaneously by 10- (2,4,6- trimethylphenyls)
[1,2-a] indoles, 10- (4- fluorophenyls) imido grpup-indoles simultaneously [1,2-a] indoles, imido grpup-indoles is simultaneously by 10- (4- bromophenyls)
[1,2-a] indoles, 10- (4- chlorphenyls) imido grpup-indoles simultaneously [1,2-a] indoles, 10- (4- methyl formates phenyl) imido grpup-
Indoles simultaneously [1,2-a] indoles, 2- methoxyl group -10- phenyl imines base-indoles simultaneously [1,2-a] indoles, 2- methyl isophthalic acid 0- phenyl imines
Base-indoles simultaneously [1,2-a] indoles, 4- methyl isophthalic acid 0- phenyl imines base-indoles simultaneously fluoro- 10- phenyl imines of [1,2-a] indoles, 2-
Base-indoles simultaneously the chloro- 10- phenyl imines base-indoles of [1,2-a] indoles, 2- simultaneously the fluoro- 10- phenyl imines base of [1,2-a] indoles, 3--
Indoles simultaneously [1,2-a] indoles or the chloro- 10- phenyl imines base-indoles of 3- simultaneously any of [1,2-a] indoles.
Compound described in the Formula II specifically may be selected from N- (2- cyanophenyls)-indoles, 5- methoxyl groups-N- (2- itrile group benzene
Base)-indoles, 5- methyl-N- (2- cyanophenyls)-indoles, 7- methyl-N- (2- cyanophenyls)-indoles, 5- fluoro- N- (2- itrile groups
Phenyl)-indoles, the chloro- N- of 5- (2- cyanophenyls)-indoles, the fluoro- N- of 6- (2- cyanophenyls)-indoles or 6- chloro- N- (2- itrile groups
Any of phenyl)-indoles.
Compound described in the formula III specifically may be selected from diphenyl iodine trifluoro-methanyl sulfonate, two (4- aminomethyl phenyls) iodine
Trifluoro-methanyl sulfonate, two (4- tert-butyl-phenyls) iodine trifluoro-methanyl sulfonates, two (2,5- 3,5-dimethylphenyls) iodine fluoroforms
Sulfonate, two (2,4,6- trimethylphenyls) iodine trifluoro-methanyl sulfonates, two (4- fluorophenyls) iodine trifluoro-methanyl sulfonates, two
(4- bromophenyls) iodine trifluoro-methanyl sulfonate, two (4- chlorphenyls) iodine trifluoro-methanyl sulfonates or two (4- methyl formates phenyl) iodine
Any of trifluoro-methanyl sulfonate.
In above-mentioned preparation method, the catalyst is selected from Cu (OTf)2, CuCl and CuBr2At least one of, preferably Cu
(OTf)2。
Compound shown in the Formula II, compound shown in the formula III and the mol ratio of the catalyst are 1：(1-3)：
(0.05-0.2), concretely 1：2：0.1.
The reaction temperature of the intramolecular cyclization reaction is 100~120 DEG C, specially 110 DEG C.
The reaction time of the intramolecular cyclization reaction regards the difference of compound shown in the Formula II and changed, and whether reaction
Finishing can be monitored by thin-layer chromatography or gas-chromatography, specifically, the reaction time of the intramolecular cyclization reaction
For 6~10h, specially 6h.
The solvent specifically may be selected from 1,2- dichloroethanes and/or toluene, preferably 1,2- dichloroethanes.
The intramolecular cyclization reaction is carried out under an inert atmosphere, the inert atmosphere concretely nitrogen.
The intramolecular cyclization reaction can be carried out in the reaction vessel of closed reaction unit or additional reflow device, tool
Body is closed reaction unit, such as：Glass tube sealing etc..
In above-mentioned preparation method, in addition to reaction system after terminating to the intramolecular cyclization reaction carries out separation and carried
Pure, the step of obtaining compound shown in the Formulas I comprises the following steps that：Reaction after terminating to the intramolecular cyclization reaction
50-80mL saturated aqueous common salt is added in system, is extracted three times in separatory funnel, merges organic phase, by organic phase through anhydrous
Magnesium sulfate is dried, filtering；The silica gel of 5-8g 100~200 mesh is added, be concentrated under reduced pressure removing solvent, obtains the silicon containing product
Glue；Post, dry method upper prop are filled using the silica gel and petroleum ether of 100~200 mesh, and the silica gel containing product is loaded on silicon gel column
Upper end；(wherein, both petrol ether/ethyl acetate in the mixed solvents are eluted with petrol ether/ethyl acetate mixed solvent
Volume ratio visual response thing and the polarity of product and it is different, it is necessary to estimated by the result of thin-layer chromatography, ethyl acetate
Volume fraction is 1~5%), collect and include the solution of compound shown in Formulas I, be concentrated under reduced pressure after removing solvent, vacuum drying, title
Weigh and calculate yield.
For solid product, higher purity can be obtained by way of recrystallization, the mode typically recrystallized is：
Dichloromethane is added in the sample, and heating causes sample to be completely dissolved, then adds thereto after poor solvent n-hexane, allows it to delay
Slow vaporization, can obtain the monocrystalline of product.
Compared with prior art, the present invention has the advantages that：
1) it is economical：Reaction raw materials are conventional industrial chemicals-indoles and halogeno-benzene, and solvent is cheap and easy to get, catalyst mantoquita
Inexpensively, and compound shown in gained Formulas I be high added value heterocyclic compound.
2) it is convenient：Only need single step reaction, once feed intake can obtain final product with first separation step, because reaction has
Very high chemo-selective, so that separation process is also very simple.
3) it is pervasive：Reaction is to a variety of substrates, including various alkyl, ester group, and the substrate of donor residues or electron-withdrawing group is fitted
With so that the system can obtain the diversified fused polycycle Benzazole compounds of substituent.
4) it is green：Products therefrom is reaction substrate intramolecular cyclization gained, environmentally safe；Importantly, reaction
Another molecular product be iodo aromatic hydrocarbon, other reactions can be participated in as a new industrial chemicals, make the atom of reaction
Utilization rate is higher, environmentally safe.
Brief description of the drawings
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of the gained target product of embodiment 1.
Fig. 2 is the carbon-13 nmr spectra figure of the gained target product of embodiment 1.
Fig. 3 is the hydrogen nuclear magnetic resonance spectrogram of the gained target product of embodiment 3.
Fig. 4 is the carbon-13 nmr spectra figure of the gained target product of embodiment 3.
Fig. 5 is the hydrogen nuclear magnetic resonance spectrogram of the gained target product of embodiment 9.
Fig. 6 is the carbon-13 nmr spectra figure of the gained target product of embodiment 9.
Fig. 7 is the hydrogen nuclear magnetic resonance spectrogram of the gained target product of embodiment 14.
Fig. 8 is the carbon-13 nmr spectra figure of the gained target product of embodiment 14.
Embodiment
Experimental method used in following embodiments is conventional method unless otherwise specified.
Material, reagent used etc., unless otherwise specified, are commercially obtained in following embodiments.
Embodiment 1, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to the diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol) and 0.0180g Cu (OTf) of formula III2(0.05mmol) is in containing magnetic
In the 25mL tube sealings of stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, 110 DEG C are put into
6h is stirred in oil bath.After reaction terminates, 50mL saturated aqueous common salts are added into reaction system, are extracted three times in separatory funnel,
Merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filter；The silica gel of 5g 100~200 mesh is added, is concentrated under reduced pressure
Solvent is removed, the silica gel containing product is obtained；Post, dry method upper prop are filled using the silica gel and petroleum ether of 100~200 mesh, and incites somebody to action described
Silica gel containing product is loaded on the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 99:1) enter as eluant, eluent
Row post separation, obtains white solid 0.1249g, i.e. target product 10- phenyl imines base-indoles simultaneously [1,2-a] indoles, and it is separated
Yield is 85%.Fig. 1 and Fig. 2 are respectively the proton nmr spectra and carbon spectrum that the embodiment prepares products obtained therefrom, can by Fig. 1 and 2
Know, the compound structure is correct.
Embodiment 2, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4582g for weighing 0.1091g ownership Formula II successively return
Belong to two (4- aminomethyl phenyls) iodine trifluoro-methanyl sulfonates (1.0mmol) and 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In sealing tube sealing under condition of nitrogen gas, it is put into
6h is stirred in 110 DEG C of oil bath.After reaction terminates, 60mL saturated aqueous common salts are added into reaction system, are extracted in separatory funnel
Take three times, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filter；The silica gel of 6g 100~200 mesh is added, is subtracted
Pressure concentration removes solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop, and
The silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 98:2) it is used as and washes
De- agent carries out post separation, obtains white solid 0.1326g, i.e. target product 10- (4- aminomethyl phenyls) imido grpup-indoles simultaneously [1,
2-a] indoles, it is 86% that it, which separates yield,.
Embodiment 3, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.5424g for weighing 0.1091g ownership Formula II successively return
Belong to two (4- tert-butyl-phenyls) iodine trifluoro-methanyl sulfonates (1.0mmol) and 0.0180g Cu (OTf) of formula III2
(0.05mmol) adds 2.0mL 1,2- dichloroethanes in the 25mL tube sealings containing magnetic stirrer.In under condition of nitrogen gas, it will seal
The seal of tube, 6h is stirred in the oil bath for being put into 110 DEG C.Reaction terminate after, into reaction system add 70mL saturated aqueous common salts, in point
Extracted three times in liquid funnel, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filtered；Add the 100~200 of 7g
Purpose silica gel, be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Post is filled using the silica gel and petroleum ether of 100~200 mesh,
Dry method upper prop, and by the silica gel containing product be loaded on silicon gel column upper end；With petroleum ether-ethyl acetate, (volume ratio is
97:3) post separation is carried out as eluant, eluent, obtains white solid 0.1577g, i.e. target product 10- (4- tert-butyl-phenyls) imines
Base-indoles simultaneously [1,2-a] indoles, it is 90% that it, which separates yield,.Fig. 3 and Fig. 4 are respectively the core that the embodiment prepares products obtained therefrom
Magnetic resonance hydrogen is composed and carbon spectrum, and from Fig. 3 and Fig. 4, the compound structure is correct.
Embodiment 4, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4683g for weighing 0.1091g ownership Formula II successively return
Belong to two (2,5- 3,5-dimethylphenyls) iodine trifluoro-methanyl sulfonates (1.0mmol) and 0.0180g Cu (OTf) of formula III2
(0.05mmol) adds 2.0mL 1,2- dichloroethanes in the 25mL tube sealings containing magnetic stirrer.In under condition of nitrogen gas, it will seal
The seal of tube, 6h is stirred in the oil bath for being put into 110 DEG C.Reaction terminate after, into reaction system add 80mL saturated aqueous common salts, in point
Extracted three times in liquid funnel, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filtered；Add the 100~200 of 8g
Purpose silica gel, be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Post is filled using the silica gel and petroleum ether of 100~200 mesh,
Dry method upper prop, and by the silica gel containing product be loaded on silicon gel column upper end；With petroleum ether-ethyl acetate, (volume ratio is
96:4) post separation is carried out as eluant, eluent, obtains white solid 0.1321g, be i.e. target product 10- (2,5- 3,5-dimethylphenyl) is sub-
Amido-indoles simultaneously [1,2-a] indoles, it is 82% that it, which separates yield,.
Embodiment 5, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.5143g for weighing 0.1091g ownership Formula II successively return
Belong to two (2,4,6- trimethylphenyls) iodine trifluoro-methanyl sulfonates (1.0mmol) and 0.0180g Cu (OTf) of formula III2
(0.05mmol) adds 2.0mL 1,2- dichloroethanes in the 25mL tube sealings containing magnetic stirrer.In under condition of nitrogen gas, it will seal
The seal of tube, 6h is stirred in the oil bath for being put into 110 DEG C.Reaction terminate after, into reaction system add 50mL saturated aqueous common salts, in point
Extracted three times in liquid funnel, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filtered；Add the 100~200 of 8g
Purpose silica gel, be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Post is filled using the silica gel and petroleum ether of 100~200 mesh,
Dry method upper prop, and by the silica gel containing product be loaded on silicon gel column upper end；With petroleum ether-ethyl acetate, (volume ratio is
95:5) post separation is carried out as eluant, eluent, obtains white solid 0.1194g, i.e. target product 10- (2,4,6- trimethylphenyl)
Imido grpup-indoles simultaneously [1,2-a] indoles, it is 71% that it, which separates yield,.
Embodiment 6, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4662g for weighing 0.1091g ownership Formula II successively return
Belong to two (4- fluorophenyls) iodine trifluoro-methanyl sulfonates (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol) in containing
In the 25mL tube sealings of magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, 110 are put into
DEG C oil bath in stir 6h.After reaction terminates, 60mL saturated aqueous common salts are added into reaction system, three are extracted in separatory funnel
It is secondary, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filter；The silica gel of 7g 100~200 mesh is added, is depressurized dense
Contracting removes solvent, obtains the silica gel containing product；Post is filled using the silica gel and petroleum ether of 100~200 mesh, dry method upper prop, and by institute
State the upper end that the silica gel containing product is loaded on silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) as eluant, eluent
Carry out post separation, obtain white solid 0.0859g, i.e. target product 10- (4- fluorophenyls) imido grpup-indoles simultaneously [1,2-a] Yin
Diindyl, it is 55% that it, which separates yield,.
Embodiment 7, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.5880g for weighing 0.1091g ownership Formula II successively return
Belong to two (4- bromophenyls) iodine trifluoro-methanyl sulfonates (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol) in containing
In the 25mL tube sealings of magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, 110 are put into
DEG C oil bath in stir 6h.After reaction terminates, 70mL saturated aqueous common salts are added into reaction system, three are extracted in separatory funnel
It is secondary, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filter；The silica gel of 6g 100~200 mesh is added, is depressurized dense
Contracting removes solvent, obtains the silica gel containing product；Post is filled using the silica gel and petroleum ether of 100~200 mesh, dry method upper prop, and by institute
State the upper end that the silica gel containing product is loaded on silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) as eluant, eluent
Carry out post separation, obtain white solid 0.1157g, i.e. target product 10- (4- bromophenyls) imido grpup-indoles simultaneously [1,2-a] Yin
Diindyl, it is 62% that it, which separates yield,.
Embodiment 8, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4991g for weighing 0.1091g ownership Formula II successively return
Belong to two (4- chlorphenyls) iodine trifluoro-methanyl sulfonates (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol) in containing
In the 25mL tube sealings of magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, 110 are put into
DEG C oil bath in stir 6h.After reaction terminates, 80mL saturated aqueous common salts are added into reaction system, three are extracted in separatory funnel
It is secondary, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filter；The silica gel of 5g 100~200 mesh is added, is depressurized dense
Contracting removes solvent, obtains the silica gel containing product；Post is filled using the silica gel and petroleum ether of 100~200 mesh, dry method upper prop, and by institute
State the upper end that the silica gel containing product is loaded on silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) as eluant, eluent
Carry out post separation, obtain white solid 0.1282g, i.e. target product 10- (4- chlorphenyls) imido grpup-indoles simultaneously [1,2-a] Yin
Diindyl, it is 78% that it, which separates yield,.
Embodiment 9, prepare polysubstituted condensed indole diindyl analog derivative：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.5463g for weighing 0.1091g ownership Formula II successively return
Belong to two (4- methyl formates phenyl) iodine trifluoro-methanyl sulfonates (1.0mmol), the 0.0180g Cu (OTf) of formula III2
(0.05mmol) adds 2.0mL 1,2- dichloroethanes in the 25mL tube sealings containing magnetic stirrer.In under condition of nitrogen gas, it will seal
The seal of tube, 6h is stirred in the oil bath for being put into 110 DEG C.Reaction terminate after, into reaction system add 55mL saturated aqueous common salts, in point
Extracted three times in liquid funnel, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filtered；Add 7.5g 100~
The silica gel of 200 mesh, be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Filled using the silica gel and petroleum ether of 100~200 mesh
Post, dry method upper prop, and by the silica gel containing product be loaded on silicon gel column upper end；With petroleum ether-ethyl acetate (volume ratio
For 95:5) post separation is carried out as eluant, eluent, obtains white solid 0.1110g, i.e. target product 10- (4- methyl formates phenyl)
Imido grpup-indoles simultaneously [1,2-a] indoles, it is 63% that it, which separates yield,.Fig. 5 and Fig. 6 are respectively that the embodiment prepares products obtained therefrom
Proton nmr spectra and carbon spectrum, from Fig. 5 and Fig. 6, the compound structure is correct.
Embodiment 10, prepare polysubstituted condensed indole diindyl analog derivative：
Weigh successively 0.1241g ownership Formula II compound 5- methoxyl groups-N- (2- cyanophenyls)-indoles (0.5mmol),
0.4302g belongs to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, put
6h is stirred in the oil bath for entering 110 DEG C.After reaction terminates, 75mL saturated aqueous common salts are added into reaction system, in separatory funnel
Extraction three times, merges organic phase, organic phase is dried through anhydrous magnesium sulfate, filters；The silica gel of 6g 100~200 mesh is added,
Be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop,
And the silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) conduct
Eluant, eluent carries out post separation, obtains white solid 0.1443g, i.e. target product 2- methoxyl groups -10- phenyl imines base-indoles simultaneously
[1,2-a] indoles, it is 89% that it, which separates yield,.
Embodiment 11, prepare polysubstituted condensed indole diindyl analog derivative：
Weigh successively 0.1161g ownership Formula II compound 5- methyl-N- (2- cyanophenyls)-indoles (0.5mmol),
0.4302g belongs to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, put
6h is stirred in the oil bath for entering 110 DEG C.After reaction terminates, 70mL saturated aqueous common salts are added into reaction system, in separatory funnel
Extraction three times, merges organic phase, organic phase is dried through anhydrous magnesium sulfate, filters；The silica gel of 8g 100~200 mesh is added,
Be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop,
And the silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) conduct
Eluant, eluent carry out post separation, obtain white solid 0.1264g, i.e. target product 2- methyl isophthalic acids 0- phenyl imines base-indoles simultaneously [1,
2-a] indoles, it is 82% that it, which separates yield,.
Embodiment 12, prepare polysubstituted condensed indole diindyl analog derivative：
Weigh successively 0.1161g ownership Formula II compound 7- methyl-N- (2- cyanophenyls)-indoles (0.5mmol),
0.4302g belongs to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, put
6h is stirred in the oil bath for entering 110 DEG C.After reaction terminates, 70mL saturated aqueous common salts are added into reaction system, in separatory funnel
Extraction three times, merges organic phase, organic phase is dried through anhydrous magnesium sulfate, filters；The silica gel of 5g 100~200 mesh is added,
Be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop,
And the silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) conduct
Eluant, eluent carry out post separation, obtain white solid 0.1234g, i.e. target product 4- methyl isophthalic acids 0- phenyl imines base-indoles simultaneously [1,
2-a] indoles, it is 80% that it, which separates yield,.
Embodiment 13, prepare polysubstituted condensed indole diindyl analog derivative：
Weigh successively 0.1181g ownership Formula II the fluoro- N- of compound 5- (2- cyanophenyls)-indoles (0.5mmol),
0.4302g belongs to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, put
6h is stirred in the oil bath for entering 110 DEG C.After reaction terminates, 60mL saturated aqueous common salts are added into reaction system, in separatory funnel
Extraction three times, merges organic phase, organic phase is dried through anhydrous magnesium sulfate, filters；The silica gel of 7g 100~200 mesh is added,
Be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop,
And the silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) conduct
Eluant, eluent carries out post separation, obtains the fluoro- 10- phenyl imines base-indoles of white solid 0.1046g, i.e. target product 2- simultaneously [1,2-
A] indoles, it is 67% that it, which separates yield,.
Embodiment 14, prepare polysubstituted condensed indole diindyl analog derivative：
Weigh successively 0.1264g ownership Formula II the chloro- N- of compound 5- (2- cyanophenyls)-indoles (0.5mmol),
0.4302g belongs to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, put
6h is stirred in the oil bath for entering 110 DEG C.After reaction terminates, 70mL saturated aqueous common salts are added into reaction system, in separatory funnel
Extraction three times, merges organic phase, organic phase is dried through anhydrous magnesium sulfate, filters；The silica gel of 8g 100~200 mesh is added,
Be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop,
And the silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) conduct
Eluant, eluent carries out post separation, obtains the chloro- 10- phenyl imines base-indoles of white solid 0.1233g, i.e. target product 2- simultaneously [1,2-
A] indoles, it is 75% that it, which separates yield,.Fig. 7 and Fig. 8 are respectively the proton nmr spectra and carbon that the embodiment prepares products obtained therefrom
Spectrum, from Fig. 7 and Fig. 8, the compound structure is correct.
Embodiment 15, prepare polysubstituted condensed indole diindyl analog derivative：
Weigh successively 0.1181g ownership Formula II the fluoro- N- of compound 6- (2- cyanophenyls)-indoles (0.5mmol),
0.4302g belongs to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, put
6h is stirred in the oil bath for entering 110 DEG C.After reaction terminates, 50mL saturated aqueous common salts are added into reaction system, in separatory funnel
Extraction three times, merges organic phase, organic phase is dried through anhydrous magnesium sulfate, filters；The silica gel of 6g 100~200 mesh is added,
Be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop,
And the silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) conduct
Eluant, eluent carries out post separation, obtains the fluoro- 10- phenyl imines base-indoles of white solid 0.0999g, i.e. target product 3- simultaneously [1,2-
A] indoles, it is 64% that it, which separates yield,.
Embodiment 16, prepare polysubstituted condensed indole diindyl analog derivative：
Weigh successively 0.1264g ownership Formula II the chloro- N- of compound 6- (2- cyanophenyls)-indoles (0.5mmol),
0.4302g belongs to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol)
In the 25mL tube sealings containing magnetic stirrer, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, put
6h is stirred in the oil bath for entering 110 DEG C.After reaction terminates, 80mL saturated aqueous common salts are added into reaction system, in separatory funnel
Extraction three times, merges organic phase, organic phase is dried through anhydrous magnesium sulfate, filters；The silica gel of 5g 100~200 mesh is added,
Be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；Using 100~200 mesh silica gel and petroleum ether fill post, dry method upper prop,
And the silica gel containing product is loaded on to the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) conduct
Eluant, eluent carries out post separation, obtains the chloro- 10- phenyl imines base-indoles of white solid 0.1200g, i.e. target product 3- simultaneously [1,2-
A] indoles, it is 73% that it, which separates yield,.
The influence of embodiment 17, differential responses solvent to polysubstituted condensed indole diindyl analog derivative yield：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol) is stirred in containing magnetic
In the 25mL tube sealings for mixing son, 2.0mL toluene is added.In under condition of nitrogen gas, tube sealing is sealed, is put into 110 DEG C of oil bath and stirs
6h.After reaction terminates, 70mL saturated aqueous common salts are added into reaction system, are extracted three times in separatory funnel, merge organic phase,
Organic phase is dried through anhydrous magnesium sulfate, filtered；The silica gel of 7g 100~200 mesh is added, be concentrated under reduced pressure removing solvent, obtains
To the silica gel containing product；Post is filled using the silica gel and petroleum ether of 100~200 mesh, dry method upper prop, and by the silica gel containing product
Upper end loaded on silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) post separation is carried out as eluant, eluent, obtained
White solid 0.0986g, i.e. target product 10- phenyl imines base-indoles simultaneously [1,2-a] indoles separation yield be 67%.
The influence of embodiment 18, different catalysts to polysubstituted condensed indole diindyl analog derivative yield：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to the diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol) of formula III, 0.0050g CuCl (0.05mmol) in containing magnetic stirrer
25mL tube sealings in, add 2.0mL 1,2- dichloroethanes.In under condition of nitrogen gas, tube sealing is sealed, in the oil bath for being put into 110 DEG C
Stir 6h.After reaction terminates, 65mL saturated aqueous common salts are added into reaction system, extracts three times, is associated with separatory funnel
Machine phase, organic phase is dried through anhydrous magnesium sulfate, filtering；The silica gel of 7g 100~200 mesh is added, the removing that is concentrated under reduced pressure is molten
Agent, obtains the silica gel containing product；Post, dry method upper prop are filled using the silica gel and petroleum ether of 100~200 mesh, and described will contain product
Silica gel be loaded on silicon gel column upper end；With petroleum ether-ethyl acetate, (volume ratio is 95:5) post point is carried out as eluant, eluent
From, obtain white solid 0.1045g, i.e. target product 10- phenyl imines base-indoles simultaneously [1,2-a] indoles, its separate yield be
71%.
The influence of embodiment 19, different catalysts to polysubstituted condensed indole diindyl analog derivative yield：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0090g CuBr of formula III2(0.05mmol) is in containing magnetic stirring
In the 25mL tube sealings of son, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, 110 DEG C of oil bath is put into
Middle stirring 6h.After reaction terminates, 60mL saturated aqueous common salts are added into reaction system, are extracted three times in separatory funnel, are merged
Organic phase, organic phase is dried through anhydrous magnesium sulfate, filtering；The silica gel of 6g 100~200 mesh is added, be concentrated under reduced pressure removing
Solvent, obtains the silica gel containing product；Post, dry method upper prop are filled using the silica gel and petroleum ether of 100~200 mesh, and described will contain production
The silica gel of thing is loaded on the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) post is carried out as eluant, eluent
Separation, obtains white solid 0.0839g, i.e. target product 10- phenyl imines base-indoles simultaneously [1,2-a] indoles, and it separates yield
For 57%.
The influence of comparative example 1, differential responses solvent to polysubstituted condensed indole diindyl analog derivative yield：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol) is stirred in containing magnetic
In the 25mL tube sealings for mixing son, 2.0mL acetonitriles are added.In under condition of nitrogen gas, tube sealing is sealed, is put into 110 DEG C of oil bath and stirs
6h, without target product 10- phenyl imines base-indoles, simultaneously [1,2-a] indoles is generated.
The influence of comparative example 2, differential responses solvent to polysubstituted condensed indole diindyl analog derivative yield：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol) is stirred in containing magnetic
In the 25mL tube sealings for mixing son, 2.0mL tetrahydrofurans are added.In under condition of nitrogen gas, tube sealing is sealed, in the oil bath for being put into 110 DEG C
6h is stirred, simultaneously [1,2-a] indoles is generated without target product 10- phenyl imines base-indoles.
The influence of comparative example 3, differential responses temperature to polysubstituted condensed indole diindyl analog derivative yield：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol), the 0.0180g Cu (OTf) of formula III2(0.05mmol) is stirred in containing magnetic
In the 25mL tube sealings for mixing son, 2.0mL 1,2- dichloroethanes are added.In under condition of nitrogen gas, tube sealing is sealed, 80 DEG C of oil is put into
6h is stirred in bath.After reaction terminates, 60mL saturated aqueous common salts are added into reaction system, are extracted three times in separatory funnel, are closed
And organic phase, organic phase is dried through anhydrous magnesium sulfate, filtered；The silica gel of 6g 100~200 mesh is added, is concentrated under reduced pressure and removes
Solvent is removed, the silica gel containing product is obtained；Post, dry method upper prop are filled using the silica gel and petroleum ether of 100~200 mesh, and is contained described
The silica gel of product is loaded on the upper end of silicon gel column；With petroleum ether-ethyl acetate, (volume ratio is 95:5) carried out as eluant, eluent
Post separation, obtains white solid 0.0515g, i.e. target product 10- phenyl imines base-indoles simultaneously [1,2-a] indoles, and it separates production
Rate is 35%.
Comparative example 4, differential responses temperature and without shadow of the catalyst to polysubstituted condensed indole diindyl analog derivative yield
Ring：
Compound N-(2- cyanophenyls)-indoles (0.5mmol), the 0.4302g for weighing 0.1091g ownership Formula II successively return
Belong to the diphenyl iodine trifluoro-methanyl sulfonate (1.0mmol) of formula III in the 25mL tube sealings containing magnetic stirrer, add 2.0mL
1,2- dichloroethanes.In under condition of nitrogen gas, tube sealing is sealed, 12h is stirred in the oil bath for being put into 110 DEG C, does not have target product 10-
Simultaneously [1,2-a] indoles is generated phenyl imine base-indoles.
Claims (8)
1. the preparation method of compound shown in Formulas I, comprises the following steps：In the presence of a catalyst, by compound shown in Formula II and
Compound shown in formula III carries out intramolecular cyclization reaction in organic solvent, obtains compound shown in Formulas I,
In the Formulas I and formula III, R1Selected from least one of hydrogen, methyl, isopropyl, the tert-butyl group, fluorine, bromine, chlorine and carbomethoxy；
R1Number be 1-5, R1In the remaining binding site of phenyl ring at least one at；
In the Formulas I and Formula II, R2Selected from least one of H, methyl, methoxyl group, fluorine, chlorine and bromine；R2Number be 1-4,
R2In the remaining binding site of phenyl ring at least one at；
In the formula III, Ar be selected from phenyl, p-methylphenyl, to 2-methyl-2-phenylpropane base, 2,5- xylyls, 2,4,6- trimethylphenyls,
P-fluorophenyl, p-bromophenyl, rubigan or to methyl formate phenyl；
The catalyst is selected from Cu (OTf)2, CuCl and CuBr2At least one of.
2. preparation method as claimed in claim 1, it is characterised in that：Compound shown in the Formula II, formula III shownization
The mol ratio of compound and the catalyst is 1：(1-3)：(0.05-0.2).
3. preparation method as claimed in claim 1 or 2, it is characterised in that：The reaction temperature of the intramolecular cyclization reaction is
100~120 DEG C, the reaction time is 6~10h.
4. preparation method as claimed in claim 1 or 2, it is characterised in that：The organic solvent be selected from 1,2- dichloroethanes and/
Or toluene.
5. preparation method as claimed in claim 1 or 2, it is characterised in that：It is sub- that compound described in the Formulas I is selected from 10- phenyl
Amido-indoles simultaneously [1,2-a] indoles, 10- (4- aminomethyl phenyls) imido grpup-indoles simultaneously [1,2-a] indoles, 10- (4- tert-butyl benzenes
Base) imido grpup-indoles simultaneously [1,2-a] indoles, 10- (2,5- 3,5-dimethylphenyls) imido grpup-indoles simultaneously [1,2-a] indoles, 10-
Simultaneously [1,2-a] indoles, 10- (4- fluorophenyls) imido grpup-indoles be simultaneously [1,2-a] for (2,4,6- trimethylphenyls) imido grpup-indoles
Simultaneously [1,2-a] indoles, 10- (4- chlorphenyls) imido grpup-indoles be simultaneously [1,2-a] for indoles, 10- (4- bromophenyls) imido grpup-indoles
Indoles, 10- (4- methyl formates phenyl) imido grpup-indoles simultaneously [1,2-a] indoles, 2- methoxyl group -10- phenyl imines base-indoles
And [1,2-a] indoles, 2- methyl isophthalic acid 0- phenyl imines base-indoles simultaneously [1,2-a] indoles, 4- methyl isophthalic acid 0- phenyl imine bases-Yin
The diindyl simultaneously fluoro- 10- phenyl imines base-indoles of [1,2-a] indoles, the 2- simultaneously chloro- 10- phenyl imines base-indoles of [1,2-a] indoles, 2-
And simultaneously [1,2-a] indoles or the chloro- 10- phenyl imines base-indoles of 3- be simultaneously for the fluoro- 10- phenyl imines base-indoles of [1,2-a] indoles, 3-
Any of [1,2-a] indoles；
Compound described in the Formula II is selected from N- (2- cyanophenyls)-indoles, 5- methoxyl groups-N- (2- cyanophenyls)-indoles, 5-
Methyl-N- (2- cyanophenyls)-indoles, 7- methyl-N- (2- cyanophenyls)-indoles, the fluoro- N- of 5- (2- cyanophenyls)-indoles,
In the chloro- N- of 5- (2- cyanophenyls)-indoles, the fluoro- N- of 6- (2- cyanophenyls)-indoles or the chloro- N- of 6- (2- cyanophenyls)-indoles
It is any；
Compound described in the formula III is selected from diphenyl iodine trifluoro-methanyl sulfonate, two (4- aminomethyl phenyls) iodine fluoroform sulphurs
Hydrochlorate, two (4- tert-butyl-phenyls) iodine trifluoro-methanyl sulfonates, two (2,5- 3,5-dimethylphenyls) iodine trifluoro-methanyl sulfonates, two
(2,4,6- trimethylphenyls) iodine trifluoro-methanyl sulfonate, two (4- fluorophenyls) iodine trifluoro-methanyl sulfonates, two (4- bromophenyls)
Iodine trifluoro-methanyl sulfonate, two (4- chlorphenyls) iodine trifluoro-methanyl sulfonates or two (4- methyl formates phenyl) iodine fluoroform sulphurs
Any of hydrochlorate.
6. preparation method as claimed in claim 1 or 2, it is characterised in that：The intramolecular cyclization reaction is in inert atmosphere
Lower progress；
The intramolecular cyclization reaction is carried out in the reaction vessel of closed reaction unit or additional reflow device.
7. preparation method as claimed in claim 1 or 2, it is characterised in that：Also include terminating the intramolecular cyclization reaction
Reaction system afterwards carries out separating-purifying, the step of obtaining compound shown in the Formulas I.
8. preparation method as claimed in claim 7, it is characterised in that：The step of separating-purifying for it is following 1) or 2)：
Step 1)：For fluid sample：
(1) 50-80mL saturated aqueous common salts are added in the reaction system after terminating to the intramolecular cyclization reaction, in separatory funnel
It is middle to extract three times, merge organic phase, organic phase is dried through anhydrous magnesium sulfate, filter；
(2) silica gel of 5-8g 100~200 mesh is added, be concentrated under reduced pressure removing solvent, obtains the silica gel containing product；
(3) using silica gel and petroleum ether the dress post of 100~200 mesh, dry method upper prop, and the silica gel containing product is loaded on silica gel
The upper end of pillar；
(4) eluted with petrol ether/ethyl acetate mixed solvent, collect the solution for including compound shown in Formulas I, be concentrated under reduced pressure
Remove after solvent, vacuum drying obtains compound shown in Formulas I, wherein, the petrol ether/ethyl acetate in the mixed solvent acetic acid
The volume fraction of ethyl ester is 1~5%；
Or, step 2)：For solid sample：
Using recrystallization, the intramolecular cyclization reaction is terminated into rear products therefrom and is dissolved in dichloromethane, then is added thereto not
Good solvent n-hexane, makes dichloromethane and n-hexane volatilize, obtains compound shown in Formulas I.
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| WO2014081134A1 (en) * | 2012-11-21 | 2014-05-30 | 주식회사 두산 | Novel compound and organic electroluminescent element comprising same |
| CN103980282A (en) * | 2014-06-10 | 2014-08-13 | 中国科学院昆明植物研究所 | Method for synthesizing 3-oxo-pyrrol[2,3-b]indole compounds |
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| WO2012059583A1 (en) * | 2010-11-04 | 2012-05-10 | Biosynth Ag | Novel applications of indoloindole and indoloquinoline dyes |
| WO2014081134A1 (en) * | 2012-11-21 | 2014-05-30 | 주식회사 두산 | Novel compound and organic electroluminescent element comprising same |
| CN103980282A (en) * | 2014-06-10 | 2014-08-13 | 中国科学院昆明植物研究所 | Method for synthesizing 3-oxo-pyrrol[2,3-b]indole compounds |
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| Title |
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| Pd-catalyzed dehydrogenative C–H activation of iminyl hydrogen with the indole C3–H and C2–H bond: an elegant synthesis of indeno[1,2-b]indoles and indolo[1,2-a]indoles;Somjit Hazra等;《RSC Adv.》;20150220;第5卷(第29期);第22480-22489页，参见全文 * |
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