CN104557474B - 一种α-萘酚类化合物的制备方法 - Google Patents
一种α-萘酚类化合物的制备方法 Download PDFInfo
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- CN104557474B CN104557474B CN201410840627.8A CN201410840627A CN104557474B CN 104557474 B CN104557474 B CN 104557474B CN 201410840627 A CN201410840627 A CN 201410840627A CN 104557474 B CN104557474 B CN 104557474B
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- Prior art keywords
- alpha
- copper
- preparation
- sodium
- naphthol compounds
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- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 150000004782 1-naphthols Chemical class 0.000 title claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 239000003513 alkali Substances 0.000 claims abstract description 10
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052802 copper Inorganic materials 0.000 claims abstract description 9
- 239000010949 copper Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 230000000694 effects Effects 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 12
- -1 halobenzene ethanone derivatives Chemical group 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 150000001879 copper Chemical class 0.000 claims description 6
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 6
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 239000011630 iodine Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 claims description 2
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 17
- 238000003786 synthesis reaction Methods 0.000 abstract description 17
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 abstract description 10
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 238000006482 condensation reaction Methods 0.000 abstract description 3
- 238000009432 framing Methods 0.000 abstract description 3
- 241001597008 Nomeidae Species 0.000 abstract description 2
- 150000005171 halobenzenes Chemical group 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 238000003756 stirring Methods 0.000 description 22
- 239000002904 solvent Substances 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 2
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 2
- LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 2
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 2
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 2
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 2
- RPPXRDXGHUWZFX-UHFFFAOYSA-N 3-(2-bromo-4-fluorophenyl)-6-fluoronaphthalen-1-ol Chemical compound BrC1=C(C=CC(=C1)F)C=1C=C(C2=CC=C(C=C2C1)F)O RPPXRDXGHUWZFX-UHFFFAOYSA-N 0.000 description 2
- NLNXENNISDJVIH-UHFFFAOYSA-N 3-(2-bromo-4-methoxyphenyl)-6-methoxynaphthalen-1-ol Chemical compound BrC1=C(C=CC(=C1)OC)C=1C=C(C2=CC=C(C=C2C=1)OC)O NLNXENNISDJVIH-UHFFFAOYSA-N 0.000 description 2
- BKHPRVAXIOAUCD-UHFFFAOYSA-N 3-(2-bromo-4-methylphenyl)-6-methylnaphthalen-1-ol Chemical compound BrC1=C(C=CC(=C1)C)C=1C=C(C2=CC=C(C=C2C=1)C)O BKHPRVAXIOAUCD-UHFFFAOYSA-N 0.000 description 2
- MYSOERABJFLPKT-UHFFFAOYSA-N 3-(2-chloro-4-methoxyphenyl)-6-methoxynaphthalen-1-ol Chemical compound ClC1=C(C=CC(=C1)OC)C=1C=C(C2=CC=C(C=C2C=1)OC)O MYSOERABJFLPKT-UHFFFAOYSA-N 0.000 description 2
- ZXEZXEZERZBAII-UHFFFAOYSA-N 3-(2-chlorophenyl)naphthalen-1-ol Chemical compound ClC1=C(C=CC=C1)C=1C=C(C2=CC=CC=C2C=1)O ZXEZXEZERZBAII-UHFFFAOYSA-N 0.000 description 2
- UXOBTLGWPCKLEN-UHFFFAOYSA-N 3-(2-iodophenyl)naphthalen-1-ol Chemical compound IC1=C(C=CC=C1)C=1C=C(C2=CC=CC=C2C=1)O UXOBTLGWPCKLEN-UHFFFAOYSA-N 0.000 description 2
- DZKPORASJSESAJ-UHFFFAOYSA-N 3-[2-chloro-5-(trifluoromethyl)phenyl]-7-(trifluoromethyl)naphthalen-1-ol Chemical compound ClC1=C(C=C(C=C1)C(F)(F)F)C=1C=C(C2=CC(=CC=C2C=1)C(F)(F)F)O DZKPORASJSESAJ-UHFFFAOYSA-N 0.000 description 2
- SJVFEVTWAWFVIE-UHFFFAOYSA-N 6-chloro-3-(2,4-dichlorophenyl)naphthalen-1-ol Chemical compound ClC=1C=C2C=C(C=C(C2=CC=1)O)C1=C(C=C(C=C1)Cl)Cl SJVFEVTWAWFVIE-UHFFFAOYSA-N 0.000 description 2
- TYYCNSUODPEVQP-UHFFFAOYSA-N 8-[(4-fluorophenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid Chemical compound C=1C=CN=CC=1CCCC(CCC(=O)O)CCCCNS(=O)(=O)C1=CC=C(F)C=C1 TYYCNSUODPEVQP-UHFFFAOYSA-N 0.000 description 2
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 2
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 2
- PQSFVPCWPQKDHN-UHFFFAOYSA-N benzo[f][1,3]benzodioxol-5-ol Chemical compound C1=C2C(O)=CC=CC2=CC2=C1OCO2 PQSFVPCWPQKDHN-UHFFFAOYSA-N 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical group C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
- 150000004780 naphthols Chemical class 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SFCCOHHWKRVDHH-UHFFFAOYSA-N 1-(2-bromophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC=C1Br SFCCOHHWKRVDHH-UHFFFAOYSA-N 0.000 description 1
- ZDOYHCIRUPHUHN-UHFFFAOYSA-N 1-(2-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1Cl ZDOYHCIRUPHUHN-UHFFFAOYSA-N 0.000 description 1
- CERJZAHSUZVMCH-UHFFFAOYSA-N 2,2-dichloro-1-phenylethanone Chemical compound ClC(Cl)C(=O)C1=CC=CC=C1 CERJZAHSUZVMCH-UHFFFAOYSA-N 0.000 description 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
- CBLLCYODFDSRQA-UHFFFAOYSA-N 2-bromo-2-fluoro-1-phenylethanone Chemical compound FC(Br)C(=O)C1=CC=CC=C1 CBLLCYODFDSRQA-UHFFFAOYSA-N 0.000 description 1
- CREOHKRPSSUXCW-UHFFFAOYSA-N 2-iodo-1-phenylethanone Chemical group ICC(=O)C1=CC=CC=C1 CREOHKRPSSUXCW-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical group C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
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- C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
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- C07D317/70—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with ring systems containing two or more relevant rings
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Abstract
本发明属于医药化工中间体及相关化学技术领域，涉及到一种α-萘酚类化合物的制备方法。以邻卤苯乙酮及其衍生物为原料，在铜催化剂和碱的作用下，于有机溶剂中发生自身缩合反应，得到α-萘酚类化合物。本发明所述的α-萘酚的制备方法，反应步骤少，原料简单易得，催化剂价格低廉，反应条件温和，便于操作。由于α-萘酚类化合物是一类重要的骨架结构，在药物合成领域有着非常广泛的应用，因此，本发明具有较大的使用价值和社会经济效益。
Description
技术领域
本发明属于医药化工中间体及相关化学技术领域，涉及到一种α-萘酚类化合物的制备方法。
背景技术
α-萘酚类化合物广泛应用于化学领域的多个方面，其作为骨架结构往往出现在药物、农用化学品、颜料和光学材料等与人们衣食住行密切相关的分子结构中，具有广阔的市场前景。
传统的合成萘酚的方法有三种，一是α-萘磺酸碱熔法，以萘为起始原料,然后进行磺化、碱熔，最终得到萘酚类化合物，这种方法不但合成步骤多，而且在底物的广谱性、反应的选择性等方面都有缺陷；二是α-萘胺水解法,以α-萘胺为原料，在15％～20％的硫酸中加压水解得到萘酚，这种方法使用的原料有毒,设备腐蚀和废水处理问题较为严重；三是四氢萘法,以萘为原料，经加氢得到四氢萘，再经氧化、脱氢得到α-萘酚，该法步骤繁多,需要高温高压操作。
相对于传统的合成方法，在过渡金属催化剂的作用下合成α-萘酚类化合物得到了较大的关注。目前使用的过渡贵金属催化剂主要包括：钯催化剂(R.M.Patel,N.P.Argade,Org.Lett.2013,15,14–17)、金催化剂(V.Gudla,R.Balamurugan,Chem.AsianJ.2013,8,414–428)和铑催化剂(W.W.Chan,S.F.Lo,Z.Y.Zhou,W.Y.Yu,J.Am.Chem.Soc.2012,134,13565–13568)。由于以上贵金属催化剂价格昂贵，化学研究者又发现了铜做催化剂合成α-萘酚的方法(R.M.Patel,N.P.Argade,Org.Lett.2013,15,14–17)。但是目前已知的铜做催化剂制备α-萘酚类化合物的方法大多需要复杂的起始原料，苛刻的反应条件，所以其应用受到限制。
发明内容
本发明的目的是提供了一种α-萘酚类化合物的制备方法，该方法的合成路线短、起始原料简单、反应条件温和、催化剂价廉，且该方法无需额外添加配体，节约了成本。
本发明是以邻卤苯乙酮衍生物为原料，在碱和铜盐催化剂的作用下发生自身缩合反应，得到α-萘酚类化合物，合成路线如下：
在上述制备方法的反应中，R选自氢、烷基、芳基、卤素、氰基、三氟甲基、烷氧基、亚甲二氧基；X选自氯、溴、碘。
在上述制备方法的反应中，所用的铜盐催化剂为碘化亚铜、溴化亚铜、氯化亚铜、三氟甲磺酸亚铜、氧化亚铜、醋酸铜、三氟甲磺酸铜、硫酸铜、氯化铜、溴化铜中的一种或两种以上混合。优选碘化亚铜、三氟甲磺酸铜、醋酸铜、氧化亚铜中的一种或两种以上混合。邻卤苯乙酮衍生物与所用铜盐催化剂的摩尔比为1:0.05～0.50。
在上述制备方法的反应中，所用的溶剂为N,N-二甲基甲酰胺、乙腈、四氢呋喃、1,4-二氧六环、1,2-二氯乙烷、二甲基亚砜、甲基叔丁基醚、乙二醇二甲醚、三氯甲烷、二氯甲烷、乙醚、正丁醚、四氯化碳、甲苯、环己烷等，优选N,N-二甲基甲酰胺、乙腈、四氢呋喃、二甲基亚砜中的一种或两种以上混合；有机溶剂的加入量为邻卤苯乙酮衍生物重量的2～100倍。
在上述制备方法的反应中，所用的碱为叔丁醇钠、叔丁醇钾、叔丁醇锂、氢氧化钠、氢氧化钾、碳酸钠、碳酸钾、碳酸氢钠、氢化钠、醋酸钠、乙醇钠、磷酸三钾、碳酸铯、乙酸铯、1,8-二氮杂二环十一碳-7-烯中的一种或两种以上混合。优选叔丁醇钠、叔丁醇钾、叔丁醇锂、氢氧化钠中的一种或两种以上混合；邻卤苯乙酮衍生物与碱的摩尔比为1:1～50。
在上述制备方法的反应中，反应温度在0～150℃。
本发明的有益效果是：以邻卤苯乙酮及其衍生物为原料，在铜催化剂和碱的作用下，于有机溶剂中发生自身缩合反应，得到α-萘酚类化合物。本发明所述的α-萘酚的制备方法，反应步骤少，原料简单易得，催化剂价格低廉，反应条件温和，便于操作。由于α-萘酚类化合物是一类重要的骨架结构，在药物合成领域有着非常广泛的应用，因此，本发明具有较大的使用价值和社会经济效益。
附图说明
图1是化合物1a的1H核磁谱图。
图2是化合物1a的13C核磁谱图。
图3是化合物2a的1H核磁谱图。
图4是化合物2a的13C核磁谱图。
图5是化合物3a的1H核磁谱图。
图6是化合物3a的13C核磁谱图。
图7是化合物4a的1H核磁谱图。
图8是化合物4a的13C核磁谱图。
图9是化合物5a的1H核磁谱图。
图10是化合物5a的13C核磁谱图。
图11是化合物6a的1H核磁谱图。
图12是化合物6a的13C核磁谱图。
图13是化合物7a的1H核磁谱图。
图14是化合物7a的13C核磁谱图。
图15是化合物8a的1H核磁谱图。
图16是化合物8a的13C核磁谱图。
图17是化合物9a的1H核磁谱图。
图18是化合物9a的13C核磁谱图。
图19是化合物10a的1H核磁谱图。
图20是化合物10a的13C核磁谱图。
图21是化合物11a的1H核磁谱图。
图22是化合物11a的13C核磁谱图。
图23是化合物12a的1H核磁谱图。
图24是化合物12a的13C核磁谱图。
具体实施方式
下面结合具体实施例，进一步阐述本发明。这些实施例仅用于说明本发明而不用于限制本发明的范围。在本领域内的技术人员对本发明所做的简单替换或改进均属于本发明所保护的技术方案之内。
实施例1：3-(2-bromophenyl)naphthalen-1-ol(1a)的合成
在25mL反应器中，加入叔丁醇钾(0.112g,,1mmol)和醋酸铜(0.010g，0.050mmol)，氮气置换3次后，在氮气保护中加入无水四氢呋喃0.40mL，搅拌下加入邻溴苯乙酮(0.198g,1mmol)，30℃搅拌5h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-bromophenyl)naphthalen-1-ol0.119g，产率80％。Paleyellowoil；IR(neat)ν3396,3054,1702,1599,1257,1019,911,849,758,531cm-1；1H-NMR(400MHz,CDCl3)δ5.96(s,1H),6.78(s,1H),7.07–7.11(m,1H),7.20–7.25(m,2H),7.37(d,J＝5.2Hz,1H),7.42(dd,J＝8.0,4.0Hz,2H),7.59(d,J＝8.0Hz,1H),7.73–7.76(m,1H)；13C-NMR(100MHz,CDCl3)δ110.9,121.4,121.8,122.8,123.9,125.9,127.1,127.6,128.2,129.0,131.6,133.3,134.5,139.0,142.4,150.9；HRMS(EI)calcdforC16H21BrO:297.9993[M]+；found:298.0000.
实施例2：3-(2-bromo-4-methoxyphenyl)-6-methoxynaphthalen-1-ol(2a)的合成
在25mL反应器中，加入叔丁醇钠(1.920g,20mmol)和氧化亚铜(0.016g，0.100mmol)，氮气置换3次后，在氮气保护中加入无水N,N-二甲基甲酰胺3.40mL，搅拌下加入4-甲氧基-2-溴苯乙酮(0.228g,1mmol)，0℃搅拌5h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-bromo-4-methoxyphenyl)-6-methoxynaphthalen-1-ol0.116g，产率65％。Mp105.0–105.2℃；IR(neat)ν3424,1634,1605,1394,1220,1024,813,574cm-1；1H-NMR(d6-DMSO,400MHz)δ3.83(s,3H),3.86(s,3H),6.75(s,1H),7.04(dd,J＝8.4,2.0Hz,1H),7.12(dd,J＝9.2,2.0Hz,1H),7.20(s,1H),7.26(d,J＝1.6Hz,1H),7.34(dd,J＝13.2,5.3Hz,2H),8.07(d,J＝8.8Hz,1H)10.20(s,1H)；13C-NMR(d6-DMSO,100MHz)δ55.6,56.1,106.5,108.5,114.3,117.6,118.4,118.5,119.3,122.5,124.0,132.3,135.2,136.0,139.6,153.2,158.3,159.5；HRMS(EI)calcdforC18H15O3Br:358.0205[M]+；found:358.0198.
实施例3：3-(2-bromo-4-fluorophenyl)-6-fluoronaphthalen-1-ol(3a)的合成
在25mL反应器中，加入叔丁醇钠(1.920g,20mmol)和氧化亚铜(0.032g，0.200mmol)，氮气置换3次后，在氮气保护中加入无水N,N-二甲基甲酰胺3.40mL，搅拌下加入4-氟-2-溴苯乙酮(0.217g,1mmol)，0℃搅拌5h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-bromo-4-fluorophenyl)-6-fluoronaphthalen-1-ol0.104g，产率62％。Mp99.0–99.4℃；IR(neat)ν3073,1581,1489,1397,1025,859,820,759cm-1；1H-NMR(d6-DMSO,400MHz)δ6.59(s,1H),6.94–7.02(m,3H),7.09–7.13(m,1H),7.25–7.31(m,2H),7.90–7.94(m,1H),10.27(s,1H)；13C-NMR(d6-DMSO,100MHz)δ109.6,111.1(d,JC-F＝20.4Hz),115.2,115.5(d,JC-F＝8.2Hz),118.7(d,JC-F＝4.9Hz),120.3(d,JC-F＝24.2Hz),121.5,122.5(d,JC-F＝9.7Hz),125.5(d,JC-F＝9.2Hz),132.8(d,JC-F＝8.3Hz),135.5(d,JC-F＝9.5Hz),139.0(d,JC-F＝3.4Hz),139.8,153.5,161.2(d,JC-F＝242.6Hz),161.6(d,JC-F＝247.6Hz)；HRMS(EI)calcdforC16H9BrF2O:333.9805[M]+；found:333.9808.
实施例4：3-(2-bromo-4-methylphenyl)-6-methylnaphthalen-1-ol(4a)的合成
在25mL反应器中，加入叔丁醇钠(1.920g,20mmol)和氧化亚铜(0.008g，0.050mmol)，氮气置换3次后，在氮气保护中加入无水N,N-二甲基甲酰胺7.40mL，搅拌下加入4-甲基-2-溴苯乙酮(0.212g,1mmol)，60℃搅拌5h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-bromo-4-methylphenyl)-6-methylnaphthalen-1-ol0.106g，产率65％。Mp101.0–101.6℃；IR(neat)ν3404,2920,1662,1602,1392,1299,910,821,732cm-1；1H-NMR(400MHz,CDCl3)δ2.33(s,3H),2.47(s,3H),5.80(s,1H),6.76(d,J＝1.2Hz,1H),7.10(dd,J＝8.0,0.8Hz,1H),7.20(d,J＝7.6Hz,1H),7.27–7.30(m,2H),7.47(s,1H),7.55(s,1H)8.07(d,J＝8.4Hz,1H)；13C-NMR(100MHz,CDCl3)δ20.8,21.8,110.0,120.6,121.5,121.9,122.4,127.0,127.8,128.3,131.2,134.0,134.8,136.5,138.9,139.0,139.6150.9；HRMS(EI)calcdforC18H15OBr:326.0306[M]+；found:326.0297.
实施例5：3-(2-chlorophenyl)naphthalen-1-ol(5a)的合成
在25mL反应器中，加入叔丁醇锂(4.000g,50mmol)和碘化亚铜(0.010g，0.050mmol)，氮气置换3次后，在氮气保护中加入无水二甲亚砜7.80mL，搅拌下加入邻氯苯乙酮(0.155g,1mmol)，100℃搅拌12h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-chlorophenyl)naphthalene-1-ol0.102g，产率58％。Paleyellowoil；IR(neat)ν3542,3407,3056,1600,1575,1398,1259,1064,912,850,759,706cm-1；1H-NMR(400MHz,CDCl3)δ5.66(s,1H),6.80(d,J＝1.2Hz,1H),7.14–7.17(m,2H),7.21–7.24(m,1H),7.36–7.41(m,4H),7.73(dd,J＝5.2,1.6Hz,1H),8.16(dd,J＝6.0,3.2Hz,1H)；13C-NMR(100MHz,CDCl3)δ110.9,121.6,121.8,124.0,125.9,127.1,128.2,128.9,130.1,131.7,132.7,134.6,137.3,140.4,151.0；HRMS(EI)calcdforC16H11OCl:254.0498[M]+；found:254.0499.
实施例6：3-(2-chloro-5-(trifluoromethyl)phenyl)-7-(trifluoromethyl)naphthalen-1-ol(6a)的合成
在25mL反应器中，加入氢氧化钠(0.400g,10mmol)和碘化亚铜(0.020g，0.010mmol)，氮气置换3次后，在氮气保护中加入无水N,N-二甲基甲酰胺16.70mL，搅拌下加入5-三氟甲基-2-氯苯乙酮(0.223g,1mmol)，150℃搅拌12h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-chloro-5-(trifluoromethyl)phenyl)-7-(trifluoromethyl)naphthalen-1-ol0.141g，产率72％。Mp105.8–106.2℃；IR(neat)ν3317,1641,1612,1581,1429,1320,1199,1172,1083,904,823,691,665cm-1；1H-NMR(400MHz,CDCl3)δ5.74(s,1H),6,98(d,J＝1.2Hz,1H),7.51(s,1H),7.57–7.64(m,2H),7.68–7.71(m,2H),7.94(d,J＝8.4Hz,1H),8.58(d,J＝0.8Hz,1H)；13C-NMR(100MHz,CDCl3)δ111.0,121.0,122.3,122.9,123.0(JC-F＝550Hz),125.0,125.5(JC-F＝550Hz),128.5(JC-F＝190Hz),128.8(JC-F＝190Hz),129.0,130.7,135.5,136.4,138.1,140.5,152.0；HRMS(EI)calcdforC18H9F6OCl:390.0246[M]+；found:390.0236.
实施例7：3-(2-chloro-4-methoxyphenyl)-6-methoxynaphthalen-1-ol(7a)的合成
在25mL反应器中，加入氢氧化钠(1.200g,30mmol)和碘化亚铜(0.010g，0.050mmol)，氮气置换3次后，在氮气保护中加入无水乙腈18.4mL，搅拌下加入4-甲氧基-2-氯苯乙酮(0.184g,1mmol)，90℃搅拌12h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-chloro-4-methoxyphenyl)-6-methoxynaphthalen-1-ol0.113g，产率60％。Mp92.6–97.5℃；IR(neat)ν3429,1633,1606,1394,1285,1220,1021,869,848,810,576cm-1；1H-NMR(d6-DMSO,400MHz)δ3.81(s,3H),3.85(s,3H),6.84(s,1H),6.98(dd,J＝8.4,2.4Hz,1H),7.10–7.16(m,2H),7.37(d,J＝8.8Hz,1H),8.10(d,J＝9.2Hz,1H),10.21(s,1H)；13C-NMR(d6-DMSO,100MHz)δ55.5,56.0,106.5,108.5,113.8,115.4,117.6,118.5,119.4,124.1,132.5,132.6,133.2,136.1,138.0,153.3,158.3,159.6；HRMS(EI)calcdforC18H15ClO3:314.0710[M]+；found:314.0721.
实施例8：6-chloro-3-(2,4-dichlorophenyl)naphthalen-1-ol(8a)的合成
在25mL反应器中，加入氢氧化钠(1.200g,30mmol)和碘化亚铜(0.060g，0.300mmol)，氮气置换3次后，在氮气保护中加入无水乙腈18.4mL，搅拌下加入4-氯-2-氯苯乙酮(0.189g,1mmol)，90℃搅拌12h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到6-chloro-3-(2,4-dichlorophenyl)naphthalene-1-ol0.088g，产率70％。Mp129.2–129.5℃；IR(neat)ν3382,1592,1476,1389,1260,1094,920,896,820,796cm-1；1H-NMR(d6-DMSO,400MHz)δ7.02(d,J＝1.2Hz,1H),7.40(s,1H),7.50–7.56(m,3H),7.76(d,J＝1.6Hz,1H),8.02(d,J＝2.0Hz,1H),8.23(d,J＝8.8Hz,1H),10.65(s,1H)；13C-NMR(d6-DMSO,100MHz)δ110.2,118.6,122.8,124.8,126.1,126.8,128.0,129.7,132.0.132.9,133.1,133.5,135.3,137.8,139.2,153.6；HRMS(EI)calcdforC16H9OCl3:321.9719[M]+；found:321.9709.
实施例9：3-(2-iodophenyl)naphthalen-1-ol(9a)的合成
在25mL反应器中，加入叔丁醇钾(0.112g,,1mmol)和醋酸铜(0.080g，0.400mmol)，氮气置换3次后，在氮气保护中加入无水四氢呋喃0.40mL，搅拌下加入邻碘苯乙酮(0.246g,1mmol)，30℃搅拌5h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(2-iodophenyl)naphthalen-1-ol0.112g，产率65％。Paleyellowoil；IR(neat)ν3534,3051,1598,1574,1477,1397,1255,1083,1013,911,849,776,759cm-1；1H-NMR(400MHz,CDCl3)δ5.84(s,1H),6.73(d,J＝1.2Hz,1H),6.94–6.98(m,1H),7.24–7.30(m,2H),7.32(d,J＝3.6Hz,1H),7.41–7.47(m,2H),7.77(dd,J＝4.8,2.4Hz,1H),7.90(d,J＝8.0Hz,1H),8.17–8.19(m,1H)；13C-NMR(100MHz,CDCl3)δ98.73,110.8,121.2,121.8,123.9,125.8,127.1,128.2,128.3,129.1,130.5,134.4,139.6,141.9,146.4,150.8；HRMS(EI)calcdforC16H11OI:345.9855[M]+；found:345.9864.
实施例10：3-(4-iodo-[1,1'-biphenyl]-3-yl)-7-phenylnaphthalen-1-ol(10a)的合成
在25mL反应器中，加入氢氧化钠(1.600g,40mmol)和三氟甲磺酸铜(0.036g，0.100mmol)，氮气置换3次后，在氮气保护中加入无水乙腈5.0mL，搅拌下加入5-苯基-2-碘苯乙酮(0.322g,1mmol)，室温搅拌12h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到3-(4-iodo-[1,1'-biphenyl]-3-yl)-7-phenylnaphthalen-1-ol0.154g，产率62％。Mp128.5–129.1℃；IR(neat)ν3529,3056,1599,1572,1478,1406,1224,759,697cm-1；1H-NMR(400MHz,CDCl3)δ5.47(s,1H),6.78(s,1H),7.18(dd,J＝8.4,2.4Hz,1H),7.27–7.31(m,2H),7.33–7.40(m,5H),7.49–7.51(m,3H),7.67–7.72(m,3H),7.80(d,J＝8.4Hz,1H),7.90(d,J＝8.4Hz,1H),8.45(s,1H)；13C-NMR(100MHz,CDCl3)δ97.4,111.1,120.0,120.8,124.3,127.1,127.6,128.0,128.7,129.0,133.6,138.4,139.8,140.0,141.2,141.3,141.9,146.8,151.5；HRMS(EI)calcdforC28H19OI:498.0481[M]+；found:498.0490.
实施例11：7-(6-iodobenzo[d][1,3]dioxol-5-yl)naphtho[2,3-d][1,3]dioxol-5-ol(11a)的合成
在25mL反应器中，加入氢氧化钠(1.200g,30mmol)和碘化亚铜(0.500g，0.500mmol)，氮气置换3次后，在氮气保护中加入无水乙腈18.4mL，搅拌下加入4，5-亚甲二氧基-2-碘苯乙酮(0.288g,1mmol)，90℃搅拌12h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到7-(6-iodobenzo[d][1,3]dioxol-5-yl)naphtha[2,3-d][1,3]dioxol-5-ol0.150g，产率74％。Mp151.4–152.0℃；IR(neat)ν3299,2890,1624,1473,1440,1227,1039,935,859cm-1；1H-NMR(d6-DMSO,400MHz)δ6.10(s,2H),6.12(s,2H),6.69(s,1H),6.97(s,1H),7.06(s,1H),7.25(s,1H),7.43(s,1H),7.47(s,1H),10.09(s,1H)；13C-NMR(d6-DMSO,100MHz)δ87.5,98.7,101.6,102.4,104.2,109.6,110.5,118.5,118.7,120.4,131.6,140.4,140.8,147.2,147.9,148.3,148.4,152.4；HRMS(EI)calcdforC18H11O5I:433.9651[M]+；found:433.9647.
实施例12：6-(5-cyano-2-iodophenyl)-8-hydroxy-2-naphthonitrile(12a)的合成
在25mL反应器中，加入氢氧化钠(1.600g,40mmol)和三氟甲磺酸铜(0.036g，0.100mmol)，氮气置换3次后，在氮气保护中加入四氢呋喃1.0mL和甲苯2.0mL，搅拌下加入5-氰基-2-碘苯乙酮(0.271g,1mmol)，室温搅拌12h，柱层析(硅胶，200–300目；展开剂，石油醚：乙酸乙酯＝20:1)得到6-(5-cyano-2-iodophenyl)-8-hydroxy-2-naphthonitrile0.162g，产率82％。Mp138.5–139.1℃；IR(neat)ν2956,2922,2226,1571,1458,1406,1377,1018,865,821cm-1；1H-NMR(d6-DMSO,400MHz)δ6.94(s,1H),7.43(s,1H),7.60(d,J＝8.0Hz,1H),7.80(d,J＝8.4Hz,1H),7.87(s,1H),8.07(d,J＝8.4Hz,1H),8.23(d,J＝8.0Hz,1H),8.60(s,1H),11.04(s,1H)；13C-NMR(d6-DMSO,100MHz)δ106.2,108.0,111.3,111.9,118.6,119.2,119.8,123.5,127.7,129.0,130.0,132.8,133.0,135.7,141.0,144.2,147.3,153.8；HRMS(EI)calcdforC18H9N2IO:395.9760[M]+；found:395.9750.
Claims (3)
1.一种α-萘酚类化合物的制备方法，其特征在于，以邻卤苯乙酮衍生物为原料，在碱和铜盐催化剂的作用下发生自身缩合，得到α-萘酚类化合物，合成路线如下：
在上述制备方法的反应中，R选自氢、烷基、芳基、卤素、氰基、三氟甲基、烷氧基；X选自氯、溴、碘；
邻卤苯乙酮衍生物与铜盐催化剂的摩尔比为1:0.05～0.50；
有机溶剂的加入量为邻卤苯乙酮衍生物重量的2～100倍；
邻卤苯乙酮衍生物与碱的摩尔比为1:1～50；
反应温度为0～150℃；
所述的铜盐催化剂为碘化亚铜、溴化亚铜、氯化亚铜、三氟甲磺酸亚铜、氧化亚铜、醋酸铜、三氟甲磺酸铜、硫酸铜、氯化铜、溴化铜中的一种或两种以上混合。
2.如权利要求1所述的制备方法，其特征在于，所述的有机溶剂为N,N-二甲基甲酰胺、乙腈、四氢呋喃、1,4-二氧六环、1,2-二氯乙烷、二甲基亚砜、甲基叔丁基醚、乙二醇二甲醚、三氯甲烷、二氯甲烷、乙醚、正丁醚、四氯化碳、甲苯、环己烷中的一种或两种以上混合。
3.如权利要求1或2所述的制备方法，其特征在于，所述的碱为丁醇钠、叔丁醇钾、叔丁醇锂、碳酸钠、碳酸钾、碳酸氢钠、氢化钠、醋酸钠、乙醇钠、磷酸三钾、碳酸铯、乙酸铯、1,8-二氮杂二环十一碳-7-烯中的一种或两种以上混合。
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