CN105330522B - 一种苯并[b]芴酮系列化合物的制备方法 - Google Patents
一种苯并[b]芴酮系列化合物的制备方法 Download PDFInfo
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- CN105330522B CN105330522B CN201510700797.0A CN201510700797A CN105330522B CN 105330522 B CN105330522 B CN 105330522B CN 201510700797 A CN201510700797 A CN 201510700797A CN 105330522 B CN105330522 B CN 105330522B
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- benzo
- fluorenone
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- phenyl
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- -1 benzo [ b ] fluorenone series compounds Chemical class 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 98
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000005406 washing Methods 0.000 claims abstract description 27
- 239000007800 oxidant agent Substances 0.000 claims abstract description 21
- 230000001590 oxidative effect Effects 0.000 claims abstract description 20
- 239000000047 product Substances 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 13
- 239000000758 substrate Substances 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 238000007243 oxidative cyclization reaction Methods 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 48
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 37
- 239000012043 crude product Substances 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 10
- 238000001953 recrystallisation Methods 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- AGCQBGSDLGORJV-UHFFFAOYSA-N benzo[h]fluoren-1-one Chemical class C1=CC=C2C=C3C4=CC=CC(=O)C4=CC3=CC2=C1 AGCQBGSDLGORJV-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 4
- 229930194224 Kinamycin Natural products 0.000 claims description 3
- 238000000862 absorption spectrum Methods 0.000 claims description 3
- 230000003115 biocidal effect Effects 0.000 claims description 3
- 150000002894 organic compounds Chemical class 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 239000003905 agrochemical Substances 0.000 claims description 2
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002989 phenols Chemical class 0.000 claims description 2
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 2
- 235000019394 potassium persulphate Nutrition 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 2
- WOAHJDHKFWSLKE-UHFFFAOYSA-N 1,2-benzoquinone Chemical compound O=C1C=CC=CC1=O WOAHJDHKFWSLKE-UHFFFAOYSA-N 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 abstract description 10
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 229910052751 metal Inorganic materials 0.000 abstract description 4
- 239000002184 metal Substances 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000012670 alkaline solution Substances 0.000 abstract 1
- 239000006227 byproduct Substances 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 239000012295 chemical reaction liquid Substances 0.000 description 24
- 125000003983 fluorenyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 20
- 229940049706 benzodiazepine Drugs 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000010792 warming Methods 0.000 description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 9
- 239000002585 base Substances 0.000 description 7
- 235000010290 biphenyl Nutrition 0.000 description 7
- 239000004305 biphenyl Substances 0.000 description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 7
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- LDCVEPMPZLHMMK-UHFFFAOYSA-N 11h-benzo[a]fluoren-1-ol Chemical compound C1=CC=C2CC3=C4C(O)=CC=CC4=CC=C3C2=C1 LDCVEPMPZLHMMK-UHFFFAOYSA-N 0.000 description 3
- HKMTVMBEALTRRR-UHFFFAOYSA-N Benzo[a]fluorene Chemical compound C1=CC=CC2=C3CC4=CC=CC=C4C3=CC=C21 HKMTVMBEALTRRR-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- FRIJWEQBTIZQMD-UHFFFAOYSA-N Benzo[c]fluorene Chemical compound C1=CC2=CC=CC=C2C2=C1CC1=CC=CC=C12 FRIJWEQBTIZQMD-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical group FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 2
- 150000008376 fluorenones Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229940095102 methyl benzoate Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- AIDLAEPHWROGFI-UHFFFAOYSA-N 2-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=C(C(O)=O)C=CC=C1C(O)=O AIDLAEPHWROGFI-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- KSZVOXHGCKKOLL-UHFFFAOYSA-N 4-Ethynyltoluene Chemical group CC1=CC=C(C#C)C=C1 KSZVOXHGCKKOLL-UHFFFAOYSA-N 0.000 description 1
- HAPOJKSPCGLOOD-UHFFFAOYSA-N Benzo[b]fluorene Chemical class C1=CC=C2C=C3CC4=CC=CC=C4C3=CC2=C1 HAPOJKSPCGLOOD-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LNDCACGXQMKLOV-UHFFFAOYSA-N C=12C(=O)C3=CC=CC=C3C2=CC2=CC=CC=C2C=1C1=CC=CC=C1 Chemical class C=12C(=O)C3=CC=CC=C3C2=CC2=CC=CC=C2C=1C1=CC=CC=C1 LNDCACGXQMKLOV-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229910003803 Gold(III) chloride Inorganic materials 0.000 description 1
- 241000219000 Populus Species 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000010719 annulation reaction Methods 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000004054 benzoquinones Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012969 di-tertiary-butyl peroxide Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000011737 fluorine Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- RJHLTVSLYWWTEF-UHFFFAOYSA-K gold trichloride Chemical compound Cl[Au](Cl)Cl RJHLTVSLYWWTEF-UHFFFAOYSA-K 0.000 description 1
- 229940076131 gold trichloride Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 230000005622 photoelectricity Effects 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
- C07C45/512—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being a free hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1011—Condensed systems
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- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明涉及一种苯并[b]芴酮系列化合物的制备方法。方法步骤为:以1,1‑二芳基‑3‑(2‑(对甲苯基乙炔基)苯基)丙‑2‑炔‑1‑醇作为反应底物,使其在氧化剂的作用下,无需任何金属元素参与,直接在有机溶剂中发生分子内的“一锅法”串联氧化环化反应,高效地合成苯并[b]芴酮系列化合物。反应完毕,采用碳酸钠碱性溶液洗涤以及乙醇重结晶即可得到纯净的产品。反应无需任何金属元素参与,是一种“绿色”的化学合成方法,反应的产率极高、化学选择性良好、条件温和、底物适用性广、操作简便、成本较低、副产物少、便于分离提纯、可适用于较大规模的制备。
Description
技术领域
本发明属有机化学技术领域,具体涉及一种苯并[b]芴酮系列化合物的制备方法。
背景技术
基于芴并环结构的化合物由于含有较大的π共轭体系,因而具有良好的潜在光电功能特性,目前,含芴结构的小分子化合物或聚合物已被广泛用作光电功能材料领域((a)Shimizu,A.;Tobe,Y.Angew.Chem.Int.Ed.2011,50,6906;(b)Allard,S.;Forster,M.;Souharce,B.;Thiem,H.;Scherf,U.Angew.Chem.Int.Ed.2008,47,4070;(c)J.E.Anthony,Chem.Rev.2006,106,5028;(d)J.E.Anthony,Angew.Chem.Int.Ed.2008,47,452.)。
含芴并环结构的化合物在医药工业中也有十分重要的应用。例如,苯并芴醇是一种很好的抗疟药,对恶性疟疾有很好的治疗作用(时云林,丁德本,崔世斌等,复方苯芴并醇治疗索马里恶性疟的疗效观察[J],中国寄生虫病防治杂志,1999,12(3):173-174);吴达龙等发现苯并芴的衍生物对乳腺癌有很好的治疗作用(吴达龙,吕焕章,黄丰等,苯并芴醇衍生物LY980503逆转入乳腺癌多药耐药细胞株MCF/DOM对多柔比星的耐药性[J],中国药理与毒物学杂志,2002,16(3):211-215)。
将芴环的9-位的亚甲基氧化得到的化合物,9-芴酮类衍生物也广 泛应用于药物及药物合成中。例如,9-芴酮在医药工业中可以用于合成抗癌药、交感神经抑制剂和止痉挛剂等(杨威,高占先,李令东,芴衍生物的合成及研究进展[J],辽宁化工,2004,33(2):88-91.);具有芴并环结构的化合物苯并[b]芴酮在医药工业中用作抗菌素醌那霉素的生物合成的重要前体(Gould,S.;Melville,C.Bioorganic Med.Chem.Lett.1995,6,51.)。此外在农业上,芴骨架结构广泛存在于杀虫剂、除草剂和植物生长调节剂,其中最重要的是9-芴羧酸酯类衍生物(杨威,高占先,李令东.芴衍生物的合成及研究进展[J].辽宁化工,2004,33(2):88-91.)。
因此,研究和发展一些简单有效的方法合成芴类多环化合物具有十分重要的科学意义和应用价值。然而,文献报道的合成此类化合物的方法却十分有限,并且反应都存在着一些局限性。例如,2000年前后,Saá等人将化合物3-芳基基-1-(2-(2-芳乙炔基)苯基)炔丙基-2-醇加热到170℃,使其在高温下发生自由基热芳构化反应,合成了苯并[b]芴类化合物((a)Rodríguez,D.;Castedo,L.;Domínguez,D.;Saá,C.Tetrahedron Lett.1999,40,7701.(b)Rodríguez,D.;Navarro,A.;Castedo,L.;Domínguez,D.;Saá,C.Org.Lett.2000,2,1497.(c)Rodríguez,D.;Navarro-Vázquez,A.;Castedo,L.;Domínguez,D.;Saá,C.Tetrahedron Lett.2002,43,2717)。2004年,该小组报道将1-(2-(苯基乙炔基)苯基)-3-(三甲基甲硅烷)丙-2-炔-1-酮类化合物在甲苯中加热到150℃,可发生分子内的脱氢自由基环合反应,合成苯并[b]芴和苯并[c]芴类衍生物(Rodríguez,D.;Martínez-Esperón,M.;Navarro-Vázquez,A.;Castedo,L.;Domínguez,D.;Saá,C.;J.Org.Chem.2004,69,3842.);2008年,Cheng等人利用芳香的乙醛肟醚类和芳基卤代物在甲苯中回流温度下,通过钯催化双碳氢键活化Heck环化反应直接构建芴酮类衍生物(Thirunavukkarasu,V.;Parthasarathy,K.;Cheng,C.;Angew.Chem.Int.Ed.2008,47,9462)。此几种方法需要将反应物加热到比较高的温度才能发生转化,条件比较苛刻,并且反应时间较长,高温下对官能团的兼容性比较差,难以大规模地生产和应用。华东师范大学的张俊良教授报道利用过渡金属三氯化金和三氟甲磺酸银共同催化的分子内串联反应合成苯并[a]芴衍生物(Liu,L.;Zhang,J.Angew.Chem.Int.Ed.2009,48,6093.)。通过该方法所得产物收率50-73%,化学选择性较好,不过该反应对底物官能团的要求比较专一,该文献中也仅报道了四例实施案例。
最近我们小组发展了新的方法,在非常温和的条件下可以快速合成苯并芴类化合物。我们采用3-芳基基-1-(2-(2-芳乙炔基)苯基)炔丙基-2-醇作为反应底物,使其在过渡金属银盐作为催化剂的条件下,可与卤素亲电试剂在室温下发生成环反应,一锅法高效率、高化学选择性地制得含卤素的苯并芴醇衍生物。所得的产物中的卤素原子还可以在钯催化剂的作用下继续发生偶联反应,在产物分子骨架上引入多样性的有机官能团。((a)Chen,Z.;Zeng.M.;Yuan,J.;Yang,Q.;Peng,Y.;Org.Lett.2012,14,3588.(b)陈知远,曾梦静,杨琴,彭以元,中国专利,ZL201210144087.0)。
此反应要用到过渡金属作为催化剂,因而在工业级大规模应用中 有可能存在重金属离子微量残留的问题。为了解决这个问题,最近,我们通过研究发现,利用1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇作为反应底物,可在有机氧化剂的作用下,无需任何金属催化剂即可氧化环化反应,高化学选择性、高效率地合成苯并芴酮系列化合物。本方法反应条件温和、操作简便,无需贵重金属元素催化剂,成本较低、副反应少、产品纯度高、便于分离提纯,可适合于较大规模的制备,所得产物具有良好的光电功能特性以及潜在的生物和药物活性,因此可应用于光电功能材料、生物医药和农药领域,具有非常好的应用前景。
发明内容
本发明目的在于提供一种苯并[b]芴酮的制备方法。本方法反应条件温和、操作简便、成本较低、副反应少、产品纯度高、便于分离提纯,可适合于较大规模的制备。紫外吸收光谱测试表明产物最大吸收峰位于380-400nm,荧光发射表明产物的荧光发射峰位于460-540nm范围,是一类潜在的蓝绿色荧光发射材料,具有良好的光电功能特性以及潜在的生物或药物活性的化合物,有望在光电功能材料、生物医药和农药领域具有非常好的应用前景。
本发明是这样实现的,一种苯并[b]芴酮系列化合物的制备方法,其特征在于方法步骤为:采用1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇作为反应底物,在氧化剂作用下在有机溶剂中发生氧化环化反应,反应温度80℃,反应时间为12h,高效地合成苯并[b]芴酮系列化合物,反应完毕,加入饱和碳酸钠溶液洗涤除去酚 类还原产物,粗产品在乙醇中重结晶法即可纯品。
反应所使用的氧化剂为有机化合物氧化剂,包括叔丁基过氧化氢(TPHP)、或者二叔丁基过氧化物(DTBP)、或者过氧化氢(30%)、或者过硫酸钾、或者氧气(O2)、或者苯醌(BQ)、或者2,3,5,6-四甲基环-2,5-二烯-1,4-二酮、或者2,5-二氯环己-2,5-二烯-1,4-二酮、或者2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ),或者3,3′,5,5′-四-叔丁基-[1,1′-双(环己基)]-2,2′,5,5′-四烯-4,4′-二酮。
其中以2,5-二氯环己-2,5-二烯-1,4-二酮、2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)反应效果最佳。
底物1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇与氧化剂的摩尔数比例为1:1。
反应体系所使用的有机溶剂为二氯甲烷、三氯甲烷,1,2-二氯乙烷,乙腈,或甲苯。其中以乙腈作为溶剂时反应效果最佳。
反应所得的化合物具有比较明显的光电特性,紫外吸收光谱测试表明产物最大吸收峰位于380-400nm,荧光发射表明产物的荧光发射峰位于460-540nm范围,是一类潜在的蓝绿色荧光发射材料;同时,由于苯并[b]芴酮衍生物亦可用作抗菌素醌那霉素的生物合成的重要前体,因此此方法所得的产品在光电功能材料领域以及生物医药以及农药等领域具有潜在的应用前景。
反应体系所使用的有机溶剂为乙腈。
反应方程式如下:
其中R1、R2、R3和R4为氢或烷基、烷氧基等各种供电子基团,或者氟、氯、溴、三氟甲基、硝基、酯基以及氰基等各种吸电子基团。
具体操作:在一个装有磁力搅拌子的25mL反应瓶中,加入氧化剂DDQ(0.4mmol,1.0eq.)、1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇(0.4mmol,1.0eq.)和乙腈(4mL),氮气保护。反应液先在室温下搅拌10min后升温至80℃,反应约12h,薄板层析(TLC)检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的苯并[b]芴酮衍生物。
在本发明中,反应的原子经济性很高,反应物1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇)与氧化剂(DDQ)的比例为1:1就能非常顺利地进行,由此反应体现出良好的绿色化。同时,反应操作简便,无需柱层析或其他分离设备,产物收率高,化学选择性优秀,所得的产物在材料科学领域或生物农药领域具有潜在的应用前景。
附图说明
图1为10-苯基-5-(对甲苯基)-11H-苯并[b]芴-11-酮化合物2b的单晶结构图。
图2为10-苯基-5-(对甲苯基)-11H-苯并[b]芴-11-酮化合物2b的单晶结构对应的化合物分子结构图。
图3为10-对氟苯基-5-(对甲苯基)-11H-苯并[b]芴-11-酮化合物2f的单晶结构图。
图4为10-苯基-5-(对甲苯基)-11H-苯并[b]芴-11-酮化合物2f的单晶结构对应的化合物分子结构图。
具体实施方式
如图1、图2所示,下面的实施例是对本发明的进一步说明,而不是限制本发明的范围。
实例1
在一个装有磁力搅拌子的25mL反应管中,加入氧化剂DDQ(0.4mmol,1.0equiv.)、1,1-二苯基-3-(2-(苯基乙炔基)苯基)丙-2-炔-1-醇(0.4mmol,1.0equiv.)和乙腈(4mL),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤 反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的5,10-二苯基-11H-苯并[b]芴-11-酮2a。产率:83%;1H NMR(400MHz,CDCl3)δ7.67-7.64(m,1H),7.62-7.57(m,4H),7.55-7.52(m,3H),7.49-7.47(m,1H),7.45-7.42(m,2H),7.41-7.38(m,3H),7.36-7.32(m,1H),7.19-7.12(m,2H),6.30-6.28(m,1H);13C NMR(100MHz,CDCl3)δ192.4,144.4,140.7,137.8,136.7,136.7,135.9,135.4,134.4,134.3,133.7,129.9,129.6,129.4,129.0,128.7,128.4,128.2,128.0,127.1,126.7,123.9,123.8.
实例2
在一个装有磁力搅拌子的25mL反应管中,加入氧化剂DDQ(0.2mmol,1.0equiv.)、1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇(0.2mmol,1.0equiv.)和乙腈(4mL),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的10-苯基-5-(对甲苯基)-11H-苯并[b]芴-11-酮2b。产率:89%; 1H NMR(400MHz,CDCl3)δ7.65(d,J=8.0Hz,1H),7.59-7.50(m, 5H),7.44-7.40(m,5H),7.34(t,J=7.6Hz,3H),7.18-7.16(m,2H),6.39-6.37(m,1H),2.55(s,3H);13C NMR(100MHz,CDCl3)δ192.5,144.5,140.5,138.1,136.9,136.7,136.0,135.4,134.6,134.4,134.4,133.7,130.1,129.7,129.6,128.9,128.6,128.4,128.2,127.9,127.2,126.6,123.9,21.5.
实例3
在一个装有磁力搅拌子的25mL反应管中,加入氧化剂DDQ(0.2mmol,1.0equiv.)、3-(2-((4-氯苯基)乙炔基)苯基)-1,1-二苯基丙-2-炔-1-醇(0.2mmol,1.0equiv.)和乙腈(4mL),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的5-(4-氯苯基)-10-苯基-11H-苯并[b]芴-11-酮2c。产率:91%; 1H NMR(400MHz,CDCl3)δ7.66(d,J=8.2Hz,1H),7.62-7.57(m,3H),7.54-7.53(m,2H),7.43-7.33(m,8H),7.21-7.18(m,2H),6.39-6.37(m,1H);13C NMR(100MHz,CDCl3)δ192.1,144.0,141.0,136.7,136.5,136.2,135.7,135.5,134.5,133.7,132.8,131.4,129.8,129.6,129.1, 128.9,128.9,128.3,128.2,128.1,126.8,126.8,124.1,123.7.
实例4
在一个装有磁力搅拌子的25ml Schlenk反应管中,加入氧化剂DDQ(0.2mmol,1.0eq.)、甲基4-((2-(3-羟基-3,3-二苯基丙-1-炔-1-基)苯基)乙炔基)苯甲酸甲酯(0.2mmol,1.0eq.)和乙腈(4ml),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的甲基4-(11-氧代-10-苯基-11H-苯并[b]芴-5-基)苯甲酸甲酯2d。产率:92%;1H NMR(400MHz,CDCl3)δ8.32(d,J=8.0Hz,2H),7.67(d,J=8.4Hz,1H),7.60-7.53(m,6H),7.41-7.36(m,5H),7.20-7.13(m,2H),6.29(d,J=7.2Hz,1H),4.03(s,3H);13C NMR(100MHz,CDCl3)δ192.1,166.9,143.9,142.9,141.1,136.7,136.1,135.7,135.3,134.5,133.7,133.0,130.7,130.3,130.2,129.6,129.1,129.0,128.9,128.3,128.2,128.1,126.9,126.7,124.1,123.6,52.4.
实例5
在一个装有磁力搅拌子的25ml Schlenk反应管中,加入氧化剂DDQ(0.2mmol,1.0eq.)、3-(5-甲基-2-(对-甲苯基乙炔基)苯基)-1,1-二苯基丙-2-炔-1-醇(0.2mmol,1.0eq.)和乙腈(4ml),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的2-甲基-10-苯基-5-(对甲苯基)-11H-苯并[b]芴-11-酮2e。产率:83%;1H NMR(400MHz,CDCl3)δ7.63(d,J=8.4Hz,1H),7.55-7.48(m,4H),7.42-7.37(m,6H),7.34-7.30(m,3H),6.99-6.97(m,1H),6.26(d,J=7.6Hz,1H),2.54(s,3H),2.27(s,3H);13C NMR(100MHz,CDCl3)δ192.6,142.0,140.3,138.8,138.0,137.0,136.9,136.0,135.6,135.2,134.7,133.7,133.6,130.0,129.7,129.7,128.9,128.7,128.5,128.2,127.9,127.0,126.4,124.3,123.7,21.57,21.3.
实例6
在一个装有磁力搅拌子的25mL反应管中,加入氧化剂DDQ(0.2mmol,1.0equiv.)、1,1-双(4-溴苯基)-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇(0.2mmol,1.0eq.)和乙腈(4mL),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10mL饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的7-溴-10-(4-溴苯基)-5-(对甲苯基)-11H-苯并[b]芴-11-酮2f。产率:83%;1HNMR(400MHz,CDCl3)δ7.54-7.51(m,2H),7.43-7.40(m,2H),7.35-7.29(m,4H),7.24-7.21(m,2H),7.17-7.13(m,2H),6.84(d,J=2.4Hz,1H),6.76(s,1H),6.35-6.31(m,1H),3.69(s,3H),2.56(s,3H);13C NMR(100MHz,CDCl3)δ192.0,162.6(d,1J=245.1Hz),159.9,145.2,139.6,138.0,137.3,136.5,136.0,135.4,135.1,134.9,134.1,131.4,131.3,130.3,130.1,129.5,128.6,123.79,123.71,117.7,115.2(d,2J=22.2Hz),107.3,55.2,21.5.
在一个装有磁力搅拌子的25ml Schlenk反应管中,加入氧化剂DDQ(0.2mmol,1.0eq.)、3-(4-氟-2-(对-甲苯基乙炔基)苯基)-1,1-二苯基丙-2-炔-1-醇(0.2mmol,1.0eq.)和乙腈(4ml),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的3-氟-10-苯基-5-(对甲苯基)-11H-苯并[b]芴-11-酮2g。产率:86%;1H NMR(400MHz,CDCl3)δ7.67-7.64(m,1H),7.58-7.51(m,5H),7.43(d,J=8.0Hz,2H),7.40-7.36(m,4H),7.30(d,J=8.0Hz,2H),6.86-6.81(m,1H),6.03-6.00(m,1H),2.55(s,3H);13C NMR(100MHz,CDCl3)δ190.7,166.7(d,J=253.3Hz),147.2,147.1,140.5,138.4,136.7,135.7,135.1,134.1,134.0,134.0,132.9,132.9,130.2,129.6,129.5,129.0,128.7,128.5,128.2,128.0,127.3,127.0,125.9,125.8,115.6(d,J=23.7Hz),111.4(d,J=25.4Hz),21.5.
实例7
在一个装有磁力搅拌子的25ml Schlenk反应管中,加入氧化剂DDQ(0.2mmol,1.0eq.)、1,1-双(4-甲苯基)-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇(0.2mmol,1.0eq.)和乙腈(4ml),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的7-甲基-5,10-二对甲苯基-11H-苯并[b]芴-11-酮2h。产率:86%; 1H NMR(400MHz,CDCl3)δ7.60-7.55(m,2H),7.41(d,J=7.6Hz,2H),7.36-7.26(m,7H),7.17-7.13(m,3H),6.33-6.31(m,1H),2.54(s,3H),2.49(s,3H),2.34(s,3H);13C NMR(100MHz,CDCl3)δ192.5,144.5,140.7,138.9,137.9,137.5,137.1,136.9,135.7,134.8,134.2,133.8,133.0,132.0,130.1,129.8,129.6,129.0,128.9,128.7,128.5,127.7,126.5,123.8,123.8,21.9,21.6,21.6.
实例8
在一个装有磁力搅拌子的25ml Schlenk反应管中,加入氧化剂DDQ(0.2mmol,1.0eq.)、1,1-双(4-甲氧基苯基)-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇(0.2mmol,1.0eq.)和乙腈(4ml),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的7-甲氧基-10-(4-甲氧基苯基)-5-(对甲苯基)-11H-苯并[b]芴-11-酮2i。产率:82%;1H NMR(400MHz,CDCl3)δ7.63(d,J=9.2Hz,1H),7.58-7.56(m,1H),7.41(d,J=8.0Hz,2H),7.33-7.30(m,4H),7.16-7.13(m,2H),7.07(d,J=8.8Hz,2H),7.00-6.97(m,1H),6.82(d,J=2.4Hz,1H),6.33-6.31(m,1H),3.91(s,3H),3.69(s,3H),2.54(s,3H);13C NMR(100MHz,CDCl3)δ192.5,159.9,159.4,144.3,140.6,138.9,138.0,137.0,136.4,134.8,134.0,133.2,131.0,130.7,130.2,129.7,128.9,128.5,128.0,126.7,123.8,123.7,117.5,113.60,107.3,55.3,55.3,21.6.
实例9
在一个装有磁力搅拌子的25ml Schlenk反应管中,加入氧化剂DDQ(0.2mmol,1.0eq.)、1,1-双(4-氯苯基)-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇(0.2mmol,1.0eq.)和乙腈(4ml),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的7-氯-10-(4-氯苯基)-5-(对甲苯基)-11H-苯并[b]芴-11-酮2j。产率:83%;1H NMR(400MHz,CDCl3)δ7.59-7.57(m,1H),7.55-7.50(m,3H),7.47(d,J=2.0Hz,1H),7.44(d,J=7.6Hz,2H),7.31-7.27(m,5H),7.20-7.18(m,2H),6.37-6.35(m,1H),2.56(s,3H); 13C NMR(100MHz,CDCl3)δ192.1,144.0,138.8,138.5,137.9,136.7,136.5,135.3,134.6,134.3,133.8,133.8,133.7,131.8,131.1,130.3,130.1,129.5,129.1,128.6,127.5,126.2,124.1,124.0,21.6.
实例10
在一个装有磁力搅拌子的25ml Schlenk反应管中,加入氧化剂DDQ(0.2mmol,1.0eq.)、1,1-双(4-溴苯基)-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇(0.2mmol,1.0eq.)和乙腈(4ml),氮气保护。反应液先在室温下搅拌10min后升温至80℃反应约12h,TLC检测至反应完全。将反应液冷却至室温,加入5mL乙酸乙酯稀释反应液,加入10ml饱和Na2CO3溶液洗涤反应液三次,然后用饱和NaCl溶液洗涤反应液一次,浓缩得粗产品。粗产物在乙醇中重结晶即可得到纯净的7-溴-10-(4-溴苯基)-5-(对甲苯基)-11H-苯并[b]芴-11-酮2k。产率:68%;1H NMR(400MHz,CDCl3)δ7.65(t,J=5.3Hz,3H),7.59-7.56(m,1H),7.47-7.40(m,4H),7.30-7.23(m,4H),7.20-7.18(m,2H),6.36-7.34(m,1H),2.56(s,3);13C NMR(100MHz,CDCl3)δ192.0,144.0,138.8,138.6,138.2,136.6,136.5,134.7,134.2,133.8,133.6,132.0,131.5,131.4,130.4,130.2,130.1,129.5,129.5,129.1,128.6,124.1,124.0,124.0,122.5,21.6。
Claims (5)
1.一种苯并[b]芴酮系列化合物的制备方法,其特征在于方法步骤为:采用1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇作为反应底物,在有机化合物作为氧化剂的作用下,在有机溶剂中发生氧化环化反应,反应温度80 oC,反应时间为12h,高效地合成苯并[b]芴酮系列化合物,反应完毕,加入饱和碳酸钠溶液洗涤除去酚类还原产物,粗产品在乙醇中重结晶法即可纯品;
其中,反应体系所使用的氧化剂为有机化合物氧化剂,包括叔丁基过氧化氢(TPHP)、或者二叔丁基过氧化物(DTBP)、或者过氧化氢(30 %)、或者过硫酸钾、或者氧气(O2)、或者苯醌(BQ)、或者2, 3, 5, 6-四甲基环-2, 5-二烯-1, 4-二酮、或者2, 5-二氯环己-2, 5-二烯-1,4-二酮、或者2, 3-二氯-5, 6-二氰基-1, 4-苯醌(DDQ),或者3, 3',5, 5'-四 - 叔丁基 - [1, 1'-双(环己基)] - 2, 2', 5, 5'-四烯-4, 4'-二酮;
反应体系所使用的有机溶剂为二氯甲烷、三氯甲烷, 1, 2-二氯乙烷,乙腈,或甲苯。
2.根据权利要求1所述的苯并[b]芴酮系列化合物的制备方法,其特征是其中氧化剂以2, 5-二氯环己-2, 5-二烯-1,4-二酮、2, 3-二氯-5, 6-二氰基-1, 4-苯醌(DDQ)反应效果最佳。
3.根据权利要求1所述的苯并[b]芴酮系列化合物的制备方法,其特征是底物1,1-二苯基-3-(2-(对甲苯基乙炔基)苯基)丙-2-炔-1-醇与氧化剂的摩尔数比例为1: 1。
4.根据权利要求1所述的卤代苯并[b]芴酮的制备方法,其特征是反应体系所使用的有机溶剂为以乙腈时反应效果最佳。
5.根据权利要求1所述的苯并[b]芴酮系列化合物的制备方法,其特征是反应所得的化合物具有比较明显的光电特性,紫外吸收光谱测试表明产物最大吸收峰位于380-400 nm,荧光发射表明产物的荧光发射峰位于460-540 nm范围,是一类潜在的蓝绿色荧光发射材料;同时,由于苯并[b]芴酮衍生物亦可用作抗菌素醌那霉素的生物合成的重要前体,因此此方法所得的产品在光电功能材料领域以及生物医药以及农药等领域具有潜在的应用前景。
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