CN114634438B - 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
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- CN114634438B CN114634438B CN202210360187.0A CN202210360187A CN114634438B CN 114634438 B CN114634438 B CN 114634438B CN 202210360187 A CN202210360187 A CN 202210360187A CN 114634438 B CN114634438 B CN 114634438B
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- methyl
- indole
- mmol
- indol
- reaction
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- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 title description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 97
- 238000000034 method Methods 0.000 claims abstract description 35
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 28
- VFTRKSBEFQDZKX-UHFFFAOYSA-N 3,3'-diindolylmethane Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4NC=3)=CNC2=C1 VFTRKSBEFQDZKX-UHFFFAOYSA-N 0.000 claims abstract description 21
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 18
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 18
- TWJAXIHBWPVMIR-UHFFFAOYSA-N diindolylmethane Natural products C1=CC=C2NC(CC=3NC4=CC=CC=C4C=3)=CC2=C1 TWJAXIHBWPVMIR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 150000002475 indoles Chemical class 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 10
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 9
- VPVIYKRQVDIGOH-UHFFFAOYSA-N 2-chloro-1,3-dithiane Chemical compound ClC1SCCCS1 VPVIYKRQVDIGOH-UHFFFAOYSA-N 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical group Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 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
- 238000005580 one pot reaction Methods 0.000 claims description 6
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 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 4
- 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
- UHUUYVZLXJHWDV-UHFFFAOYSA-N trimethyl(methylsilyloxy)silane Chemical compound C[SiH2]O[Si](C)(C)C UHUUYVZLXJHWDV-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
- OBAJXDYVZBHCGT-UHFFFAOYSA-N tris(pentafluorophenyl)borane Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1B(C=1C(=C(F)C(F)=C(F)C=1F)F)C1=C(F)C(F)=C(F)C(F)=C1F OBAJXDYVZBHCGT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- IJFBKVGMIVYTFV-UHFFFAOYSA-N C1CCSCC1.C1=CC=C2NC=CC2=C1 Chemical class C1CCSCC1.C1=CC=C2NC=CC2=C1 IJFBKVGMIVYTFV-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
- JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 claims description 2
- 229940054051 antipsychotic indole derivative Drugs 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
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 229960000905 indomethacin Drugs 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
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 2
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 claims description 2
- 229940044631 ferric chloride hexahydrate Drugs 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 229940094989 trimethylsilane Drugs 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 3
- 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
- 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
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
- -1 diindolylmethane heterocyclic compounds Chemical class 0.000 description 36
- 238000001514 detection method Methods 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 20
- 238000004090 dissolution Methods 0.000 description 19
- 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-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 10
- LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical compound C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 6
- 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 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
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-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
- 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 2
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-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
- 238000005727 Friedel-Crafts reaction Methods 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 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
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- RDSVSEFWZUWZHW-UHFFFAOYSA-N 7-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1NC=C2 RDSVSEFWZUWZHW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 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
- 206010008631 Cholera Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 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
- 238000007306 functionalization reaction Methods 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
- 125000004356 hydroxy functional group Chemical group O* 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
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- YCUNOXSUHVGZRI-XMHBHJPISA-N isorhamnetin 7-O-beta-D-glucopyranoside Chemical compound C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C=C3O2)O)=C1 YCUNOXSUHVGZRI-XMHBHJPISA-N 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- RMUKCGUDVKEQPL-UHFFFAOYSA-K triiodoindigane Chemical compound I[In](I)I RMUKCGUDVKEQPL-UHFFFAOYSA-K 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
- C07D209/26—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 with an acyl radical attached to the ring nitrogen atom
- C07D209/28—1-(4-Chlorobenzoyl)-2-methyl-indolyl-3-acetic acid, substituted in position 5 by an oxygen or nitrogen atom; Esters thereof
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
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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,0.05 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 (3)
1.一种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,还原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;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、三(五氟苯)硼烷中的一种或多种;还原剂为二甲基氯硅烷、三甲基硅烷、三乙基硅烷、二苯基硅烷、三苯基硅烷、苯硅烷、四甲基二硅氧烷;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。
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,所述的催化剂,还原剂和反应物的摩尔比为催化剂:还原剂:噻烷吲哚衍生物(Ⅰ):吲哚衍生物(Ⅱ)=(0.01~1.0):(1.0~3.0):1:(1.0~2.0)。
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:所述制备方法以吲哚衍生物(Ⅱ)与2-氯-1,3-二噻烷为原料一锅实现双吲哚甲烷衍生物(Ⅲ)合成。
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