CN115403501B - Preparation method and application of 3,3' -diaryl methane compound - Google Patents
Preparation method and application of 3,3' -diaryl methane compound Download PDFInfo
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- CN115403501B CN115403501B CN202211147203.4A CN202211147203A CN115403501B CN 115403501 B CN115403501 B CN 115403501B CN 202211147203 A CN202211147203 A CN 202211147203A CN 115403501 B CN115403501 B CN 115403501B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 231
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims description 94
- -1 C 5 Aldehyde Chemical class 0.000 claims description 89
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical group FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 46
- 150000001875 compounds Chemical class 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical compound N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 147
- 239000002994 raw material Substances 0.000 abstract description 7
- 125000003118 aryl group Chemical group 0.000 abstract description 6
- 239000003963 antioxidant agent Substances 0.000 abstract description 5
- 230000003078 antioxidant effect Effects 0.000 abstract description 5
- 229940124599 anti-inflammatory drug Drugs 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 125000001664 diethylamino group Chemical class [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 abstract 1
- 230000007613 environmental effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 523
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 172
- 239000000047 product Substances 0.000 description 144
- 239000012074 organic phase Substances 0.000 description 88
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- 239000012264 purified product Substances 0.000 description 49
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 46
- 238000004440 column chromatography Methods 0.000 description 45
- 238000010791 quenching Methods 0.000 description 45
- PSWCIARYGITEOY-UHFFFAOYSA-N 6-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2C=CNC2=C1 PSWCIARYGITEOY-UHFFFAOYSA-N 0.000 description 44
- 239000008346 aqueous phase Substances 0.000 description 44
- 238000003786 synthesis reaction Methods 0.000 description 44
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 43
- 230000015572 biosynthetic process Effects 0.000 description 43
- 238000012512 characterization method Methods 0.000 description 43
- 238000001035 drying Methods 0.000 description 43
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 43
- 239000003480 eluent Substances 0.000 description 43
- 239000000203 mixture Substances 0.000 description 43
- 239000003208 petroleum Substances 0.000 description 43
- 239000000843 powder Substances 0.000 description 43
- 238000005406 washing Methods 0.000 description 43
- 239000011734 sodium Substances 0.000 description 41
- 230000000171 quenching effect Effects 0.000 description 28
- 238000004821 distillation Methods 0.000 description 27
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 5
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 5
- CRBJBYGJVIBWIY-UHFFFAOYSA-N 2-isopropylphenol Chemical compound CC(C)C1=CC=CC=C1O CRBJBYGJVIBWIY-UHFFFAOYSA-N 0.000 description 5
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 5
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical compound OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 description 5
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 5
- 125000003172 aldehyde group Chemical group 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- ADZUEEUKBYCSEY-UHFFFAOYSA-N 1h-indole-5-carbaldehyde Chemical compound O=CC1=CC=C2NC=CC2=C1 ADZUEEUKBYCSEY-UHFFFAOYSA-N 0.000 description 3
- KUFFULVDNCHOFZ-UHFFFAOYSA-N 2,4-xylenol Chemical compound CC1=CC=C(O)C(C)=C1 KUFFULVDNCHOFZ-UHFFFAOYSA-N 0.000 description 3
- IXQGCWUGDFDQMF-UHFFFAOYSA-N 2-Ethylphenol Chemical compound CCC1=CC=CC=C1O IXQGCWUGDFDQMF-UHFFFAOYSA-N 0.000 description 3
- QIRNGVVZBINFMX-UHFFFAOYSA-N 2-allylphenol Chemical compound OC1=CC=CC=C1CC=C QIRNGVVZBINFMX-UHFFFAOYSA-N 0.000 description 3
- ONMSBNJJCUCYED-UHFFFAOYSA-N 2-bromo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1Br ONMSBNJJCUCYED-UHFFFAOYSA-N 0.000 description 3
- WGNNILPYHCKCFF-UHFFFAOYSA-N 2-chloro-n-methylaniline Chemical compound CNC1=CC=CC=C1Cl WGNNILPYHCKCFF-UHFFFAOYSA-N 0.000 description 3
- KXPBTNCFONSVIA-UHFFFAOYSA-N 2-iodo-5-methylaniline Chemical compound CC1=CC=C(I)C(N)=C1 KXPBTNCFONSVIA-UHFFFAOYSA-N 0.000 description 3
- MOYHVSKDHLMMPS-UHFFFAOYSA-N 3-methoxy-n,n-dimethylaniline Chemical compound COC1=CC=CC(N(C)C)=C1 MOYHVSKDHLMMPS-UHFFFAOYSA-N 0.000 description 3
- DPKTVUKEPNBABS-UHFFFAOYSA-N 3-tert-butylaniline Chemical compound CC(C)(C)C1=CC=CC(N)=C1 DPKTVUKEPNBABS-UHFFFAOYSA-N 0.000 description 3
- QHPQWRBYOIRBIT-UHFFFAOYSA-N 4-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(O)C=C1 QHPQWRBYOIRBIT-UHFFFAOYSA-N 0.000 description 3
- OLSJHVZRUFFIPL-UHFFFAOYSA-N 5-bromo-2-methoxyphenol Chemical compound COC1=CC=C(Br)C=C1O OLSJHVZRUFFIPL-UHFFFAOYSA-N 0.000 description 3
- OONJCAWRVJDVBB-UHFFFAOYSA-N 5-bromo-2-methylphenol Chemical compound CC1=CC=C(Br)C=C1O OONJCAWRVJDVBB-UHFFFAOYSA-N 0.000 description 3
- ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methyl-1h-indole Chemical compound CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 3
- FBGJJTQNZVNEQU-UHFFFAOYSA-N n,3-dimethylaniline Chemical compound CNC1=CC=CC(C)=C1 FBGJJTQNZVNEQU-UHFFFAOYSA-N 0.000 description 3
- QCIFLGSATTWUQJ-UHFFFAOYSA-N n,4-dimethylaniline Chemical compound CNC1=CC=C(C)C=C1 QCIFLGSATTWUQJ-UHFFFAOYSA-N 0.000 description 3
- GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 3
- TXTHKGMZDDTZFD-UHFFFAOYSA-N n-cyclohexylaniline Chemical compound C1CCCCC1NC1=CC=CC=C1 TXTHKGMZDDTZFD-UHFFFAOYSA-N 0.000 description 3
- FRCFWPVMFJMNDP-UHFFFAOYSA-N n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=CC=C1 FRCFWPVMFJMNDP-UHFFFAOYSA-N 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- GOFIUEUUROFVMA-UHFFFAOYSA-N 1-(1h-indol-5-yl)ethanone Chemical compound CC(=O)C1=CC=C2NC=CC2=C1 GOFIUEUUROFVMA-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
- ZXDMUHFTJWEDEF-UHFFFAOYSA-N 1h-indol-4-yl acetate Chemical compound CC(=O)OC1=CC=CC2=C1C=CN2 ZXDMUHFTJWEDEF-UHFFFAOYSA-N 0.000 description 2
- SZSZDBFJCQKTRG-UHFFFAOYSA-N 1h-indole-6-carbonitrile Chemical compound N#CC1=CC=C2C=CNC2=C1 SZSZDBFJCQKTRG-UHFFFAOYSA-N 0.000 description 2
- MNVMYTVDDOXZLS-UHFFFAOYSA-N 4-methoxyguaiacol Natural products COC1=CC=C(O)C(OC)=C1 MNVMYTVDDOXZLS-UHFFFAOYSA-N 0.000 description 2
- ILINOHVVKWYAFM-UHFFFAOYSA-N 5,6-dichloro-1h-indole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC=C2 ILINOHVVKWYAFM-UHFFFAOYSA-N 0.000 description 2
- SBOITLSQLQGSLO-UHFFFAOYSA-N 5-bromo-1-methylindole Chemical compound BrC1=CC=C2N(C)C=CC2=C1 SBOITLSQLQGSLO-UHFFFAOYSA-N 0.000 description 2
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 2
- TVQLYTUWUQMGMP-UHFFFAOYSA-N 5-iodo-1h-indole Chemical compound IC1=CC=C2NC=CC2=C1 TVQLYTUWUQMGMP-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
- BPYBYPREOVLFED-UHFFFAOYSA-N 6-(trifluoromethyl)-1h-indole Chemical compound FC(F)(F)C1=CC=C2C=CNC2=C1 BPYBYPREOVLFED-UHFFFAOYSA-N 0.000 description 2
- MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 2
- FPMICYBCFBLGOZ-UHFFFAOYSA-N 6-phenylmethoxy-1h-indole Chemical compound C=1C=C2C=CNC2=CC=1OCC1=CC=CC=C1 FPMICYBCFBLGOZ-UHFFFAOYSA-N 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- JFDDFGLNZWNJTK-UHFFFAOYSA-N indole-4-carbaldehyde Chemical compound O=CC1=CC=CC2=C1C=CN2 JFDDFGLNZWNJTK-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- KPFSQBKJYHWFME-UHFFFAOYSA-N methyl 6-bromo-1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC(Br)=CC2=C1C=CN2 KPFSQBKJYHWFME-UHFFFAOYSA-N 0.000 description 2
- 235000010292 orthophenyl phenol Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical group CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical group COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
- C07D209/12—Radicals substituted by oxygen atoms
-
- 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
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Indole Compounds (AREA)
Abstract
The invention provides a preparation method of 3,3 '-diaryl methane compounds, which takes aryl compounds, methylene dichloride and diethyl amine compounds as preparation raw materials and can efficiently synthesize the 3,3' -diaryl methane compounds. The method has the advantages of environmental friendliness, low price and the like, the reaction condition is mild, no catalyst is needed, the operation is simple, the yield is high, the post-treatment of the reaction is simple and convenient, and the method is suitable for industrial production. The invention also provides application of the 3,3' -diaryl methane compound prepared by the preparation method in preparing anti-inflammatory drugs, antioxidant drugs and anticancer drugs.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method and application of a 3,3' -diaryl methane compound.
Background
3,3' -Diarylmethanes (DIM) are a special nitrogen-containing benzoheterocycle compound, which is an important skeleton of natural products, and possess various physiological activities, such as antihyperlipidemic, antioxidant, antimicrobial, anti-inflammatory and anticancer, etc.
At present, 3' -diaryl methane compounds are mainly constructed through indole, aldehyde, ketone and amine compounds through Friedel-crafts reaction, but most of symmetrical diaryl methane derivatives synthesized by the construction method still face a plurality of challenges for synthesizing asymmetric diaryl methane derivatives.
How to construct diarylmethane and its derivatives from cheap and readily available raw materials by a simple and fast operation method is a problem to be solved in the field at present.
Disclosure of Invention
The present invention aims to solve at least one of the above technical problems in the prior art. Therefore, the invention provides a preparation method of the 3,3' -diaryl methane compound, which has the advantages of easily available raw materials and low preparation cost.
The invention also provides the 3,3' -diaryl methane compound prepared by the preparation method.
The invention also provides application of the 3,3' -diaryl methane compound prepared by the preparation method in preparing anti-inflammatory drugs, antioxidant drugs and anticancer drugs.
In a first aspect the present invention provides a process for the preparation of 3,3' -diarylmethanes comprising the steps of:
the 3,3' -diaryl methane compound shown in the formula (VI) is prepared by mixing and reacting the compounds shown in the formula (I), the formula (II), the formula (III) and the formula (IV) in a solvent;
Or mixing a compound shown in a formula (I), a formula (II) and a formula (III) and a phenol or aniline compound shown in a formula (V) in a solvent for reaction to prepare a 3,3' -diarylmethane compound shown in a formula (VII);
in the formula (VI), R 1 Independently selected from hydrogen, alkyl, alkoxy, halogenA plain atom, an ester group, an aldehyde group, a carboxyl group, or an aryl group;
in the formula (VII), R 2 Independently selected from substituted phenols or substituted anilines.
The invention relates to a technical scheme in a preparation method of 3,3' -diaryl methane compounds, which has at least the following beneficial effects:
in the preparation raw materials of the preparation method, methylene dichloride is one of carbon-one synthons, and the 3, 3-diaryl methane compound can be constructed by a two-step one-pot method. Specifically, the aryl and the carbon-one synthon methylene dichloride are subjected to two-step Friedel-crafts reaction under the action of diethylamine to construct the asymmetric diaryl methane.
Other types of asymmetric diarylmethanes may also be constructed by the process of the present invention.
The preparation method disclosed by the invention has the advantages of no need of a catalyst, simple and easily obtained preparation raw materials, environment friendliness, low price, mild reaction conditions, simplicity in operation and high yield, and is simple and convenient in post-reaction treatment and suitable for industrial production.
According to some embodiments of the invention, the compound of formula (I) is a 6-nitroindole compound.
According to some embodiments of the invention, the compound of formula (II) is Dichloromethane (DCM).
In the preparation method of the invention, methylene dichloride is used as a reaction raw material and is also used as one of reaction solvents.
According to some embodiments of the invention, the compound of formula (III) is a diethylamine compound (Et 2 NH).
According to some embodiments of the invention, the compound of formula (IV) is an R1 substituted indole.
R1 represents substituents at all positions of the indole on the right side in formula (VI).
According to some embodiments of the invention, the compound of formula (V) is R 2 Substituted phenols.
According to some embodiments of the invention, the alkyl is C 1 ～C 5 Is a hydrocarbon group.
According to some embodiments of the invention, the alkyl group comprises at least one of methyl, trifluoromethyl.
According to some embodiments of the invention, the alkoxy group comprises C 1 ～C 10 Alkoxy groups of (a).
According to some embodiments of the invention, the alkoxy group comprises at least one of methoxy, benzyloxy.
According to some embodiments of the invention, the ester group comprises C 1 ～C 5 Ester groups of (a) are present.
According to some embodiments of the invention, the ester group comprises at least one of an ethyl formate group and a methyl acetate group.
According to some embodiments of the invention, the aldehyde group is C 1 ～C 5 Is an aldehyde group of (a).
According to some embodiments of the invention, the aldehyde group comprises a formaldehyde group.
According to some embodiments of the invention, the aryl is C 1 ～C 10 Aryl groups of (a).
According to some embodiments of the invention, the aryl group is 2-phenylindole.
According to some embodiments of the invention, the substituted phenol is C 1 ～C 10 Is a phenol of (2).
According to some embodiments of the invention, the C 1 ～C 10 Comprises at least one of 2-aminophenol, o-isopropylphenol, o-allylphenol, o-ethylphenol, o-phenylphenol, p-tert-butylphenol, 2, 4-dimethylphenol, 2-methoxy-5-bromophenol, catechol, 2-methyl-5-bromophenol and 2, 6-dimethylphenol.
According to some embodiments of the invention, the carboxyl group is C 1 ～C 5 Carboxyl groups of (a) are provided.
According to some embodiments of the invention, the carboxy group is 5-carboxyindole.
According to some embodiments of the invention, the substituted aniline is C 1 ～C 10 Is an aniline of (a).
According to some embodiments of the invention, the aniline comprises at least one of o-chloro-N-methylaniline, o-bromo-N, N-dimethylaniline, N-isopropylaniline, m-methoxy-N, N-dimethylaniline, N-cyclohexylaniline, N-benzylaniline, N-diethylaniline, m-methyl-N-methylaniline, 2-iodo-5-methylaniline, N-methylaniline, m-t-butylaniline and p-methyl-N-methylaniline.
According to some embodiments of the invention, the halogen atom comprises at least one of a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
According to some embodiments of the invention, the molar ratio of the compounds of formula (I), formula (III), formula (IV) and formula (V) or the aniline compound is 1:3:1:1.
According to some embodiments of the invention, the solvent is hexafluoroisopropanol.
According to some embodiments of the invention, the volume molar ratio of the solvent to the compound of formula (I) is between 5mL and 10mL of solvent per millimole of compound of formula (I).
According to some embodiments of the invention, the temperature of the reaction is 80 ℃ to 90 ℃.
According to some embodiments of the invention, the reaction time is 4h to 12h.
According to some embodiments of the invention, after the reaction is completed, quenching, extraction, washing, concentration and column chromatography are also included.
According to some embodiments of the invention, after the reaction is completed, adding pure water to quench the reaction, adding ethyl acetate to wash, layering to obtain an organic phase, extracting the aqueous phase with ethyl acetate, combining the organic phases, drying, distilling under reduced pressure to remove the solvent, and subjecting to column chromatography.
In a second aspect, the present invention provides 3,3' -diarylmethanes prepared by the preparation method of the present invention.
The third aspect of the invention provides the application of the 3,3' -diaryl methane compound prepared by the preparation method in preparing anti-inflammatory drugs, antioxidant drugs and anticancer drugs.
The 3,3' -diaryl methane compound prepared by the preparation method has good metabolic stability when preparing anti-inflammatory drugs, antioxidant drugs and anticancer drugs.
According to some embodiments of the invention, the 3,3' -diarylmethane comprises 1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 5-iodo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 5-fluoro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 5, 6-dichloro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 6-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 6-nitro-3- ((6- (trifluoromethyl) -1H-indol-3-yl) methyl) -1H-indole, 3- ((3-nitro-1H-indol-3-yl) methyl) -1H-indole, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 6-Nitro-3- ((2-phenyl-1H-indol-3-yl) methyl) -1H-indole, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylic acid methyl ester, 5-methoxy-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 6-bromo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-carboxylic acid methyl ester, 5-bromo-1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-acetic acid, 6- (benzyloxy) -3- (6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-indole, 6- (6-nitro-1H-indol-3-yl) methyl) -1H-indole, 1- (3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indol-5-yl) ethan-1-one, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indol-5-al, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carbonitrile, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylic acid methyl ester, 2-chloro-N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 2-bromo-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 3-methoxy-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-cyclohexyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-benzyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N, N-diethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N, 3-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 2-iodo-5-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 3- (tert-butyl) -4- (6-nitro-1H-indol-3-yl) methyl) aniline, N, 4-dimethyl-3- ((6-nitro-1H-indol-3-yl) methyl) aniline, 2-amino-5- ((6-nitro-1H-indol-3-yl) methyl) phenol, 2-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 2-allyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 2-ethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 5- ((6-nitro-1H-indol-3-yl) methyl) - [1,1' -biphenyl ] -2-ol, 4- (tert-butyl) -3- (6-nitro-1H-indol-3-yl) methyl) phenol, 3, 5-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 5-bromo-2-methoxy-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 4- ((6-nitro-1H-indol-3-yl) methyl) benzene-1, 2-diol, at least one of 5-bromo-2-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol and 2, 6-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol.
Detailed Description
The following are specific embodiments of the present invention, and the technical solutions of the present invention will be further described with reference to the embodiments, but the present invention is not limited to these embodiments.
Specific embodiments of the present invention are described in detail below.
The yield calculation method of the embodiment of the invention comprises the following steps: yield = product mass/(molecular weight x amount of material charged) specific examples of the invention are described in detail below.
The yield calculation method of the embodiment of the invention comprises the following steps: yield = product mass/(molecular weight) amount of material dosed.
Example 1: synthesis of 1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole
A15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole (CAS number: 4769-96-4), 62.0. Mu.L (0.60 mmol) of diethylamine (CAS number: 109-89-7) and 1mL (0.2M) of methylene chloride (CAS number: 75-09-2) were added, the temperature was 90℃overnight, the solvent was dried after the reaction was completed, and then 26.2mg (0.2 mmol) of 1-methylindole (CAS number: 603-76-9) and 2mL of hexafluoroisopropanol (CAS number: 920-66-1) were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, then 10mL of ethyl acetate (CAS number: 141-78-6) and 5mL of saturated saline water are added for washing, the organic phase is collected in a layered manner, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.87), the purified product weighs 36.3mg and is yellow powder, and the yield is 59%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.31(d,J＝1.8Hz,1H),7.83(dd,J＝8.8,1.8Hz,1H),7.69(d,J＝8.8Hz,1H),7.64–7.62(d,1H),7.53(d,J＝7.9Hz,1H),7.35(d,J＝8.2Hz,1H),7.13–7.09(m,2H),6.97(t,J＝7.5Hz,1H),4.18(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.7,131.8,130.3,127.3,121.1,118.9,118.8,118.3,113.5,113.0,109.6,108.3,32.3,20.4.
ESI-MS:calculated for C 18 H 15 N 3 O 2 [M+Na] - :328.1056,found:328.1052.
example 2: synthesis of 5-iodo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 48.6mg (0.2 mmol) of 5-iodoindole (CAS number: 16066-91-4) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.76), the purified product weighs 49.2mg and is yellow powder, and the yield is 59%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),11.03(s,1H),8.30(d,J＝2.0Hz,1H),7.84–7.81(m,2H),7.68(d,J＝8.8Hz,1H),7.64(d,J＝2.3Hz,1H),7.29(dd,J＝8.5,1.5Hz,1H),7.19(d,J＝8.5Hz,2H),4.15(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.5,134.8,131.8,130.3,129.8,128.9,127.1,124.2,118.9,115.6,114.0,113.5,113.1,108.4,82.1,20.4.
ESI-MS:calculated for C 17 H 12 IN 3 O 2 [M+Na]-:439.9866,found:439.9862.
example 3: 5-fluoro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 27.0mg (0.2 mmol) of 5-fluoroindole (CAS number: 399-52-0) and 2mL of hexafluoroisopropanol were added, the temperature was 80℃and the reaction was carried out for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.70), the purified product is 35.0mg, and the yield is 57 percent, wherein the purified product is brown powder.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),10.92(s,1H),8.29(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.71–7.68(m,2H),7.31(dd,J＝8.8,4.6Hz,1H),7.28(d,J＝2.2Hz,1H),7.24(dd,J＝10.1,2.5Hz,1H),6.89–6.85(m,1H),4.15(s,2H).
13 C NMR(125MHz,DMSO-d6)δ155.6-155.6(d,J＝229.37),141.7,134.7,133.1,130.30,125.1,118.9,115.6,113.9,113.4,112.3,108.3,103.3,20.5.
ESI-MS:calculated for C 17 H 12 FN3O 2 [M+Na] - :332.0805,found:332.0802.
example 4: synthesis of 5, 6-dichloro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 37.2mg (0.2 mmol) of 5, 6-dichloroindole (CAS number: 121859-57-2) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.69), and the purified product is light yellow powder with the yield of 82 percent, wherein the weight of 59.0 mg.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.13(s,1H),8.30(s,1H),7.82(d,J＝8.0Hz,1H),7.73–7.66(m,3H),7.58(s,1H),7.32(s,1H),4.17(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.3,134.8,131.8,130.4,127.1,125.9,123.3,120.9,119.8,118.9,115.4,113.8,113.6,113.0,108.4,20.4.
ESI-MS:calculated for C 17 H 11 Cl 2 N 3 O 2 [M+Na] - :382.0120,found:382.0111.
example 5: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-5-carboxylic acid:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, and then 32.2mg (0.2 mmol) of indole-5-carboxylic acid (CAS No.: 1670-81-1) and 2mL of hexafluoroisopropanol were added, the temperature was 80℃and the reaction was carried out for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.19), and the purified product is 44.4mg and is light yellow powder with the yield of 66%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ12.35(s,1H),11.60(s,1H),11.19(s,1H),8.30(s,1H),8.16(s,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.70–7.66(m,2H),7.60(d,J＝2.1Hz,1H),7.38(d,J＝8.5Hz,1H),7.30–7.28(d,1H),4.23(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,139.0,134.8,131.8,130.3,126.6,124.7,122.3,121.4,120.9,118.9,115.6,115.0,113.5,111.2,108.3,20.5.
ESI-MS:calculated for C 18 H 13 N 3 O 4 [M+Na]-:385.0798,found:358.0792.
example 6: synthesis of 6-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, then 26.2mg (0.2 mmol) of 6-methylindole (CAS number: 3420-02-8) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.80), and the purified product is light yellow powder with the yield of 53 percent, wherein the weight of the purified product is 35.0 mg.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),10.63(s,1H),8.30–8.27(d,1H),7.83–7.80(dd,1H),7.68(d,J＝8.8Hz,1H),7.61–7.59(d,1H),7.35(d,J＝8.0Hz,1H),7.10(s,1H),7.07(s,1H),6.74(d,J＝8.0Hz,1H),4.14(s,2H),2.34(s,3H).
13 C NMR(126MHz,DMSO-d6)δ141.7,136.9,134.7,131.9,130.2,129.8,125.0,122.2,119.9,118.9,118.3,116.0,113.4,113.4,111.3,108.3,21.4,20.7.
ESI-MS:calculated for C 18 H 15 N 3 O 2 [M+Na]-:328.1056,found:328.1051.
example 7: synthesis of 6-nitro-3- ((6- (trifluoromethyl) -1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 37.0mg (0.2 mmol) of 6-trifluoromethylindole (CAS number: 13544-43-9) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.51), and the purified product is in a brown yellow powder shape with the yield of 44%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.29(s,1H),8.30(d,J＝1.9Hz,1H),7.83(dd,J＝8.8,1.9Hz,1H),7.69(d,J＝7.9Hz,3H),7.64(d,J＝1.8Hz,1H)),7.45(s,1H),7.21(d,J＝8.5Hz,1H),4.23(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.2,134.8,131.7,130.3,129.4,126.7,126.6,124.5,121.5,121.3,119.4,118.9,115.5,114.5,114.2,113.5,108.8,108.3,20.4..
ESI-MS:calculated for C 18 H 12 F 3 N 3 O 2 [M+Na] - :382.0773,found:382.0770.
example 8: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indol-4-aldehyde:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 29.0mg (0.2 mmol) of 4-indolecarboxaldehyde (CAS number: 1074-86-8) and 2mL of hexafluoroisopropanol were added, the temperature was 80℃and the reaction was carried out for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.23), and the purified product is 46.1mg in yellow powder, and has a yield of 72%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.39(s,1H),9.92(s,1H),8.30(d,J＝2.0Hz,1H),8.16(s,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.72(d,J＝8.8Hz,1H),7.66(d,J＝2.4Hz,1H),7.60(dd,J＝8.5,1.5Hz,1H),7.48(d,J＝8.4Hz,1H),7.35(d,J＝2.1Hz,1H),4.26(s,2H).
13 C NMR(125MHz,DMSO-d6)δ192.5,139.9,131.7,130.3,128.3,126.9,125.2,124.1,121.1,118.9,115.4,113.5,112.2,108.3,20.4.
ESI-MS:calculated for C 18 H 13 N 3 O 3 [M+Na] - :342.0849,found:342.0845.
example 9: synthesis of 6-nitro-3- ((2-phenyl-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 38.6mg (0.2 mmol) of 2-phenylindole (CAS number: 948-65-2) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.83), the purified product is 38.9mg, and the product is yellow powder with the yield of 53 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.52(s,1H),11.31(s,1H),8.31(d,J＝2.1Hz,1H),7.81(dd,J＝8.8,2.1Hz,1H),7.65(d,J＝7.3Hz,2H),7.55(d,J＝8.8Hz,1H),7.47(t,J＝7.7Hz,2H),7.62(d,J＝8.5Hz,2H),7.36(t,J＝7.4Hz,1H),7.28(d,J＝2.3Hz,1H),7.12–7.08(td,1H),6.96–6.92(td,1H),4.33(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,136.3,13.6,134.7,134.6,132.9,131.5,130.1,128.9,127.7,127.5,121.6,118.8,118.8,118.6,117.2,116.0,113.5,111.3,109.8,108.4,20.2.
ESI-MS:calculated for C 23 H 17 N 3 O 2 [M+Na] - :390.1212,found:390.1207.
example 10: synthesis of methyl 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylate:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 35.0mg (0.2 mmol) of indole-6-carboxylic acid methyl ester (CAS number: 50820-65-0) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.30), and the purified product is 34.9mg in yellow powder, and has the yield of 50%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.26(s,1H),8.30(d,J＝2.1Hz,1H),8.03(s,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.68(d,J＝8.8Hz,1H),7.63(d,J＝2.3Hz,1H),7.60(d,J＝8.4Hz,1H),7.56(dd,J＝8.4,1.1Hz,1H),7.45(d,J＝2.2Hz,1H),4.21(s,2H),3.83(s,3H).
13 C NMR(125MHz,DMSO-d6)δ167.4,141.8,135.7,134.8,131.8,130.5,130.3,127.2,122.0,119.0,118.9,118.4,115.6,114.3,113.5,113.5,108.3,51.8,20.4
ESI-MS:calculated for C 19 H 15 N 3 O 4 [M+Na]-:372.0954,found:372.0952.
example 11: synthesis of 5-methoxy-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 29.4mg (0.2 mmol) of 5-methoxyindole (CAS number: 1006-94-6) and 2mL of hexafluoroisopropanol were added, the temperature was 80℃and the reaction was carried out for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.37), the purified product is 35.8mg, and the product is yellow powder with the yield of 56 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),10.63(s,1H),8.30(d,J＝2.1Hz,1H),7.85–7.82(m,1H),7.71(d,J＝8.8Hz,1H),7.64(d,J＝2.4Hz,1H),7.22(d,J＝8.7Hz,1H),7.11(d,J＝2.3Hz,1H),6.99(d,J＝2.4Hz,1H),6.71–6.68(m,1H),4.15(s,2H),3.70(s,3H).
13 C NMR(125MHz,DMSO-d6)δ152.9,141.7,134.7,131.9,131.6,130.2,127.3,123.6,118.9,115.9,113.4,113.3,112.0,110.9,108.3,100.6,55.4,20.6.
ESI-MS:calculated for C 18 H 15 N 3 O 3 [M+Na]-:344.1005,found:344.1001.
example 12: synthesis of 6-bromo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, and then 39.2mg (0.2 mmol) of 6-bromoindole (CAS No.: 52415-29-9) and 2mL of hexafluoroisopropanol were added, the temperature was 80℃and the reaction was carried out for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline to wash, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate to dry, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.42), and the purified product is 47.2mg in yellow powder with the yield of 64%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),10.96(s,1H),8.30(d,J＝2.1Hz,1H),7.83–7.81(m,1H),7.66(d,J＝8.8Hz,1H),7.62(d,J＝2.4Hz,1H),7.52(d,J＝1.7Hz,1H),7.44(d,J＝8.4Hz,1H),7.22(d,J＝2.3Hz,1H),7.05(d,J＝6.7Hz,1H),4.17(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,137.3,134.7,131.8,130.2,126.1,124.1,121.1,120.4,118.9,115.6,114.0,114.0,113.8,113.5,108.3,20.5.
ESI-MS:calculated for C 17 H 12 BrN 3 O 2 [M+Na] - :392.0005found：391.9999.
example 13: synthesis of methyl 6-bromo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-carboxylate:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 50.8mg (0.2 mmol) of methyl 6-bromo-indole-4-carboxylate (CAS number: 107650-22-6) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.34), the purified product is 57.4mg, and the product is yellow powder with the yield of 67 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.50–11.49(m,1H),11.41(d,J＝2.0Hz,1H),8.30(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.79(d,J＝1.8Hz,1H),7.60(d,J＝8.8Hz,1H),7.44(d,J＝1.8Hz,1H),7.32(d,J＝2.4Hz,1H),7.22(d,J＝2.5Hz,1H),4.26(s,2H),3.58(s,3H).
13 C NMR(125MHz,DMSO-d6)δ167.0,141.8,138.8,134.7,131.7,130.0,127.9,125.2,123.2,122.6,118.8,117.9,115.9,114.0,113.3,112.1,108.2,52.0,22.4.
ESI-MS:calculated for C 19 H 14 BrN 3 O 4 [M+Na]-:450.0059,found:450.0051.
example 14: synthesis of 5-bromo-1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 42.0mg (0.2 mmol) of 5-bromo-1-methylindole (CAS number: 10075-52-2) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.53), the purified product is 23.8mg, and the product is yellow powder with the yield of 31 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),8.30(d,J＝2.1Hz,1H),7.84–7.82(m,1H),7.69–7.67(m,3H),7.35(d,J＝8.7Hz,1H),7.22–7.20(m,1H),7.19(s,1H),4.15(s,2H),3.70(s,3H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.5,134.7,131.7,130.3,129.0,128.9,123.5,121.0,118.9,115.4,113.5,112.8,111.8,111.1,108.3,32.5,20.2.
ESI-MS:calculated for C 18 H 14 BrN 3 O 2 [M+Na] - :406.0161,found:406.0154.
example 15: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indol-4-acetic acid:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, and then 35.0mg (0.2 mmol) of 4-acetoxyindole (CAS number: 5585-96-6) and 2mL of hexafluoroisopropanol were added, the temperature was 80℃and the reaction was carried out for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.36), and the purified product is 34.0mg and is yellow powder with the yield of 49 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.56(s,1H),11.04(s,1H),8.33(d,J＝2.1Hz,1H),7.85(dd,J＝8.8,2.1Hz,1H),7.66(d,J＝8.8Hz,1H),7.33(d,J＝2.2Hz,1H),7.26(d,J＝8.0Hz,1H),7.05(t,J＝7.9Hz,1H),6.99(d,J＝2.0Hz,1H),6.65(d,J＝7.5Hz,1H),4.16(s,2H),2.01(s,3H).
13 C NMR(125MHz,DMSO-d6)δ169.6,143.8,141.8,138.9,134.8,131.7,130.3,124.3,121.2,119.6,118.8,116.2,113.6,111.9,111.8,109.6,108.4,21.6,20.7.
ESI-MS:calculated for C 19 H 15 N 3 O 4 [M+Na]-:372.0954,found:372.0951.
example 16: synthesis of 6- (benzyloxy) -3- (6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, and then 44.6mg (0.2 mmol) of 6-benzyloxyindole (CAS number: 15903-94-3) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.49), and the purified product is 32.2mg and is yellow powder with the yield of 41 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),10.59(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.68(d,J＝8.8Hz,1H),7.61(d,J＝2.2Hz,1H),7.44(d,J＝7.2Hz,2H),7.37(t,J＝6.4Hz,3H),7.30(d,J＝7.3Hz,1H),7.02(d,J＝1.9Hz,1H),6.90(d,J＝2.2Hz,1H),6.66(dd,J＝8.6,2.2Hz,1H),5.07(s,2H),4.13(s,2H).
13 C NMR(125MHz,DMSO-d6)δ154.5,141.7,137.7,137.1,134.7,131.9,130.2,128.4,127.7,127.5,121.7,119.2,118.9,116.0,113.6,113.4,109.1,108.3,96.0,69.5,20.7.
ESI-MS:calculated for C 24 H 19 N 3 O 3 [M+Na] - :420.1318,found:420.1313.
example 17: synthesis of 1- (3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indol-5-yl) ethan-1-one:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, and then 31.8mg (0.2 mmol) of 5-acetylindole (CAS number: 53330-94-2) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.21), and the purified product is 44.9mg and is yellow powder with the yield of 67 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),11.21(s,1H),8.30(d,J＝2.1Hz,1H),8.23–8.23(m,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.72(d,J＝8.9Hz,1H),7.69(dd,J＝8.7,1.7Hz,1H),7.66(d,J＝2.2Hz,1H),7.39(d,J＝8.6Hz,1H),7.27(d,J＝2.0Hz,1H),4.26(s,2H),2.55(s,3H).
13 C NMR(125MHz,DMSO-d6)δ197.5,141.8,139.1,134.8,131.8,130.3,128.3,126.6,124.8,121.3,120.9,118.9,115.7,115.6,113.5,111.4,108.4,26.6,20.4.
ESI-MS:calculated for C 19 H 15 N 3 O 3 [M+Na]-:356.1005,found:356.0999.
example 18: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indol-5-aldehyde:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 29.0mg (0.2 mmol) of 5-indolecarboxaldehyde (CAS number: 1196-69-6) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.23), and the purified product is 46.1mg in yellow powder, and has a yield of 72%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),11.38(s,1H),9.92(s,1H),8.30(d,J＝2.0Hz,1H),8.16–8.15(m,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.72(d,J＝8.8Hz,1H),7.66(s,1H),7.61–7.59(m,1H),7.48(d,J＝8.5Hz,1H),7.35(d,J＝1.6Hz,1H),4.26(s,2H).
13 C NMR(125MHz,DMSO-d6)δ192.5,141.8,139.9,134.8,131.8,130.3,128.3,126.9,125.2,124.1,121.1,118.9,115.9,115.4,113.5,112.2,108.3,20.4.
ESI-MS:calculated for C 18 H 13 N 3 O 3 [M+Na] - :342.0849found:342.0844.
example 19: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carbonitrile:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, and then 28.4mg (0.2 mmol) of 6-cyanoindole (CAS number: 15861-36-6) and 2mL of hexafluoroisopropanol were added, the temperature was 80℃and the reaction was carried out for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.38), and the purified product is 22.1mg in yellow powder, and has the yield of 35%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.42(s,1H),8.29(d,J＝2.0Hz,1H),7.82(dd,J＝8.9,2.0Hz,2H),7.67(dd,J＝8.9,8.2Hz,2H),7.65(d,J＝2.4Hz,1H),7.51(d,J＝2.4Hz,1H),7.26(dd,J＝8.2,1.4Hz,1H),4.22(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.2,134.7,131.7,130.3,130.0,127.8,121.0,120.8,119.8,118.8,116.4,115.4,114.8,113.5,108.3,102.3,20.3.
ESI-MS:calculated for C 18 H 12 N 4 O 2 [M+Na]-:339.0852,found:339.0851.
example 20: synthesis of methyl 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylate:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 35.0mg (0.2 mmol) of indole-6-carboxylic acid methyl ester (CAS number: 50820-65-0) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.30), and the purified product is 34.9mg in yellow powder, and has the yield of 50%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.26(s,1H),8.30(d,J＝2.1Hz,1H),8.03(s,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.68(d,J＝8.8Hz,1H),7.63(d,J＝2.3Hz,1H),7.60(d,J＝8.4Hz,1H),7.56(dd,J＝8.4,1.1Hz,1H),7.45(d,J＝2.2Hz,1H),4.21(s,2H),3.83(s,3H).
13 C NMR(125MHz,DMSO-d6)δ167.4,141.8,135.7,134.8,131.8,130.5,130.3,127.2,122.0,119.0,118.9,118.4,115.6,114.3,113.5,113.5,108.3,51.8,20.4.
ESI-MS:calculated for C 19 H 15 N 3 O 4 [M+Na]-:372.0954,found:372.0952.
example 21: synthesis of 2-chloro-N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after the reaction was completed, and then 28.3mg (0.2 mmol) of o-chloro-N-methylaniline (CAS number: 932-32-1) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.75), and the purified product is 39.8mg in yellow powder, and the yield is 63%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.64(s,1H),8.30(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.61(d,J＝2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.12(d,J＝1.9Hz,1H),7.07(dd,J＝8.3,1.8Hz,1H),6.54(d,J＝8.3Hz,1H),5.28(d,J＝4.9Hz,1H),3.95(s,2H),2.70(d,J＝5.0Hz,3H).
13 C NMR(125MHz,DMSO-d6)δ143.4,141.8,134.8,131.6,130.4,129.1,128.6,128.0,118.8,117.6,115.9,113.6,110.6,108.3,30.0,29.3.
ESI-MS:calculated for C 16 H 14 ClN 3 O 2 [M+Na]-:338.0666,found:338.0661.
example 22: synthesis of 2-bromo-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 40.0mg (0.2 mmol) of o-bromo-N, N-dimethylaniline (CAS number: 698-00-0) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.75), and the purified product is yellow powder with the yield of 25 percent, wherein the weight of the purified product is 19.0 mg.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.68(s,1H),8.31(d,J＝2.0Hz,1H),7.85(dd,J＝8.8,2.0Hz,1H),7.67(d,J＝2.4Hz,1H),7.63(d,J＝8.8Hz,1H),7.46(d,J＝2.0Hz,1H),7.23(dd,J＝8.2,2.0Hz,1H),7.07(d,J＝8.2Hz,1H),4.03(s,2H),2.63(s,6H).
13 C NMR(125MHz,DMSO-d6)δ149.4,141.9,137.4,134.7,133.1,131.5,130.6,128.4,120.9,118.8,118.4,115.2,113.7,108.4,43.9,29.2.
ESI-MS:calculated for C 17 H 16 BrN 3 O 2 [M+Na] - :396.0318,found:396.0315.
example 23: synthesis of N-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, then 27.0mg (0.2 mmol) of N-isopropylaniline (CAS No.: 768-52-5) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.69), the purified product is 28.1mg, and the product is yellow powder with the yield of 45 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.56(d,J＝2.4Hz,1H),6.97(d,J＝8.4Hz,2H),6.45(d,J＝8.4Hz,2H),5.11(d,J＝7.9Hz,1H),3.90(s,2H),3.47–3.43(m,1H),1.08(d,J＝6.3Hz,6H).
13 C NMR(125MHz,DMSO-d6)δ146.8,142.2,135.2,132.2,130.6,129.4,127.9,119.3,117.1,113.9,112.9,108.7,43.5,30.2,23.0.
ESI-MS:calculated for C 18 H 19 N 3 O 2 [M+Na] - :332.1369,found:332.1365.
example 24: synthesis of 3-methoxy-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 30.2mg (0.2 mmol) of M-methoxy-N, N-dimethylaniline (CAS number: 15799-79-8) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.63), the purified product is 20.7mg, and the product is yellow powder with the yield of 32 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),8.29(d,J＝2.0Hz,1H),7.83(dd,J＝8.8,2.0Hz,1H),7.61(d,J＝8.8Hz,1H),7.48(d,J＝2.1Hz,1H),6.88(d,J＝8.3Hz,1H),6.31(d,J＝2.1Hz,1H),6.17(dd,J＝8.3,2.1Hz,1H),3.89(s,2H),3.80(s,3H),2.84(s,6H).
13 C NMR(125MHz,DMSO-d6)δ157.4,150.5,141.7,134.6,131.9,130.4,129.8,118.9,116.7,116.0,113.5,108.3,104.5,96.4,55.1,40.5,23.9.
ESI-MS:calculated for C 18 H 19 N 3 O 3 [M+Na] - :348.1318,found:348.1314.
example 25: synthesis of N-cyclohexyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 35.1mg (0.2 mmol) of N-cyclohexylaniline (CAS No.: 1821-36-9) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.75), the purified product is 43.0mg, and the yield is 62 percent, wherein the purified product is yellow powder.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.56(d,J＝2.4Hz,1H),6.95(d,J＝8.5Hz,2H),6.46(d,J＝8.5Hz,2H),5.16(d,J＝7.6Hz,1H),3.89(s,2H),1.87(d,J＝12.4Hz,2H),1.67(dt,J＝12.7,3.4Hz,2H),1.58–1.54(m,1H),1.30–1.22(m,3H),1.16–1.06(m,3H).
13 C NMR(125MHz,DMSO-d6)δ146.2,141.7,134.7,131.7,130.2,128.9,127.4,118.9,116.7,113.5,112.4,108.2,50.6,32.7,29.8,25.7,24.6.
ESI-MS:calculated for C 21 H 23 N 3 O 2 [M+Na]-:372.1682,found:372.1674.
example 26: synthesis of N-benzyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 36.7mg (0.2 mmol) of N-benzylaniline (CAS number: 103-32-2) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.75), and the purified product is in a yellow powder shape with the yield of 45 percent, wherein the weight of the purified product is 32.2 mg.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.28(d,J＝2.1Hz,1H),7.81(dd,J＝8.8,2.1Hz,1H),7.57(d,J＝8.8Hz,1H),7.55(s,1H),7.32(d,J＝7.2Hz,2H),7.29(t,J＝7.6Hz,2H),7.20(d,J＝7.2Hz,1H),6.95(d,J＝8.4Hz,2H),6.48(d,J＝8.4Hz,2H),6.05(t,J＝6.0Hz,1H),4.20(d,J＝6.0Hz,2H),3.89(s,2H).
13 C NMR(125MHz,DMSO-d6)δ146.8,141.7,140.5,134.7,131.7,130.2,128.8,128.3,128.1,127.2,126.6,118.9,116.6,113.5,112.3,108.3,46.7,29.8.
ESI-MS:calculated for C 22 H 19 N 3 O 2 [M+Na] - :380.1369,found:380.1362.
example 27: synthesis of N, N-diethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the temperature was 90℃and the reaction was carried out overnight, after completion of the reaction, the solvent was dried by spin, then 29.9mg (0.2 mmol) of N, N-diethylaniline (CAS number: 91-66-7) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.69), and the purified product is 41.8mg and is yellow powder with the yield of 65 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),8.30(s,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝11.0Hz,2H),7.04(d,J＝8.5Hz,2H),6.53(d,J＝8.5Hz,2H),3.92(s,2H),3.24(q,J＝5.9,5.1Hz,4H),1.01(t,J＝6.9Hz,6H).
13 C NMR(125MHz,DMSO-d6)δ145.7,141.8,134.8,131.7,130.2,129.1,127.3,118.9,116.6,113.5,111.7,108.3,43.7,29.6,12.4.
ESI-MS:calculated for C 19 H 21 N 3 O 2 [M+Na] - :346.1525,found:346.1520.
example 28: synthesis of N, 3-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 24.2mg (0.2 mmol) of M-methyl-N-methylaniline (CAS number: 696-44-6) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.56), the purified product is 23.0mg, and the product is yellow powder with the yield of 39 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.30(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.58(d,J＝8.8Hz,1H),7.37(d,J＝2.3Hz,1H),6.87(d,J＝8.2Hz,1H),6.35(d,J＝2.1Hz,1H),6.28(dd,J＝8.2,2.3Hz,1H),5.34(s,1H),3.90(s,2H),2.62(s,3H),2.15(s,3H).
13 C NMR(125MHz,DMSO-d6)δ148.3,141.8,136.1,134.8,131.8,130.3,129.7,125.8,118.9,115.8,113.8,113.5,109.3,108.3,30.0,27.7,19.6.
ESI-MS:calculated for C 17 H 17 N 3 O 2 [M+H] - :296.1393,found:296.1390.
example 29: synthesis of 2-iodo-5-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 46.6mg (0.2 mmol) of 2-iodo-5-methylaniline (CAS number: 13194-69-9) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.63), the purified product is 30.3mg, and the product is yellow powder with the yield of 37 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.64(s,1H),8.31(d,J＝2.0Hz,1H),7.84(dd,J＝8.8,2.0Hz,1H),7.58(d,J＝8.8Hz,1H),7.40(d,J＝2.3Hz,1H),7.26(s,1H),6.59(s,1H),4.95(s,2H),3.88(s,2H),2.10(s,3H).
13 C NMR(125MHz,DMSO-d6)δ146.7,141.9,138.2,137.1,134.7,131.0,130.5,129.2,118.8,116.3,115.1,113.6,108.4,80.0,27.0,19.1.
ESI-MS:calculated for C 16 H 14 IN 3 O 2 [M+Na] - :430.0022,found:430.0019.
example 30: synthesis of N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 21.4mg (0.2 mmol) of N-methylaniline (CAS number: 100-61-8) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.56), and the purified product is 16.6mg in yellow powder, and has the yield of 30%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),8.29(s,1H),7.82(dd,J＝8.8,1.9Hz,1H),7.57(d,J＝9.3Hz,2H),6.99(d,J＝8.3Hz,2H),6.44(d,J＝8.3Hz,2H),5.41(s,1H),3.91(s,2H),2.61(s,3H).
13 C NMR(125MHz,DMSO-d6)δ148.2,141.8,134.8,131.8,130.2,128.9,127.8,118.9,116.7,113.5,111.7,108.3,30.0,29.9.
ESI-MS:calculated for C 16 H 15 N 3 O 2 [M+Na] - :304.1056,found:304.1053.
example 31: synthesis of 3- (tert-butyl) -4- (6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the temperature was 90℃and the reaction was carried out overnight, after completion of the reaction, the solvent was dried by spin, then 29.9mg (0.2 mmol) of M-tert-butylaniline (CAS number: 5369-19-7) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.44), and the purified product is 21.6mg and is yellow powder with the yield of 33 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),8.31(d,J＝2.1Hz,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.64(d,J＝8.8Hz,1H),7.62(d,J＝2.3Hz,1H),6.79(d,J＝7.9Hz,1H),6.67(d,J＝1.9Hz,1H),6.48(dd,J＝7.9,1.9Hz,1H),4.83(s,2H),3.86(s,2H),1.19(s,9H).
13 C NMR(125MHz,DMSO-d6)δ149.0,145.5,141.7,134.7,132.0,130.7,128.8,121.2,119.0,114.4,113.5,113.3,111.9,108.3,33.9,31.3,25.8.
ESI-MS:calculated for C 19 H 21 N 3 O 2 [M+Na] - :346.1525,found:346.1522.
example 32: synthesis of N, 4-dimethyl-3- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 24.2mg (0.2 mmol) of p-methyl-N-methylaniline (CAS number: 623-08-5) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.62), and the purified product is 11.9mg in yellow powder, and has the yield of 20%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.63(s,1H),8.32(d,J＝1.8Hz,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.55(d,J＝2.1Hz,1H),6.84(d,J＝8.0Hz,1H),6.69(d,J＝1.8Hz,1H),6.43(d,J＝8.0Hz,1H),4.97(s,1H),3.88(s,2H),2.70(s,3H),2.06(s,3H).
13 C NMR(125MHz,DMSO-d6)δ145.0,141.8,134.7,132.1,130.8,129.5,127.4,124.4,123.8,119.0,114.1,113.6,109.3,108.4,30.5,26.0,20.2.
ESI-MS:calculated for C 17 H 17 N 3 O 2 [M+H] - :296.1393,found:296.1390.
example 33: synthesis of 2-amino-5- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 21.8mg (0.2 mmol) of 2-aminophenol (CAS number: 95-55-6) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=1/1, rf=0.20), and the purified product is 29.0mg and is yellow powder with the yield of 51%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),8.84(s,1H),8.30(d,J＝2.0Hz,1H),7.82(dd,J＝8.8,2.0Hz,1H),7.56(d,J＝1.8Hz,1H),7.54(d,J＝8.8Hz,1H),6.50(d,J＝6.2Hz,3H),4.34(s,2H),3.87(s,2H).
13 C NMR(125MHz,DMSO-d6)δ144.1,141.8,134.8,134.5,131.8,130.3,129.1,119.4,119.0,116.5,114.6,114.4,113.5,108.3,30.1.
ESI-MS:calculated for C 15 H 13 N 3 O 3 [M+Na] - :306.0849,found:306.0848.
example 34: synthesis of 2-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 27.2mg (0.2 mmol) of o-isopropyl phenol (CAS number: 88-69-7) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.54), the purified product is 28.3mg, and the product is yellow powder with the yield of 46%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),9.02(s,1H),8.29(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.60(d,J＝8.8Hz,1H),7.56(d,J＝2.4Hz,1H),7.06(d,J＝2.3Hz,1H),6.83(dd,J＝8.1,2.2Hz,1H),6.65(d,J＝8.1Hz,1H),3.96(s,2H),3.16–3.12(m,1H),1.11(d,J＝6.9Hz,6H).
13 C NMR(125MHz,DMSO-d6)δ152.4,141.8,134.7,133.9,131.7,131.1,130.2,126.1,126.0,118.9,116.4,114.8,113.5,108.3,30.1,26.4,22.6.
ESI-MS:calculated for C 18 H 18 N 2 O 3 [M+Na] - :333.1209,found:333.1210.
example 35: synthesis of 2-allyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, then 26.8mg (0.2 mmol) of o-allylphenol (CAS No.: 1745-81-9) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.60), the purified product is 25.2mg, and the product is yellow powder with the yield of 41 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),9.15(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.58–7.55(m,2H),6.95(d,J＝2.1Hz,1H),6.90(dd,J＝8.1,2.1Hz,1H),6.69(d,J＝8.1Hz,1H),5.94–5.88(m,1H),5.01–4.94(m,2H),3.94(s,2H),3.22(d,J＝6.6Hz,2H).
13 C NMR(125MHz,DMSO-d6)δ153.1,141.8,137.2,134.7,131.7,131.2,130.3,129.8,127.0,125.7,118.9,116.3,115.2,114.8,113.5,108.3,33.9,29.9.
ESI-MS:calculated for C 18 H 16 N 2 O 3 [M+Na] - :331.1053,found:331.1049.
example 36: synthesis of 2-ethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 24.4mg (0.2 mmol) of o-ethylphenol (CAS number: 90-00-6) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.44), the purified product is 24.2mg, and the product is yellow powder with the yield of 41 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),9.01(s,1H),8.29(d,J＝2.0Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.57(d,J＝2.5Hz,1H),6.98(d,J＝2.1Hz,1H),6.87(dd,J＝8.1,2.2Hz,1H),6.65(d,J＝8.1Hz,1H),3.94(s,2H),2.46(t,J＝7.5Hz,2H),1.07(t,J＝7.5Hz,3H).
13 C NMR(125MHz,DMSO-d6)δ153.1,141.8,134.7,131.7,131.2,130.3,129.7,129.1,126.5,118.9,116.4,114.7,113.6,108.3,29.9,22.9,14.4.
ESI-MS:calculated for C 17 H 16 N 2 O 3 [M+Na] - :319.1053,found:319.1050.
example 37: synthesis of 5- ((6-nitro-1H-indol-3-yl) methyl) - [1,1' -biphenyl ] -2-ol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 34.0mg (0.2 mmol) of o-phenylphenol (CAS number: 90-43-7) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering manner, extracting an aqueous phase with ethyl acetate for 2 times, wherein the amount of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove a solvent, and obtaining a product through column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.38), and the purified product is 16.6mg in yellow powder, and has the yield of 24%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.64(s,1H),9.35(s,1H),8.30(d,J＝2.1Hz,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.64(m,2H),7.50–7.47(m,2H),7.36(t,J＝7.6Hz,2H),7.26(t,J＝7.4Hz,1H),7.17(d,J＝2.1Hz,1H),7.06(dd,J＝8.2,2.1Hz,1H),6.84(d,J＝8.2Hz,1H),4.03(s,2H).
13 C NMR(125MHz,DMSO-d6)δ152.4,141.8,138.7,134.7,131.9,131.7,130.4,130.3,129.1,128.4,127.9,127.5,126.5,118.9,116.1,116.0,113.6,108.3,29.8.
ESI-MS:calculated for C 21 H 16 N 2 O 3 [M+Na] - :367.1053,found:367.1048.
example 38: synthesis of 4- (tert-butyl) -3- (6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, then 30.0mg (0.2 mmol) of p-tert-butylphenol (CAS number: 98-54-4) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.43), and the purified product is 11.0mg and is yellow powder with the yield of 17 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),9.23(s,1H),8.29(d,J＝1.9Hz,1H),7.84(dd,J＝8.8,1.9Hz,1H),7.73(d,J＝8.8Hz,1H),7.54(s,1H),7.14(d,J＝2.1Hz,1H),6.99(dd,J＝8.3,2.1Hz,1H),6.71(d,J＝8.3Hz,1H),3.97(s,2H),1.15(s,9H).
13 C NMR(125MHz,DMSO-d6)δ152.5,141.7,140.9,134.5,131.9,130.5,126.8,126.3,123.5,119.0,115.7,114.5,113.4,108.3,33.6,31.5,25.0.
ESI-MS:calculated for C 19 H 20 N 2 O 3 [M+Na] - :347.1366,found:347.1364.
example 39: synthesis of 3, 5-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 24.4mg (0.2 mmol) of 2, 4-dimethylphenol (CAS number: 105-67-9) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.58), and the purified product is 14.4mg and is yellow powder with the yield of 28 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.29(d,J＝2.1Hz,1H),8.13(s,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.66(d,J＝8.8Hz,1H),7.52(d,J＝2.4Hz,1H),6.69(d,J＝13.8Hz,2H),3.99(s,2H),2.14(s,3H),2.06(s,3H).
13 C NMR(125MHz,DMSO-d6)δ150.3,141.7,134.5,131.9,130.6,129.1,127.8,127.7,127.6,124.5,118.9,115.5,113.5,108.3,24.9,20.2,16.7.
ESI-MS:calculated for C 17 H 16 N 2 O 3 [M+Na] - :319.1053,found:319.1049.
example 40: synthesis of 5-bromo-2-methoxy-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 40.6mg (0.2 mmol) of 2-methoxy-5-bromophenol (CAS number: 37942-01-1) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.31), and the purified product is in yellow powder with the yield of 49 percent, wherein the weight of the purified product is 37.0 mg.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.66(s,1H),9.39(s,1H),8.31(d,J＝2.1Hz,1H),7.87(dd,J＝8.8,2.1Hz,1H),7.70(d,J＝8.8Hz,1H),7.48(d,J＝2.3Hz,1H),6.97(s,1H),6.96(s,1H),4.06(s,2H),3.46(s,3H).
13 C NMR(125MHz,DMSO-d6)δ147.4,146.1,141.9,134.7,131.5,130.7,130.0,118.9,118.8,114.6,114.5,113.7,113.4,108.4,55.8,30.6.
ESI-MS:calculated for C 16 H 13 BrN 2 O 4 [M+Na] - :398.9950,found:398.9948.
example 41: synthesis of 4- ((6-nitro-1H-indol-3-yl) methyl) benzene-1, 2-diol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the temperature was 90℃and the reaction was carried out overnight, after completion of the reaction, the solvent was dried by spin, then 22.0mg (0.2 mmol) of catechol (CAS number: 120-80-9) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=1/1, rf=0.58), the purified product is 7.0mg, and the product is yellow powder with the yield of 11 percent.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),8.68(d,J＝34.2Hz,2H),8.30(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.58(s,1H),7.55(d,J＝8.8Hz,1H),6.61(d,J＝8.0Hz,1H),6.59(d,J＝2.0Hz,1H),6.53(dd,J＝8.0,2.0Hz,1H),3.90(s,2H).
13 C NMR(125MHz,DMSO-d6)δ145.1,143.4,141.8,134.7,131.9,131.8,130.4,119.0,118.9,116.1,115.8,115.4,113.5,108.3,29.9.
ESI-MS:calculated for C 15 H 12 N 2 O 4 [M+Na] - :307.0689,found:307.0685.
example 42: synthesis of 5-bromo-2-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 37.4mg (0.2 mmol) of 2-methyl-5-bromophenol (CAS number: 36138-76-8) and 2mL of hexafluoroisopropanol were added, and the reaction was carried out at 80℃for 5 hours to give the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.54), the purified product is 54.9mg, and the product is yellow powder with the yield of 76%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.65(s,1H),9.64(s,1H),8.31(d,J＝2.1Hz,1H),7.85(dd,J＝8.8,2.1Hz,1H),7.63(d,J＝8.8Hz,1H),7.48(d,J＝2.3Hz,1H),7.00(d,J＝6.0Hz,2H),4.02(s,2H),1.99(s,3H).
13 C NMR(125MHz,DMSO-d6)δ154.7,141.9,134.7,132.3,131.6,130.7,129.5,124.0,120.2,118.7,118.0,114.7,113.7,108.4,30.0,15.6.
ESI-MS:calculated for C 16 H 13 BrN 2 O 3 [M+Na] - :383.0001,found:383.0001.
example 43: synthesis of 2, 6-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure-resistant tube was taken, 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of methylene chloride were added, the reaction was carried out at 90℃overnight, the solvent was dried after completion of the reaction, and then 24.4mg (0.2 mmol) of 2, 6-dimethylphenol (CAS number: 576-26-1) and 2mL of hexafluoroisopropanol were added to react at 80℃for 5 hours to obtain the product. After the reaction, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline water are added for washing, the organic phase is collected in a layering way, the aqueous phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, the product is obtained through column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA=2/1, rf=0.57), and the purified product is 39.7mg in yellow powder, and the yield is 67%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),8.29(d,J＝2.1Hz,1H),7.97(s,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.58(d,J＝8.9Hz,2H),6.80(s,2H),3.90(s,2H),2.08(s,6H).
13 C NMR(125MHz,DMSO-d6)δ151.2,141.8,134.7,131.7,131.4,130.3,128.1,124.0,118.8,116.3,113.5,108.3,29.8,16.7.
ESI-MS:calculated for C 17 H 16 N 2 O 3 [M+Na] - :319.1053,found:319.1051.
as can be seen from the above examples 1 to 43: suitable substrates for this reaction are mainly alkyl, alkoxy, halo, haloalkyl, phenyl, phenol and anilino substituted 3,3' -diarylmethanes. The reaction is carried out by indole and carbon-atom synthon dichloromethane under diethylamine, and constructing 3,3' -diaryl methane compound by two-step Friedel-crafts reaction. Compared with the synthesis of other 3,3' -diaryl methane compounds, the method has the advantages of simple operation, no need of catalyst, and cheap and easily obtained reaction raw materials. The substrate suitable for the reaction is rich in types, which shows that the reaction functional group has good tolerance, so that the application range is wide; the reaction yield is high, and the partial reaction yield is up to more than 80%; the reaction process is fast, the operation is simple and safe, and the method has the potential of large-scale production.
While the embodiments of the present invention have been described in detail with reference to the specific embodiments, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art. Furthermore, embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Claims (3)
1. A preparation method of 3,3' -diaryl methane compounds is characterized in that: the method comprises the following steps:
the 3,3' -diaryl methane compound shown in the formula (VI) is prepared by mixing and reacting the compounds shown in the formula (I), the formula (II), the formula (III) and the formula (IV) in a solvent; the solvent is hexafluoroisopropanol;
wherein R is 1 Independently selected from hydrogen, C 1 ~C 5 Alkyl, C of (2) 1 ~C 10 Alkoxy, halogen atom, C 1 ~C 5 Ester group, C 1 ~C 5 Aldehyde, carboxyl or 2-phenylindole.
2. The method of manufacturing according to claim 1, characterized in that: the reaction temperature is 80-90 ℃.
3. The method of manufacturing according to claim 1, characterized in that: the reaction time is 4-12 hours.
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