CN114634438A - 双吲哚甲烷及其衍生物的制备方法 - Google Patents
双吲哚甲烷及其衍生物的制备方法 Download PDFInfo
- Publication number
- CN114634438A CN114634438A CN202210360187.0A CN202210360187A CN114634438A CN 114634438 A CN114634438 A CN 114634438A CN 202210360187 A CN202210360187 A CN 202210360187A CN 114634438 A CN114634438 A CN 114634438A
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- China
- Prior art keywords
- indole
- reaction
- methyl
- indol
- derivatives
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- TWJAXIHBWPVMIR-UHFFFAOYSA-N diindolylmethane Natural products C1=CC=C2NC(CC=3NC4=CC=CC=C4C=3)=CC2=C1 TWJAXIHBWPVMIR-UHFFFAOYSA-N 0.000 title claims abstract description 21
- VFTRKSBEFQDZKX-UHFFFAOYSA-N 3,3'-diindolylmethane Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4NC=3)=CNC2=C1 VFTRKSBEFQDZKX-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 117
- 238000000034 method Methods 0.000 claims abstract description 51
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 22
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 15
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 9
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 7
- 150000002475 indoles Chemical class 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims description 33
- JKNHZOAONLKYQL-UHFFFAOYSA-K tribromoindigane Chemical compound Br[In](Br)Br JKNHZOAONLKYQL-UHFFFAOYSA-K 0.000 claims description 28
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- VPVIYKRQVDIGOH-UHFFFAOYSA-N 2-chloro-1,3-dithiane Chemical class ClC1SCCCS1 VPVIYKRQVDIGOH-UHFFFAOYSA-N 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 claims description 6
- 238000005580 one pot reaction Methods 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims description 4
- UHUUYVZLXJHWDV-UHFFFAOYSA-N trimethyl(methylsilyloxy)silane Chemical compound C[SiH2]O[Si](C)(C)C UHUUYVZLXJHWDV-UHFFFAOYSA-N 0.000 claims description 4
- GBYPTTGTFMAEJL-UHFFFAOYSA-N B.Fc1cc(F)c(F)c(F)c1F.Fc1cc(F)c(F)c(F)c1F.Fc1cc(F)c(F)c(F)c1F Chemical compound B.Fc1cc(F)c(F)c(F)c1F.Fc1cc(F)c(F)c(F)c1F.Fc1cc(F)c(F)c(F)c1F GBYPTTGTFMAEJL-UHFFFAOYSA-N 0.000 claims description 3
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 3
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 claims description 3
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 claims description 3
- AKQNYQDSIDKVJZ-UHFFFAOYSA-N triphenylsilane Chemical compound C1=CC=CC=C1[SiH](C=1C=CC=CC=1)C1=CC=CC=C1 AKQNYQDSIDKVJZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- JGGNJDKQZHDKHQ-UHFFFAOYSA-N 1H-indole Chemical compound C1=CC=C2NC=CC2=C1.C1=CC=C2NC=CC2=C1 JGGNJDKQZHDKHQ-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- JHXKRIRFYBPWGE-UHFFFAOYSA-K bismuth chloride Chemical compound Cl[Bi](Cl)Cl JHXKRIRFYBPWGE-UHFFFAOYSA-K 0.000 claims description 2
- QABCGOSYZHCPGN-UHFFFAOYSA-N chloro(dimethyl)silicon Chemical group C[Si](C)Cl QABCGOSYZHCPGN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 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 claims description 2
- 229960000905 indomethacin Drugs 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 2
- RMUKCGUDVKEQPL-UHFFFAOYSA-K triiodoindigane Chemical compound I[In](I)I RMUKCGUDVKEQPL-UHFFFAOYSA-K 0.000 claims description 2
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 claims description 2
- XGDLHLISLBPXPR-UHFFFAOYSA-N C.C1=CC=C2NC=CC2=C1.C1=CC=C2NC=CC2=C1 Chemical class C.C1=CC=C2NC=CC2=C1.C1=CC=C2NC=CC2=C1 XGDLHLISLBPXPR-UHFFFAOYSA-N 0.000 claims 1
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical class S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 claims 1
- -1 diindolylmethane compound Chemical class 0.000 abstract description 42
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000006477 desulfuration reaction Methods 0.000 abstract description 2
- 230000023556 desulfurization Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 238000011160 research Methods 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract 2
- QLYYEOXVDDIUMJ-UHFFFAOYSA-N 2-(1,3-dithian-2-yl)-1h-indole Chemical compound S1CCCSC1C1=CC2=CC=CC=C2N1 QLYYEOXVDDIUMJ-UHFFFAOYSA-N 0.000 abstract 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical group C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 abstract 1
- 229910001385 heavy metal Inorganic materials 0.000 abstract 1
- 239000000047 product Substances 0.000 description 50
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 29
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- 238000004440 column chromatography Methods 0.000 description 27
- 238000001514 detection method Methods 0.000 description 25
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- 238000001704 evaporation Methods 0.000 description 17
- 230000008020 evaporation Effects 0.000 description 17
- RGRMVTODKXTRFC-UHFFFAOYSA-N 3-(1,3-dithian-2-yl)-1H-indole Chemical compound C1CSC(SC1)c1c[nH]c2ccccc12 RGRMVTODKXTRFC-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
- LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 7
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical compound C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 6
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- JCQLPDZCNSVBMS-UHFFFAOYSA-N 5-phenylmethoxy-1h-indole Chemical compound C=1C=C2NC=CC2=CC=1OCC1=CC=CC=C1 JCQLPDZCNSVBMS-UHFFFAOYSA-N 0.000 description 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 2
- WLWCAURHWLTEKS-UHFFFAOYSA-N 1-bromo-3-[(3-methyl-1H-indol-2-yl)methyl]indole Chemical compound CC1=C(CC(C2=CC=CC=C22)=CN2Br)NC2=CC=CC=C12 WLWCAURHWLTEKS-UHFFFAOYSA-N 0.000 description 2
- ZACMZGNBTFBTPV-UHFFFAOYSA-N 1-methyl-3-[(1-methylindol-3-yl)methyl]indole Chemical compound C12=CC=CC=C2N(C)C=C1CC1=CN(C)C2=CC=CC=C12 ZACMZGNBTFBTPV-UHFFFAOYSA-N 0.000 description 2
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 2
- FQBRYPYOWSKCMK-UHFFFAOYSA-N 2-(1h-indol-3-ylmethyl)-3-methyl-1h-indole Chemical compound N1C2=CC=CC=C2C(C)=C1CC1=CNC2=CC=CC=C12 FQBRYPYOWSKCMK-UHFFFAOYSA-N 0.000 description 2
- WBXCXNJFRGPFRH-UHFFFAOYSA-N 2-[(5-chloro-1H-indol-3-yl)methyl]-3-methyl-1H-indole Chemical compound CC1=C(CC(C2=C3)=CNC2=CC=C3Cl)NC2=CC=CC=C12 WBXCXNJFRGPFRH-UHFFFAOYSA-N 0.000 description 2
- OEDDTQJUQNWLCJ-UHFFFAOYSA-N 3-[(4-methoxy-1H-indol-3-yl)methyl]-1H-indol-5-ol Chemical compound COC1=C(C(CC(C2=C3)=CNC2=CC=C3O)=CN2)C2=CC=C1 OEDDTQJUQNWLCJ-UHFFFAOYSA-N 0.000 description 2
- MYTGFBZJLDLWQG-UHFFFAOYSA-N 5-chloro-1h-indole Chemical compound ClC1=CC=C2NC=CC2=C1 MYTGFBZJLDLWQG-UHFFFAOYSA-N 0.000 description 2
- ZPDALSGUMJKPKN-UHFFFAOYSA-N 5-chloro-3-[(5-chloro-1h-indol-3-yl)methyl]-1h-indole Chemical compound C1=C(Cl)C=C2C(CC3=CNC4=CC=C(C=C43)Cl)=CNC2=C1 ZPDALSGUMJKPKN-UHFFFAOYSA-N 0.000 description 2
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 description 2
- QXRRIIRICIOADU-UHFFFAOYSA-N 5-methyl-3-[(5-methyl-1h-indol-3-yl)methyl]-1h-indole Chemical compound C1=C(C)C=C2C(CC3=CNC4=CC=C(C=C43)C)=CNC2=C1 QXRRIIRICIOADU-UHFFFAOYSA-N 0.000 description 2
- YPKBCLZFIYBSHK-UHFFFAOYSA-N 5-methylindole Chemical compound CC1=CC=C2NC=CC2=C1 YPKBCLZFIYBSHK-UHFFFAOYSA-N 0.000 description 2
- UMDWFMPGQLTSFR-UHFFFAOYSA-N 5-phenylmethoxy-3-[(5-phenylmethoxy-1H-indol-3-yl)methyl]-1H-indole Chemical compound C(Oc1ccc2[nH]cc(Cc3c[nH]c4ccc(OCc5ccccc5)cc34)c2c1)c6ccccc6 UMDWFMPGQLTSFR-UHFFFAOYSA-N 0.000 description 2
- ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methylindole Natural products CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 2
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 2
- POEXERAQSHGAMH-UHFFFAOYSA-N Cn1cc(Cc2c[nH]c3ccccc23)c2ccccc12 Chemical compound Cn1cc(Cc2c[nH]c3ccccc23)c2ccccc12 POEXERAQSHGAMH-UHFFFAOYSA-N 0.000 description 2
- IHQDGXUYTSZGOG-UHFFFAOYSA-N Erucin Chemical compound CSCCCCN=C=S IHQDGXUYTSZGOG-UHFFFAOYSA-N 0.000 description 2
- BKSFTNBSMIREGF-UHFFFAOYSA-N acetic acid;3-methyl-1h-indole Chemical compound CC(O)=O.C1=CC=C2C(C)=CNC2=C1 BKSFTNBSMIREGF-UHFFFAOYSA-N 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- PBMFUBPKVFLXQY-UHFFFAOYSA-N 1h-indol-3-yl propanoate Chemical compound C1=CC=C2C(OC(=O)CC)=CNC2=C1 PBMFUBPKVFLXQY-UHFFFAOYSA-N 0.000 description 1
- YABOIMHEAYDBKN-UHFFFAOYSA-N 2-(1,3-dithian-2-yl)-3-methyl-1H-indole Chemical compound N1C2=CC=CC=C2C(C)=C1C1SCCCS1 YABOIMHEAYDBKN-UHFFFAOYSA-N 0.000 description 1
- YQPGAIOHVLIRNB-UHFFFAOYSA-N 3-(1,3-dithian-2-yl)-2-methyl-1H-indole Chemical compound CC=1NC2=CC=CC=C2C=1C1SCCCS1 YQPGAIOHVLIRNB-UHFFFAOYSA-N 0.000 description 1
- BOYXWNFUFCDCNC-UHFFFAOYSA-N 3-(1,3-dithian-2-yl)-5-methoxy-1H-indole Chemical compound COC1=CC=C2NC=C(C3SCCCS3)C2=C1 BOYXWNFUFCDCNC-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- GDQXDVJFMLNXHX-UHFFFAOYSA-N 5-bromo-3-methyl-1h-indole Chemical compound C1=C(Br)C=C2C(C)=CNC2=C1 GDQXDVJFMLNXHX-UHFFFAOYSA-N 0.000 description 1
- GAUCZJDSZBGRTC-UHFFFAOYSA-N 5-fluoro-3-(1H-indol-3-ylmethyl)-1H-indole Chemical compound Fc1ccc2[nH]cc(Cc3c[nH]c4ccccc34)c2c1 GAUCZJDSZBGRTC-UHFFFAOYSA-N 0.000 description 1
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
- RDSVSEFWZUWZHW-UHFFFAOYSA-N 7-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1NC=C2 RDSVSEFWZUWZHW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 235000004221 Brassica oleracea var gemmifera Nutrition 0.000 description 1
- 235000017647 Brassica oleracea var italica Nutrition 0.000 description 1
- 244000308368 Brassica oleracea var. gemmifera Species 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 1
- IVYPNXXAYMYVSP-UHFFFAOYSA-N indole-3-methanol Chemical class C1=CC=C2C(CO)=CNC2=C1 IVYPNXXAYMYVSP-UHFFFAOYSA-N 0.000 description 1
- JBOPQACSHPPKEP-UHFFFAOYSA-N indoxyl acetate Natural products C1=CC=C2C(OC(=O)C)=CNC2=C1 JBOPQACSHPPKEP-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- QXTIBZLKQPJVII-UHFFFAOYSA-N triethylsilicon Chemical compound CC[Si](CC)CC QXTIBZLKQPJVII-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
本发明属于有机合成领域，涉及双吲哚甲烷及其衍生物的制备方法。双吲哚甲烷化合物在合成与药物活性方面具有重要的研究价值，但常规的合成步骤繁琐、条件苛刻、涉及到昂贵重金属和底物具有局限性等问题。本发明提供了双吲哚甲烷及其衍生物的制备方法，以3‑或者2‑(1,3‑二噻烷‑2‑基)‑1H‑吲哚和取代吲哚为原料，在催化剂和还原剂共同作用下，通过噻烷环的脱硫而实现合成双吲哚甲烷衍生物。本发明为高效而简易的合成方法，该方法具有反应温和、高效性、操作简单和原料经济的优点，具有很强的实用性。
Description
技术领域
本发明属于有机合成领域，涉及双吲哚甲烷及其衍生物的制备方法。
背景技术
双吲哚甲烷类化合物(Bisindolylmethanes，BIMs)本身是由糖苷芥菜素产生的吲哚-3-甲醇的主要代谢物，这种糖苷在十字花科蔬菜中发现，如西兰花、球芽甘蓝和花椰菜；据报道，BIMs具有抗氧化、抗炎、抗血管生成、抗癌等多种活性，BIMs自然界中重要的杂环结构之一，广泛存在于具有生物活性的天然产物、药物和功能材料中；因此，构筑二吲哚甲烷类杂环化合物备受关注，传统的合成方法是吲哚衍生物与羰基化合物经傅-克反应缩合得到；目前，经1，3-二噻烷脱硫生成双吲哚甲烷类化合物结构的相关研究开展得较少，鲜有报道。
目前合成双吲哚甲烷类化合物的主要合成方法包括：吲哚与醛类化合物发生傅-克反应和吲哚3位进行修饰后再与吲哚化合物进行反应。
通过傅-克反应制备双吲哚甲烷衍生物，制备方法如下式：
此方法缺点在于原料限于吲哚3位没有取代基和另一底物必须是醛，底物较受限，此外产物只能是左右对称的3，3’-双吲哚甲烷类化合物。
霍等报道了光催化的吲哚-3-乙酸酯与吲哚的脱羧偶联反应，实现吲哚C-H官能化和脱羧，合成制备了相应的双吲哚甲烷类化合物，制备方法如式：
此方法缺点在于反应底物具有局限性，必需以3-乙酸酯吲哚形式参与反应，此外还需使用昂贵光敏催化剂，对环境存在潜在危害，该反应过程中需要氩气保护，反应条件苛刻。
发明内容
为了实现双吲哚甲烷类化合物的高效制备，本发明提供双吲哚甲烷及其衍生物的制备方法，该方法不仅操作简单、选择性好、官能团耐受性高、收率高，而且所合成的化合物结构丰富，容易分离纯化，适合于大量生产。
双吲哚甲烷及其衍生物的制备方法特征在于包括以下步骤：在反应器中加入噻烷吲哚衍生物(Ⅰ)和吲哚衍生物(Ⅱ)在合适的溶剂和催化剂作用下反应，实现双吲哚衍生物(Ⅲ) 的合成，化学反应方程式如下：
取代基R1、R2为氢、甲基；R3、R4为吲哚2-7位取代基，选自氢、甲基、C1-C6烷氧基、苯基、羟基、硝基、氰基、卤素、乙酸甲酯、金刚烷酸酯、吲哚美辛酸酯、乙酸叔丁酯、苄氧基，n＝0或1。
双吲哚甲烷及其衍生物的制备方法其特征在于：所用的催化剂为三氯化铟、三溴化铟、三碘化铟、三氯化铁、六水合三氯化铁、三氯化铋、碘单质，三氟化硼乙醚，三(五氟苯)硼烷中的一种或多种。
双吲哚甲烷及其衍生物的制备方法其特征在于：所用的还原剂为二甲基氯硅烷、三甲基硅烷、三乙基硅烷、四甲基二硅氧烷、二苯基硅烷、三苯基硅烷、苯硅烷、四甲基二硅氧烷中的一种或多种。
双吲哚甲烷及其衍生物的制备方法其特征在于，所用的溶剂为1,2-二氯乙烷、二氯甲烷、乙醚、氯仿、甲苯、氯苯中的一种或多种。
双吲哚甲烷及其衍生物的制备方法其特征在于：所述的催化剂，还原剂和反应物的摩尔比为催化剂：还原剂：噻烷吲哚:吲哚＝(0.01～1.0)：(1.0～3.0)：1:(1.0～2.0)。
双吲哚甲烷及其衍生物的制备方法其特征在于：本反应可实现从取代吲哚与2-氯-1,3- 二噻烷一锅实现合成。
具体实施方式
下面的实施例可以使本专业技术人员更全面的理解本发明，但不以任何方式限制本发明。本发明所用原料均为已知化合物，可由市场购得或可采用本领域已知方法合成得到。
实施1：制备di(1H-indol-3-yl)methane方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和吲哚(12.9mg，0.11mmol)，用3毫升二氯甲烷溶解后加入三溴化铟(17.8mg，0.05 mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率68％)。
实施例1所得产品(di(1H-indol-3-yl)methane的结构、核磁数据如下：
1H NMR(400MHz,DMSO-d6)δ10.75(s,2H),7.54(d,J＝7.9Hz,2H),7.33(d,J＝8.1Hz,2H),7.17–7.10(m,2H),7.07–7.00(m,2H),6.99–6.87(m,2H),4.14(s,2H).
13C NMR(101MHz,DMSO-d6)δ136.4,127.2,122.8,120.7,118.7,118.0,114.2,111.3,20.9.
实施2：制备3-((1H-indol-3-yl)methyl)-1-methyl-1H-indole方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和N-甲基吲哚(14.4mg，0.11mmol)，用3毫升乙醚溶解后加入三溴化铟(17.8mg， 0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率60％)。
实施例2所得产品3-((1H-indol-3-yl)methyl)-1-methyl-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,DMSO-d6)δ10.72(s,2H),7.54–7.48(m,2H),7.33–7.28(m,2H),7.13(d,J＝2.3Hz,2H),7.05–6.99(m,2H),6.94–6.88(m,2H),4.12(d,J＝1.0Hz,2H).
13C NMR(101MHz,Chloroform-d)δ137.2,136.5,134.3,128.1,127.9,127.6,127.0,122.2, 121.9,121.4,119.3,119.3,119.2,118.6,115.9,114.1,111.1,109.1,32.6,21.1.
实施3：制备((1H-indol-3-yl)methyl)-5-methyl-1H-indole方法的反应步骤：
在 25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol)和5-甲基吲哚(14.4mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率67％)。
实施例3所得产品((1H-indol-3-yl)methyl)-5-methyl-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.81(s,1H),7.72(s,1H),7.64–7.60(m,1H),7.40 (s,1H),7.32(d,J＝8.1Hz,1H),7.24–7.16(m,2H),7.12–7.06(m,1H),7.01(dd,J＝8.2,1.7 Hz,1H),6.89–6.81(m,2H),4.19(d,J＝1.1Hz,2H),2.42(s,3H).
13C NMR(101MHz,Chloroform-d)δ136.6,134.9,128.5,127.9,127.7,123.6,122.5,122.3, 122.0,119.4,119.3,119.0,115.9,115.2,111.2,110.8,21.6,21.3.
实施4：制备2-((1H-indol-3-yl)methyl)-3-methyl-1H-indole方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和3-甲基吲哚(14.4mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三氯化铟(10.4 mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率75％)。
实施例4所得产品2-((1H-indol-3-yl)methyl)-3-methyl-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.94(s,1H),7.62(s,1H),7.55–7.51(m,1H),7.48 (dd,J＝8.0,1.1Hz,1H),7.37–7.33(m,1H),7.22–7.18(m,1H),7.14–7.11(m,1H),7.10–
7.05(m,3H),6.96(d,J＝2.3Hz,1H),4.21(s,2H),2.37(s,3H).
13C NMR(151MHz,Chloroform-d)δ136.4,135.1,133.4,129.4,127.2,122.5,122.4,120.9, 119.8,118.9,118.1,113.0,111.2,110.3,106.8,22.2,8.6.
实施5：制备((1H-indol-3-yl)methyl)-5-bromo-3-methyl-1H-indole方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和3-甲基-5-溴吲哚(23.1mg，0.11mmol)，用2毫升1,2-二氯乙烷和1毫升氯仿溶解后加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率74％)。
实施例5所得产品((1H-indol-3-yl)methyl)-5-bromo-3-methyl-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.94(s,1H),7.63(d,J＝2.0Hz,1H),7.60(s,1H), 7.45–7.40(m,1H),7.34(d,J＝8.1Hz,1H),7.22–7.17(m,1H),7.11(dd,J＝8.6,1.9Hz,1H), 7.09–7.04(m,1H),6.96–6.85(m,2H),4.17(s,2H),2.31(s,3H).
13C NMR(101MHz,Chloroform-d)δ136.5,135.1,133.8,131.3,127.2,123.6,122.7,122.5, 120.8,119.9,118.9,112.5,112.2,111.8,111.3,106.6,77.4,77.1,76.8,22.3,8.5.
实施6：制备((1H-indol-3-yl)methyl)-5-methoxy-1H-indole方法的反应步骤：
在 25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol)和5-甲氧基吲哚(16.2mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三三氯化铁(8.1mg，0.05mmol)和六水合三氯化铁(13.5mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率50％)。
实施例6所得产品((1H-indol-3-yl)methyl)-5-methoxy-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.84(s,1H),7.74(s,1H),7.65–7.59(m,1H),7.35– 7.29(m,1H),7.24–7.15(m,2H),7.12–7.06(m,1H),7.05(d,J＝2.5Hz,1H),6.90–6.81(m, 3H),4.19(d,J＝1.1Hz,2H),3.80(s,3H).
13C NMR(101MHz,Chloroform-d)δ153.8,136.5,134.4,131.6,128.0,127.6,123.1,122.3, 121.9,119.2,119.2,115.6,115.4,112.1,111.8,111.1,101.1,56.0,21.3.
实施7：制备((1H-indol-3-yl)methyl)-5-(benzyloxy)-1H-indole方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和5-苄氧基吲哚(24.5mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和三苯基硅氢(25μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率54％)。
实施例7所得产品((1H-indol-3-yl)methyl)-5-(benzyloxy)-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,DMSO-d6)δ10.73(s,1H),10.59(s,1H),7.54(d,J＝7.9Hz,1H),7.47–7.41(m,2H),7.40–7.28(m,4H),7.22(d,J＝8.7Hz,1H),7.14(t,J＝2.9Hz,2H),7.10(d,J＝2.3Hz,1H),7.07–7.02(m,1H),6.96–6.90(m,1H),6.78(dd,J＝8.7,2.4Hz,1H),5.04(s,2H),4.09(s,2H).
13C NMR(101MHz,DMSO-d6)δ152.2,138.3,136.9,132.2,128.8,128.1,128.0,127.9,127.7, 124.0,123.2,121.2,119.1,118.5,114.6,114.5,112.4,111.9,111.8,102.8,70.3,21.3.
实施8：制备((1H-indol-3-yl)methyl)-1H-indol-5-ol方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和5-羟基吲哚(14.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和苯硅烷(13μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率65％)。
实施例8所得产品((1H-indol-3-yl)methyl)-1H-indol-5-ol的结构、核磁数据如下：
1H NMR(600MHz,Methanol-d4)δ7.52–7.49(m,1H),7.32–7.29(m,1H),7.15(d,J＝8.6Hz,1H),7.07–7.04(m,1H),6.96–6.93(m,1H),6.93–6.90(m,2H),6.90(d,J＝2.4Hz,1H),6.65(dd,J＝8.6,2.4Hz,1H),4.12(s,2H).
13C NMR(151MHz,Methanol-d4)δ152.4,138.2,133.3,129.6,128.9,124.4,123.5,122.0,119.7, 119.3,116.0,115.2,112.5,112.0,104.0,22.7.
实施9：制备3-((1H-indol-3-yl)methyl)-5-fluoro-1H-indole方法的反应步骤：
在 25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol)和5-氟吲哚(14.9mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8mg，0.05mmol) 和三乙基硅氢(16μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率58％)。
实施例9所得产品3-((1H-indol-3-yl)methyl)-5-fluoro-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.88(d,J＝13.8Hz,2H),7.62–7.55(m,1H),7.38–7.31(m,1H),7.27–7.14(m,3H),7.12–7.04(m,1H),7.00–6.95(m,1H),6.95–6.86(m, 2H),4.18(t,J＝1.1Hz,2H),1.25(s,1H),0.85(s,1H).
13C NMR(101MHz,Chloroform-d)δ157.78(d,J＝234.0Hz),128.06(d,J＝8.7Hz),116.01(d, J＝4.8Hz),111.73(d,J＝9.9Hz),110.38(d,J＝26.5Hz),104.28(d,J＝23.2Hz).
实施10：制备bis(7-bromo-1H-indol-3-yl)methane方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-7-溴吲哚(31.4mg，0.1mmol)和7-溴吲哚(21.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三(五氟苯)硼烷(25.6mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率71％)。
实施例10所得产品bis(7-bromo-1H-indol-3-yl)methane的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ8.13–8.03(m,2H),7.51(dt,J＝7.8,0.8Hz,2H),7.33(dd,J＝7.6,0.9Hz,2H),7.00–6.93(m,4H),4.19(t,J＝1.1Hz,2H).
13C NMR(101MHz,Chloroform-d)δ135.1,128.6,124.4,122.8,120.5,118.4,116.6,104.7, 21.6.
实施11：制备methyl 2-(2-((1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和3-乙酸甲酯吲哚(20.8mg，0.11mmol)，用5毫升甲苯溶解后加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率63％)。
实施例11所得产品methyl 2-(2-((1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ8.04(s,1H),7.78(s,1H),7.60–7.55(m,1H),7.49– 7.44(m,1H),7.35(dt,J＝8.2,1.0Hz,1H),7.22–7.17(m,1H),7.12–7.04(m,4H),6.92(dd,J ＝2.3,1.1Hz,1H),4.25(d,J＝0.9Hz,2H),3.84(s,2H),3.67(s,3H).
13C NMR(101MHz,Chloroform-d)δ172.6,136.4,135.6,135.0,128.6,127.2,123.0,122.4, 121.3,119.8,119.6,118.9,118.2,112.1,111.3,110.6,104.1,77.4,77.1,76.7,52.0,30.2,22.3.
实施12：制备methyl 2-(2-((2-methyl-1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate方法的反应步骤：
在25毫升圆底烧瓶中，加入2-甲基-3-(1,3-二噻烷-2-基)-1H-吲哚(24.9mg，0.1mmol) 和3-乙酸甲酯吲哚(37.8mg，0.2mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率66％)。
实施例12所得产品methyl 2-(2-((2-methyl-1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate 的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.86(s,1H),7.71(s,1H),7.56(d,J＝7.5Hz,1H), 7.32(dd,J＝7.9,1.1Hz,1H),7.23(dd,J＝8.1,1.0Hz,1H),7.14–7.10(m,1H),7.09–7.06(m, 1H),7.05–6.98(m,3H),4.18(s,2H),3.85(s,2H),3.66(s,3H),2.24(s,3H).
13C NMR(101MHz,Chloroform-d)δ172.7,136.0,135.3,134.9,132.7,128.7,128.7,121.4, 121.2,119.8,119.6,118.1,118.0,110.7,110.5,107.0,103.5,52.0,30.3,21.1,11.5.
实施13：制备methyl 2-(2-((5-bromo-1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-5-溴吲哚(31.5mg，0.1mmol)和3-乙酸甲酯吲哚(20.8mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率70％)。
实施例13所得产品methyl 2-(2-((5-bromo-1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate 的结构、核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ8.07(s,1H),7.79(s,1H),7.60(d,J＝1.9Hz,1H), 7.59–7.55(m,1H),7.27–7.24(m,2H),7.18(d,J＝8.6Hz,1H),7.15–7.12(m,1H),7.12–
7.07(m,2H),6.84(d,J＝2.4Hz,1H),4.16(t,J＝1.5Hz,2H),3.82(s,2H),3.68(s,3H).
13C NMR(151MHz,Chloroform-d)δ172.8,135.2,135.1,135.1,129.0,128.6,125.4,124.3, 121.6,121.4,119.8,118.4,113.1,112.9,112.1,110.8,104.4,52.2,30.3,22.2.
实施14：制备5-chloro-3-((3-methyl-1H-indol-2-yl)methyl)-1H-indole方法的反应步骤：
在25毫升圆底烧瓶中，加入3-甲基-2-(1,3-二噻烷-2-基)-1H-吲哚(24.9mg，0.1mmol) 和5-氯吲哚(16.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8mg， 0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率71％)。
实施例14所得产品5-chloro-3-((3-methyl-1H-indol-2-yl)methyl)-1H-indole的结构、核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ7.99(s,1H),7.62(s,1H),7.56–7.53(m,1H),7.48 (d,J＝2.0Hz,1H),7.26(d,J＝8.6Hz,1H),7.18–7.14(m,2H),7.12–7.08(m,2H),6.96(dd,J ＝2.3,1.1Hz,1H),4.16(s,2H),2.37(s,3H).
13C NMR(151MHz,Chloroform-d)δ135.3,134.9,134.5,133.0,129.5,128.4,125.6,124.0, 122.9,121.3,119.2,118.5,118.4,113.1,112.4,110.5,107.3,22.2,8.7.
实施15：制备methyl 2-(2-((6-chloro-1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-5-氯-1H-吲哚(27.0mg，0.1mmol) 和3-乙酸甲酯吲哚(18.9mg，0.1mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率62％)。
实施例15所得产品methyl 2-(2-((6-chloro-1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate 的结构、核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ8.01(s,1H),7.77(s,1H),7.57(dd,J＝7.2,1.9Hz, 1H),7.30(d,J＝8.4Hz,1H),7.27(d,J＝1.9Hz,1H),7.12–7.07(m,3H),6.99(dd,J＝8.5,1.8 Hz,1H),6.78(dd,J＝2.3,1.3Hz,1H),4.17(d,J＝1.0Hz,2H),3.81(s,2H),3.65(s,3H).
13C NMR(151MHz,Chloroform-d)δ172.9,136.8,135.3,135.1,128.6,128.3,125.8,123.7, 121.6,120.5,119.8,118.3,112.4,111.3,110.8,104.3,52.1,30.2,22.3.
实施16：制备((1-methyl-1H-indol-3-yl)methyl)-1H-indol-5-ol方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1-甲基-吲哚(24.9mg，0.1mmol) 和5-羟基吲哚(14.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率61％)。
实施例16所得产品((1-methyl-1H-indol-3-yl)methyl)-1H-indol-5-ol的结构、核磁数据如下：
1H NMR(400MHz,Methanol-d4)δ7.52(dt,J＝7.9,1.0Hz,1H),7.24(dt,J＝8.1,1.0Hz, 1H),7.15(d,J＝8.6Hz,1H),7.13–7.07(m,1H),7.00–6.94(m,1H),6.93(s,1H),6.89(d,J＝ 2.4Hz,1H),6.79(d,J＝1.2Hz,1H),6.65(dd,J＝8.6,2.3Hz,1H),4.09(d,J＝1.0Hz,2H),3.62 (s,3H).
13C NMR(101MHz,Methanol-d4)δ150.8,138.7,133.2,129.5,129.4,128.1,124.4,122.2,120.0, 119.3,115.5,115.2,112.6,112.2,110.0,104.1,32.5,22.1
实施17：制备((5-methyl-1H-indol-3-yl)methyl)-1H-indol-5-ol方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-5-甲基-1H-吲哚(24.9mg，0.1mmol) 和5-羟基吲哚(14.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率78％)。
实施例17所得产品((5-methyl-1H-indol-3-yl)methyl)-1H-indol-5-ol的结构、核磁数据如下：
1H NMR(400MHz,Methanol-d4)δ7.32–7.28(m,1H),7.22–7.13(m,2H),6.94–6.83(m,4H),6.64(dd,J＝8.6,2.4Hz,1H),4.08(s,2H),2.37(s,3H).
13C NMR(101MHz,Methanol-d4)δ150.7,136.6,133.3,129.6,129.1,128.3,124.4,123.7,123.7, 119.4,115.5,115.3,112.5,112.0,111.7,104.1,22.2,21.7.
实施18：制备3-((4-methoxy-1H-indol-3-yl)methyl)-1H-indol-5-ol方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-5-甲氧基-1H-吲哚(26.5mg，0.1 mmol)和5-羟基吲哚(14.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率73％)。
实施例18所得产品3-((4-methoxy-1H-indol-3-yl)methyl)-1H-indol-5-ol的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.78(s,2H),7.20(d,J＝8.6Hz,1H),7.08(t,J＝8.0 Hz,1H),7.01(d,J＝2.4Hz,1H),6.96(d,J＝2.5Hz,1H),6.93(dd,J＝8.2,0.7Hz,1H),6.74(dd, J＝8.7,2.5Hz,1H),6.62–6.57(m,1H),6.50(d,J＝7.7Hz,1H),4.36(d,J＝1.1Hz,2H),3.91 (s,3H).
13C NMR(101MHz,Chloroform-d)δ155.3,149.2,138.2,131.9,128.6,123.6,122.8,121.1,
117.6,116.7,116.3,111.7,111.5,104.6,104.2,99.6,55.3,22.9.
实施19：制备((6-chloro-1H-indol-3-yl)methyl)-1H-indol-5-ol方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-6-氯-1H-吲哚(27.0mg，0.1mmol) 和5-羟基吲哚(14.6mg，0.11mmol)，用3毫升氯苯溶解后加入三溴化铟(17.8mg，0.05 mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率74％)。
实施例19所得产品((6-chloro-1H-indol-3-yl)methyl)-1H-indol-5-ol的结构、核磁数据如下：
1H NMR(400MHz,Methanol-d4)δ7.44(d,J＝8.5Hz,1H),7.32(d,J＝1.9Hz,1H),7.16 (d,J＝8.6Hz,1H),6.99–6.87(m,4H),6.66(dd,J＝8.6,2.4Hz,1H),4.08(s,2H).
13C NMR(101MHz,Methanol-d4)δ149.5,137.2,131.9,128.1,126.6,126.2,123.2,123.1,119.6, 118.5,115.1,113.6,111.3,110.9,110.6,102.8,20.8.
实施20：制备3-((5-bromo-1H-indol-3-yl)methyl)-1H-indol-5-ol方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-5-溴-1H-吲哚(31.4mg，0.1mmol) 和5-羟基吲哚(14.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率75％)。
实施例20所得产品3-((5-bromo-1H-indol-3-yl)methyl)-1H-indol-5-ol的结构、核磁数据如下：
1H NMR(400MHz,Methanol-d4)δ7.61(d,J＝1.9Hz,1H),7.22(d,J＝8.6Hz,1H),7.18 –7.11(m,2H),6.94(d,J＝13.3Hz,2H),6.87(d,J＝2.4Hz,1H),6.66(dd,J＝8.6,2.4Hz,1H), 4.07(s,2H).
13C NMR(101MHz,Methanol-d4)δ150.8,136.8,133.3,130.7,129.5,125.1,124.7,124.4,122.3, 115.9,114.8,113.7,112.6,112.5,112.2,104.1,22.1.
实施21：制备((1H-indol-3-yl)methyl)-1H-indol-5-yl(3r,5r,7r)-adamantane-1-carboxylate 方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和1H-吲哚-5-基(3r，5r，7r)-金刚烷-1-羧酸酯(32.5mg，0.11mmol)，用3毫升1,2- 二氯乙烷溶解后加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率57％)。
实施例21所得产品((1H-indol-3-yl)methyl)-1H-indol-5-yl (3r,5r,7r)-adamantane-1-carboxylate的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.80(dd,J＝29.7,2.5Hz,2H),7.57(d,J＝7.8Hz, 1H),7.29(d,J＝8.1Hz,1H),7.19–7.13(m,3H),7.11–7.06(m,1H),6.80(dd,J＝8.6,2.2Hz, 1H),6.56(d,J＝2.4Hz,1H),6.28(d,J＝2.4Hz,1H),4.04(s,2H),2.09(s,9H),1.77(d,J＝2.4 Hz,6H).
13C NMR(101MHz,Chloroform-d)δ178.0,144.1,136.5,134.3,128.0,127.5,123.9,122.5, 121.8,119.0,119.0,115.9,115.3,115.3,111.7,111.3,111.3,41.1,39.0,36.6,36.6,28.1,21.0.
实施22：制备3-((1H-indol-3-yl)methyl)-1H-indol-5-yl-2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3 -yl)acetate方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1H-吲哚(23.6mg，0.1mmol) 和1H-吲哚-5-基2-(1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-基)醋酸酯(52.0mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率55％)。
实施例22所得产品 3-((1H-indol-3-yl)methyl)-1H-indol-5-yl-2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3 -yl)acetate的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ7.93(s,2H),7.69–7.64(m,2H),7.57(d,J＝7.9Hz, 1H),7.48–7.43(m,2H),7.33(d,J＝8.1Hz,1H),7.26–7.22(m,2H),7.17(d,J＝1.2Hz,1H), 7.11–7.05(m,2H),6.93(d,J＝9.0Hz,1H),6.89(d,J＝2.3Hz,1H),6.84(dd,J＝8.7,2.3Hz, 1H),6.76(d,J＝2.3Hz,1H),6.73–6.68(m,1H),4.14(s,2H),3.91(s,2H),3.80(s,3H),2.44(s, 3H).
13C NMR(151MHz,Chloroform-d)δ163.8,161.5,149.2,137.0,132.4,129.5,129.2,127.4, 127.0,124.3,124.0,123.8,122.3,120.9,120.5,116.9,115.4,114.9,112.2,112.1,108.7,108.2, 105.5,105.0,104.6,104.3,104.2,94.4,48.8,23.7,14.2,6.7.
实施23：制备bis(1-methyl-1H-indol-3-yl)methane方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-1-甲基吲哚(24.9mg，0.1mmol)和1-甲基吲哚(14.4mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8 mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率69％)。
实施例23所得产品bis(1-methyl-1H-indol-3-yl)methane的结构、核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ7.62(dt,J＝8.1,1.0Hz,2H),7.28(d,J＝8.2Hz,2H),7.23–7.20(m,2H),7.10–7.07(m,2H),6.78(s,2H),4.22(d,J＝1.2Hz,2H),3.69(s,6H). 13C NMR(151MHz,Chloroform-d)δ137.3,128.1,127.1,121.5,119.4,118.7,114.5,109.2,32.7, 21.1.
实施24：制备bis(5-chloro-1H-indol-3-yl)methane方法的反应步骤：
在25毫升圆底烧瓶中，加入3-(1,3-二噻烷-2-基)-5-氯-1H-吲哚(27.0mg，0.1mmol) 和5-氯吲哚(16.6mg，0.11mmol)，用3毫升1,2-二氯乙烷溶解后加入三溴化铟(17.8mg， 0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率75％)。
实施例24所得产品bis(5-chloro-1H-indol-3-yl)methane的结构、核磁数据如下：
1H NMR(600MHz,DMSO-d6)δ10.99(d,J＝2.4Hz,2H),7.52(d,J＝2.1Hz,2H),7.34(d,J＝8.6Hz,2H),7.30(d,J＝2.3Hz,2H),7.03(dd,J＝8.6,2.1Hz,2H),4.10(s,2H).
13C NMR(151MHz,Chloroform-d)δ144.4,137.7,134.3,132.3,130.2,127.4,123.3,122.4, 30.1.
实施25：一锅法制备bis(5-methyl-1H-indol-3-yl)methane方法的反应步骤：
在25毫升圆底烧瓶中，加入5-甲基吲哚(49.8mg，0.2mmol)和2-氯-1,3-二噻烷(15.5 mg，0.1mmol)用10毫升1,2-二氯乙烷溶解，之后撤去冰浴，体系恢复到室温之后，加入三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率72％)。
实施例25所得产品bis(5-methyl-1H-indol-3-yl)methane的结构、核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ7.71(s,2H),7.41(s,2H),7.22(d,J＝8.1Hz,2H), 7.01(dd,J＝8.3,1.7Hz,2H),6.82(dd,J＝2.3,1.2Hz,2H),4.16(d,J＝1.1Hz,2H),2.43(s, 6H).
13C NMR(151MHz,Chloroform-d)δ134.9,128.5,127.9,123.6,122.6,119.0,115.3,110.8,21.6, 21.3.
实施26：一锅法制备bis(5-(benzyloxy)-1H-indol-3-yl)methane方法的反应步骤：
在25毫升圆底烧瓶中，0℃下加入5-苄氧基-1H-吲哚(34.1mg，0.1mmol)和2-氯 -1,3-二噻烷(15.5mg，0.1mmol)用4毫升1,2-二氯乙烷溶解，之后撤去冰浴，体系恢复到室温之后，加入5-苄氧基吲哚(24.5mg，0.11mmol)、三溴化铟(17.8mg，0.05mmol) 和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率76％)。
实施例26所得产品bis(5-(benzyloxy)-1H-indol-3-yl)methane的结构、核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ7.74–7.69(m,2H),7.44–7.41(m,4H),7.34(dd,J＝8.4,6.8Hz,4H),7.32–7.27(m,2H),7.20(d,J＝8.7Hz,2H),7.13(d,J＝2.4Hz,2H),6.92(dd,J＝8.8,2.5Hz,2H),6.81(d,J＝2.3Hz,2H),5.04(s,4H),4.11(s,2H).
13C NMR(151MHz,Chloroform-d)δ153.1,137.8,131.9,128.6,128.0,127.8,127.7,123.2, 115.3,112.8,111.9,102.9,71.0,21.4.
实施27：制备tert-butyl 2-(2-((1H-indol-3-yl)methyl)-1H-indol-3-yl)
acetate方法的反应步骤：
在25毫升圆底烧瓶中，0℃下加入5-甲氧基吲哚(14.7mg，0.1mmol)和2-氯-1,3-二噻烷(15.5mg，0.1mmol)用4毫升1,2-二氯乙烷溶解，之后撤去冰浴，体系恢复到室温之后，加入3-乙酸甲酯吲哚(20.8mg，0.11mmol)、三溴化铟(17.8mg，0.05mmol) 和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率72％)。
实施例27所得产品tert-butyl 2-(2-((1H-indol-3-yl)methyl)-1H-indol-3-yl)acetate的结构、核磁数据如下：
1H NMR(600MHz,Chloroform-d)δ7.97(s,1H),7.82(s,1H),7.59–7.56(m,1H),7.28 (d,J＝8.8Hz,1H),7.18–7.15(m,1H),7.11–7.08(m,2H),7.03(s,1H),6.93(d,J＝2.3Hz, 1H),6.90–6.85(m,1H),4.26(s,2H),3.85(s,2H),3.76(s,3H),3.69(s,3H).
13C NMR(151MHz,Chloroform-d)δ172.7,154.4,135.6,135.1,131.7,128.7,123.8,121.5, 119.7,118.3,112.8,112.1,112.0,110.7,104.2,100.8,77.4,77.2,77.0,52.1,30.4,29.9,22.5.
实施28：一锅法制备bromo-3-((3-methyl-1H-indol-2-yl)methyl)-1H-indole方法的反应步骤：
在25毫升圆底烧瓶中，0℃下加入3-甲基吲哚(13.1mg，0.1mmol)和2-氯-1,3-二噻烷(15.5mg，0.1mmol)用4毫升1,2-二氯乙烷溶解，之后撤去冰浴，体系恢复到室温之后，加入5-溴吲哚(21.6mg，0.11mmol)、三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率69％)。
实施例28所得产品bromo-3-((3-methyl-1H-indol-2-yl)methyl)-1H-indole的结构、核磁数据如下：
1H NMR(400MHz,Chloroform-d)δ8.02(s,1H),7.65(d,J＝1.8Hz,1H),7.63(d,J＝5.8Hz,1H),7.57–7.51(m,1H),7.29(dd,J＝8.6,1.8Hz,1H),7.25(d,J＝1.2Hz,1H),7.20–7.16(m,1H),7.13–7.07(m,2H),6.96(dd,J＝2.4,1.1Hz,1H),4.17(s,2H),2.36(s,3H).
13C NMR(151MHz,DMSO-d6)δ135.6,135.4,134.8,129.3,129.2,125.3,123.8,121.1,120.5, 118.4,118.0,113.8,112.7,111.4,111.0,105.3,22.1,9.0.
实施29：一锅法制备bromo-3-((3-methyl-1H-indol-2-yl)methyl)-1H-indole方法的反应步骤：
在25毫升圆底烧瓶中，0℃下加入3-甲基吲哚(13.1mg，0.1mmol)和2-氯-1,3-二噻烷(15.5mg，0.1mmol)用4毫升1,2-二氯乙烷溶解，之后撤去冰浴，体系恢复到室温之后，加入5-羟基吲哚(14.6mg，0.11mmol)、三溴化铟(17.8mg，0.05mmol)和二苯基硅氢(22μL，0.1mol)，在室温下搅拌反应，TLC检测待反应完全后停止反应，蒸除溶剂后柱层析得产品(收率69％)。
实施例29所得产品bromo-3-((3-methyl-1H-indol-2-yl)methyl)-1H-indole的结构、核磁数据如下：
1H NMR(600MHz,DMSO-d6)δ10.78–10.72(m,2H),8.79(s,1H),7.61(d,J＝7.7Hz,1H),7.43(d,J＝7.9Hz,1H),7.34(d,J＝8.5Hz,1H),7.27(d,J＝2.4Hz,1H),7.20–7.17(m,1H),7.16–7.12(m,1H),6.99(d,J＝2.3Hz,1H),6.80(dd,J＝8.6,2.3Hz,1H),4.26(s,2H),2.50(s,3H).
13C NMR(151MHz,DMSO-d6)δ150.5,135.7,135.3,131.3,129.3,128.0,120.4,118.3,117.9, 112.0,111.7,110.9,105.1,102.9,22.5,9.0。
Claims (6)
1.本发明涉及双吲哚甲烷及其衍生物的制备方法，其特征在于包括以下步骤：在反应器中加入噻烷吲哚衍生物(Ⅰ)和吲哚衍生物(Ⅱ)在合适的溶剂和催化剂作用下反应，实现双吲哚甲烷衍生物(Ⅲ)的合成，化学反应方程式如下：
取代基R1、R2为氢、甲基；R3、R4为吲哚2-7位取代基，选自氢、甲基、C1-C6烷氧基、苯基、羟基、硝基、氰基、卤素、乙酸甲酯、金刚烷酸酯、吲哚美辛酸酯、乙酸叔丁酯、苄氧基，n＝0或1。
2.根据权利要求1所述的双吲哚甲烷及其衍生物的制备方法，其特征在于，催化剂为三氯化铟、三溴化铟、三碘化铟、三氯化铁、六水合三氯化铁、三氯化铋、碘单质，三氟化硼乙醚，三(五氟苯)硼烷中的一种或多种。
3.根据权利要求1所述的双吲哚甲烷及其衍生物的制备方法，其特征在于，还原剂为二甲基氯硅烷、三甲基硅烷、三乙基硅烷、四甲基二硅氧烷、二苯基硅烷、三苯基硅烷、苯硅烷、四甲基二硅氧烷。
4.根据权利要求1所述的双吲哚甲烷及其衍生物的制备方法，其特征在于，所用的溶剂为1,2-二氯乙烷、二氯甲烷、乙醚、氯仿、甲苯、氯苯中的一种或多种。
5.根据权利要求1所述的双吲哚甲烷及其衍生物的制备方法，其特征在于，所述的催化剂，还原剂和反应物的摩尔比为催化剂：还原剂：噻烷吲哚:吲哚＝(0.01～1.0)：(1.0～3.0)：1:(1.0～2.0)。
6.根据权利要求1所述的双吲哚甲烷及其衍生物的制备方法，其特征在于：本反应可实现从取代吲哚与2-氯-1,3-二噻烷一锅实现合成。
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