WO2022155981A1 - 氮杂环卡宾基混配型镍 (II) 配合物在合成α - 苄基苯并呋喃类化合物中的应用 - Google Patents
氮杂环卡宾基混配型镍 (II) 配合物在合成α - 苄基苯并呋喃类化合物中的应用 Download PDFInfo
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- WO2022155981A1 WO2022155981A1 PCT/CN2021/073678 CN2021073678W WO2022155981A1 WO 2022155981 A1 WO2022155981 A1 WO 2022155981A1 CN 2021073678 W CN2021073678 W CN 2021073678W WO 2022155981 A1 WO2022155981 A1 WO 2022155981A1
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- benzofuran
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- IANQTJSKSUMEQM-UHFFFAOYSA-N benzofuran Natural products C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title claims abstract description 70
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 8
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 53
- 238000006243 chemical reaction Methods 0.000 claims abstract description 50
- -1 2,4,6-trimethylphenyl Chemical group 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 150000007530 organic bases Chemical class 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical group [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 40
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 38
- 239000002904 solvent Substances 0.000 claims description 33
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 30
- 229910052786 argon Inorganic materials 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 125000003609 aryl vinyl group Chemical group 0.000 claims description 10
- 150000001907 coumarones Chemical class 0.000 claims description 9
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 claims description 8
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 239000011261 inert gas Substances 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- SFBTTWXNCQVIEC-UHFFFAOYSA-N o-Vinylanisole Chemical compound COC1=CC=CC=C1C=C SFBTTWXNCQVIEC-UHFFFAOYSA-N 0.000 claims description 4
- JZHGRUMIRATHIU-UHFFFAOYSA-N 1-ethenyl-3-methylbenzene Chemical compound CC1=CC=CC(C=C)=C1 JZHGRUMIRATHIU-UHFFFAOYSA-N 0.000 claims description 3
- UEPFNQXGOLWTAD-UHFFFAOYSA-N 2-ethenyl-1-benzothiophene Chemical compound C1=CC=C2SC(C=C)=CC2=C1 UEPFNQXGOLWTAD-UHFFFAOYSA-N 0.000 claims description 3
- QFESLBHYZUIJJY-UHFFFAOYSA-N 4-ethenyl-1-N,4-N-diphenylcyclohexa-1,5-diene-1,4-diamine Chemical compound C=CC1(CC=C(C=C1)NC2=CC=CC=C2)NC3=CC=CC=C3 QFESLBHYZUIJJY-UHFFFAOYSA-N 0.000 claims description 3
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 3
- HDBWAWNLGGMZRQ-UHFFFAOYSA-N p-Vinylbiphenyl Chemical group C1=CC(C=C)=CC=C1C1=CC=CC=C1 HDBWAWNLGGMZRQ-UHFFFAOYSA-N 0.000 claims description 3
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- AHNYHYYIECFEQY-UHFFFAOYSA-N 2-phenylethenylsilicon Chemical compound [Si]C=CC1=CC=CC=C1 AHNYHYYIECFEQY-UHFFFAOYSA-N 0.000 claims description 2
- 150000004996 alkyl benzenes 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
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 abstract description 8
- 239000000758 substrate Substances 0.000 abstract description 5
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 abstract description 2
- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 abstract 1
- 239000005977 Ethylene Substances 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 25
- 239000007795 chemical reaction product Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 238000012512 characterization method Methods 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- JJXPTUWJVQUHKN-UHFFFAOYSA-N 5-methoxy-1-benzofuran Chemical compound COC1=CC=C2OC=CC2=C1 JJXPTUWJVQUHKN-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 4
- IGGDKDTUCAWDAN-UHFFFAOYSA-N 1-vinylnaphthalene Chemical compound C1=CC=C2C(C=C)=CC=CC2=C1 IGGDKDTUCAWDAN-UHFFFAOYSA-N 0.000 description 3
- KXYAVSFOJVUIHT-UHFFFAOYSA-N 2-vinylnaphthalene Chemical compound C1=CC=CC2=CC(C=C)=CC=C21 KXYAVSFOJVUIHT-UHFFFAOYSA-N 0.000 description 3
- ZRXHLJNBNWVNIM-UHFFFAOYSA-N 3-methyl-1-benzofuran Chemical compound C1=CC=C2C(C)=COC2=C1 ZRXHLJNBNWVNIM-UHFFFAOYSA-N 0.000 description 3
- KCZQNAOFWQGLCN-UHFFFAOYSA-N 5-methyl-1-benzofuran Chemical compound CC1=CC=C2OC=CC2=C1 KCZQNAOFWQGLCN-UHFFFAOYSA-N 0.000 description 3
- JCYWCSGERIELPG-UHFFFAOYSA-N imes Chemical compound CC1=CC(C)=CC(C)=C1N1C=CN(C=2C(=CC(C)=CC=2C)C)[C]1 JCYWCSGERIELPG-UHFFFAOYSA-N 0.000 description 3
- OXHSYXPNALRSME-UHFFFAOYSA-N (4-ethenylphenyl)-trimethylsilane Chemical compound C[Si](C)(C)C1=CC=C(C=C)C=C1 OXHSYXPNALRSME-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- PECUPOXPPBBFLU-UHFFFAOYSA-N 1-ethenyl-3-methoxybenzene Chemical compound COC1=CC=CC(C=C)=C1 PECUPOXPPBBFLU-UHFFFAOYSA-N 0.000 description 1
- BGGDZDRRHQTSPV-UHFFFAOYSA-N 4-ethenyl-n,n-diphenylaniline Chemical compound C1=CC(C=C)=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 BGGDZDRRHQTSPV-UHFFFAOYSA-N 0.000 description 1
- 239000007848 Bronsted acid Substances 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/04—Nickel compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
Definitions
- the invention belongs to the technical field of organic synthesis preparation, in particular to the application of nitrogen heterocyclic carbene-based mixed nickel (II) complexes in synthesizing ⁇ -benzylbenzofuran compounds.
- Benzofurans and their derivatives are not only widely found in natural products and biologically active molecules, but are also general building blocks for building drug molecules (see Horton, DA; Bourne, GT; Smythe, ML Chem. Rev. 2003 , 103 , 893 ).
- the alkylation of the ⁇ -position on the benzofuran backbone can currently be catalyzed by Lewis or Bronsted acids (see Rueping, M.; demosheim, BJ Beilstein J. Org. Chem. 2010 , 6 , 6).
- Rueping, M.; Häsheim, BJ Beilstein J. Org. Chem. 2010 , 6 , 6 there are few methods for the alkylation of the ⁇ -position on the benzofuran skeleton, and there are obvious limitations.
- Yoshiaki's group used an air-sensitive zero-valent nickel catalyst to realize the hydroheteroarylation of styrene and benzofuran, but this is only one case, and no substrate expansion has been seen (see Nakao, Y.; Kashihara, N. ; Kanyiva, KS; Hiyama, T. Angew. Chem., Int. Ed. 2010 , 49 , 4451).
- the object of the present invention is to provide a new method for synthesizing ⁇ -benzyl benzofuran compounds, namely using an air-stable mixed-type nickel (II) complex Ni[P(OEt) 3 ] ⁇ [R ⁇ NC( CH 3 )C(CH 3 )NR ⁇ ]C ⁇ Br 2 is a catalyst (R ⁇ is 2,4,6-trimethylphenyl), in the presence of an organic base, through aryl vinyl compounds and benzofuran
- the ⁇ -benzylbenzofuran compound is synthesized by the hydrogen heteroarylation reaction of the compound, and the operability of the catalyst and the suitability of the substrate are obviously better than those of the prior art.
- the present invention adopts the following technical scheme: the application of nitrogen heterocyclic carbene-based mixed nickel (II) complex as a catalyst in the reaction of synthesizing ⁇ -benzyl benzofuran compounds; the application comprises the following steps, in an inert gas atmosphere In the process, a mixed catalyst, an organic base, a benzofuran compound, an aryl vinyl compound and a solvent are reacted to obtain an ⁇ -benzylbenzofuran compound.
- II nitrogen heterocyclic carbene-based mixed nickel
- the method for synthesizing ⁇ -benzyl benzofuran compounds is as follows: in an inert gas atmosphere, using benzofuran compounds and aryl vinyl compounds as raw materials, in the presence of a catalyst and an organic base, react in a solvent, ⁇ -benzyl benzofuran compounds are obtained.
- the catalyst is a nitrogen-heterocyclic carbene-based mixed nickel (II) complex, and its chemical structural formula is as follows: .
- R ⁇ has the following structural formula: .
- the temperature of the reaction is 100-130°C, and the time is 36-60 hours; preferably, the temperature of the reaction is 110°C, and the reaction time is 48 hours.
- the inert gas is argon;
- the solvent is an alkylbenzene solvent, such as toluene;
- the organic base is sodium tert-butoxide, lithium tert-butoxide, potassium tert-butoxide, sodium methoxide or potassium methoxide, Sodium tert-butoxide is preferred.
- the molar ratio of catalyst, organic base, benzofuran compound and aryl vinyl compound is (0.08-0.11): (0.8-1.2): 1: 1.5, preferably 0.10: 1: 1: 1.5 .
- the amount of the aryl vinyl compound is 1.5 times that of the benzofuran compound
- the amount of the organic base is 1 times that of the benzofuran compound
- the amount of the catalyst is benzofuran. 10% of the molar amount of the compound.
- benzofuran-based compound is represented by the following chemical structural formula.
- R 1 is hydrogen or alkyl
- R 2 is hydrogen, methyl or methoxy
- Ar is a group with an aromatic ring; specifically, aryl vinyl compounds include styrene, o-methoxystyrene, m-methylstyrene, p-methoxystyrene, p-fluorostyrene, p-trimethylstyrene Silylstyrene, p-dianilinostyrene, 1-vinylnaphthalene, 2-vinylnaphthalene, 4-vinylbiphenyl, p-morpholinestyrene or 2-vinylbenzothiophene.
- R 1 and R 2 are derived from benzofuran compounds, and Ar is derived from aryl vinyl compounds.
- IMes Me is [R ⁇ NC( CH3 )C( CH3 )NR ⁇ ]C, wherein R ⁇ is 2,4,6-trimethylphenyl, and has the following structural formula: .
- the present invention has the following advantages.
- the present invention uses air-stable nitrogen heterocyclic carbene-based mixed nickel (II) complexes as catalysts, and realizes the hydrogen heteroarylation of aryl vinyl compounds and benzofuran compounds in the presence of organic bases
- the reaction provides a new synthesis method for ⁇ -benzylbenzofurans.
- the preparation method disclosed in the present invention has better substrate applicability, and at the same time, because of the air stability and easier synthesis of nickel-based catalysts, it has more practical application value.
- Coordinated nickel (II) complex with a yield of 85% was used as a catalyst in the following examples to catalyze the hydrogen heteroarylation reaction of aryl vinyl compounds and benzofuran compounds to prepare the product ⁇ -benzyl benzo Furan compounds; and the catalyst does not change color in the air for two days, which can prove that the catalyst of the present invention has good stability in the air.
- R ⁇ has the following structural formula.
- Example Two Divalent nickel (II) complexes are used as catalysts to catalyze the hydroheteroarylation of styrene and benzofuran.
- Example 3 Divalent nickel (II) complex is used as a catalyst to catalyze the hydrogen heteroarylation reaction of o-methoxystyrene and benzofuran.
- Example 4 Divalent nickel (II) complex is used as a catalyst to catalyze the hydrogen heteroarylation reaction of m-methylstyrene and benzofuran.
- Example 5 A divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation of p-methoxystyrene and benzofuran.
- Example 6 Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation of p-fluorostyrene and benzofuran.
- Example 7 Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of p-trimethylsilyl styrene and benzofuran.
- Example 8 A divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of p-dianilinostyrene and benzofuran.
- Example 9 Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of 1-vinylnaphthalene and benzofuran.
- Dodecavalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation of 2-vinylnaphthalene with benzofuran.
- Example 11 Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of p-4-vinylbiphenyl and benzofuran.
- Example 12 A divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation of p-2-vinylbenzothiophene and benzofuran.
- Example 13 Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation of p-morpholine styrene and benzofuran.
- Example 14 Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation of styrene and 3-methylbenzofuran.
- Example 15 Divalent nickel (II) complex was used as a catalyst to catalyze the hydrogen heteroarylation reaction of styrene and 5-methylbenzofuran.
- Example 16 A divalent nickel (II) complex was used as a catalyst to catalyze the hydrogen heteroarylation reaction of styrene and 5-methoxybenzofuran.
- Example 17 Other divalent nickel(II) complexes were used as catalysts to catalyze the hydroheteroarylation of styrene and benzofuran.
- catalyst 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 ⁇ l, 0.5 mmol), styrene were added to the reaction flask in sequence (86 ⁇ l, 0.75 mmol), toluene (1.5 ml) as solvent, react at 110 o C for 48 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and separate and purify by column chromatography (using petroleum ether as developing agent), the yield is 31%; the above catalyst is Ni[IMes][P(OEt) 3 ]Br 2 , IMes is [(R ⁇ NCHCHNR ⁇ )C] (R ⁇ is 2,4,6-trimethyl phenyl), has the following structural formula: .
- the structural formula of the catalyst is as follows: .
- R ⁇ is the following structural formula: .
- the invention utilizes the stable divalent nickel (II) complex in the air as a catalyst to realize the hydrogen heteroarylation reaction of a series of aryl vinyl compounds and benzofuran compounds, and has originality, and can be ⁇ -benzyl Benzofurans provide new synthetic methods with good substrate applicability, with obvious innovation and potential practical application value.
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- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了氮杂环卡宾基混配型镍(II)配合物在合成α-苄基苯并呋喃类化合物中的应用。本发明以空气稳定的混配型镍(II)配合物Ni[P(OEt) 3]{[R`NC(CH 3)C(CH 3)NR`]C}Br 2为催化剂，其中R`为2,4,6-三甲基苯基，在有机碱存在下，通过芳基乙烯类化合物与苯并呋喃类化合物的氢杂芳基化反应来合成α-苄基苯并呋喃类化合物，催化剂的可操作性和底物适用性都要明显优于现有技术，同时因为镍系催化剂的空气稳定性和较易合成，因此更具实际应用价值。
Description
本发明属于有机合成制备技术领域，具体涉及到氮杂环卡宾基混配型镍(II)配合物在合成α-苄基苯并呋喃类化合物中的应用。
苯并呋喃及其衍生物不仅广泛存在于天然产物和生物活性分子中，同时也是构建药物分子的通用结构单元（参见Horton, D. A.;
Bourne, G. T.; Smythe, M. L.
Chem. Rev.
2003,
103, 893）。在苯并呋喃系衍生物中，苯并呋喃骨架上β位的烷基化目前可以通过路易斯酸或者布朗斯特酸催化实现（参见Rueping, M.;
Nachtsheim, B. J.
Beilstein J. Org. Chem.
2010,
6, 6）。但是，针对苯并呋喃骨架上α位的烷基化的方法目前还是比较少的，并且存在着明显的局限性。例如Yoshiaki课题组利用对空气敏感的零价镍催化剂实现了苯乙烯与苯并呋喃的氢杂芳基化反应，但是仅此一例，未见底物拓展（参见Nakao,
Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T.
Angew. Chem.,Int. Ed.
2010,
49, 4451）。
本发明的目的是提供一种合成α-苄基苯并呋喃类化合物的新方法，即以空气稳定的混配型镍(II)配合物Ni[P(OEt)
3]{[R`NC(CH
3)C(CH
3)NR`]C}Br
2为催化剂（R`为2,4,6-三甲基苯基），在有机碱存在下，通过芳基乙烯类化合物与苯并呋喃类化合物的氢杂芳基化反应来合成α-苄基苯并呋喃类化合物，催化剂的可操作性和底物适用性都要明显优于现有技术。
本发明采用如下技术方案：氮杂环卡宾基混配型镍(II)配合物作为催化剂在合成α-苄基苯并呋喃类化合物反应中的应用；所述应用包括以下步骤，在惰性气体气氛中，混配型催化剂、有机碱、苯并呋喃类化合物、芳基乙烯类化合物和溶剂，反应得到α-苄基苯并呋喃类化合物。
具体的，合成α-苄基苯并呋喃类化合物的方法为，在惰性气体气氛中，以苯并呋喃类化合物、芳基乙烯类化合物为原料，在催化剂、有机碱存在下，溶剂中反应，得到α-苄基苯并呋喃类化合物。
本发明中，所述催化剂为氮杂环卡宾基混配型镍(II)配合物，其化学结构式如下：
。
R`具有以下结构式：
。
上述技术方案中，反应结束后进行常规提纯，得到α-苄基苯并呋喃类化合物；比如反应结束后，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯，得到产物，可进行定量分析收率。
上述技术方案中，所述反应的温度为100～130℃，时间为36～60小时；优选的，反应的温度是110℃，反应的时间为48小时。
上述技术方案中，所述惰性气体为氩气；所述溶剂为烷基苯类溶剂，比如甲苯；有机碱为叔丁醇钠、叔丁醇锂、叔丁醇钾、甲醇钠或者甲醇钾，优选叔丁醇钠。
上述技术方案中，催化剂、有机碱、苯并呋喃类化合物、芳基乙烯类化合物的摩尔比为（0.08～0.11）∶（0.8～1.2）∶1∶1.5，优选为0.10∶1∶1∶1.5。优选的技术方案中，以物质的量计，芳基乙烯类化合物的用量是苯并呋喃类化合物的1.5倍，有机碱的用量是苯并呋喃类化合物的1倍，催化剂的用量是苯并呋喃类化合物摩尔量的10 %。
本发明中，苯并呋喃类化合物由下列化学结构式表达。
其中，R
1为氢或者烷基，R
2为氢，甲基或者甲氧基。
本发明中，芳基乙烯类化合物的化学结构式如下：
。
Ar为带有芳环的基团；具体的，芳基乙烯类化合物包括苯乙烯、邻甲氧基苯乙烯、间甲基苯乙烯、对甲氧基苯乙烯、对氟苯乙烯、对三甲基硅基苯乙烯、对二苯胺基苯乙烯、1-乙烯基萘、2-乙烯基萘、4-乙烯基联苯、对吗啉苯乙烯或者2-乙烯基苯并噻吩。
本发明中，α-苄基苯并呋喃类化合物的化学结构式如下：
。
其中，R
1、R
2来自苯并呋喃类化合物，Ar来自芳基乙烯类化合物。
本发明的技术方案可表示如下。
IMes
Me为[R`NC(CH
3)C(CH
3)NR`]C，其中R`为2,4,6-三甲基苯基，具有以下结构式：
。
由于上述技术方案的运用，本发明具有下列优点。
1. 本发明以空气稳定的氮杂环卡宾基混配型镍(II)配合物为催化剂，在有机碱的存在下实现了芳基乙烯类化合物与苯并呋喃类化合物的氢杂芳基化反应，为α-苄基苯并呋喃类化合物提供了一种新的合成方法。
2. 本发明公开的制备方法，具有较好的底物适用性，同时因为镍系催化剂的空气稳定性和较易合成，因此更具实际应用价值。
本发明所有原料为常规产品，涉及的具体操作方法为常规方法；本发明在惰性气体气氛中，以苯并呋喃类化合物、芳基乙烯类化合物为原料，在催化剂、有机碱存在下，溶剂中反应，得到α-苄基苯并呋喃类化合物；无需其他原料或者添加剂。下面结合实施例对本发明作进一步描述。
实施例一：Ni[P(OEt)
3]{[R`NC(CH
3)C(CH
3)NR]C}Br
2（R` = 2,4,6-三甲基苯基）的合成。
氩气保护下，氮杂环卡宾[R`NC(CH
3)C(CH
3)NR`]C（0.3325 g，1.0毫摩尔）加入到二(亚磷酸三乙酯)二溴化镍(II)（0.5508克，1.0毫摩尔）的四氢呋喃溶液中，常温反应2小时，真空除去溶剂，以正己烷洗涤剩余物，所得剩余物以甲苯萃取，转移清液并除去溶剂甲苯，得红色固体为混配型镍(II)配合物，产率为85%，作为催化剂用于以下实施例，催化芳基乙烯类化合物与苯并呋喃类化合物的氢杂芳基化反应制备产物α-苄基苯并呋喃类化合物；且该催化剂在空气中存在两天不变色，可证实本发明催化剂空气中具有良好稳定性。
对产物进行元素分析，结果如表1所示。
对产物进行核磁表征，结果如下所示：将产物溶于CDCl
3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.06 (s, 4H),
3.98 (q,
J = 7.0 Hz, 6H), 2.41 (s, 6H), 2.24(s, 12H), 1.89 (s, 6H), 1.22
(t,
J = 6.9 Hz, 9H) ppm。
产物混配型镍(II)配合物的化学结构式如下。
R`具有以下结构式。
实施例二 二价镍(II)配合物为催化剂，催化苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率92%，产物结构式如下。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.61 (dd, J =
7.4, 1.9 Hz, 1H), 7.51 (dd, J = 6.9, 2.3 Hz, 1H), 7.46 – 7.27 (m, 7H), 6.54 (s, 1H), 4.36 (q, J = 7.2 Hz, 1H),
1.81 (d, J = 7.2 Hz, 3H)。
将上述叔丁醇钠分别更换为等摩尔量叔丁醇锂、叔丁醇钾、甲醇钠、甲醇钾，其余不变，产物产率分别为80%、60%、60%、68%。
将上述反应条件更换为130℃下反应6小时，其余不变，产物产率85%。
实施例三 二价镍(II)配合物为催化剂，催化邻甲氧基苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、邻甲氧基苯乙烯（100微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率90%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.63 – 7.57 (m, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.35 – 7.27 (m, 3H), 7.21 (dd, J = 7.8, 1.7 Hz, 1H), 7.04 – 6.94 (m, 2H), 6.55 (s, 1H), 4.87 (q, J = 7.2, 6.7 Hz,
1H), 3.93 (s, 3H), 1.74 (d, J = 7.1 Hz, 3H)。
实施例四 二价镍(II)配合物为催化剂，催化间甲基苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、间甲氧苯乙烯（98微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率85%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.67 – 7.58 (m, 1H), 7.57 – 7.48 (m, 1H), 7.37 – 7.29
(m, 3H), 7.25 – 7.17 (m, 3H), 6.57 (s, 1H), 4.34 (q, J
= 7.2 Hz, 1H), 2.46 (s, 3H), 1.82 (dd, J = 7.2, 2.3 Hz, 3H)。
实施例五 二价镍(II)配合物为催化剂，催化对甲氧基苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、对甲氧基苯乙烯（100微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率92%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.39 – 7.34 (m, 1H), 7.27 (dd, J = 7.4, 2.7 Hz, 1H), 7.13 – 7.03 (m, 4H), 6.78 – 6.71
(m, 2H), 6.28 (d, J = 1.1 Hz, 1H), 4.09 (q, J = 7.6, 7.2 Hz, 1H), 3.65 (s, 3H),
1.56 (d, J = 7.2 Hz, 3H)。
实施例六 二价镍(II)配合物为催化剂，催化对氟苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、对氟苯乙烯（89微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率90%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3):δ 7.60 – 7.54 (m, 1H), 7.47 (d, J = 6.9 Hz, 1H), 7.40 – 7.23 (m, 4H), 7.12 – 7.02
(m, 2H), 6.50 (s, 1H), 4.31 (q, J = 7.2 Hz, 1H), 1.75 (d, J = 7.2 Hz, 3H)。
实施例七 二价镍(II)配合物为催化剂，催化对三甲基硅基苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、对三甲基硅基苯乙烯（154微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率95%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.61 – 7.21 (m, 9H), 6.52 (s, 1H), 4.32 (q, J = 7.2 Hz, 1H),
1.77 (d, J = 7.2 Hz, 3H), 0.33 (s, 9H)。
实施例八 二价镍(II)配合物为催化剂，催化对二苯胺基苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、对二苯胺基苯乙烯（271毫克，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率85%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3):δ 7.61 – 7.55 (m, 1H), 7.52 – 7.47
(m, 1H), 7.33 – 7.27 (m, 5H), 7.24 (d, J = 10.1 Hz,
3H), 7.18 – 7.04 (m, 8H), 6.52 (s, 1H), 4.29 (q, J
= 7.2 Hz, 1H), 1.77 (d, J = 7.3 Hz, 3H)。
实施例九 二价镍(II)配合物为催化剂，催化1-乙烯基萘与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、1-乙烯基萘（154毫克，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率94%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 8.32 – 8.24 (m, 1H), 8.02 (dd, J = 7.8, 1.8 Hz, 1H), 7.90 (d, J
= 8.0 Hz, 1H), 7.68 – 7.46 (m, 6H),
7.38 – 7.30 (m, 2H), 6.57 (s, 1H), 5.23 (q, J
= 7.1 Hz, 1H), 1.97 (d, J = 7.1 Hz, 3H)。
实施例十 二价镍(II)配合物为催化剂，催化对2-乙烯萘与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、2-乙烯萘（154毫克，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率90%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.81 – 7.73 (m, 3H), 7.71 (d, J = 1.8 Hz, 1H), 7.51 – 7.33 (m, 5H), 7.22 – 7.11
(m, 2H), 6.44 (s, 1H), 4.39 (q, J = 7.2 Hz, 1H), 1.75 (d, J = 7.3 Hz, 3H)。
实施例十一 二价镍(II)配合物为催化剂，催化对4-乙烯基联苯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、4-乙烯基联苯（135毫克，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率94%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.77 – 7.31 (m, 13H), 6.63 (s, 1H), 4.45 (q, J = 7.2 Hz, 1H),
1.88 (d, J = 7.2 Hz, 3H)。
实施例十二 二价镍(II)配合物为催化剂，催化对2-乙烯基苯并噻吩与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、2-乙烯基苯并噻吩（170毫克，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于130
oC下反应60小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率85%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl
3): δ 7.72 (d, J =
10.8 Hz, 1H), 7.66 – 7.63 (m, 1H),
7.49 – 7.46 (m, 1H), 7.42 – 7.38 (m, 1H), 7.30 – 7.14
(m, 4H), 7.11 (s, 1H), 6.50 (s, 1H), 4.56 (q, J = 8.1, 7.6 Hz, 1H), 1.80 (d, J
= 7.2 Hz, 3H)。
实施例十三 二价镍(II)配合物为催化剂，催化对吗啉苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、对吗啉苯乙烯（142毫克，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率92%。
将产物溶于CDCl
3中（约40 mg），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR (400 MHz, CDCl
3):
δ 7.60 – 7.52
(m, 1H), 7.45 (d, J = 7.5 Hz, 1H), 7.29 – 7.20
(m, 4H), 6.93 (d, J = 8.7 Hz, 2H), 6.47 (s, 1H), 4.26 (q, J = 7.2 Hz, 1H), 3.95
– 3.86 (m, 4H), 3.25 – 3.14 (m, 4H), 1.73 (d, J = 7.2 Hz, 3H)。
实施例十四 二价镍(II)配合物为催化剂，催化苯乙烯与3-甲基苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、3-甲基苯并呋喃（63微升，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于100
oC下反应36小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率93%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl3): δ 7.57 – 7.27 (m, 9H), 4.47 (q, J = 7.2 Hz, 1H), 2.28 (s, 3H),
1.85 (d, J = 7.3 Hz, 3H)。
实施例十五 二价镍(II)配合物为催化剂，催化苯乙烯与5-甲基苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、5-甲基苯并呋喃（63微升，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应36小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率93%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl3): δ 7.31 – 7.15 (m, 7H), 6.97 (d, J = 10.1 Hz, 1H), 6.33 (s, 1H),
4.19 (q, J = 7.2 Hz, 1H), 2.38 (s, 3H), 1.65 (d, J = 7.2 Hz, 3H)。
实施例十六 二价镍(II)配合物为催化剂，催化苯乙烯与5-甲氧基苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（35.9毫克，0.05毫摩尔，10 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、5-甲氧基苯并呋喃（74毫克，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应36小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率93%。
将产物溶于CDCl
3中（约0.4
mL），封管，室温下于Unity Inova-400型NMR仪上测定表征：
1H NMR
(400 MHz, CDCl3): δ 7.47 – 7.32 (m, 6H), 7.09 (s, 1H), 6.93 (dd, J = 8.9, 2.6 Hz,
1H), 6.49 (s, 1H), 4.34 (q, J = 7.2 Hz, 1H), 3.91 (s, 3H), 1.80 (d, J = 7.3 Hz,
3H)。
实施例十七 其他二价镍(II)配合物为催化剂，催化苯乙烯与苯并呋喃的氢杂芳基化反应。
氩气保护下，在反应瓶中依次加入催化剂（0.05毫摩尔，10
mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、苯并呋喃（55微升，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110
oC下反应48小时，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯（以石油醚为展开剂），产率31%；上述催化剂为Ni[IMes][P(OEt)
3]Br
2，IMes为[(R`NCHCHNR`)C]（R`为2,4,6-三甲基苯基），具有以下结构式：
。
催化剂结构式如下：
。
R`为以下结构式：
。
本发明利用空气中稳定的二价镍(II)配合物为催化剂，实现一系列芳基乙烯类化合物与苯并呋喃类化合物的氢杂芳基化反应，具有独创性，可以为α-苄基苯并呋喃类化合物提供具有良好底物适用性的新合成方法，具有显而易见的创新性和潜在实际应用价值的。
Claims (10)
- 氮杂环卡宾基混配型镍(II)配合物在合成α-苄基苯并呋喃类化合物中的应用；所述氮杂环卡宾基混配型镍(II)配合物的化学结构式如下：
R`具有以下结构式：。
- 根据权利要求1所述的应用，其特征在于，所述合成的温度为100～130℃，时间为36～60小时。
- 根据权利要求1所述的应用，其特征在于，在惰性气体气氛中，以苯并呋喃类化合物、芳基乙烯类化合物为原料，以氮杂环卡宾基混配型镍(II)配合物为催化剂，在有机碱存在下，溶剂中反应，得到α-苄基苯并呋喃类化合物。
- 根据权利要求3所述的应用，其特征在于，催化剂、有机碱、苯并呋喃类化合物、芳基乙烯类化合物的摩尔比为（0.08～0.11）∶（0.8～1.2）∶1∶1.5。
- 根据权利要求3所述的应用，其特征在于，所述惰性气体为氩气；所述溶剂为烷基苯类溶剂。
- 根据权利要求3所述的应用，其特征在于，苯并呋喃类化合物由下列化学结构式表达：
其中，R 1为氢或者烷基；R 2为氢、甲基或者甲氧基。 - 根据权利要求3所述的应用，其特征在于，芳基乙烯类化合物的化学结构式如下：
Ar为带有芳基的基团。 - 根据权利要求7所述的应用，其特征在于，芳基乙烯类化合物为苯乙烯、邻甲氧基苯乙烯、间甲基苯乙烯、对甲氧基苯乙烯、对氟苯乙烯、对三甲基硅基苯乙烯、对二苯胺基苯乙烯、4-乙烯基联苯、对吗啉苯乙烯或者2-乙烯基苯并噻吩。
- 根据权利要求3所述的应用，其特征在于，有机碱为叔丁醇钠、叔丁醇锂、叔丁醇钾、甲醇钠或者甲醇钾。
- 根据权利要求3所述的应用，其特征在于，反应结束后进行提纯，得到α-苄基苯并呋喃类化合物。
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