CN115504953A - 3-异香豆素基色酮化合物的制备方法 - Google Patents
3-异香豆素基色酮化合物的制备方法 Download PDFInfo
- Publication number
- CN115504953A CN115504953A CN202211237972.3A CN202211237972A CN115504953A CN 115504953 A CN115504953 A CN 115504953A CN 202211237972 A CN202211237972 A CN 202211237972A CN 115504953 A CN115504953 A CN 115504953A
- Authority
- CN
- China
- Prior art keywords
- arh
- compound
- isocoumarin
- chromone
- nmr
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 90
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- -1 ketone compound Chemical class 0.000 claims abstract description 26
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 239000012074 organic phase Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 7
- 238000001035 drying Methods 0.000 claims abstract description 5
- 238000012544 monitoring process Methods 0.000 claims abstract description 4
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 3
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 3
- 238000004809 thin layer chromatography Methods 0.000 claims abstract description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical group [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- 229910001923 silver oxide Inorganic materials 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 229910021607 Silver chloride Inorganic materials 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940071536 silver acetate Drugs 0.000 claims description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 2
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 2
- 229940096017 silver fluoride Drugs 0.000 claims description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 claims description 2
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 50
- 238000002844 melting Methods 0.000 description 50
- 230000008018 melting Effects 0.000 description 50
- 239000003208 petroleum Substances 0.000 description 26
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 230000005311 nuclear magnetism Effects 0.000 description 25
- 239000007787 solid Substances 0.000 description 25
- 229940125782 compound 2 Drugs 0.000 description 24
- 238000004896 high resolution mass spectrometry Methods 0.000 description 24
- 229940125904 compound 1 Drugs 0.000 description 23
- XZIMBBUYLQLSFF-UHFFFAOYSA-N 2-(2-phenylacetyl)benzaldehyde Chemical compound O=CC1=CC=CC=C1C(=O)CC1=CC=CC=C1 XZIMBBUYLQLSFF-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 6
- 150000004777 chromones Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 2
- QMGHHBHPDDAGGO-IIWOMYBWSA-N (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound CN(CCCNC1=NC(NC2=CC=C(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCC3=CC=C(C=C3)C3=C(C)N=CS3)C(C)(C)C)C=C2)=NC=C1Br)C(=O)C1CCC1 QMGHHBHPDDAGGO-IIWOMYBWSA-N 0.000 description 2
- RTTUBUXMNUJHRR-DXRVJIQQSA-N (3s)-4-[[(e)-2-[1-(4-fluorophenyl)-3-propan-2-ylindol-2-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2C(C(C)C)=C(\C=C\P(O)(=O)C[C@@H](O)CC(O)=O)N1C1=CC=C(F)C=C1 RTTUBUXMNUJHRR-DXRVJIQQSA-N 0.000 description 2
- AOSODOHQJJPEAM-VUVZNRFTSA-N (3s)-4-[[(e)-2-[3'-(4-fluorophenyl)spiro[cyclopentane-1,1'-indene]-2'-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)\C=C\C1=C(C=2C=CC(F)=CC=2)C2=CC=CC=C2C11CCCC1 AOSODOHQJJPEAM-VUVZNRFTSA-N 0.000 description 2
- WHQUHTXULUACFD-KRWDZBQOSA-N (3s)-4-[[2-(4-fluoro-3-methylphenyl)-4-methyl-6-propan-2-ylphenyl]methoxy-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=CC(C)=CC(C=2C=C(C)C(F)=CC=2)=C1COP(O)(=O)C[C@@H](O)CC(O)=O WHQUHTXULUACFD-KRWDZBQOSA-N 0.000 description 2
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 2
- BOOYHBPHFVNWNH-OAHLLOKOSA-N 1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-5-[(4-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C[C@H](C1=CC=C(C=C1)Cl)NC2=NC3=C(C=NN3C(C)(C)C)C(=O)N2CC4=CC=C(C=C4)F BOOYHBPHFVNWNH-OAHLLOKOSA-N 0.000 description 2
- JWHYSEDOYMYMNM-QGZVFWFLSA-N 2-[4-[(2r)-2-ethoxy-3-[4-(trifluoromethyl)phenoxy]propyl]sulfanyl-2-methylphenoxy]acetic acid Chemical compound C([C@@H](OCC)CSC=1C=C(C)C(OCC(O)=O)=CC=1)OC1=CC=C(C(F)(F)F)C=C1 JWHYSEDOYMYMNM-QGZVFWFLSA-N 0.000 description 2
- QLVGHFBUSGYCCG-UHFFFAOYSA-N 2-amino-n-(1-cyano-2-phenylethyl)acetamide Chemical compound NCC(=O)NC(C#N)CC1=CC=CC=C1 QLVGHFBUSGYCCG-UHFFFAOYSA-N 0.000 description 2
- 229940126650 Compound 3f Drugs 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- XJTWGMHOQKGBDO-GOSISDBHSA-N N-[(3-Fluorophenyl)methyl]-1-[(1r)-1-Naphthalen-1-Ylethyl]piperidine-4-Carboxamide Chemical compound C1CN([C@H](C)C=2C3=CC=CC=C3C=CC=2)CCC1C(=O)NCC1=CC=CC(F)=C1 XJTWGMHOQKGBDO-GOSISDBHSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- HFIVLLBFACNAFN-UHFFFAOYSA-N [1-amino-2-[2-(4-methoxyphenyl)ethylamino]ethyl]phosphonic acid Chemical compound COc1ccc(CCNCC(N)P(O)(O)=O)cc1 HFIVLLBFACNAFN-UHFFFAOYSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 2
- 229940125796 compound 3d Drugs 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- MUTCAPXLKRYEPR-ITWZMISCSA-N methyl (e,3r,5s)-7-[4-bromo-2,3-bis(4-fluorophenyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyhept-6-enoate Chemical compound COC(=O)C[C@H](O)C[C@H](O)\C=C\N1C(C(C)C)=C(Br)C(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 MUTCAPXLKRYEPR-ITWZMISCSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- YLIUOQLKDHZJFT-UHFFFAOYSA-N 1-(2-phenylethynyl)naphthalene-2-carbaldehyde Chemical compound O=CC1=CC=C2C=CC=CC2=C1C#CC1=CC=CC=C1 YLIUOQLKDHZJFT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
- AGQZBHGVONTLIO-UHFFFAOYSA-N 2-(2-cyclopropylethynyl)benzaldehyde Chemical compound O=CC1=CC=CC=C1C#CC1CC1 AGQZBHGVONTLIO-UHFFFAOYSA-N 0.000 description 1
- RQTHKXCTKUDHTJ-UHFFFAOYSA-N 2-[2-(3-methylphenyl)ethynyl]benzaldehyde Chemical compound CC1=CC=CC(C#CC=2C(=CC=CC=2)C=O)=C1 RQTHKXCTKUDHTJ-UHFFFAOYSA-N 0.000 description 1
- XMGKEDVRDQOIRZ-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)ethynyl]benzaldehyde Chemical compound C1=CC(F)=CC=C1C#CC1=CC=CC=C1C=O XMGKEDVRDQOIRZ-UHFFFAOYSA-N 0.000 description 1
- RLDUQRLGSISLMK-UHFFFAOYSA-N 2-[2-(4-methoxyphenyl)ethynyl]benzaldehyde Chemical compound C1=CC(OC)=CC=C1C#CC1=CC=CC=C1C=O RLDUQRLGSISLMK-UHFFFAOYSA-N 0.000 description 1
- WBXZJUGIVVHLBD-UHFFFAOYSA-N 2-[2-(4-methylphenyl)ethynyl]benzaldehyde Chemical compound C1=CC(C)=CC=C1C#CC1=CC=CC=C1C=O WBXZJUGIVVHLBD-UHFFFAOYSA-N 0.000 description 1
- VPPQEXJIFCBTFX-UHFFFAOYSA-N 2-[2-(4-tert-butylphenyl)ethynyl]benzaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C#CC1=CC=CC=C1C=O VPPQEXJIFCBTFX-UHFFFAOYSA-N 0.000 description 1
- NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 1
- ZEDSAJWVTKUHHK-UHFFFAOYSA-N 2-ethynylbenzaldehyde Chemical compound O=CC1=CC=CC=C1C#C ZEDSAJWVTKUHHK-UHFFFAOYSA-N 0.000 description 1
- IHNINSVQYKIZIC-UHFFFAOYSA-N 2h-quinolin-3-one Chemical class C1=CC=CC2=CC(=O)CN=C21 IHNINSVQYKIZIC-UHFFFAOYSA-N 0.000 description 1
- PSEXLMVGZSOBRS-UHFFFAOYSA-N 4-chloro-2-(2-phenylethynyl)benzaldehyde Chemical compound ClC1=CC(=C(C=O)C=C1)C#CC1=CC=CC=C1 PSEXLMVGZSOBRS-UHFFFAOYSA-N 0.000 description 1
- DQWGIUIRDYPGKU-UHFFFAOYSA-N 4-fluoro-2-(2-phenylethynyl)benzaldehyde Chemical compound FC1=CC=C(C=O)C(C#CC=2C=CC=CC=2)=C1 DQWGIUIRDYPGKU-UHFFFAOYSA-N 0.000 description 1
- GGXHBCZKCJBKML-UHFFFAOYSA-N 4-methyl-2-(2-phenylethynyl)benzaldehyde Chemical compound CC1=CC=C(C=O)C(C#CC=2C=CC=CC=2)=C1 GGXHBCZKCJBKML-UHFFFAOYSA-N 0.000 description 1
- VKNYGCKCEGJBLZ-UHFFFAOYSA-N 6-(2-phenylethynyl)-1,3-benzodioxole-5-carbaldehyde Chemical compound O=CC1=CC=2OCOC=2C=C1C#CC1=CC=CC=C1 VKNYGCKCEGJBLZ-UHFFFAOYSA-N 0.000 description 1
- NTKWACUFTVLKFG-UHFFFAOYSA-N C1=CC=C2OC(=O)C=CC2=C1.C1=CC=C2C(=O)C=COC2=C1 Chemical compound C1=CC=C2OC(=O)C=CC2=C1.C1=CC=C2C(=O)C=COC2=C1 NTKWACUFTVLKFG-UHFFFAOYSA-N 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- KGPGFQWBCSZGEL-ZDUSSCGKSA-N GSK690693 Chemical compound C=12N(CC)C(C=3C(=NON=3)N)=NC2=C(C#CC(C)(C)O)N=CC=1OC[C@H]1CCCNC1 KGPGFQWBCSZGEL-ZDUSSCGKSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UEXCJVNBTNXOEH-UHFFFAOYSA-N phenyl acethylene Natural products C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/92—Naphthopyrans; Hydrogenated naphthopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Abstract
本发明公开了一种3‑异香豆素基色酮化合物的制备方法，该方法是在溶剂、催化剂存在条件下，2‑羟基‑N,N‑二甲基烯胺酮化合物和2‑炔基苯甲醛化合物在空气、40~120℃下反应，薄层色谱监测反应进程，直至反应完全，反应产物用乙酸乙酯萃取2~3次，收集有机相用无水硫酸钠干燥，然后减压浓缩，残渣经硅胶柱层析分离纯化得到目标化合物3‑异香豆素基色酮；本发明方法具有条件温和，操作方便，合成路线短，合成方法等特点，且该方法产率较高，适用于工业化生产，具有较好的工业应用前景；
。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种合成多取代3-异香豆素基色酮的方法。
背景技术
色酮，化学名苯并-γ-吡喃酮，具有良好的生物活性，是一类重要的药物合成中间体，也是目前备受关注的天然活性产物之一。研究发现，色酮类化合物具有广泛的生理活性，例如抗炎、抗血小板凝聚、降血脂血糖、抑菌、抗癌、抗人体免疫缺陷病毒(HIV)等，具有很高的研究价值。
近年来，随着科研工作者对色酮类化合物的深入研究，许多新型的色酮类衍生物被大量报道，特别是3-取代色酮具有重要的生物和药理活性，例如抗癌、抗菌和抗氧化等。因此，3-取代色酮是当今有机化学合成以及新药开发领域的研究热点之一，已引起研究者们的极大兴趣。
3-取代色酮类化合物合成的传统策略是通过过渡金属催化3-卤代色酮而获得，这就需要对色酮进行预先官能团化反应，从而限制了工业生成中的应用。近年来，通过分子间的串联环化反应构建3-取代色酮取得了显著进展（Chinese Chemical Letters 2020, 31,3073-3082.）。然而，开发更加简洁高效、环境友好的制备方法和策略制备具有潜在应用价值的3取代色酮化合物仍具有极其迫切需求和重要意义。据我们所知，到目前为止，3-异香豆素基色酮是一类未开发的新化合物，而以简单易得的2-羟基-N,N-二甲基烯胺酮化合物和2-炔基苯甲醛化合物合成3-异香豆素基色酮衍生物还未见专利和文献报道。
发明内容
为了解决现有技术不足，本发明提供了一种简单高效的3-异香豆素基色酮制备方法。
为解决上述技术问题，本发明采用的技术方案是：在溶剂、催化剂存在条件下，2-羟基-N,N-二甲基烯胺酮化合物和2-炔基苯甲醛化合物在空气、40~120℃下反应，薄层色谱监测反应进程，直至反应完全，反应产物用乙酸乙酯萃取2~3次，收集有机相用无水硫酸钠干燥，然后减压浓缩，残渣经硅胶柱层析分离纯化得到目标化合物3-异香豆素基色酮，反应方程式如下：
其中Ar1、Ar2为芳基， Ar1、Ar2能替换为取代的芳基、芳香杂环；R选自芳基、取代的芳基、烷基。
所述取代的芳基中的取代基选自卤素、烷基、烷氧基、硝基。
所述催化剂选自氧化银、硝酸银、碳酸银、氯化银、氟化银、醋酸银、三氟乙酸银；溶剂选自丙酮、二甲基亚砜、氯苯、1,4-二氧六环、乙酸乙酯、苯甲醚、乙腈、1,2-二氯乙烷、乙醇、四氢呋喃、环己烷。
所述2-羟基-N,N-二甲基烯胺酮化合物与催化剂的摩尔比为1:0.05~1，2-羟基-N,N-二甲基烯胺酮化合物和2-炔基苯甲醛化合物的摩尔比为1:1~4。
所述2-羟基-N,N-二甲基烯胺酮化合物按常规方法制备，例如参照SandipBalasahebWakade, Dipak Kumar Tiwari. Synthesis of 3-keto-quinolinesfrom enaminones, anilines and DMSO: Transition metal free one pot cascade.Tetrahedron 75 (2019) 4024-4030文献中方法制得。
所述2-炔基苯甲醛化合物按常规方法制备，例如参照Wu D, Hao W J, Rao Q, etal. Engaging 1, 7-diynes in a photocatalytic Kharasch-type addition/1, 5-(SN′′)-substitution cascade toward β-gem-dihalovinyl carbonyls. ChemicalCommunications, 2021, 57(15): 1911-1914文献方法制备。
上述3-异香豆素基色酮化合物制备是在银催化作用下，2-乙炔基苯甲醛自身环化形成异色烯，而后2-羟基-N,N-二甲基烯胺酮对异色烯进行亲核进攻得到中间体，中间体自身环合并脱去金属配体，再经过脱氢与脱N,N-二甲胺得到最终产物。
本发明与现有技术相比，具有以下优点：
1、本发明合成的3-异香豆素基色酮化合物是一类全新的杂环化合物；
2、本发明利用简单易得的原料：N,N-二甲基烯胺酮是通过广泛存在的α-甲基酮类化合物在N,N-二甲基甲酰胺二甲基缩醛（DMF-DMA）中加热反应12h，通过后处理即可得到；2-苯基乙炔基苯甲醛化合物由2-溴苯甲醛与苯乙炔化合物通过Suzuki偶联反应获得；
3、本发明通过简单的银催化即可实现2-羟基-N,N-二甲基烯胺酮与2-炔基苯甲醛的二次环化得到目标产物；
4、所获得的产物结构丰富，底物适应性较好；
5、本发明的合成方法简洁高效，操作简便，环境友好，产率高等特点，适用于工业生产。
附图说明
图1为化合物3l的单晶结构图。
具体实施方式
下面通过实施例对本发明作进一步详细说明，但本发明保护范围不局限于所述内容，实施例中试剂如无特殊说明，均为常规市售试剂或按常规方法制得的试剂，产物结构经过核磁共振、高分辨质谱以及代表性产物的单晶衍射测试等确证；
实施例1：本实施例3-异香豆素基色酮的制备如下：
在空气气氛、80℃下，在15mL反应管中加入2-羟基-N,N-二甲基烯胺酮1(0.5mmol)、2-炔基苯甲醛2 (1.0mmol)、氧化银(0.2mmol)，加入1mL丙酮作为溶剂，磁力搅拌下反应，通过TCL监测反应，直至原料反应完全后，添加乙酸乙酯萃取3次，收集合并上层有机相，加入无水Na2SO4进行干燥，将干燥后的有机层50℃下浓缩，最后浓缩物进行硅胶柱层析分离，硅胶柱采用石油醚-乙酸乙酯的混合溶剂洗脱分离，收集洗脱液，50℃干燥后，得到目标化合物3-异香豆素基色酮化合物3a；反应通式如下：
化合物3a的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 12:1, R f = 0.2; 白色固体: 142 mg,产率 80%; 熔点 = 160–161℃;1H NMR (600 MHz, CDCl3): δ = 8.32 (d, J = 8.0 Hz, 1H, ArH), 7.71–7.68(m, 2H, ArH), 7.67–7.64 (m, 1H, ArH), 7.62 (s, 1H, C=CH), 7.44–7.39 (m, 2H,ArH), 7.36–7.33 (m, 2H, ArH), 7.32–7.29 (m, 2H, ArH), 7.20 (t, J = 8.3 Hz,2H, ArH), 7.09 (d, J = 7.5 Hz, 1H, ArH), 6.83 (s, 1H, C=CH), 6.52 (s, 1H, C-CH);13C NMR (150 MHz, CDCl3): δ = 176.3, 156.0 156.0, 151.6, 134.0, 133.7,131.3, 128.8, 128.5, 128.2, 128.2, 127.9, 126.9, 126.0, 125.2, 125.1, 125.1,125.0, 124.0, 123.8, 122.2, 118.0, 100.5, 71.1;HRMS (TOF ES+): m/z calcd forC24H16O3 [(M+H)+], 353.1172, found, 353.1182.
实施例2：本实施例3-异香豆素基色酮化合物3b的制备方法同实施例1，不同在于：化合物1为2-羟基-5-甲基-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3b的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 9:1, R f = 0.2; 白色固体: 143 mg, 产率 78%; 熔点 = 100–101℃;1H NMR (600 MHz, CDCl3) δ = 8.10 (s, 1H, ArH), 7.69 (d, J = 7.7 Hz, 2H,ArH), 7.59 (s, 1H, C=CH), 7.46 (d, J = 8.7 Hz, 1H, ArH), 7.34 (t, J = 7.4 Hz,2H, ArH), 7.30 (t, J = 7.8 Hz, 3H, ArH), 7.18 (d, J = 7.6 Hz, 2H, ArH), 7.09(d, J = 7.5 Hz, 1H, ArH), 6.82 (s, 1H, C=CH), 6.51 (s, 1H, C-CH), 2.46 (s,3H, ArCH3); 13C NMR (150 MHz, CDCl3) δ = 175.4, 154.9, 153.3, 150.6, 134.2,133.9, 133.0, 130.3, 127.7, 127.5, 127.2, 127.2, 126.9, 125.9, 124.2, 124.1,124.1, 124.0, 122.8, 122.6, 121.0, 116.7, 99.5, 70.1, 19.8; HRMS (TOF ES+):m/z calcd for C25H18O3 [(M+H)+], 367.1329, found, 367.1335.
实施例3：本实施例3-异香豆素基色酮化合物3c的制备方法同实施例1，不同在于：化合物1为2-羟基-5-氟-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3c的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 9:1, R f = 0.2; 黄色固体: 141 mg,产率 76%; 熔点 = 159–160℃;1H NMR (600 MHz, CDCl3) δ = 7.95 (d, J = 5.3 Hz, 1H, ArH), 7.69 (d, J = 7.5Hz, 2H, ArH), 7.60 (s, 1H,C=CH), 7.42–7.38 (m, 2H, ArH), 7.36–7.30 (m, 4H,ArH), 7.22–7.18 (m, 2H, ArH), 7.09 (d, J = 7.4 Hz, 1H,ArH), 6.81 (s, 1H, C=CH), 6.52 (s, 1H, C-CH); 13C NMR (150 MHz, CDCl3) δ = 175.8, 159.6 (C–F, J =247.5 Hz), 156.3, 152.4, 151.7, 134.1, 131.2, 129.0, 128.8, 128.4, 128.4,127.8, 127.1, 125.3, 125.3, 125.3, 125.2, 124.1, 122.1, (C–F, J = 25.5 Hz),121.8, 120.3, (C–F, J = 8.0 Hz), 111.0, (C–F, J = 23.9 Hz), 100.7, 71.2;HRMS(TOF ES+): m/z calcd for C24H15FO3 [(M+H)+], 371.1078, found, 371.1083.
实施例4：本实施例3-异香豆素基色酮化合物3d的制备方法同实施例1，不同在于：化合物1为2-羟基-5-氯-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3d的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 10:1, R f = 0.2; 白色固体: 128 mg,产率 66%; 熔点 = 173–174℃;1H NMR (600 MHz, CDCl3) δ = 8.28 (d, J = 2.6 Hz, 1H, ArH), 7.68 (d, J =7.6 Hz, 2H, ArH), 7.60 (d, J = 2.6 Hz, 1H, ArH), 7.58 (s, 1H, C=CH), 7.35 (t,J = 7.9 Hz, 3H, ArH), 7.31 (t, J = 7.2 Hz, 2H), 7.22–7.18 (m, 2H, ArH), 7.09(d, J = 7.5 Hz, 1H, ArH), 6.80 (s, 1H, C=CH), 6.51 (s, 1H, C-CH).; 13C NMR(150 MHz, CDCl3) δ= 175.4, 156.3, 154.5, 151.6, 134.1, 134.1, 131.2, 131.3,129.0, 128.8, 128.4, 128.4, 127.7, 127.1, 125.5, 125.3, 125.3, 125.2, 125.1,124.1, 122.4, 119.9, 100.7, 71.1;HRMS (TOF ES+): m/z calcd for C24H15ClO3 [(M+H)+], 387.0782, found, 387.0787.
实施例5：本实施例3-异香豆素基色酮化合物3e的制备方法同实施例1，不同在于：化合物2-羟基-5-溴-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3e的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 10:1, R f = 0.2; 白色固体: 151 mg, 产率 70%; 熔点 = 204–205℃;1H NMR (600 MHz, CDCl3) δ = 8.44 (d, J = 2.5 Hz, 1H, ArH), 7.73 (dd, J =8.8, 2.5 Hz, 1H, ArH), 7.69 – 7.67 (m, 2H, ArH), 7.58 (s, 1H, C=CH), 7.35 (t,J = 7.3 Hz, 2H, ArH), 7.33–7.29 (m, 3H, ArH), 7.22–7.18 (m, 2H, ArH), 7.09(d, J = 7.5 Hz, 1H, ArH), 6.80 (s, 1H, C=CH), 6.51 (s, 1H, C-CH); 13C NMR (150MHz, CDCl3) δ = 175.3, 156.3, 155.0, 151.6, 136.8, 134.1, 131.4, 129.0,128.8, 128.7, 128.4, 128.4, 127.6, 127.1, 125.4, 125.3, 125.3, 125.2, 124.1,122.5, 120.1, 118.8, 100.7, 71.1; HRMS (TOF ES+): m/z calcd for C24H15BrO3 [(M+H)+], 431.0277, found, 431.0275.
实施例6：本实施例3-异香豆素基色酮化合物3f的制备方法同实施例1，不同在于：化合物1为2-羟基-4-溴-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3f的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 11:1, R f = 0.2; 白色固体: 155 mg, 产率 72%; 熔点 = 137–138℃;1H NMR (600 MHz, CDCl3) δ = 8.17 (d, J = 8.6 Hz, 1H, ArH), 7.74–7.65 (m,2H, ArH), 7.59 (s, 1H, C=CH), 7.56–7.46 (m, 2H, ArH), 7.36–7.30 (m, 4H, ArH),7.24–7.16 (m, 2H, ArH), 7.08 (d, J = 7.5 Hz, 1H, ArH), 6.79 (s, 1H, C=CH),6.51 (s, 1H, C-CH); 13C NMR (150 MHz, CDCl3) δ = 175.8, 156.2, 156.1, 151.6,134.1, 131.4, 129.0, 129.0, 128.8, 128.4, 128,4, 128.1, 127.7, 127.5, 127.1,125.3, 125.3, 125.2, 124.1, 123.0, 122.7, 121.2, 100.7, 71.1; HRMS (TOF ES+):m/z calcd for C24H15BrO3 [(M+H)+], 431.0277, found, 431.0280.
实施例7：本实施例3-异香豆素基色酮化合物3g的制备方法同实施例1，不同在于：化合物1为2-羟基-5-甲氧基-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
产品3g的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯= 8:1, R f = 0.2; 白色固体: 153 mg , 产率80%; 熔点 = 136–137℃;1H NMR (600 MHz, DMSO-d 6) δ = 7.88 (s, 1H), 7.69 (d, J = 7.6 Hz, 1H, ArH),7.60 (d, J = 9.2 Hz, 1H, ArH), 7.51 (s, 1H, C=CH), 7.42 (dd, J = 9.2, 3.0 Hz,1H, ArH), 7.37 (d, J = 7.3 Hz, 2H, ArH), 7.34 (t, J = 7.2 Hz, 2H, ArH), 7.28(d, J = 7.6 Hz, 1H, ArH), 7.21 (t, J = 7.5 Hz, 1H, ArH), 7.06 (d, J = 7.5 Hz,1H, ArH), 6.81 (s, 1H, ArH), 6.59 (s, 1H, C=CH), 5.76 (s, 1H, C-CH), 3.87 (s,3H, ArOCH3);13C NMR (150 MHz, DMSO-d 6) δ = 175.5, 157.2, 156.8, 151.5, 150.9,134.2, 131.8, 129.5, 129.1, 129.0, 129.0, 128.5, 127.5, 125.4, 125.3, 125.3,124.6, 124.5, 124.2, 121.0, 120.7, 105.3, 101.6, 72.0, 56.2; HRMS (TOF ES+):m/z calcd for C25H18O4 [(M+H)+], 383.1278, found, 383.1287.
实施例8：本实施例3-异香豆素基色酮化合物3h的制备方法同实施例1，不同在于：化合物1为2-羟基-4-甲基-5-氯-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3h的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 9:1, R f = 0.2; 白色固体: 132 mg, 产率 66%; 熔点 = 142–143℃;1H NMR (600 MHz, CDCl3) δ = 8.26 (s, 1H, ArH), 7.68 (d, J = 7.6 Hz, 2H,ArH), 7.55 (s, 1H, C=CH), 7.36–7.30 (m, 5H, ArH), 7.19 (dd, J = 7.5, 3.9 Hz,2H, ArH), 7.08 (d, J = 7.4 Hz, 1H, ArH), 6.79 (s, 1H, C=CH), 6.51 (s, 1H, C-CH), 2.47 (s, 3H, ArCH3);13C NMR (150 MHz, CDCl3) δ = 175.4, 156.1, 154.5,151.7, 143.2, 134.1, 132.1, 131.4, 129.0, 128.8, 128.4, 128.4, 127.8, 127.2,125.8, 125.3, 125.3, 125.2, 124.1, 123.2, 122.3, 119.9, 100.7, 71.2, 20.9;HRMS (TOF ES+): m/z calcd for C25H17ClO3 [(M+H)+], 401.0939, found, 401.0940.
实施例9：本实施例3-异香豆素基色酮化合物3i的制备方法同实施例1，不同在于：化合物1为2-羟基-5-硝基-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3i的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 6:1, R f = 0.2; 白色固体: 120 mg, 产率 60%;熔点 = 120–121℃;1H NMR (600 MHz, CDCl3) δ = 9.18 (d, J = 2.8 Hz, 1H, ArH), 8.48 (dd, J =9.1, 2.8 Hz, 1H, ArH), 7.68 (d, J = 7.6 Hz, 2H, ArH), 7.61 (s, 1H, C=CH),7.55 (d, J = 9.1 Hz, 1H, ArH), 7.37–7.32 (m, 4H, ArH), 7.22 (q, J = 7.4 Hz,2H, ArH), 7.12 (d, J = 7.5 Hz, 1H, ArH), 6.81 (s, 1H, CH C=CH), 6.53 (s, 1H,C-H);13C NMR (150 MHz, CDCl3) δ = 175.2, 159.0, 156.4, 151.5, 144.8, 133.9,131.3, 129.2, 129.1, 128.5, 128.5, 128.2, 127.3, 127.1, 125.3, 125.3, 125.3,124.3, 124.2, 123.1, 123.0, 120.0, 100.7, 70.9; HRMS (TOF ES+): m/z calcd forC24H15NO5 [(M+H)+], 398.1023, found, 398.1028.
实施例10：本实施例3-异香豆素基色酮化合物3j的制备方法同实施例1，不同在于：化合物1为2-羟基-3-甲基-5-甲基-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3j的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 8:1, R f = 0.2; 白色固体: 128 mg, 产率 67%; 熔点 = 178–179℃;1H NMR (600 MHz, DMSO-d 6) δ = 7.81 (s, 1H, ArH), 7.77 (s, 1H, ArH),7.70–7.66 (m, 2H, ArH), 7.51 (s, 1H, C=CH), 7.39–7.32 (m, 4H, ArH), 7.28 (d,J = 7.6 Hz, 1H, ArH), 7.23–7.20 (m, 1H, ArH), 7.09 (d, J = 7.5 Hz, 1H, ArH),6.82 (s, 1H, C=CH), 6.61 (s, 1H, C-H), 2.39 (s, 3H, ArCH3), 2.35 (s, 3H,ArCH3); 13C NMR (151 MHz, DMSO-d 6) δ = 176.0, 156.6, 152.9, 151.3, 136.7,135.3, 134.3, 131.7, 129.5, 129.1, 129.0, 129.0, 128.4, 127.9, 127.6, 125.5,125.3, 125.3, 124.5, 123.6, 122.5, 121.2, 101.6, 71.8, 20.9, 15.4; HRMS (TOFES+): m/z calcd for C26H20O3 [(M+H)+], 381.1485, found, 381.1489.
实施例11：本实施例3-异香豆素基色酮化合物3k的制备方法同实施例1，不同在于：化合物1为2-羟基-1-萘-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3k的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 8:1, R f = 0.2; 白色固体: 109 mg, 产率 54%; 熔点 = 198–199℃;1H NMR (600 MHz, DMSO-d 6) δ = 8.36 (d, J = 8.3 Hz, 1H, ArH), 8.07 (dd, J= 12.7, 8.4 Hz, 2H, ArH), 8.01 (s, 1H, C=CH), 7.94 (d, J = 8.8 Hz, 1H, ArH),7.79 (t, J = 7.5 Hz, 1H, ArH), 7.74 (d, J = 7.8 Hz, 1H, ArH), 7.71 (d, J =7.9 Hz, 2H, ArH), 7.39–7.35 (m, 3H, ArH), 7.34–7.30 (m, 2H, ArH), 7.23 (t, J= 7.5 Hz, 1H, ArH), 7.15 (d, J = 7.5 Hz, 1H, ArH), 6.85 (s, 1H, C=CH), 6.67(s, 1H, C-H); 13C NMR (150 MHz, DMSO-d 6) δ = 175.5, 156.2, 153.5, 151.4,135.8, 134.2, 131.7, 130.3, 129.5, 129.2, 129.0, 129.0, 128.7, 128.3, 128.3,127.6, 126.2, 125.6, 125.3, 125.3, 124.6, 123.67 123.1, 122.3, 120.6, 120.3,101.7, 71.9; HRMS (TOF ES+): m/z calcd for C28H18O3 [(M+H)+], 403.1329, found,403.1326.
实施例12：本实施例3-异香豆素基色酮化合物3l的制备方法同实施例1，不同在于：化合物1为2-羟基-3-硝基-5-甲基-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
产品3l的结构、形态、熔点、核磁、高分辨质谱数据如下，化合3l的单晶结构图见图1；
V石油醚/V乙酸乙酯= 8:1, R f = 0.2; 白色固体: 130 mg, 产率 63%; 熔点 = 199–200℃;1H NMR (600 MHz, DMSO-d 6) δ = 8.38 (s, 1H, ArH), 8.29 (s, 1H, ArH), 7.98(s, 1H, C=CH), 7.71–7.67 (m, 2H, ArH), 7.40–7.33 (m, 4H, ArH), 7.28 (d, J =7.5 Hz, 1H, ArH), 7.21 (t, J = 7.5 Hz, 1H, ArH), 7.11 (d, J = 7.5 Hz, 1H,ArH), 6.83 (s, 1H, C=CH), 6.57 (s, 1H, C-H), 2.51 (s, 3H, ArCH3);13C NMR (150MHz, DMSO-d 6) δ = 174.4, 156.9, 151.4, 146.6, 138.8, 136.1, 134.1, 131.7,131.4, 131.1, 129.5, 129.2, 129.0, 129.0, 128.0, 127.6, 125.5, 125.3, 125.3,125.3, 124.6, 122.3, 101.7, 71.8, 20.5; HRMS (TOF ES+): m/z calcd for C28H18O3[(M+H)+], 412.1179, found, 412.1180.
实施例13：本实施例3-异香豆素基色酮化合物3m的制备方法同实施例1，不同在于：化合物1为2-羟基-4-氟-N,N-二甲基烯胺酮，化合物2为2-苯基乙炔基苯甲醛；
化合物3m的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 10:1, R f = 0.2; 白色固体: 130 mg , 产率70%; 熔点 = 163–164℃; 1H NMR (600 MHz, DMSO-d 6) δ = 8.20 (dd, J = 9.0, 6.4 Hz, 1H, ArH), 7.90(s, 1H, C=CH), 7.68 (d, J = 7.3 Hz, 1H, ArH), 7.61 (dd, J = 9.5, 2.5 Hz, 1H,ArH), 7.43–7.40 (m, 1H, ArH), 7.37 (t, J = 7.3 Hz, 2H, ArH), 7.35–7.32 (m,2H, ArH), 7.28 (d, J = 7.5 Hz, 1H, ArH), 7.22–7.19 (m, 1H, ArH), 7.07 (d, J =7.5 Hz, 1H, ArH), 6.81 (s, 1H, C=CH), 6.56 (s, 1H, C-H); 13C NMR (151 MHz,DMSO-d 6) δ = 175.1, 165.6 (C–F, J = 252.7 Hz), 157.4, 157.3, (C–F, J = 14Hz), 151.4, 134.2, 131.7, 129.5, 129.1, 129.0, 129.0, 128.7, (C–F, J = 11Hz), 128.3, 127.6, 125.4, 125.3, 125.3, 124.5, 121.9, 121.1, 115.0, (C–F, J =23,1 Hz), 105.9, (C–F, J = 25.8 Hz), 101.7, 71.9; HRMS (TOF ES+): m/z calcdfor C24H15FO3 [(M+H)+], 371.1078, found, 371.1081.
实施例14：本实施例3-异香豆素基色酮化合物3n的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为2-[2-（3-甲基苯基）乙炔基]苯甲醛；
化合物3n的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 10:1, R f = 0.2; 白色固体: 130 mg, 产率71%; 熔点 = 164–165℃;1H NMR (600 MHz, DMSO-d 6) δ = 8.15 (d, J = 8.0 Hz, 1H, ArH), 7.93 (s,1H, C=CH), 7.82 (t, J = 7.8 Hz, 1H, ArH), 7.63 (d, J = 8.5 Hz, 1H, ArH), 7.53(d, J = 8.8 Hz, 2H, ArH), 7.47 (d, J = 8.0 Hz, 1H, ArH), 7.33 (t, J = 7.5 Hz,1H, ArH), 7.26 (dd, J = 13.0, 7.2 Hz, 2H, ArH), 7.20 (t, J = 7.5 Hz, 1H,ArH), 7.14 (d, J = 7.5 Hz, 1H, ArH), 7.06 (d, J = 7.5 Hz, 1H, ArH), 6.79 (s,1H, C=CH), 6.55 (s, 1H, C-H), 2.29 (s, 3H, ArCH3); 13C NMR (150 MHz, DMSO-d 6)δ = 175.8, 157.1, 156.2, 151.7, 138.1, 135.1, 134.2, 131.8, 130.2, 129.1,128.9, 128.5, 127.5, 126.4, 125.8, 125.7, 125.4, 124.4, 123.9, 122.6, 121.8,119.0, 101.6, 72.0, 21.5; HRMS (TOF ES+): m/z calcd for C25H18O3 [(M+H)+],367.1329, found, 367.1332.
实施例15：本实施例3-异香豆素基色酮化合物3o的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为2-[2-（4-叔丁基苯基）乙炔基]苯甲醛；
化合物3o的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 12:1, R f = 0.2; 白色固体: 100 mg, 产率,49%; 熔点 = 184–185℃;1H NMR (600 MHz, DMSO-d 6) δ = 8.16 (dd, J = 8.0, 1.6 Hz, 1H, ArH), 7.86–7.81 (m, 2H, ArH), 7.63–7.61 (m, 2H, ArH), 7.60 (s, 1H, C=CH), 7.54 (t, J =7.6 Hz, 1H, ArH), 7.39 (d, J = 8.2 Hz, 2H, ArH), 7.35 (t, J = 7.5 Hz, 1H,ArH), 7.28 (d, J = 7.5 Hz, 1H, ArH), 7.21 (t, J = 7.4 Hz, 1H, ArH), 7.10 (d,J = 7.5 Hz, 1H,ArH), 6.76 (s, 1H, C=CH), 6.61 (s, 1H, C-H), 1.24 (s, 9H, Me);13C NMR (150 MHz, DMSO-d 6) δ = 175.8, 157.0, 156.1, 152.2, 151.4, 135.1,131.9, 131.5, 129.1, 128.2, 127.4, 126.3, 125.8, 125.8, 125.7, 125.5, 125.2,125.2, 124.4, 123.9, 121.7, 119.0, 100.9, 71.7, 34.9, 31.4, 31.4, 31.4; HRMS(TOF ES+): m/z calcd for C28H24O3 [(M+H)+], 409.1798, found, 409.1799.
实施例16：本实施例3-异香豆素基色酮化合物3p的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为2-[2-（4-甲基苯基）乙炔基]苯甲醛；
化合物3p的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 10:1, R f = 0.2; 白色固体: 136 mg, 产率74%; 熔点 = 162–163℃;1H NMR (600 MHz, DMSO-d 6) δ = 8.16 (d, J = 8.1 Hz, 1H, ArH), 7.91 (s,1H, ArH, C=CH), 7.84 (t, J = 7.9 Hz, 1H, ArH), 7.64 (d, J = 8.5 Hz, 1H, ArH),7.58 (d, J = 7.8 Hz, 2H, ArH), 7.54 (t, J = 7.6 Hz, 1H, ArH), 7.34 (t, J =7.5 Hz, 1H, ArH), 7.26 (d, J = 7.6 Hz, 1H, ArH), 7.19 (d, J = 8.1 Hz, 3H,ArH), 7.08 (d, J = 7.6 Hz, 1H, ArH), 6.76 (s, 1H, C=CH), 6.56 (s, 1H, C-H),2.29 (s, 3H, ArCH3);13C NMR (150 MHz, DMSO-d 6) δ = 175.8, 157.1, 156.2, 151.6,139.1, 135.1, 131.9, 131.5, 129.6, 129.6, 129.1, 128.4, 127.3, 126.3, 125.7,125.4, 125.3, 125,3, 124.3, 123.9, 121.7, 119.0, 100.9, 71.9, 21.3; HRMS (TOFES+): m/z calcd for C25H18O3 [(M+H)+], 367.1329, found, 367.1332.
实施例17：本实施例3-异香豆素基色酮化合物3q的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为2-(1-辛基乙炔基)苯甲醛；
化合物3q的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 12:1, R f = 0.2; 白色固体: 94 mg, 产率52%; 熔点 = 88–89℃;1H NMR (600 MHz, DMSO-d6) δ = 8.14 (d, J = 7.9 Hz, 1H, ArH), 7.84 (t, J =7.8 Hz, 1H, ArH), 7.68 (s, 1H, C=CH), 7.64 (d, J = 8.3 Hz, 1H, ArH), 7.54 (t,J = 7.5 Hz, 1H, ArH), 7.26 (t, J = 7.2 Hz, 1H, ArH), 7.13 (t, J = 7.4 Hz,1H), 7.07 (d, J = 7.5 Hz, 1H), 7.01 (d, J = 7.5 Hz, 1H)., 6.45 (s, 1H, C=CH),5.82 (s, 1H, C-H), 2.16–2.12 (m, 1H, CH2), 2.07–2.02 (m, 1H, CH2), 1.32–1.24(m, 2H, CH2), 1.12–1.05 (m, 1H, CH2), 1.02–0.97 (m, 3H, CH2), 0.95–0.88 (m,1H, CH2), 0.86–0.80 (m, 1H, CH2), 0.65 (t, J = 7.0 Hz, 3H, Me); 13C NMR (150MHz, DMSO-d 6) δ 175.7, 157.0, 156.2, 156.0, 135.0, 131.9, 129.0, 127.2,126.7, 126.3, 125.7, 125.4, 124.0, 123.2, 121.8, 118.9, 101.6, 71.1, 33.4,31.7, 28.6, 26.5, 22.4, 14.3; HRMS (TOF ES+): m/z calcd for C24H24O3 [(M+H)+],361.1798, found, 361.1802.
实施例18：本实施例3-异香豆素基色酮化合物3r的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为2-（2-环丙基乙炔基）苯甲醛；
化合物3r的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 8:1, R f = 0.2; 白色固体: 92 mg, 产率58%; 熔点 = 148–149℃;1H NMR (600 MHz, DMSO-d 6) δ = 8.13 (d, J = 8.0 Hz, 1H, ArH), 7.85 (d, J =8.4 Hz, 1H, ArH), 7.83 (s, 1H, C=CH), 7.66 (d, J = 8.5 Hz, 1H, ArH), 7.54 (t,J = 7.7 Hz, 1H, ArH), 7.24 (t, J = 7.6 Hz, 1H, ArH), 7.08 (t, J = 7.5 Hz, 1H,ArH), 7.04 (d, J = 7.7 Hz, 1H, ArH), 6.95 (d, J = 7.6 Hz, 1H, ArH), 6.30 (s,1H, C=CH), 5.95 (s, 1H, C-H), 1.63–1.54 (m, 1H, CH), 0.72–0.63 (m, 2H, CH2),0.60 – 0.51 (m, 2H, CH2); 13C NMR (150 MHz, DMSO-d 6) δ = 175.7, 156.9, 156.4,156.1, 135.1, 132.0, 129.0, 127.5, 126.3, 126.3, 125.7, 125.3, 123.9, 122.8,121.7, 119.0, 100.2, 71.5, 13.9, 5.3, 5.2; HRMS (TOF ES+): m/z calcd forC21H16O3 [(M+H)+], 317.1172, found, 317.1175.
实施例19：本实施例3-异香豆素基色酮化合物3s的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为2-[2-（4-氟苯基）乙炔基]苯甲醛；
化合物3s的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 7:1, R f = 0.2; 白色固体: 113 mg, 产率61%; 熔点 = 161–162℃; 1H NMR (600 MHz, DMSO-d 6) δ = 8.19–8.14 (m, 1H, ArH), 7.91 (s, 1H, C=CH),7.86–7.82 (m, 1H, ArH), 7.74 (dd, J = 8.6, 5.4 Hz, 2H. ArH), 7.65 (d, J = 8.4Hz, 1H, ArH), 7.55 (t, J = 7.6 Hz, 1H, ArH), 7.35 (t, J = 7.5 Hz, 1H, ArH),7.28 (d, J = 7.5 Hz, 1H, ArH), 7.25–7.20 (m, 3H, ArH), 7.09 (d, J = 7.5 Hz,1H, ArH), 6.81 (s, 1H, C=CH), 6.60 (s, 1H, C-H); 13C NMR (150 MHz, DMSO-d 6) δ= 175.8, 162.9, (C–F, J = 246.6 Hz), 157.2, 156.2, 150.6, 135.1, 131.7,130.8, 130.8, 129.1, 128.3, 127.6, 127.6, 127.5, 126.4, 125.7, 125.5, 124.5,123.9, 121.8, 119.0, 116.0, (C–F, J = 21.8 Hz), 101.5, 72.1; HRMS (TOF ES+):m/z calcd for C24H15FO3 [(M+H)+], 371.1078, found, 371.1081.
实施例20：本实施例3-异香豆素基色酮化合物3t的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为2-[2-（4-甲氧基苯基）乙炔基]苯甲醛；
化合物3t的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 6:1, R f = 0.2; 白色固体: 140 mg, 产率73%; 熔点 = 137–138℃; 1H NMR (600 MHz, DMSO-d 6) δ = 8.16 (d, J = 7.9 Hz, 1H, ArH), 7.88 (s, 1H,C=CH), 7.83 (t, J = 7.8 Hz, 1H, ArH), 7.63 (t, J = 8.3 Hz, 3H, ArH), 7.54 (t,J = 7.6 Hz, 1H, ArH), 7.33 (t, J = 7.5 Hz, 1H, ArH), 7.25 (d, J = 7.6 Hz, 1H,ArH), 7.18 (t, J = 7.4 Hz, 1H, ArH), 7.08 (d, J = 7.5 Hz, 1H, ArH), 6.95 (s,1H, ArH), 6.93 (s, 1H, ArH), 6.68 (s, 1H, C=CH), 6.56 (s, 1H, C-H), 3.76 (s,3H, ArOCH3); 13C NMR (150 MHz, DMSO-d 6) δ = 175.8, 160.5, 157.0, 156.2, 151.5,135.1, 132.1, 129.1, 128.1, 127.1, 127.0, 127.0, 126.7, 126.3, 125.7, 125.4,124.1, 123.9, 121.7, 119.0, 114.4, 114,4, 99.9, 71.9, 55.7; HRMS (TOF ES+):m/z calcd for C25H18O4 [(M+H)+], 383.1278, found, 383.1282.
实施例21：本实施例3-异香豆素基色酮化合物3u的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为4-氟-2-（2-苯乙炔基）苯甲醛；
化合物3u的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 8:1, R f = 0.2; 白色固体: 145 mg, 产率78%; 熔点 = 192–193℃; 1H NMR (600 MHz, DMSO-d 6) δ = 8.16 (d, J = 8.0 Hz, 1H, ArH), 7.95 (s, 1H,C=CH), 7.84 (t, J = 7.8 Hz, 1H, ArH), 7.68 (d, J = 7.6 Hz, 2H, ArH), 7.65 (d,J = 8.5 Hz, 1H, ArH), 7.54 (t, J = 7.6 Hz, 1H, ArH), 7.41–7.36 (m, 3H, ArH),7.16–7.11 (m, 2H, ArH), 7.06–6.98 (m, 1H, ArH), 6.82 (s, 1H, C=CH), 6.61 (s,1H, C-H); 13C NMR (150 MHz, DMSO-d 6) δ = 175.8, 162,8, (C–F, J = 242.9 Hz),157.3, 156.2, 152.5, 135.1, 134.2, (C–F, J = 9.3 Hz), 133.9, 129.9, 129.1,129.1, 127.6, (C–F, J = 8.9 Hz), 126.4, 125.7, 125.5, 125.5, 124.3, (C–F, J =2.7 Hz), 123.94, 121.54, 119.03, 113.8, (C–F, J = 22 Hz), 110.8, (C–F, J =22.7 Hz), 101.0, 71.8; HRMS (TOF ES+): m/z calcd for C24H15O3 [(M+H)+],371.1078, found, 371.1081.
实施例22：本实施例3-异香豆素基色酮化合物3v的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为4-氯-2-（2-苯乙炔基）苯甲醛；
化合物3v的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 8:1, R f = 0.2; 白色固体: 145 mg, 产率75%;熔点 = 180–181℃; 1H NMR (600 MHz, DMSO-d 6) δ = 8.14 (d, J = 7.9 Hz, 1H, ArH), 7.98 (s, 1H,C=CH), 7.82 (t, J = 7.8 Hz, 1H, ArH), 7.67 (d, J = 7.6 Hz, 2H, ArH), 7.63 (d,J = 8.4 Hz, 1H, ArH), 7.53 (t, J = 7.6 Hz, 1H, ArH), 7.41–7.33 (m, 4H, ArH),7.27–7.20 (m, 1H, ArH), 7.11 (d, J = 8.1 Hz, 1H, ArH), 6.81 (s, 1H, C=CH),6.59 (s, 1H, C-H); 13C NMR (150 MHz, DMSO-d 6) δ = 175.7, 157.4, 156.2, 152.8,135.1, 134.0, 133.9, 133.6, 129.9, 129.1, 129.1, 127.4, 127.1, 127.0, 126.4,125.7, 125.5, 125.5, 123.9, 123.9, 121.3, 119.1, 100.6, 71.9; HRMS (TOF ES+):m/z calcd for C24H15ClO3 [(M+H)+], 387.0782, found, 387.0788.
实施例23：本实施例3-异香豆素基色酮化合物3w的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为4-甲基-2-（2-苯乙炔基）苯甲醛；
化合物3w的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 9:1, R f = 0.2; 白色固体: 150 mg, 产率82%; 熔点 = 159–160℃; 1H NMR (600 MHz, DMSO-d 6) δ = 8.15 (d, J = 8.0 Hz, 1H, ArH), 7.85 (s, 1H,C=CH), 7.81 (t, J = 7.9 Hz, 1H, ArH), 7.67 (d, J = 7.7 Hz, 2H, ArH), 7.61 (d,J = 8.4 Hz, 1H, ArH), 7.53 (t, J = 7.6 Hz, 1H, ArH), 7.36 (t, J = 7.5 Hz, 2H,ArH), 7.33 (d, J = 7.1 Hz, 1H, ArH), 7.08 (s, 1H, ArH), 7.02 (d, J = 7.7 Hz,1H, ArH), 6.97 (d, J = 7.7 Hz, 1H, ArH), 6.75 (s, 1H, C=CH), 6.56 (s, 1H, C-H), 2.31 (s, 3H, ArCH3); 13C NMR (150 MHz, DMSO-d 6) δ = 175.9, 157.1, 156.1,151.3, 138.3, 135.1, 134.3, 131.6, 129.5, 129.0, 129.0, 128.2, 126.4, 125.7,125.5, 125.4, 125.3, 125.3, 125.1, 123.9, 121.8, 119.0, 101.6, 71.8, 21.3;HRMS (TOF ES+): m/z calcd for C25H18O3 [(M+H)+], 367.1329, found, 367.1337.
实施例24：本实施例3-异香豆素基色酮化合物3x的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为1-（2-苯基乙炔基）-2-萘甲醛；
化合物3x的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 8:1, R f = 0.2; 白色固体: 111 mg, 产率55%; 熔点 = 158–159℃;1H NMR (600 MHz, DMSO-d 6) δ = 8.56 (d, J = 7.5 Hz, 1H, ArH), 8.17 (s, 1H, C=CH), 7.93 (d, J = 6.5 Hz, 1H, C=CH), 7.87 (d, J = 7.6 Hz, 2H, ArH), 7.82–7.78 (m, 2H, ArH), 7.77–7.74 (m, 1H, ArH), 7.63 (d, J = 8.6 Hz, 1H, ArH),7.60–7.53 (m, 4H, ArH), 7.44–7.37 (m, 2H, ArH), 7.37–7.34 (d, J = 5.9 Hz, 1H,ArH), 7.28 (s, 1H, C=CH), 6.83 (s, 1H, C-H); 13C NMR (150 MHz, DMSO-d 6) δ =176.0, 157.6, 156.1, 151.9, 135.1, 134.5, 133.7, 129.6, 129.0, 129.0, 128.9,128.0, 127.9, 127.5, 127.0, 126.7, 126.4, 125.7, 125.7, 125.7, 124.5, 124.1,124.0, 123.9, 121.1, 119.0, 97.9, 72.2; HRMS (TOF ES+): m/z calcd for C28H18O3[(M+H)+], 403.1329, found, 403.1332.
实施例25：本实施例3-异香豆素基色酮化合物3y的制备方法同实施例1，不同在于：化合物1为2-羟基-N,N-二甲基烯胺酮，化合物2为6-（2-苯基乙炔基）-1,3-苯并二氧杂环-5-甲醛；
化合物3y的结构、形态、熔点、核磁、高分辨质谱数据如下：
V石油醚/V乙酸乙酯 = 7:1, R f = 0.2; 黄色固体: 139 mg, 产率70%; 熔点 = 234–235℃; 1H NMR (600 MHz, DMSO-d 6) δ = 8.16 (d, J = 8.0 Hz, 1H, ArH), 7.82 (t, J =7.9 Hz, 1H), 7.78 (s, 1H, C=CH), 7.62 (t, J = 6.6 Hz, 3H, ArH), 7.53 (t, J =7.7 Hz, 1H, ArH), 7.37–7.29 (m, 3H, ArH), 6.90 (s, 1H, ArH), 6.80 (s, 1H,ArH), 6.71 (s, 1H, C=CH), 6.55 (s, 1H, C-H), 6.03 (d, J = 7.0 Hz, 2H, CH2);13C NMR (150 MHz, DMSO-d 6) δ = 175.9, 157.2, 156.2, 149.4, 147.9, 146.8,135.0, 134.4, 129.2, 129.0, 129.0, 126.3, 126.2, 125.7, 125.0, 125.0, 124.0,121.5, 121.3, 119.0, 106.6, 105.2, 101.8, 101.6, 71.5; HRMS (TOF ES+): m/zcalcd for C25H16O5 [(M+H)+], 397.1071, found, 397.1073.
Claims (5)
1.一种3-异香豆素基色酮化合物的制备方法，其特征在于：在溶剂、催化剂存在条件下，2-羟基-N,N-二甲基烯胺酮化合物和2-炔基苯甲醛化合物在空气、40~120℃下反应，薄层色谱监测反应进程，直至反应完全，反应产物用乙酸乙酯萃取2~3次，收集有机相用无水硫酸钠干燥，然后减压浓缩，残渣经硅胶柱层析分离纯化得到目标化合物3-异香豆素基色酮，反应方程式如下：
其中Ar1、Ar2为芳基， Ar1、Ar2能替换为取代的芳基、芳香杂环；R选自芳基、取代的芳基、烷基。
2.根据权利要求1所述的3-异香豆素基色酮的制备方法，其特征在于：催化剂选自氧化银、硝酸银、碳酸银、氯化银、氟化银、醋酸银、三氟乙酸银。
3.根据权利要求1所述的3-异香豆素基色酮的制备方法，其特征在于：溶剂选自丙酮、二甲基亚砜、氯苯、1,4-二氧六环、乙酸乙酯、苯甲醚、乙腈、1,2-二氯乙烷、乙醇、四氢呋喃、环己烷。
4.根据权利要求1所述的3-异香豆素基色酮的制备方法，其特征在于：取代的芳基中的取代基选自卤素、烷基、烷氧基、硝基。
5.根据权利要求1所述的3-异香豆素基色酮的制备方法，其特征在于：2-羟基-N,N-二甲基烯胺酮化合物与催化剂的摩尔比为1:0.05~1，2-羟基-N,N-二甲基烯胺酮化合物和2-炔基苯甲醛化合物的摩尔比为1:1~4。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211237972.3A CN115504953A (zh) | 2022-10-11 | 2022-10-11 | 3-异香豆素基色酮化合物的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211237972.3A CN115504953A (zh) | 2022-10-11 | 2022-10-11 | 3-异香豆素基色酮化合物的制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115504953A true CN115504953A (zh) | 2022-12-23 |
Family
ID=84507687
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211237972.3A Pending CN115504953A (zh) | 2022-10-11 | 2022-10-11 | 3-异香豆素基色酮化合物的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115504953A (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102746224A (zh) * | 2012-06-27 | 2012-10-24 | 天津大学 | 2-芳基-3,4-二取代异喹啉-1(2h)-酮类衍生物的制备方法 |
| CN103265518A (zh) * | 2013-05-24 | 2013-08-28 | 陕西师范大学 | 光化学反应合成异黄酮 |
| CN104262316A (zh) * | 2014-09-15 | 2015-01-07 | 云南民族大学 | 一种黄酮类化合物及其制备方法和应用 |
| CN106187922A (zh) * | 2016-07-20 | 2016-12-07 | 江西师范大学 | 一种碱催化烯胺酮和磺酰叠氮环加成反应合成1,4‑二取代‑1,2,3‑三氮唑的方法 |
| CN110128393A (zh) * | 2019-06-21 | 2019-08-16 | 华侨大学 | 一种取代异香豆素衍生物的制备方法 |
-
2022
- 2022-10-11 CN CN202211237972.3A patent/CN115504953A/zh active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102746224A (zh) * | 2012-06-27 | 2012-10-24 | 天津大学 | 2-芳基-3,4-二取代异喹啉-1(2h)-酮类衍生物的制备方法 |
| CN103265518A (zh) * | 2013-05-24 | 2013-08-28 | 陕西师范大学 | 光化学反应合成异黄酮 |
| CN104262316A (zh) * | 2014-09-15 | 2015-01-07 | 云南民族大学 | 一种黄酮类化合物及其制备方法和应用 |
| CN106187922A (zh) * | 2016-07-20 | 2016-12-07 | 江西师范大学 | 一种碱催化烯胺酮和磺酰叠氮环加成反应合成1,4‑二取代‑1,2,3‑三氮唑的方法 |
| CN110128393A (zh) * | 2019-06-21 | 2019-08-16 | 华侨大学 | 一种取代异香豆素衍生物的制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| ZHANG, MINGSHUAI ET AL.: "Synthesis of Functionalized 3-(1H-Isochromen)-chromones via Ag2O-Catalyzed Cascade Cyclization Reaction of o-Hydroxyarylenaminones with o-Alkynylbenzaldehydes", 《ADVANCED SYNTHESIS & CATALYSIS》, vol. 364, no. 24, pages 4440 - 4446 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109053625B (zh) | 一种取代苯并噻唑c2烷基化衍生物的制备方法 | |
| CN108314658B (zh) | 一种多取代噁唑衍生物的制备方法 | |
| Ghashang et al. | An eco-friendly catalytic route for one-pot synthesis of 2-amino-6-(2-oxo-2 H chromen-3-yl)-4-arylnicotinonitrile derivatives by silica-supported perchloric acid (HClO 4–SiO 2) under solvent-free conditions | |
| CN106831632B (zh) | 一种4h-3,1-苯并噁嗪类化合物催化氧化合成方法 | |
| UA73336C2 (en) | A method for the preparation of 5-cyano-phtalid | |
| CN104557957B (zh) | 螺‑氧化吲哚环氧乙烷衍生物的合成方法 | |
| Zhan et al. | Solvent-and catalyst-free synthesis of dihydropyrimidinthiones in one-pot under focused microwave irradiation conditions | |
| CN102675223B (zh) | 一种多取代喹唑啉及杂环并嘧啶衍生物的制备方法 | |
| CN115504953A (zh) | 3-异香豆素基色酮化合物的制备方法 | |
| CN110204533B (zh) | 一种4-(异色烯-1-基)异喹啉衍生物的制备方法 | |
| CN110256451B (zh) | 一种苯并呋喃并[2,3-b]喹啉衍生物的合成方法 | |
| CN108558785A (zh) | 一种5-芳基-2-芳硒基-1,3-噁唑化合物及制备方法 | |
| CN104327025B (zh) | 一种4-芳基萘内酯类衍生物的制备方法 | |
| CN109651385A (zh) | 一种吡喃[3,2-a]咔唑类化合物的制备方法 | |
| CN111100085B (zh) | 一种3-芳基-2H-苯并[β][1,4]苯并恶嗪-2-酮化合物的制备方法 | |
| CN110698426B (zh) | 叔丁醇钾高效催化制备1,3-苯并噻唑衍生物的方法 | |
| CN107954960B (zh) | 一种1,3-二氢异苯并呋喃类化合物的合成方法 | |
| CN105272953A (zh) | 一种合成苯并呋喃萘醌衍生物的方法 | |
| CN106831610B (zh) | 一种喹唑啉类化合物的催化氧化合成方法 | |
| CN111875549A (zh) | 一种在水相中光催化合成喹唑啉酮化合物的方法 | |
| CN109320482B (zh) | 一种α取代2H-色烯衍生物的合成方法 | |
| CN101555248B (zh) | 一种多取代1,5-萘啶化合物的制备方法 | |
| CN109456155A (zh) | 一种快速的基于取代环丁醇氧化开环/环化反应制备萘满酮衍生物的方法 | |
| CN111892582B (zh) | 一种苯并呋喃香豆素化合物的制备方法 | |
| Yin et al. | An efficient synthesis of 8-aryl-9H-cyclopenta [a][4, 7] phenanthroline derivatives catalyzed by iodine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |