CN114560837B - Chromone compound and preparation method and application thereof - Google Patents
Chromone compound and preparation method and application thereof Download PDFInfo
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- CN114560837B CN114560837B CN202210121098.0A CN202210121098A CN114560837B CN 114560837 B CN114560837 B CN 114560837B CN 202210121098 A CN202210121098 A CN 202210121098A CN 114560837 B CN114560837 B CN 114560837B
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- reaction
- chromone
- ethyl acetate
- nmr
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- -1 Chromone compound Chemical class 0.000 title claims abstract description 93
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 110
- 239000002904 solvent Substances 0.000 claims description 48
- SMQUZDBALVYZAC-UHFFFAOYSA-N ortho-hydroxybenzaldehyde Natural products OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims description 33
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 25
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 8
- 150000004777 chromones Chemical class 0.000 claims description 8
- 125000004185 ester group Chemical group 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 229910052741 iridium Inorganic materials 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 229920002554 vinyl polymer Polymers 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 150000001299 aldehydes Chemical class 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- MMAGMBCAIFVRGJ-UHFFFAOYSA-J iridium(3+);1,2,3,4,5-pentamethylcyclopenta-1,3-diene;tetrachloride Chemical compound Cl[Ir+]Cl.Cl[Ir+]Cl.CC=1C(C)=C(C)[C-](C)C=1C.CC=1C(C)=C(C)[C-](C)C=1C MMAGMBCAIFVRGJ-UHFFFAOYSA-J 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical class CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 7
- 150000001412 amines Chemical class 0.000 claims 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 150000004679 hydroxides Chemical class 0.000 claims 1
- 125000005547 pivalate group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000007867 post-reaction treatment Methods 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 362
- 239000012074 organic phase Substances 0.000 description 83
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 76
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- 238000004440 column chromatography 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 42
- 238000010791 quenching Methods 0.000 description 42
- 238000003786 synthesis reaction Methods 0.000 description 42
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 41
- 230000015572 biosynthetic process Effects 0.000 description 41
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 40
- 238000012512 characterization method Methods 0.000 description 39
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 39
- 230000000171 quenching effect Effects 0.000 description 39
- 239000008346 aqueous phase Substances 0.000 description 38
- 238000001035 drying Methods 0.000 description 38
- 238000005406 washing Methods 0.000 description 37
- NEUPUPPESCHLPS-UHFFFAOYSA-N 2-(2,2-difluoroethenyl)-4-methylbenzenesulfonic acid Chemical compound Cc1ccc(c(C=C(F)F)c1)S(O)(=O)=O NEUPUPPESCHLPS-UHFFFAOYSA-N 0.000 description 25
- 239000010948 rhodium Substances 0.000 description 25
- 229910018286 SbF 6 Inorganic materials 0.000 description 22
- LGVUAXNPXVXCCW-UHFFFAOYSA-M cesium;2,2-dimethylpropanoate Chemical compound [Cs+].CC(C)(C)C([O-])=O LGVUAXNPXVXCCW-UHFFFAOYSA-M 0.000 description 21
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 20
- 239000000920 calcium hydroxide Substances 0.000 description 20
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 20
- 229910000027 potassium carbonate Inorganic materials 0.000 description 20
- 125000003118 aryl group Chemical group 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 9
- 150000002430 hydrocarbons Chemical group 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- FZHSPPYCNDYIKD-UHFFFAOYSA-N 5-methoxysalicylaldehyde Chemical compound COC1=CC=C(O)C(C=O)=C1 FZHSPPYCNDYIKD-UHFFFAOYSA-N 0.000 description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 7
- YZVFSQQHQPPKNX-UHFFFAOYSA-N 1,3-thiazole-5-carboxylic acid Chemical compound OC(=O)C1=CN=CS1 YZVFSQQHQPPKNX-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 125000003172 aldehyde group Chemical group 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- LSRYDXKYMCAGFS-UHFFFAOYSA-N 1h-naphthalene Chemical compound C1=CC=C2C=C[CH]CC2=C1 LSRYDXKYMCAGFS-UHFFFAOYSA-N 0.000 description 4
- JODRRPJMQDFCBJ-UHFFFAOYSA-N 2-Hydroxy-4-methylbenzaldehyde Chemical compound CC1=CC=C(C=O)C(O)=C1 JODRRPJMQDFCBJ-UHFFFAOYSA-N 0.000 description 4
- NTCCNERMXRIPTR-UHFFFAOYSA-N 2-hydroxy-1-naphthaldehyde Chemical compound C1=CC=CC2=C(C=O)C(O)=CC=C21 NTCCNERMXRIPTR-UHFFFAOYSA-N 0.000 description 4
- ILEIUTCVWLYZOM-UHFFFAOYSA-N 2-hydroxy-5-methylbenzaldehyde Chemical compound CC1=CC=C(O)C(C=O)=C1 ILEIUTCVWLYZOM-UHFFFAOYSA-N 0.000 description 4
- IHFRMUGEILMHNU-UHFFFAOYSA-N 2-hydroxy-5-nitrobenzaldehyde Chemical compound OC1=CC=C([N+]([O-])=O)C=C1C=O IHFRMUGEILMHNU-UHFFFAOYSA-N 0.000 description 4
- ROILLNJICXGZQQ-UHFFFAOYSA-N 3-tert-butyl-2-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC=CC(C=O)=C1O ROILLNJICXGZQQ-UHFFFAOYSA-N 0.000 description 4
- QNZWAJZEJAOVPN-UHFFFAOYSA-N 4-chloro-2-hydroxybenzaldehyde Chemical compound OC1=CC(Cl)=CC=C1C=O QNZWAJZEJAOVPN-UHFFFAOYSA-N 0.000 description 4
- MKKSTJKBKNCMRV-UHFFFAOYSA-N 5-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Br)C=C1C=O MKKSTJKBKNCMRV-UHFFFAOYSA-N 0.000 description 4
- FUGKCSRLAQKUHG-UHFFFAOYSA-N 5-chloro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Cl)C=C1C=O FUGKCSRLAQKUHG-UHFFFAOYSA-N 0.000 description 4
- FDUBQNUDZOGOFE-UHFFFAOYSA-N 5-fluoro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(F)C=C1C=O FDUBQNUDZOGOFE-UHFFFAOYSA-N 0.000 description 4
- WQNTWZJPCLUXQC-UHFFFAOYSA-N 5-tert-butyl-2-hydroxybenzene-1,3-dicarbaldehyde Chemical compound CC(C)(C)C1=CC(C=O)=C(O)C(C=O)=C1 WQNTWZJPCLUXQC-UHFFFAOYSA-N 0.000 description 4
- BGGDEYLNSNKIGJ-UHFFFAOYSA-N CC1=C(C(C(F)F)O)C2=CC(C)=CC=C2N1 Chemical compound CC1=C(C(C(F)F)O)C2=CC(C)=CC=C2N1 BGGDEYLNSNKIGJ-UHFFFAOYSA-N 0.000 description 4
- JBYBJRNVSDFUMS-UHFFFAOYSA-N OC(C(F)F)C1=CNC2=C1C(C=O)=CC=C2 Chemical compound OC(C(F)F)C1=CNC2=C1C(C=O)=CC=C2 JBYBJRNVSDFUMS-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- LBZHVONZEAUDNM-UHFFFAOYSA-N benzo[h]chromen-4-one Chemical compound C1=CC=CC2=CC=C3C(=O)C=COC3=C21 LBZHVONZEAUDNM-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000004428 fluoroalkoxy group Chemical group 0.000 description 4
- 125000004438 haloalkoxy group Chemical group 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- ADSJCWKOKYOJSZ-UHFFFAOYSA-N methyl 3-formyl-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C(C=O)=C1 ADSJCWKOKYOJSZ-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 235000019260 propionic acid Nutrition 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- OITQDWKMIPXGFL-UHFFFAOYSA-N 1-hydroxy-2-naphthaldehyde Chemical compound C1=CC=C2C(O)=C(C=O)C=CC2=C1 OITQDWKMIPXGFL-UHFFFAOYSA-N 0.000 description 3
- WQUZBERVMUEJTD-UHFFFAOYSA-N 2-hydroxy-5-(trifluoromethoxy)benzaldehyde Chemical compound OC1=CC=C(OC(F)(F)F)C=C1C=O WQUZBERVMUEJTD-UHFFFAOYSA-N 0.000 description 3
- DCYKYFMFAFQHSE-UHFFFAOYSA-N 3-(3-formyl-4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=C(O)C(C=O)=C1 DCYKYFMFAFQHSE-UHFFFAOYSA-N 0.000 description 3
- IPPQNXSAJZOTJZ-UHFFFAOYSA-N 3-methylsalicylaldehyde Chemical compound CC1=CC=CC(C=O)=C1O IPPQNXSAJZOTJZ-UHFFFAOYSA-N 0.000 description 3
- XFVZSRRZZNLWBW-UHFFFAOYSA-N 4-(Diethylamino)salicylaldehyde Chemical compound CCN(CC)C1=CC=C(C=O)C(O)=C1 XFVZSRRZZNLWBW-UHFFFAOYSA-N 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
- ZVCQQLGWGRTXGC-UHFFFAOYSA-N 5-tert-butyl-2-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC=C(O)C(C=O)=C1 ZVCQQLGWGRTXGC-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- JEUUNKOFKDUVMN-UHFFFAOYSA-N benzo[f]chromen-1-one Chemical compound C1=CC=CC2=C3C(=O)C=COC3=CC=C21 JEUUNKOFKDUVMN-UHFFFAOYSA-N 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- NJRGQNNSIAFIJC-UHFFFAOYSA-N ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OCC)SC(C=2C=C(C=O)C(O)=CC=2)=N1 NJRGQNNSIAFIJC-UHFFFAOYSA-N 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- VVPNFGSOEZZIAM-UHFFFAOYSA-N 6-(trifluoromethoxy)chromen-4-one Chemical compound O1C=CC(=O)C2=CC(OC(F)(F)F)=CC=C21 VVPNFGSOEZZIAM-UHFFFAOYSA-N 0.000 description 2
- XVNBWGGBXOJIDR-UHFFFAOYSA-N 6-bromochromen-4-one Chemical compound O1C=CC(=O)C2=CC(Br)=CC=C21 XVNBWGGBXOJIDR-UHFFFAOYSA-N 0.000 description 2
- VFZQATFTQAZCMO-UHFFFAOYSA-N 6-chlorochromen-4-one Chemical compound O1C=CC(=O)C2=CC(Cl)=CC=C21 VFZQATFTQAZCMO-UHFFFAOYSA-N 0.000 description 2
- WHIGSYZUTMYUAX-UHFFFAOYSA-N 6-fluorochromen-4-one Chemical compound O1C=CC(=O)C2=CC(F)=CC=C21 WHIGSYZUTMYUAX-UHFFFAOYSA-N 0.000 description 2
- ORWADBVBOPTYQT-UHFFFAOYSA-N 6-nitrochromen-4-one Chemical compound O1C=CC(=O)C2=CC([N+](=O)[O-])=CC=C21 ORWADBVBOPTYQT-UHFFFAOYSA-N 0.000 description 2
- JQQABSXUHNBEPB-UHFFFAOYSA-N 7-chlorochromen-4-one Chemical compound O1C=CC(=O)C=2C1=CC(Cl)=CC=2 JQQABSXUHNBEPB-UHFFFAOYSA-N 0.000 description 2
- MOISBGWJJHJRIH-UHFFFAOYSA-N 7-methylchromen-4-one Chemical compound O1C=CC(=O)C=2C1=CC(C)=CC=2 MOISBGWJJHJRIH-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical group CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical group CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical group CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical group CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000004490 chloroalkoxy group Chemical group 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical group CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical group COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical group COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000002004 n-butylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 229950010765 pivalate Drugs 0.000 description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical group CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
- 125000006308 propyl amino group Chemical group 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- YIEZNXKAURZSNL-UHFFFAOYSA-N 2-(diethylamino)-6-hydroxybenzaldehyde Chemical compound CCN(CC)C1=CC=CC(O)=C1C=O YIEZNXKAURZSNL-UHFFFAOYSA-N 0.000 description 1
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 1
- ZBOUXALQDLLARY-UHFFFAOYSA-N 2-hydroxy-5-methylbenzene-1,3-dicarbaldehyde Chemical compound CC1=CC(C=O)=C(O)C(C=O)=C1 ZBOUXALQDLLARY-UHFFFAOYSA-N 0.000 description 1
- HTXQVFXXVXOLCF-UHFFFAOYSA-N 6-methylchromen-4-one Chemical compound O1C=CC(=O)C2=CC(C)=CC=C21 HTXQVFXXVXOLCF-UHFFFAOYSA-N 0.000 description 1
- AEWCNPOKYFDMMA-UHFFFAOYSA-N 6-tert-butylchromen-4-one Chemical compound O1C=CC(=O)C2=CC(C(C)(C)C)=CC=C21 AEWCNPOKYFDMMA-UHFFFAOYSA-N 0.000 description 1
- DLBDWKDOHINUIM-UHFFFAOYSA-N 8-methylchromen-4-one Chemical compound O1C=CC(=O)C2=C1C(C)=CC=C2 DLBDWKDOHINUIM-UHFFFAOYSA-N 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- CIPMPQGRFNDLAP-UHFFFAOYSA-N ethyl 1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=CS1 CIPMPQGRFNDLAP-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- ABJKIHHNDMEBNA-UHFFFAOYSA-N methylchromone Chemical compound C1=CC=C2C(=O)C(C)=COC2=C1 ABJKIHHNDMEBNA-UHFFFAOYSA-N 0.000 description 1
- 229950009263 methylchromone Drugs 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 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
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- WFMNHCSATCWAAQ-UHFFFAOYSA-M potassium;2,2-dimethylpropanoate Chemical compound [K+].CC(C)(C)C([O-])=O WFMNHCSATCWAAQ-UHFFFAOYSA-M 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- SJRDNQOIQZOVQD-UHFFFAOYSA-M sodium;2,2-dimethylpropanoate Chemical compound [Na+].CC(C)(C)C([O-])=O SJRDNQOIQZOVQD-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- 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
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- 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
- 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/44—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3
- C07D311/46—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3 unsubstituted in the carbocyclic ring
-
- 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/44—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3
- C07D311/54—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3 substituted in the carbocyclic ring
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/16—Peri-condensed systems
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Abstract
The invention discloses a chromone compound, a preparation method and application thereof. The method has the advantages of environmental friendliness, low price and the like; the reaction condition is mild, the operation is simple, and the yield is high; the post-reaction treatment is simple and convenient, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a chromone compound and a preparation method and application thereof.
Background
Chromone is a special oxygen-containing benzoheterocyclic compound, exists in natural products, and has remarkable biological characteristics, such as oxidation resistance, inflammation resistance, cancer resistance and the like. At present, salicylaldehyde is widely applied to the synthesis of a chromone skeleton, the used alkynyl ligand has high cost and certain danger, and the efficient construction of the chromone skeleton is still a challenge by selecting a simple and easily available alkynyl equivalent synthon with low cost.
In summary, there is a need to provide a process for the preparation of chromone analogs, which is cost effective.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a chromone compound, and the medicine prepared by using the compound has good metabolic stability.
The invention also provides a preparation method of the chromone compound, and the preparation method has low cost.
The invention also provides application of the chromone compound.
Specifically, the first aspect of the present invention provides a chromone compound, where the structural formula is shown in the following formula (iii):
wherein R is 1 And R is 2 Independently selected from hydrogen, alkyl, alkoxy, halogen, nitro, ester, aldehyde, amino, alkenyl, carboxyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl;
x is selected from O atom, N atom or S atom;
R 1 and R is 2 Forming a ring or not;
R 1 and C atoms in benzene rings in salicylaldehyde compounds shown in the formula (III) form a ring or do not form a ring;
R 2 and C atoms in benzene rings in salicylaldehyde compounds shown in the formula (III) form a ring or do not form a ring;
R 3 selected from hydrogen or alkoxy.
According to one of the technical schemes of the chromone compounds, the invention has at least the following beneficial effects:
According to the chromone compound, chromone is used as a parent nucleus structure, substituent groups are introduced into the chromone parent nucleus, and the metabolic stability and the fat solubility of the chromone compound are improved through the introduction of the substituent groups.
According to some embodiments of the invention, the alkyl is C 1 ～C 20 Is a hydrocarbon group.
According to some embodiments of the invention, the alkyl group comprises C 1 ～C 10 Is a hydrocarbon group.
According to some embodiments of the invention, the alkyl group comprises C 1 ～C 8 Is a hydrocarbon group.
According to some embodiments of the invention, the alkyl group comprises at least one of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and tert-butyl.
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, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy and tert-butoxy.
According to some embodiments of the invention, the alkoxy group further comprises a haloalkoxy group.
According to some embodiments of the invention, the haloalkoxy group comprises at least one of fluoroalkoxy, chloroalkoxy, bromoalkoxy, and iodoalkoxy.
According to some embodiments of the invention, the fluoroalkoxy group comprises a trifluoroethoxy group or a trifluoromethoxy group.
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 ester group comprises C 1 ～C 10 Ester groups of (a) are present.
According to some embodiments of the invention, the ester group comprises at least one of a methyl formate group, an ethyl formate group, a methyl acetate group, an ethyl acetate group, and a propyl acetate group.
According to some embodiments of the invention, the aldehyde group comprises C 1 ～C 10 Is an aldehyde group of (a).
According to some embodiments of the invention, the aldehyde group comprises at least one of a formaldehyde group, an acetaldehyde group, a propionaldehyde group, a n-butyraldehyde group, an isobutyraldehyde group.
According to some embodiments of the invention, the amine group comprises C 1 ～C 10 Is a group of amino groups of (a).
According to some embodiments of the invention, the amine group comprises at least one of a methylamino group, a diethylamino group, an ethylamino group, a propylamino group, an isopropylamino group, an n-butylamino group, an isobutylamino group, and a t-butylamino group.
According to some embodiments of the invention, the alkenyl group comprises C 1 ～C 10 Alkenyl groups of (c).
According to some embodiments of the invention, the alkenyl group comprises at least one of ethenyl, propenyl, and butenyl.
According to some embodiments of the invention, the carboxyl group comprises C 1 ～C 10 Carboxyl groups of (a) are provided.
According to some embodiments of the invention, the substituted carboxyl group comprises C 1 ～C 10 Substituted carboxyl groups of (a).
According to some embodiments of the invention, the aryl is C 1 ～C 20 Aryl groups of (a).
According to some embodiments of the invention, the aryl is C 1 ～C 15 Aryl groups of (a).
According to some embodiments of the invention, the aryl group comprises salicylaldehyde group, phenyl group, or naphthyl group.
According to some embodiments of the invention, the heteroaryl is C 1 ～C 15 And a heterocyclic group containing at least one of N, O and S.
According to some embodiments of the invention, the heterocyclyl is C 1 ～C 10 Nitrogen-containing heterocycles and oxygen-containing heterocycles.
According to some embodiments of the invention, the heterocyclyl is C 1 ～C 10 Nitrogen-containing heterocyclic groups of (a).
According to some embodiments of the present invention, the chromone compounds include 3- (2, 2-difluoro-1-hydroxyethyl) -1H-indole-4-carbaldehyde, 1H-naphthalene [2,1-b ] pyran-1-one, 4H-naphtho [1,2-b ] pyran-4-one, ethyl 4-methyl-2- (4-oxo-4H-chromium-6-yl) thiazole-5-carboxylate, 2- (2, 2-trifluoroethoxy) chromone, 6-fluoro-2- (2, 2-trifluoroethoxy) chromone, 6-chloro-2- (2, 2-trifluoroethoxy) chromone, 6-bromo-2- (2, 2-trifluoroethoxy) chromone 6-methyl-2- (2, 2-trifluoroethoxy) chromone, 6-methoxy-2- (2, 2-trifluoroethoxy) chromone, 6-tert-butyl-2- (2, 2-trifluoroethoxy) chromone, 6-nitro-2- (2, 2-trifluoroethoxy) chromone methyl 6-carboxylate-2- (2, 2-trifluoroethoxy) chromone, 7-methyl-2- (2, 2-trifluoroethoxy) chromone, 7-chloro-2- (2, 2-trifluoroethoxy) chromone, 7-diethylamino-2- (2, 2-trifluoroethoxy) chromone, 8-methyl-2- (2, 2-trifluoroethoxy) chromone, 8-tert-butyl-2- (2, 2-trifluoroethoxy) chromone, 6-methyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde, 6-tert-butyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde, 3- (2, 2-trifluoroethoxy) -1H benzo [ f ] chromen-1-one at least one of 1- (2, 5-dimethyl-1H-indol-3-yl) -2, 2-difluoroethane-1-ol, 2- ((tert-butoxycarbonyl) amino) -3- (4-oxo-4H-chrome-6-yl) propionic acid and 4-methyl-2- (4-oxo-2- (2, 2-trifluoroethoxy) -4H-chrome-6-yl) thiazole-5-carboxylic acid.
The second aspect of the present invention provides a method for preparing the chromone compound of the first aspect of the present invention, comprising the steps of:
the salicylaldehyde compound shown in the formula (I) and the fluorine-containing vinyl compound shown in the formula (II) are mixed and reacted to prepare the chromone compound shown in the formula (III);
wherein R is 1 And R is 2 Independently selected from hydrogen, alkyl, alkoxy, halogen, nitro, ester, aldehyde, amino, alkenyl, carboxyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl;
x is selected from O atom, N atom or S atom;
R 1 and R is 2 Forming a ring or not;
R 1 and C atoms in benzene rings in salicylaldehyde compounds shown in the formula (I) form a ring or do not form a ring;
R 2 and C atoms in benzene rings in salicylaldehyde compounds shown in the formula (I) form a ring or do not form a ring;
R 3 selected from hydrogen or alkoxy;
R 4 selected from hydrogen or fluorine;
r is selected from benzenesulfonyl, p-toluenesulfonyl, o-toluenesulfonyl, p-fluorobenzenesulfonyl, o-fluorobenzenesulfonyl, p-trifluoromethylbenzenesulfonyl, o-trifluorobenzenesulfonyl, phenyl and naphthyl;
the catalyst of the reaction is a transition metal catalyst.
According to one of the technical schemes of the preparation method, the preparation method at least has the following beneficial effects:
The fluorine-containing vinyl compound in the preparation raw material is a fluorinated synthon, and the fluorine-containing vinyl compound is synthesized into the chromone skeleton, so that the method is a more convenient, efficient and environment-friendly chromone skeleton construction method. Meanwhile, the present invention provides various substituted chromone analogs in moderate to excellent yields based on a hydrocarbon activation reaction under the catalysis of a transition metal catalyst. The preparation raw materials are simple and easy to obtain, environment-friendly and low in price; the reaction condition is mild, the operation is simple, and the yield is high; the post-reaction treatment is simple and convenient, and is suitable for industrial production.
According to some embodiments of the present invention, the salicylaldehyde compound represented by formula (I) comprises at least one of salicylaldehyde, 5-chlorosalicylaldehyde, 5-bromosalicylaldehyde, 2-hydroxy-5-methylbenzaldehyde, 4-chloro-2-hydroxybenzaldehyde, 2-hydroxy-5-nitrobenzaldehyde, 2-hydroxy-4-methylbenzaldehyde, 2-hydroxy-3-methylbenzaldehyde, 2-hydroxy-5-methoxybenzaldehyde, methyl 3-formyl-4-hydroxybenzoate, 2-hydroxy-1-naphthaldehyde, 1-hydroxy-2-naphthaldehyde, 5- (tert-butyl) -2-hydroxybenzaldehyde, 3- (tert-butyl) -2-hydroxybenzaldehyde, 5- (tert-butyl) -2-hydroxyisophthalaldehyde, ethyl 2- (3-formyl-4-hydroxyphenyl) -4-methylthiazole-5-carboxylate, 4-diethylaminosalicylaldehyde, 5- (trifluoromethoxy) salicylaldehyde, 5-fluoro salicylaldehyde, and 2- ((tert-butoxycarbonyl) amino) -3- (3-formyl-4-hydroxyphenyl) propionic acid.
According to some embodiments of the present invention, the fluorovinyl compound represented by formula (II) comprises at least one of 2-fluorovinyl 4-methylbenzenesulfonic acid or 2, 2-difluorovinyl 4-methylbenzenesulfonic acid.
According to the preparation method, the 2, 2-difluoro vinyl 4-methylbenzenesulfonic acid or 2-fluoro vinyl 4-methylbenzenesulfonic acid is used as a fluorinated synthon, and the reagent is used as an alkynyl equivalent synthon to synthesize hydrocarbon activation reaction of the chromone skeleton, so that convenient, efficient and environment-friendly construction of the chromone skeleton is realized.
According to some embodiments of the invention, the alkyl is C 1 ～C 20 Is a hydrocarbon group.
According to some embodiments of the invention, the alkyl group comprises C 1 ～C 10 Is a hydrocarbon group.
According to some embodiments of the invention, the alkyl group comprises C 1 ～C 8 Is a hydrocarbon group.
According to some embodiments of the invention, the alkyl group comprises at least one of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and tert-butyl.
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, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy and tert-butoxy.
According to some embodiments of the invention, the alkoxy group further comprises a haloalkoxy group.
According to some embodiments of the invention, the haloalkoxy group comprises at least one of fluoroalkoxy, chloroalkoxy, bromoalkoxy, and iodoalkoxy.
According to some embodiments of the invention, the fluoroalkoxy group comprises a trifluoroethoxy group or a trifluoromethoxy group.
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 ester group comprises C 1 ～C 10 Ester groups of (a) are present.
According to some embodiments of the invention, the ester group comprises at least one of a methyl formate group, an ethyl formate group, a methyl acetate group, an ethyl acetate group, and a propyl acetate group.
According to some embodiments of the invention, the aldehyde group comprises C 1 ～C 10 Is an aldehyde group of (a).
According to some embodiments of the invention, the aldehyde group comprises at least one of a formaldehyde group, an acetaldehyde group, a propionaldehyde group, a n-butyraldehyde group, an isobutyraldehyde group.
According to some embodiments of the invention, the amine group comprises C 1 ～C 10 Is a group of amino groups of (a).
According to some embodiments of the invention, the amine group comprises at least one of a methylamino group, a diethylamino group, an ethylamino group, a propylamino group, an isopropylamino group, an n-butylamino group, an isobutylamino group, and a t-butylamino group.
According to some embodiments of the invention, the alkenyl group comprises C 1 ～C 10 Alkenyl groups of (c).
According to some embodiments of the invention, the alkenyl group comprises at least one of ethenyl, propenyl, and butenyl.
According to some embodiments of the invention, the carboxyl group comprises C 1 ～C 10 Carboxyl groups of (a) are provided.
According to some embodiments of the invention, the substituted carboxyl group comprises C 1 ～C 10 Substituted carboxyl groups of (a). According to some embodiments of the invention, the aryl is C 1 ～C 20 Aryl groups of (a).
According to some embodiments of the invention, the aryl is C 1 ～C 15 Aryl groups of (a).
According to some embodiments of the invention, the aryl group comprises salicylaldehyde group, phenyl group, or naphthyl group.
According to some embodiments of the invention, the heteroaryl refers to C 1 ～C 15 And a heterocyclic ring containing at least one of N, O and S.
According to some embodiments of the invention, the heterocycle is C 1 ～C 10 Nitrogen-containing heterocycles and oxygen-containing heterocycles.
According to some embodiments of the invention, the heterocycle is C 1 ～C 10 Nitrogen-containing heterocycles of (2).
According to some embodiments of the present invention, the chromone compounds include chromone, 6-chlorochromone, 6-bromochromone, 6-methyl chromone, 7-chlorochromone, 6-nitrochromone, 7-methyl chromone, 8-methyl chromone, 3- (2, 2-difluoro-1-hydroxyethyl) -1H-indole-4-carbaldehyde, 6-carboxylic acid methyl chromone, 1H-naphthalene [2,1-b ] pyran-1-one, 4H-naphtho [1,2-b ] pyran-4-one, 6-tert-butyl chromone, 8-tert-butyl chromone, 6- (tert-butyl) -8-carbaldehyde chromone ethyl 4-methyl-2- (4-oxo-4H-chromen-6-yl) thiazole-5-carboxylate, 7-diethylaminochromone, 6-trifluoromethoxy chromone, 6-fluorochromone, 2- (2, 2-trifluoroethoxy) chromone, 6-fluoro-2- (2, 2-trifluoroethoxy) chromone 6-chloro-2- (2, 2-trifluoroethoxy) chromone, 6-bromo-2- (2, 2-trifluoroethoxy) chromone, 6-methyl-2- (2, 2-trifluoroethoxy) chromone, 6-methoxy-2- (2, 2-trifluoroethoxy) chromone, 6-tert-butyl-2- (2, 2-trifluoroethoxy) chromone, 6-nitro-2- (2, 2-trifluoroethoxy) chromone, 6-carboxylic acid methyl ester-2- (2, 2-trifluoroethoxy) chromone, 7-methyl-2- (2, 2-trifluoroethoxy) chromone 7-chloro-2- (2, 2-trifluoroethoxy) chromone, 7-diethylamino-2- (2, 2-trifluoroethoxy) chromone, 8-methyl-2- (2, 2-trifluoroethoxy) chromone 8-tert-butyl-2- (2, 2-trifluoroethoxy) chromone, 6-methyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde, 6-tert-butyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde, 3- (2, 2-trifluoroethoxy) -1H-benzo [ f ] chromen-1-one, 1- (2, 5-dimethyl-1H-indol-3-yl) -2, 2-difluoroethane-1-ol, at least one of 2- ((tert-butoxycarbonyl) amino) -3- (4-oxo-4H-chrome-6-yl) propionic acid and 4-methyl-2- (4-oxo-2- (2, 2-trifluoroethoxy) -4H-chrome-6-yl) thiazole-5-carboxylic acid.
According to some embodiments of the present invention, the molar ratio of the salicylaldehyde compound represented by the formula (I) to the fluorovinyl compound represented by the formula (II) is 1:2-4.
According to some embodiments of the invention, the molar ratio of the salicylaldehyde compound represented by formula (I) to the fluorovinyl compound represented by formula (II) is 1:2.
According to some embodiments of the invention, the transition metal catalyst is a trivalent iridium catalyst or a trivalent rhodium catalyst.
According to some embodiments of the invention, the trivalent iridium catalyst is [ cp×ircl 2 ](dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, CAS number 12354-84-6).
According to some embodiments of the invention, the trivalent rhodium catalyst [ Cp ] Rh (CH 3 CN) 3 ](SbF 6 ) 2 ](Di (hexafluoroantimonate) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III), CAS number 125357-42-8) and [ Cp RhCl ] 2 ](dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, CAS number 212354-85-7).
According to some embodiments of the invention, the molar ratio of the salicylaldehyde compound represented by formula (I) to the catalyst is 1:0.02 to 1.
According to some embodiments of the invention, the molar ratio of the salicylaldehyde compound represented by formula (I) to the catalyst is 1:0.05 to 1.
According to some embodiments of the invention, the molar ratio of the salicylaldehyde compound represented by formula (I) to the catalyst is 1:0.05 to 0.15.
According to some embodiments of the invention, the molar ratio of the salicylaldehyde compound represented by formula (I) to the catalyst is 1:0.05.
according to some embodiments of the invention, a base is added to the reaction.
According to some embodiments of the invention, the molar ratio of the base to the salicylaldehyde compound represented by formula (I) is 1:1-3.
According to some embodiments of the invention, the molar ratio of the base to the salicylaldehyde compound represented by formula (I) is 1:1.5-3.
According to some embodiments of the invention, the base comprises a carbonate, a pivalate, or a hydroxide.
According to some embodiments of the invention, the carbonate comprises at least one of sodium carbonate, potassium carbonate, or cesium carbonate.
According to some embodiments of the invention, the pivalate comprises at least one of sodium pivalate, potassium pivalate, or cesium pivalate.
According to some embodiments of the invention, the hydroxide comprises at least one of sodium hydroxide, potassium hydroxide, cesium hydroxide, or calcium hydroxide.
According to some embodiments of the invention, the solvent of the reaction is at least one of trifluoroethanol, methanol or hexafluoroisopropanol.
According to some embodiments of the invention, when 2-fluorovinyl-4-methylbenzenesulfonic acid is used as a preparation raw material, the reaction solvent is hexafluoroisopropanol.
According to some embodiments of the invention, when 2, 2-difluorovinyl-4-methylbenzenesulfonic acid is used as a preparation raw material, the reaction solvent is trifluoroethanol.
According to some embodiments of the invention, the volume molar ratio of the solvent to the salicylaldehyde compound represented by formula (I) is 5mL/mmol to 15mL/mmol.
According to some embodiments of the invention, the volume molar ratio of the solvent to the salicylaldehyde compound of formula (I) is 10mL/mmol.
According to some embodiments of the invention, the reaction is a hydrocarbon activation reaction.
According to some embodiments of the invention, the temperature of the reaction is 25 ℃ to 120 ℃.
According to some embodiments of the invention, the reaction time is 3 to 12 hours.
According to some embodiments of the invention, the reaction time is 3 to 10 hours.
According to some embodiments of the invention, the reaction time is 3h.
According to some embodiments of the invention, the reaction temperature is about 90 ℃ when 2-fluorovinyl 4-methylbenzenesulfonic acid is used as a starting material.
According to some embodiments of the invention, the reaction time is about 10 hours when 2-fluorovinyl-4-methylbenzenesulfonic acid is used as a preparation raw material.
According to some embodiments of the invention, the reaction temperature is about 80 ℃ when 2, 2-difluorovinyl 4-methylbenzenesulfonic acid is used as a starting material.
According to some embodiments of the present invention, 2-difluorovinyl 4-methylbenzenesulfonic acid is used as a preparation starting material for a reaction time of about 3 hours.
According to some embodiments of the invention, after the reaction is completed, quenching, first washing, first extraction, second washing, second extraction, concentration, and column chromatography are further 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.
The third aspect of the invention provides application of the chromone compound in preparing any one of anti-inflammatory drugs, antioxidant drugs and anticancer drugs.
According to one technical scheme of the invention, the invention has at least the following beneficial effects:
According to the chromone compound, chromone is used as a parent nucleus structure, substituent groups are introduced into the chromone parent nucleus, and the metabolic stability and the fat solubility of the chromone compound are improved through the introduction of the substituent groups.
According to some embodiments of the present invention, the chromone compounds include 3- (2, 2-difluoro-1-hydroxyethyl) -1H-indole-4-carbaldehyde, 1H-naphthalene [2,1-b ] pyran-1-one, 4H-naphtho [1,2-b ] pyran-4-one, ethyl 4-methyl-2- (4-oxo-4H-chromium-6-yl) thiazole-5-carboxylate, 2- (2, 2-trifluoroethoxy) chromone, 6-fluoro-2- (2, 2-trifluoroethoxy) chromone, 6-chloro-2- (2, 2-trifluoroethoxy) chromone, 6-bromo-2- (2, 2-trifluoroethoxy) chromone 6-methyl-2- (2, 2-trifluoroethoxy) chromone, 6-methoxy-2- (2, 2-trifluoroethoxy) chromone, 6-tert-butyl-2- (2, 2-trifluoroethoxy) chromone, 6-nitro-2- (2, 2-trifluoroethoxy) chromone methyl 6-carboxylate-2- (2, 2-trifluoroethoxy) chromone, 7-methyl-2- (2, 2-trifluoroethoxy) chromone, 7-chloro-2- (2, 2-trifluoroethoxy) chromone, 7-diethylamino-2- (2, 2-trifluoroethoxy) chromone, 8-methyl-2- (2, 2-trifluoroethoxy) chromone, 8-tert-butyl-2- (2, 2-trifluoroethoxy) chromone, 6-methyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde, 6-tert-butyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde, 3- (2, 2-trifluoroethoxy) -1H benzo [ f ] chromen-1-one at least one of 1- (2, 5-dimethyl-1H-indol-3-yl) -2, 2-difluoroethane-1-ol, 2- ((tert-butoxycarbonyl) amino) -3- (4-oxo-4H-chrome-6-yl) propionic acid and 4-methyl-2- (4-oxo-2- (2, 2-trifluoroethoxy) -4H-chrome-6-yl) thiazole-5-carboxylic acid.
Detailed Description
The conception and the technical effects produced by the present invention will be clearly and completely described in conjunction with the embodiments below to fully understand the objects, features and effects of the present invention. It is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments, and that other embodiments obtained by those skilled in the art without inventive effort are within the scope of the present invention based on the embodiments of the present invention.
In the description of the present invention, the descriptions of the terms "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Specific embodiments of the present invention are described in detail below.
Unless otherwise specified, 5mol% in the embodiments of the invention represents the catalyst ([ Cp ] IrCl) 2 ]、[Cp*Rh(CH 3 CN) 3 ](SbF 6 ) 2 ]Or [ Cp ] RhCl 2 ]) The molar ratio of the salicylic aldehyde compound to the salicylaldehyde compound is 1:0.05.
in an embodiment of the invention 15mol% represents the catalyst ([ Cp ] IrCl) 2 ]、[Cp*Rh(CH 3 CN) 3 ](SbF 6 ) 2 ]Or [ Cp ] RhCl 2 ]) The molar ratio of the salicylic aldehyde compound to the salicylaldehyde compound is 1:0.15.
the preparation methods of the 2, 2-difluoroethylene 4-methylbenzenesulfonic acid and the 2-fluoroethylene 4-methylbenzenesulfonic acid in the embodiment of the invention are as follows:
a500 ml round bottom flask was charged with 19.0g (100 mmol) of p-toluenesulfonyl chloride (CAS number: 98-59-9), 100g (1 mol) of trifluoroethanol (CAS number: 75-89-8) and 200ml of methylene chloride, 28ml (200 mmol) of triethylamine (CAS number: 121-44-8) was added dropwise at 0℃and reacted for 1 hour, then room temperature conditions were transferred for reaction for 10 hours, after the completion of the reaction, methylene chloride and saturated sodium chloride solution were used for extraction, and the organic phase was taken up in anhydrous sodium sulfate and dried, and the solvent was distilled off under reduced pressure, followed by column chromatography to give 25g of 2, 2-trifluoroethyl p-toluenesulfonate in 98% yield.
A250 ml round bottom flask was charged with 6g (24 mmol) of 2, 2-trifluoroethyl p-toluenesulfonate and anhydrous tetrahydrofuran, the apparatus was vacuum-treated, n-butyllithium (CAS number: 109-72-8) (2.5 equiv) was added dropwise at-78deg.C, the dropwise addition was completed within 20min and after 15min of reaction, 50ml of water was added at room temperature for quenching, the reaction was suction filtered, ethyl acetate and saturated sodium chloride solution were used for extraction after the completion, the organic phase was taken and added with anhydrous sodium sulfate for drying, the solvent was distilled off under reduced pressure, and 4.2g of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid was obtained by column chromatography in 75% yield.
A100 ml round bottom flask was charged with 4.68g (20 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid and 50ml of anhydrous diethyl ether, the apparatus was vacuum-treated, lithium aluminum hydride (CAS number: 16853-85-3) (2 equiv) was added dropwise at-5℃and reacted at room temperature for four hours after 15 minutes, and after completion of the reaction, suction filtration was performed, extraction was performed using ethyl acetate and saturated sodium chloride solution, the organic phase was taken and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and 2.6g of 2-fluorovinyl 4-methylbenzenesulfonic acid was obtained by column chromatography in 60% yield.
The yield calculation method of the embodiment of the invention comprises the following steps: yield = product mass/(molecular weight) * The amount of material fed).
Example 1: synthesis of chromone
A15 mL pressure-resistant tube was charged with 24.4mg (0.20 mmol) of salicylaldehyde, 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, and [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol (CAS number: 920-66-1) were reacted at 90℃for 3 hours. After the reaction is finished, 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 water phase is extracted for 2 times by ethyl acetate, the ethyl acetate dosage is 5mL each time, the organic phases are combined, and the water phase is added Drying with anhydrous sodium sulfate, distilling under reduced pressure to remove solvent, and performing column chromatography to obtain the product with 83% yield.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.20(dd,J＝8.0,1.5Hz,1H),7.85(d,J＝6.0Hz,1H),7.67(m,J＝8.7,7.2,1.7Hz,1H),7.47–7.43(m,1H),7.43–7.38(m,1H),6.34(d,J＝6.0Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ177.79,156.65,155.45,133.91,125.94,125.39,125.01,118.31,113.13.
ESI-MS:calculated for C 9 H 6 O 2 [M+H] - :147.0440,found:147.0440.
example 2: synthesis of 6-chlorochromone:
a15 mL pressure-resistant tube was charged with 31mg (0.20 mmol) of 5-chlorosalicylaldehyde (CAS number: 635-93-8), 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 86%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.14(d,J＝2.6Hz,1H),7.85(d,J＝6.0Hz,1H),7.59(dd,J＝8.9,2.6Hz,1H),7.41(d,J＝8.9Hz,1H),6.34(d,J＝6.0Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ176.53,155.61,154.91,134.14,131.34,125.85,125.32,120.08,113.02.
ESI-MS:calculated for C 9 H 5 ClO 2 [M+H] - :181.0050,found:181.0049.
example 3: synthesis of 6-bromochromone:
a15 mL pressure-resistant tube was charged with 40.2mg (0.20 mmol) of 5-bromosalicylaldehyde (CAS number 1761-61-1), 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 81%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.31(d,J＝2.5Hz,1H),7.85(d,J＝6.0Hz,1H),7.74(dd,J＝8.9,2.5Hz,1H),7.35(d,J＝8.9Hz,1H),6.35(d,J＝6.0Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ176.37,155.61,155.36,136.89,128.55,126.23,120.31,118.84,113.14.
ESI-MS:calculated for C 9 H 5 BrO 2 [M+H] - :224.9545,found:224.9544.
example 4: synthesis of 6-methyl primary ketone:
a15 mL pressure-resistant tube was charged with 27.2mg (0.20 mmol) of 2-hydroxy-5-methylbenzaldehyde (CAS number: 613-84-3), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, 5mL of water is added for quenching reaction, and thenWashing with 10mL of ethyl acetate and 5mL of saturated saline, collecting the organic phase in a layered manner, extracting the 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 the solvent, and performing column chromatography to obtain the product with the yield of 76%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.98–7.96(m,1H),7.82(d,J＝6.0Hz,1H),7.46(dd,J＝8.6,1.9Hz,1H),7.34(d,J＝8.6Hz,1H),6.31(d,J＝6.0Hz,1H),2.43(s,3H).
13 C NMR(126MHz,Chloroform-d)δ177.87,155.28,154.81,135.27,135.06,125.10,124.51,117.96,112.78,20.95.
ESI-MS:calculated for C 10 H 8 O 2 [M+H] - :161.0597,found:161.0596.
example 5: synthesis of 7-chlorochromone:
a15 mL pressure-resistant tube was charged with 31.3mg (0.20 mmol) of 4-chloro-2-hydroxybenzaldehyde (CAS number: 2420-26-0), 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 74%.
The characterization data of the product are: 1 H NMR(500MHz,Chloroform-d)δ8.12(d,J＝8.6Hz,1H),7.82(d,J＝6.0Hz,1H),7.47(d,J＝1.9Hz,1H),7.36(dd,J＝8.6,1.9Hz,1H),6.33(d,J＝6.1Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ176.88,156.67,155.48,139.97,127.34,126.28,123.49,118.36,113.40.
ESI-MS:calculated for C 9 H 5 ClO 2 [M+H] - :181.0050,found:181.0050.
example 6: synthesis of 6-nitrochromone:
a15 mL pressure-resistant tube was charged with 33.4mg (0.20 mmol) of 2-hydroxy-5-nitrobenzaldehyde (CAS number: 97-51-8), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, and [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 68%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ9.07(d,J＝2.8Hz,1H),8.50(dd,J＝9.2,2.8Hz,1H),7.93(d,J＝6.1Hz,1H),7.63(d,J＝9.2Hz,1H),6.44(d,J＝6.1Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ176.05,159.41,155.83,144.91,128.27,125.02,122.73,120.20,113.69.
ESI-MS:calculated for C 9 H 5 NO 4 [M+H] - :192.0291,found:192.0290.
example 7: synthesis of 7-methylchromone:
a15 mL pressure-resistant tube was charged with 27.2mg (0.20 mmol) of 2-hydroxy-4-methylbenzaldehyde (CAS number: 698-27-1), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), none41.4mg (0.3 mmol) of potassium carbonate hydrate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 69%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.10(d,J＝8.1Hz,1H),7.83(d,J＝6.0Hz,1H),7.28–7.21(m,2H),6.32(d,J＝6.0Hz,1H),2.50(s,3H).
13 C NMR(126MHz,Chloroform-d)δ177.67,156.66,155.11,145.18,126.79,125.55,122.62,117.89,112.91,21.83.
ESI-MS:calculated for C 10 H 8 O 2 [M+H] - :161.0597,found:161.0596.
example 8: synthesis of 8-methyl primary ketone:
a15 mL pressure-resistant tube was charged with 27.2mg (0.20 mmol) of 2-hydroxy-3-methylbenzaldehyde (CAS number: 90111-15-2), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 94%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.01(d,J＝7.2Hz,1H),7.88(d,J＝6.0Hz,1H),7.47(d,J＝7.2Hz,1H),7.25(d,J＝7.7Hz,1H),6.32(d,J＝6.0Hz,1H),2.44(s,3H).
13 C NMR(126MHz,Chloroform-d)δ178.12,155.15,155.07,134.73,127.67,124.79,123.37,112.79,15.65.
ESI-MS:calculated for C 10 H 8 O 2 [M+H] - :161.0597,found:161.0596.
example 9: synthesis of 3- (2, 2-difluoro-1-hydroxyethyl) -1H-indole-4-carbaldehyde:
a15 mL pressure-resistant tube was charged with 30.4mg (0.20 mmol) of 2-hydroxy-5-methoxybenzaldehyde (CAS number: 672-13-9), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 81%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.86(d,J＝6.0Hz,1H),7.57(d,J＝3.1Hz,1H),7.41(d,J＝9.1Hz,1H),7.27(dd,J＝9.1,3.1Hz,1H),6.34(d,J＝6.0Hz,1H),3.90(s,3H).
13 C NMR(126MHz,Chloroform-d)δ177.72,157.07,155.21,151.52,125.58,124.07,119.76,112.24,104.87,56.06.
ESI-MS:calculated for C 10 H 8 O 3 [M+H] - :177.0546,found:177.0545.
example 10: synthesis of methyl 6-carboxylate chromone:
a15 mL pressure-resistant tube was charged with 36mg (0.20 mmol) of methyl 3-formyl-4-hydroxybenzoate (CAS number: 24589-99-9), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, and [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 86%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.89(d,J＝2.1Hz,1H),8.33(dd,J＝8.8,2.2Hz,1H),7.89(d,J＝6.1Hz,1H),7.52(d,J＝8.8Hz,1H),6.40(d,J＝6.1Hz,1H),3.97(s,3H).
13 C NMR(126MHz,Chloroform-d)δ177.12,165.83,159.03,155.57,134.54,128.45,127.42,124.61,118.81,113.59,52.61.
ESI-MS:calculated for C 11 H 8 O 4 [M+H] - :205.0495,found:205.0493.
example 11: synthesis of 1H-naphthalene [2,1-b ] pyran-1-one:
a15 mL pressure-resistant tube was charged with 34.4mg (0.20 mmol) of 2-hydroxy-1-naphthaldehyde (CAS number: 708-06-5), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, extracting an aqueous phase with ethyl acetate for 2 times, wherein the dosage of ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove the solvent, and obtaining the catalyst through column chromatography The yield of the product was 70%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d 6 )δ0.03(d,J＝8.6Hz,1H),8.08(d,J＝9.0Hz,1H),7.92–7.87(m,2H),7.76(ddd,J＝8.5,7.0,1.4Hz,1H),7.62(ddd,J＝8.1,7.0,1.1Hz,1H),7.50(d,J＝9.0Hz,1H),6.52(d,J＝5.8Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ179.60,157.86,152.82,135.65,130.66,130.62,129.40,128.29,127.26,126.81,118.36,117.73,116.15.
ESI-MS:calculated for C 13 H 8 O 2 [M+H] - :197.0597,found:197.0596.
example 12: synthesis of 4H-naphtho [1,2-b ] pyran-4-one:
a15 mL pressure-resistant tube was charged with 34.4mg (0.20 mmol) of 1-hydroxy-2-naphthaldehyde (CAS number: 574-96-9), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, and [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 92%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.48(d,J＝8.2Hz,1H),8.15(d,J＝8.7Hz,1H),8.06(d,J＝5.9Hz,1H),7.93(d,J＝7.7Hz,1H),7.78(d,J＝8.7Hz,1H),7.72(td,J＝8.1,7.6,1.4Hz,1H),7.68(td,J＝7.7,7.0,1.3Hz,1H),6.53(d,J＝5.9Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ177.64,154.70,154.18,136.01,129.52,128.27,127.34,125.57,124.15,122.48,121.36,120.87,114.50.
ESI-MS:calculated for C 13 H 8 O 2 [M+H] - :197.0597found：197.0596.
example 13: synthesis of 6-tert-Ding Jise ketone:
a15 mL pressure-resistant tube was charged with 35.6mg (0.20 mmol) of 5- (tert-butyl) -2-hydroxybenzaldehyde (CAS number: 2725-53-3), 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, and [ Cp. Times. IrCl ] 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 74%.
The characterization data of the product are:
1 H NMR(400MHz,CDCl 3 )δ8.19(d,J＝2.5Hz,1H),7.84(d,J＝6.0Hz,1H),7.75(dd,1H),7.41(d,J＝8.8Hz,1H),6.34(d,J＝6.0Hz,1H),1.38(s,9H).
13 C NMR(126MHz,Chloroform-d)δ178.18,155.31,154.85,148.70,131.86,124.33,121.64,117.92,112.94,35.00,31.43.
ESI-MS:calculated for C 13 H 14 O 2 [M+H] - :203.1066,found:203.1065.
example 14: synthesis of 8-tert-butyl chromone:
15mL of a pressure-resistant tube was taken and 35.6mg (0.20 mmol) of 3- (tert-butyl) -2-hydroxybenzaldehyde (CAS number: 24623-65-2), 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, and [ Cp ] Ir were addedCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 85%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.12(dd,J＝7.9,1.7Hz,1H),7.95(d,J＝5.9Hz,1H),7.65(dd,J＝7.6,1.6Hz,1H),7.33(t,J＝7.8Hz,1H),6.38(d,J＝5.9Hz,1H),1.49(s,9H).
13 C NMR(126MHz,Chloroform-d)δ178.21,155.52,154.53,139.33,131.12,125.72,124.95,124.10,112.65,35.23,30.07.
ESI-MS:calculated for C 13 H 14 O 2 [M+H] - 203.1066,found:203.1066.
example 15: synthesis of 6- (tert-butyl) -8-carboaldehyde chromone:
a15 mL pressure-resistant tube was charged with 41.3mg (0.20 mmol) of 5- (tert-butyl) -2-hydroxy-isophthalaldehyde (CAS number: 84501-28-0), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 80%.
The characterization data of the product are:
1 H NMR(500MHz,CDCl 3 )δ10.64(s,1H),8.48(d,J＝2.6Hz,1H),8.30(d,J＝2.6Hz,1H),7.96(d,J＝6.0Hz,1H),6.44(d,J＝6.0Hz,1H),1.41(s,9H).
13 C NMR(126MHz,Chloroform-d)δ187.46,176.84,155.26,155.01,148.91,131.42,128.70,125.13,124.88,113.66,35.21,31.29.
ESI-MS:calculated for C 14 H 14 O 3 [M+H] - :231.1015,found:231.1014.
example 16: synthesis of 4-methyl-2- (4-oxo-4H-chrome-6-yl) thiazole-5-carboxylic acid ethyl ester:
a15 mL pressure-resistant tube was charged with 58.3mg (0.20 mmol) of ethyl 2- (3-formyl-4-hydroxyphenyl) -4-methylthiazole-5-carboxylate (CAS number: 161798-01-2), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 30%.
The characterization data of the product are:
1 H NMR(400MHz,CDCl 3 )δ8.70(d,J＝2.2Hz,1H),8.37(dd,J＝8.8,2.2Hz,1H),7.89(d,J＝6.0Hz,1H),7.55(d,J＝8.8Hz,1H),6.40(d,J＝6.0Hz,1H),4.37(q,J＝7.1Hz,2H),2.79(s,3H),1.40(t,J＝7.1Hz,3H).
13 C NMR(126MHz,Chloroform-d)δ177.06,167.82,162.23,161.30,157.82,155.56,131.85,130.48,125.22,124.59,122.75,119.44,113.45,61.54,17.62,14.45.
ESI-MS:calculated for C 16 H 14 NO 4 S[M+H] - :317.0716,found:317.0711.
example 17: synthesis of 7-diethylaminochromone:
a15 mL pressure-resistant tube was charged with 38.6mg (0.20 mmol) of 4-diethylaminosalicylaldehyde (CAS number: 17754-90-4), 86.4mg (0.40 mmol) of 2-fluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 58%.
The characterization data of the product are:
1 H NMR(500MHz,CDCl 3 )δ7.99(d,J＝9.1Hz,1H),7.66(d,J＝6.0Hz,1H),6.72(dd,J＝9.1,2.5Hz,1H),6.43(d,J＝2.5Hz,1H),6.18(d,J＝6.0Hz,1H),3.44(q,J＝7.1Hz,4H),1.23(t,J＝7.1Hz,6H).
13 C NMR(126MHz,Chloroform-d)δ177.06,159.14,154.19,152.02,127.07,114.19,112.64,110.67,96.46,44.86,12.55.
ESI-MS:calculated for C 13 H 15 NO 2 [M+H] - :218.1175,found:218.1174.
example 18: synthesis of 6-trifluoromethoxy chromone:
a15 mL pressure-resistant tube was charged with 41.3mg (0.20 mmol) of 5- (trifluoromethoxy) salicylaldehyde (CAS number: 93249-62-8), 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. ReactionAfter the completion of the reaction, 5mL of water is added for quenching, then 10mL of ethyl acetate 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, and the product is obtained through column chromatography, wherein the yield is 86%.
The characterization data of the product are:
1 H NMR(500MHz,CDCl 3 )δ8.05(m,1H),7.89(d,J＝6.1Hz,1H),7.53(d,J＝1.3Hz,2H),6.38(d,J＝6.1Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ176.69,155.69,154.59,146.18,127.27,125.84,120.50(q,J＝258.3Hz),120.45,117.51,112.84.
ESI-MS:calculated for C 10 H 5 F 3 O 3 [M+H] - :231.0263found:231.0262.
example 19: synthesis of 6-fluorochromone:
a15 mL pressure-resistant tube was charged with 28mg (0.20 mmol) of 5-fluorosalicylaldehyde (CAS number 347-54-6), 86.4mg (0.40 mmol) of 2-fluorovinyl 4- (trifluoromethyl) benzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 3 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 87%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.87(d,J＝6.0Hz,1H),7.85(dd,J＝8.3,3.1Hz,1H),7.48(dd,J＝9.1,4.2Hz,1H),7.40(m,J＝9.2,7.6,3.1Hz,1H),6.34(d,J＝6.0Hz,1H).
13 C NMR(126MHz,Chloroform-d)δ177.02(d,J＝2.0Hz),160.66,158.69,155.61,152.89,126.18(d,J＝7.3Hz),122.20(d,J＝25.4Hz),120.75–120.22(m),112.41,110.85(d,J＝23.7Hz).
ESI-MS:calculated for C 9 H 5 FO 2 [M+H] - :165.0346,found:165.0345.
example 20: synthesis of 2- ((tert-Butoxycarbonyl) amino) -3- (4-oxo-4H-chromium-6-yl) propanoic acid:
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15mL of a pressure-resistant tube was taken and charged with 61.8mg (0.20 mmol) of 2- ((tert-butoxycarbonyl) amino) -3- (3-formyl-4-hydroxyphenyl) propionic acid (CAS number: 71522-60-6), 86.4mg (0.40 mmol) of 2-fluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] IrCl 2 ]8mg (5 mol%), 41.4mg (0.3 mmol) of anhydrous potassium carbonate and 2mL of hexafluoroisopropanol were reacted at 90℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 15%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ10.98(s,1H),7.85(s,1H),7.71(d,J＝8.4Hz,1H),7.59(d,J＝10.9Hz,1H),7.39(s,1H),7.19(d,J＝7.5Hz,1H),6.30(d,J＝10.9Hz,1H),4.86(t,J＝7.0Hz,1H),3.30(dd,J＝12.4,7.0Hz,1H),1.44(s,9H).
13 C NMR(126MHz,Chloroform-d)δ177.25,173.62,157.20,156.12,155.37,134.17,128.20,124.71,124.06,117.06,112.44,79.69,55.65,37.03,28.34.
ESI-MS:calculated for C 17 H 19 NO 6 [M+H] - :333.1212,found:333.1210.
example 21: synthesis of 2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 24.4mg (0.20 mmol) of salicylaldehyde (CAS number: 90-02-8), 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate (CAS number: 20442-70-0) 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol (CAS number: 75-89-8) 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 68%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.18(dd,J＝8.2,1.6Hz,1H),7.68(ddd,J＝9.1,7.4,1.7Hz,1H),7.44(t,J＝7.5Hz,2H),5.71(s,1H),4.59(q,J＝7.7Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ179.01,165.01,153.58,133.88,126.16,126.05,125.69–118.76(m),122.99,117.33,89.56,65.12(q,J＝37.8Hz).
19 F NMR(471MHz,Chloroform-d)δ-73.63–-73.77(m).
ESI-MS:calculated for C 11 H 7 F 3 O 3 [M+H] - :245.0420,found:245.0418.
example 22: synthesis of 6-fluoro-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 28mg (0.20 mmol) of 5-fluorosalicylaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 54%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.78(dd,J＝8.0,3.1Hz,1H),7.42(dd,J＝9.1,4.1Hz,1H),7.39–7.33(m,1H),5.70(s,1H),4.60(q,J＝7.6Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ178.0,165.2,160.1(d,J＝248.1Hz),149.5,124.3(d,J＝7.4Hz),122.2(q,J＝277.5Hz),121.7(d,J＝25.7Hz),119.3(d,J＝8.2Hz),111.3(d,J＝24.0Hz),89.1,65.2(q,J＝37.7Hz).
19 F NMR(471MHz,CDCl 3 )δ-73.74,-114.34.
ESI-MS:calculated for C 11 H 6 F 4 O 3 [M+H] - :263.0325,found:263.0324.
example 23: synthesis of 6-chloro-2- (2, 2-trifluoroethoxy) chromone:
15mL of a pressure-resistant tube was taken and charged with 31.3mg (0.20 mmol) of 5-chlorosalicylaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water to quench the reaction, adding 10mL of ethyl acetate and 5mL of saturated saline water to wash, collecting an organic phase in a layering manner, extracting the water phase with ethyl acetate for 2 times, wherein the dosage of ethyl acetate is 5mL each time, The organic phases were combined, dried over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure, and the product was obtained by column chromatography in a yield of 51%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.12(d,J＝2.4Hz,1H),7.61(dd,J＝8.8,2.5Hz,1H),7.38(d,J＝8.9Hz,1H),5.70(s,1H),4.59(q,J＝7.6Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ177.66,165.12,151.81,133.99,132.07,125.67,124.03,122.14(q,J＝277.7Hz),118.98,89.54,65.26(q,J＝37.8Hz).
19 F NMR(471MHz,Chloroform-d)δ-73.59–-73.76(m).
ESI-MS:calculated for C 11 H 6 ClF 3 O 3 [M+H] - :279.0030,found:279.0029.
example 24: synthesis of 6-bromo-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 40mg (0.20 mmol) of 5-bromosalicylaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 31%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.18(d,J＝2.5Hz,1H),7.67(dd,J＝8.8,2.5Hz,1H),7.25(d,J＝8.8Hz,1H),5.64(s,1H),4.54(q,J＝7.7Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ177.5,165.1,152.2,136.8,128.7,124.3,122.1(q,J＝277.9Hz),119.4,119.2,89.5,65.2(q,J＝37.9Hz).
19 F NMR(471MHz,CDCl 3 )δ-73.69.
ESI-MS:calculated for C 11 H 6 BrF 3 O 3 [M+H] - :322.9525,found:322.9523.
example 25: synthesis of 6-methyl-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 27.2mg (0.20 mmol) of 2-hydroxy-5-methylbenzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol), trifluoroethanol 2mL, and reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 48%.
The characterization data of the product are:
1 H NMR(500MHz,CDCl 3 )δ7.84(s,1H),7.37(dd,J＝8.5,2.3Hz,1H),7.21(d,J＝8.5Hz,1H),5.60(s,1H),4.53(q,J＝7.8Hz,2H),2.35(s,3H).
13 C NMR(126MHz,CDCl 3 )δ179.1,164.9,151.7,136.0,134.8,125.4,122.5,122.3(q,J＝277.8Hz),117.0,89.3,65.0(q,J＝37.6Hz),20.9.
19 F NMR(471MHz,CDCl 3 )δ-73.78.
ESI-MS:calculated for C 12 H 9 F 3 O 3 [M+H] - :259.0576,found:259.0576.
example 26: synthesis of 6-methoxy-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 30.4mg (0.20 mmol) of 2-hydroxy-5-methoxybenzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 52%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.55(d,J＝3.1Hz,1H),7.35(d,J＝9.0Hz,1H),7.24(dd,J＝9.1,3.1Hz,1H),5.70(s,1H),4.59(q,J＝7.7Hz,2H),3.89(s,3H).
13 C NMR(126MHz,Chloroform-d)δ178.96,164.87,157.57,148.07,123.65,123.34,126.07–118.81(m),118.61,105.85,89.12,65.05(q,J＝37.7Hz),56.11.
19 F NMR(471MHz,Chloroform-d)δ-73.74(t,J＝7.7Hz).
ESI-MS:calculated for C 12 H 9 F 3 O 4 [M+H] - :275.0525,found:275.0522.
example 27: synthesis of 6-tert-butyl-2- (2, 2-trifluoroethoxy) chromone:
15mL of a pressure-resistant tube was taken and 5- (tert-butyl) -2-hydroxy group was added36mg (0.20 mmol) of benzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 43%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.14(d,J＝2.4Hz,1H),7.70(dd,J＝8.8,2.4Hz,1H),7.34(d,J＝8.8Hz,1H),5.68(s,1H),4.59(q,J＝7.7Hz,2H),1.36(s,9H).
13 C NMR(126MHz,Chloroform-d)δ179.36,164.95,151.66,149.39,131.57,122.27(q,J＝277.8Hz),122.23,122.00,116.85,89.35,65.03(q,J＝37.6Hz),34.98,31.40.
19 F NMR(471MHz,Chloroform-d)δ-73.68-73.81(m).
ESI-MS:calculated for C 15 H 15 F 3 O 3 [M+H] - :301.1046,found:301.1043.
example 28: synthesis of 6-nitro-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 33.4mg (0.20 mmol) of 2-hydroxy-5-nitrobenzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, and [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the completion of the reaction, 5mL of water was added to quench the reaction, and 10mL of ethyl acetate and 5mL of saturated brine were added to washThe organic phase was collected by layers, the aqueous phase was extracted 2 times with ethyl acetate each time in an amount of 5mL, the organic phases were combined, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, and the product was obtained by column chromatography in 20% yield.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.93(d,J＝2.8Hz,1H),8.44(dd,J＝9.1,2.8Hz,1H),7.55(d,J＝9.1Hz,1H),5.73(s,1H),4.59(q,J＝7.6Hz,2H).
13 C NMR(126MHz,CDCl 3 )δ176.9,165.4,156.3,145.5,128.3,122.6,122.0(q,J＝277.9Hz),119.,89.8,65.6(q,J＝37.9Hz),27.2.
19 F NMR(471MHz,CDCl 3 )δ-73.60.
ESI-MS:calculated for C 11 H 6 F 3 NO 5 [M+H] - :290.0270,found:290.0274.
example 29: synthesis of methyl 6-carboxylate-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 36mg (0.20 mmol) of methyl 3-formyl-4-hydroxybenzoate, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol), trifluoroethanol 2mL, and reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 46%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.81(d,J＝2.3Hz,1H),8.30(dd,J＝8.7,2.3Hz,1H),7.47(d,J＝8.7Hz,1H),5.72(s,1H),4.61(q,J＝7.6Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ178.01,165.5,165.1,155.8,134.5,128.2,128.0,122.6,122.0(q,J＝278.0Hz),117.7,89.6,65.2(q,J＝37.7Hz),52.5.
19 F NMR(471MHz,CDCl 3 )δ-73.67.
ESI-MS:calculated for C 13 H 9 F 3 O 5 [M+H] - :303.0474,found:303.0472.
example 30: synthesis of 7-methyl-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 27.2mg (0.20 mmol) of 2-hydroxy-4-methylbenzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 45%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.97(d,J＝8.1Hz,1H),7.17(d,J＝8.1Hz,1H),7.15(s,1H),5.62(s,1H),4.57(q,J＝7.8Hz,2H),2.43(s,3H).
13 C NMR(126MHz,Chloroform-d)δ178.9,164.8,153.6,145.2,127.2,125.6,122.2(q,J＝276.3Hz),120.5,117.1,89.2,64.9(q,J＝37.7Hz),21.8.
ESI-MS:calculated for C 12 H 9 F 3 O 3 [M+H] - :259.0576,found:259.0576.
example 31: synthesis of 7-chloro-2- (2, 2-trifluoroethoxy) chromone:
15mL of a pressure-resistant tube was charged with 31.3mg (0.20 mmol) of 4-chloro-2-hydroxybenzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 52%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.09(d,J＝8.4Hz,1H),7.44(d,J＝1.9Hz,1H),7.39(dd,J＝8.5,1.9Hz,1H),5.69(s,1H),4.59(q,J＝7.7Hz,2H).
13 C NMR(126MHz,Chloroform-d)δ178.0,165.0,153.6,139.9,127.3,126.8,122.1(d,J＝277.8Hz),121.5,117.6,89.6,65.3(q,J＝37.7Hz).
19 F NMR(471MHz,CDCl 3 )δ-73.69.
ESI-MS:calculated for C 11 H 6 ClF 3 O 3 [M+H] - :279.0030,found:279.0030.
example 32: synthesis of 7-diethylamino-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was taken, and 38.6mg (0.20 mmol) of 6-diethylaminosalicylaldehyde and 2, 2-difluoro were added theretoVinyl 4-methylbenzenesulfonic acid 93.6mg (0.40 mmol), [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 42%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.93(d,J＝9.0Hz,1H),6.70(dd,J＝9.1,2.4Hz,1H),6.43(d,J＝2.4Hz,1H),5.50(s,1H),4.51(q,J＝7.7Hz,2H),3.43(q,J＝7.1Hz,4H),1.22(t,J＝7.1Hz,6H).
13 C NMR(126MHz,Chloroform-d)δ178.69,164.46,156.20,152.13,127.06,122.37(d,J＝277.6Hz),111.48,110.53,96.32,88.25,65.63–64.52(m),44.93,12.53.
19 F NMR(471MHz,Chloroform-d)δ-73.75(t,J＝7.7Hz).
ESI-MS:calculated for C 15 H 16 F 3 NO 3 [M+H] - :316.1155,found:316.1153.
example 33: synthesis of 8-methyl-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 27.2mg (0.20 mmol) of 2-hydroxy-3-methylbenzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, 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 was collected by layers, the aqueous phase was extracted 2 times with ethyl acetate each time in an amount of 5mL, the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the product was obtained by column chromatography in 50% yield.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.91(m,1H),7.45–7.34(m,1H),7.26–7.16(m,1H),5.61(s,1H),4.54(q,J＝7.8Hz,2H),2.39(s,3H).
13 C NMR(126MHz,Chloroform-d)δ179.4,164.8,152.0,134.9,126.8,125.4,123.6,122.8,122.3(q,J＝277.8Hz),89.23,65.0(q,J＝37.6Hz),15.45.
19 F NMR(471MHz,CDCl 3 )δ-73.65.
ESI-MS:calculated for C 12 H 9 F 3 O 3 [M+H] - :259.0576,found:259.0575.
example 34: synthesis of 8-tert-butyl-2- (2, 2-trifluoroethoxy) chromone:
a15 mL pressure-resistant tube was charged with 36mg (0.20 mmol) of 3- (tert-butyl) -2-hydroxybenzaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 45%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.07(dd,J＝7.9,1.7Hz,1H),7.65(dd,J＝7.7,1.7Hz,1H),7.34(t,J＝7.8Hz,1H),5.70(s,1H),4.57(q,J＝7.7Hz,2H),1.49(s,9H).
13 C NMR(126MHz,Chloroform-d)δ179.5,165.0,152.5,138.6,131.4,125.5,124.3,123.6,122.2(q,J＝276.0Hz),88.8,65.5(q,J＝37.6Hz),35.1,30.2.
19 F NMR(471MHz,CDCl 3 )δ-73.63.
ESI-MS:calculated for C 15 H 15 F 3 O 3 [M+H] - :301.1046,found:301.1046.
example 35: synthesis of 6-methyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde:
a15 mL pressure-resistant tube was charged with 32.8mg (0.20 mmol) of 5-methyl-2-hydroxy-isophthalaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 30%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ10.44(s,1H),8.25–8.22(d,2H),7.98(d,J＝2.0Hz,1H),5.78(s,1H),4.73(q,J＝7.7Hz,2H),2.52(s,3H).
13 C NMR(126MHz,Chloroform-d)δ187.29,177.79,164.74,151.26,136.31,136.25,132.16,124.53,123.54,125.64–118.86(m),90.14,65.25(q,J＝37.6Hz),20.89.
19 F NMR(471MHz,Chloroform-d)δ-73.64–-73.75(m).
ESI-MS:calculated for C 13 H 8 F 3 O 4 [M+H] - :286.0447,found:286.0447.
example 36: synthesis of 6-tert-butyl-4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromen-8-carbaldehyde:
a15 mL pressure-resistant tube was charged with 32.8mg (0.20 mmol) of 5- (tert-butyl) -2-hydroxy-isophthalaldehyde, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl-4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 35%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ10.48(s,1H),7.80(d,J＝2.5Hz,1H),7.61(d,J＝2.3Hz,1H),4.76(s,1H),4.74(q,J＝8.3Hz,2H),1.31(s,9H).
13 C NMR(126MHz,Chloroform-d)δ168.82,157.97,142.45,133.64,128.96,127.34,127.09,125.38,110.22,61.77,60.85(q,J＝37.2Hz),34.33,31.37.
19 F NMR(471MHz,Chloroform-d)δ-73.54(t,J＝8.2Hz).
ESI-MS:calculated for C 16 H 15 F 3 O[M+H] - :313.1046,found:313.1043.
example 37: synthesis of 3- (2, 2-trifluoroethoxy) -1H benzo [ f ] chromen-1-one:
a15 mL pressure-resistant tube was charged with 34.4mg (0.20 mmol) of 2-hydroxy-1-naphthaleneal, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 86%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d 6 )δ9.91(d,J＝8.4Hz,1H),8.33(d,J＝9.0Hz,1H),8.10(d,J＝7.6Hz,1H),7.77(ddd,J＝8.5,6.9,1.5Hz,1H),7.73(d,J＝9.1Hz,1H),7.68(ddd,J＝8.1,6.9,1.3Hz,1H),6.10(s,1H),5.16(q,J＝8.6Hz,2H).
13 C NMR(126MHz,DMSO-d 6 )δ180.2,163.5,154.2,135.5,130.7,129.6,129.0,128.6,126.6,125.8,123.0(q,J＝277.4Hz),117.2,114.8,90.8,65.0(q,J＝35.7Hz).
19 F NMR(471MHz,DMSO)δ-72.59.
ESI-MS:calculated for C 15 H 9 F 3 O 3 [M+H] - :295.0576,found:295.0573.
example 38: synthesis of 1- (2, 5-dimethyl-1H-indol-3-yl) -2, 2-difluoroethane-1-ol:
a15 mL pressure-resistant tube was charged with 54.6mg (0.20 mmol) of 9-formyl-8-hydroxy-1, 7-tetramethyl julolidine (CAS number: 115662-09-4), 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, adding 5mL of water for quenching reaction, adding 10mL of ethyl acetate and 5mL of saturated saline for washing, collecting an organic phase in a layering way, 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 yield is 39%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ7.84(s,1H),5.52(s,1H),4.47(q,J＝7.7Hz,2H),3.32–3.26(m,2H),3.24–3.19(m,2H),1.85–1.79(m,2H),1.76–1.72(m,2H),1.48(s,6H),1.31(s,6H).
13 C NMR(126MHz,Chloroform-d)δ179.15,164.54,152.71,146.88,129.99,125.88–118.77(m),121.01,114.39,111.78,87.33,65.46(q,J＝37.5Hz),47.44,46.84,39.62,35.90,32.63,32.37,30.78,29.43.
19 F NMR(471MHz,Chloroform-d)δ-73.61-73.72(m).
ESI-MS:calculated for C 21 H 24 F 3 NO 3 [M+H] - :396.1781,found:396.1779.
example 39: synthesis of 4-methyl-2- (4-oxo-2- (2, 2-trifluoroethoxy) -4H-chromium-6-yl) thiazole-5-carboxylic acid:
15mL of a pressure-resistant tube was taken and charged with 58.2mg (0.20 mmol) of ethyl 2- (3-aldehyde-4-aldehyde-phenyl) -4-methylthiazole-5-carboxylate, 93.6mg (0.40 mmol) of 2, 2-difluorovinyl 4-methylbenzenesulfonic acid, [ Cp ] Rh (CH) 3 CN) 3 ](SbF 6 ) 2 25mg (15 mol%), cesium pivalate 93.6mg (0.40 mmol), calcium hydroxide 14.8mg (0.20 mmol) and trifluoroethanol 2mL were reacted at 80℃for 10 hours. After the reaction is finished, 5mL of water is added for quenching reaction, and 10mL of ethyl acetate is addedWashing the ethyl acetate and 5mL of saturated saline water, collecting an organic phase in a layering manner, extracting the aqueous phase with ethyl acetate for 2 times, wherein the dosage of the ethyl acetate is 5mL each time, combining the organic phases, adding anhydrous sodium sulfate for drying, distilling under reduced pressure to remove the solvent, and obtaining a product through column chromatography, wherein the yield is 43%.
The characterization data of the product are:
1 H NMR(500MHz,Chloroform-d)δ8.65(d,J＝2.2Hz,1H),8.35(dd,J＝8.8,2.3Hz,1H),7.51(d,J＝8.8Hz,1H),5.73(s,1H),4.61(q,J＝7.7Hz,2H),4.36(q,J＝7.1Hz,2H),2.78(s,3H),1.39(t,J＝7.1Hz,3H).
13 C NMR(126MHz,Chloroform-d)δ178.13,167.55,165.12,162.21,161.33,154.67,131.84,131.20,124.72,123.37,125.62–118.77(m),122.96,118.40,89.82,65.30(q,J＝37.7Hz),61.57,17.62,14.45.
19 F NMR(471MHz,Chloroform-d)δ-73.60-73.71(m).
ESI-MS:calculated for C 18 H 14 F 3 NO 5 S[M+H] - :414.0617,found:414.0615.
as can be seen from the above examples 1 to 39: suitable substrates for this reaction are mainly alkyl, alkoxy, halo, haloalkyl, phenyl, nitro, heterocyclic substituents and diethylamino substituted salicylaldehyde compounds. The reaction is catalyzed by Rh (III) catalyst or Ir (III) catalyst to form five-membered ring metal species, olefin coordination and olefin insertion form seven-membered ring metal species, and then the reaction is reduced and eliminated, and then the addition elimination reaction is carried out to finally generate the ketone skeleton structure. Compared with the synthesis of other chromone compounds, the invention only needs to use the alkynyl equivalent synthon (and the fluorine-containing vinyl compound) with low cost, which is simple and easy to obtain, as the preparation raw material. 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 90%; the reaction process is fast (the reaction time is far lower than more than 12h in the related technology), 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 (9)
1. A preparation method of chromone compounds is characterized in that: the structural formula of the chromone compound is shown as the following formula (III):
；
R 1 and R is 2 Independently selected from hydrogen, alkyl, alkoxy, halogen, nitro, ester, aldehyde, amine, alkenyl, or carboxyl;
x is selected from O atom, N atom or S atom;
R 3 selected from hydrogen or alkoxy;
the preparation method comprises the following steps:
the salicylaldehyde compound shown in the formula (I) and the fluorine-containing vinyl compound shown in the formula (II) are mixed and reacted to prepare the chromone compound shown in the formula (III);
；
r in formula (II) 4 Selected from hydrogen or fluorine;
r in the formula (II) is selected from benzenesulfonyloxy, p-toluenesulfonyloxy, o-toluenesulfonyloxy, p-fluorobenzenesulfonyloxy, o-fluorobenzenesulfonyloxy, p-trifluoromethylsulfonyloxy and o-trifluorobenzenesulfonyloxy;
The catalyst for the reaction is dichloro (pentamethyl cyclopentadienyl) iridium (III) dimer, di (hexafluoroantimonic acid) triacetonitrile (pentamethyl cyclopentadienyl) rhodium (III) or dichloro (pentamethyl cyclopentadienyl) rhodium (III) dimer,
a base selected from carbonates, pivalates or hydroxides is added to the reaction.
2. The method of manufacturing according to claim 1, characterized in that: the alkyl group being C 1 ~C 20 Is a hydrocarbon group.
3. The method of manufacturing according to claim 1, characterized in that: the alkoxy group is selected from C 1 ~C 10 Alkoxy groups of (a).
4. The method of manufacturing according to claim 1, characterized in that: the ester group is selected from C 1 ~C 10 Ester groups of (a) are present.
5. The method of manufacturing according to claim 1, characterized in that: the molar ratio of the salicylaldehyde compound shown in the formula (I) to the fluorine-containing vinyl compound shown in the formula (II) is 1:2-4.
6. The method of manufacturing according to claim 1, characterized in that: the solvent for the reaction is at least one of trifluoroethanol, methanol or hexafluoroisopropanol.
7. The method of manufacturing according to claim 1, characterized in that: the volume molar ratio of the solvent of the reaction to the salicylaldehyde compound shown in the formula (I) is 5 mL/mmol-15 mL/mmol.
8. The method of manufacturing according to claim 1, characterized in that: the reaction temperature is 25-120 ℃.
9. The preparation method according to claim 1, wherein the reaction time is 3-12 hours.
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| WO2011029956A1 (en) * | 2009-09-14 | 2011-03-17 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Flavones and flavanones derivates as dna methyltransferases inhibitors |
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| WO2011029956A1 (en) * | 2009-09-14 | 2011-03-17 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Flavones and flavanones derivates as dna methyltransferases inhibitors |
Non-Patent Citations (5)
| Title |
|---|
| An Efficient Microwave-Assisted Propylphosphonic Anhydride (T3P ® )-Mediated One-Pot Chromone Synthesis via Enaminones;C. Balakrishna, et al;Synlett;第29卷(第8·期);第1087-1091页 * |
| Evaluation of inhibitory effects of flavonoids on breast cancer resistance protein (BCRP): From library screening to biological evaluation to structure-activity relationship;Xiaoqing Fan, et al;Toxicology In Vitro;第61卷;第104642 (1-14)页 * |
| Pd(OAc)2 /S==PPh3 accelerated activation of gem-dichloroalkenes for the construction of 3-arylchromones;Jianming Liu, et al;Chem. Commun.;第51卷;第17576-17579页 * |
| Rhodium(II)-Catalyzed Reaction of Salicylaldehyde and Its Derivatives with Diazocarbonyl Compounds;G. N. Sakhabutdinova, et al;Russian Journal of Organic Chemistry;第54卷(第12期);第1772–1776页 * |
| The study on structure-activity relationship between chromone derivatives and inhibition of superoxide anion generating from human neutrophils;Yi-Han Chang, et al;Bioorg. Med. Chem. Lett.;第36卷;第127822（1-3）页 * |
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