WO2023142128A1 - 一种合成 2- 苯基 -5- 苄基 - 咪唑并 [1,2-a] 吡啶类化合物的方法 - Google Patents

一种合成 2- 苯基 -5- 苄基 - 咪唑并 [1,2-a] 吡啶类化合物的方法 Download PDF

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WO2023142128A1
WO2023142128A1 PCT/CN2022/075264 CN2022075264W WO2023142128A1 WO 2023142128 A1 WO2023142128 A1 WO 2023142128A1 CN 2022075264 W CN2022075264 W CN 2022075264W WO 2023142128 A1 WO2023142128 A1 WO 2023142128A1
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imidazo
phenyl
benzyl
pyridine
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孙宏枚
李文俊
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Suzhou University
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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
    • B01J31/22—Organic complexes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • the invention belongs to the technical field of organic synthesis preparation, and in particular relates to a method for synthesizing 2-phenyl-5-benzyl-imidazo[1,2-a]pyridine compounds.
  • 2-Phenylimidazo[1,2-a]pyridine is an important nitrogen-containing heterocyclic structural unit, which exists in many natural products, drug molecules and photoelectric functional materials. Therefore, it is necessary to modify this skeleton It has important application value (see Yu, Y.; Su, Z.; Cao, H. Chem. Rec. 2019 , 19 , 2105), and there are many existing techniques for various alkylation modifications of this backbone There are many reports in the literature, but there are few reports on the use of alkenes as alkylating agents.
  • the purpose of this invention is to provide a new method for the synthesis of 2-phenyl-5-benzyl-imidazo[1,2-a]pyridine compounds, i.e. air-stable mixed-type nickel (II) complexes: Ni[P(OEt) 3 ] ⁇ [RNC(CH 3 )C(CH 3 )NR]C ⁇ Br 2 is the catalyst (R is 2,4,6-trimethylphenyl, and the molecular formula can be simplified as Ni[P (OEt) 3 ](IMes Me )Br 2 ), prepared by alkylation of arylethenes with 2-phenylimidazo[1,2-a]pyridines in the presence of sodium tert-butoxide Synthesis of 2-phenyl-5-benzyl-imidazo[1,2-a]pyridine compounds.
  • II nickel
  • the present invention adopts the following technical scheme: the application of nitrogen heterocyclic carbene mixed nickel (II) complexes as catalysts in the synthesis of 2-phenyl-5-benzyl-imidazo[1,2-a]pyridine compounds .
  • a method for synthesizing 2-phenyl-5-benzyl-imidazo[1,2-a]pyridine compounds comprising the following steps, in an inert gas atmosphere, mixing nitrogen-heterocyclic carbene group mixed type nickel (II ) complexes, additives, 2-phenylimidazo[1,2-a]pyridine compounds, arylvinyl compounds and solvents, react to obtain 2-phenyl-5-benzyl-imidazo[1,2- a] Pyridines.
  • the nitrogen heterocyclic carbene mixed nickel (II) complex is Ni(IMes Me )[P(OEt) 3 ]Br 2 , and its chemical structural formula is as follows: .
  • R is the following structural formula: .
  • the reaction is terminated with water, and the reaction product is extracted with ethyl acetate, separated and purified by column chromatography to obtain the product, which can be quantitatively analyzed.
  • the additive is tert-butoxide, preferably, the tert-butoxide is sodium tert-butoxide, potassium tert-butoxide or lithium tert-butoxide.
  • the temperature of the reaction is 80-120° C., and the time is 10-20 hours.
  • the reaction temperature is 110°C, and the reaction time is 18 hours.
  • the inert gas is argon or nitrogen;
  • the solvent is benzene solvent, ether solvent, etc., such as toluene, tetrahydrofuran, methyl tetrahydrofuran.
  • the molar ratio of nitrogen heterocyclic carbene mixed type nickel (II) complexes, additives, 2-phenylimidazo[1,2-a]pyridine compounds, and aryl vinyl compounds is (0.02 ⁇ 0.06):(0.8 ⁇ 1):1:(1 ⁇ 1.6).
  • the amount of arylethene compounds is 1.5 times that of 2-phenylimidazo[1,2-a]pyridine compounds
  • the amount of sodium tert-butoxide is 2-phenyl
  • the amount of catalyst used is 1 times that of 2-phenylimidazo[1,2-a]pyridine compounds, and the amount of catalyst is 5% of that of 2-phenylimidazo[1,2-a]pyridine compounds.
  • 2-phenylimidazo[1,2-a]pyridine compounds are expressed by the following chemical structural formula: .
  • R is one of hydrogen, methoxy or trifluoromethyl; the chemical structural formula of the aryl vinyl compound is as follows: .
  • aryl vinyl compounds include styrene, p-methylstyrene, m-methylstyrene, p-methoxystyrene, p-fluorostyrene, p-tert-butylstyrene, p-trimethylsilylbenzene Ethylene, 2,4,6-trimethylstyrene, p-dianilinostyrene, 1-vinylnaphthalene, 4-vinylbiphenyl, 2-vinylthiophene, or 2-vinyl-N-methylpyrrole .
  • R 1 is one of hydrogen, methoxy or trifluoromethyl
  • Ar comes from aryl vinyl compounds and is an aromatic group or a heterocyclic aromatic group, including phenyl, p-methylphenyl, m-methyl Phenyl, p-methoxyphenyl, p-fluorophenyl, p-tert-butylphenyl, p-trimethylsilylphenyl, 2,4,6-trimethylphenyl, p-dianilinophenyl, Naphthyl, biphenyl, thienyl or N-methylpyrrolyl.
  • the present invention uses the air-stable mixed type nickel (II) complex as a catalyzer, and realizes arylethene compound and 2 in the presence of sodium tert-butoxide -Hydroheteroarylation reaction of phenylimidazo[1,2-a]pyridine compounds, the 5-position of 2-phenylimidazo[1,2-a]pyridine skeleton can be modified by alkylation, synthesized 2-phenyl-5-benzyl-imidazo[1,2-a]pyridine compounds were obtained.
  • II air-stable mixed type nickel
  • the preparation method disclosed by the present invention has mild reaction conditions and good substrate applicability. At the same time, because the divalent nickel (II) complex has the characteristics of air stability and easy synthesis, it has practical application value.
  • R 2,4,6-tri
  • azacyclic carbene [RNC(CH 3 )C(CH 3 )NR]C (0.3325 g, 1.0 mmol) was added to bis(triethylphosphite) dibromide under argon Nickel (II) (0.5508 g, 1.0 mmol) in tetrahydrofuran solution, react at room temperature for 3 hours, remove the solvent in vacuo, wash the residue with n-hexane, extract the residue with toluene, transfer the clear liquid and remove the solvent toluene to obtain a red color
  • the solid is a divalent nickel (II) complex, called Ni[P(OEt) 3 ](IMes Me )Br 2 , and its chemical structure is as follows: R has the following structural formula: .
  • R has the following structural formula: .
  • Example Two divalent nickel (II) complexes are used as catalysts to catalyze the hydroheteroarylation reaction of styrene and 2-phenylimidazo[1,2-a]pyridine: under the protection of argon, in the reaction flask Ni[P(OEt) 3 ]( IMesMe ) Br2 catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenylimidazo[1 ,2-a]pyridine (97mg, 0.5mmol), styrene (86 ⁇ l, 0.75mmol), toluene (1.5ml) as solvent, reacted at 110°C for 18 hours, terminated the reaction with water, and the reaction product was used Extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether with a volume ratio of 1:2 as the developing
  • Example 2 On the basis of Example 2, the solvent was adjusted from toluene to 2-MeTHF, and the rest remained unchanged, and the gas phase yield of the product was 84%.
  • Embodiment Three divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is a catalyst, catalyzes the reaction of p-methylstyrene and 2-phenylimidazo[1,2-a]pyridine Hydrogen heteroarylation reaction: under the protection of argon, add catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenylimidazole in sequence in the reaction flask And[1,2-a]pyridine (97mg, 0.5mmol), p-methylstyrene (99 ⁇ l, 0.75mmol), toluene (1.5ml) as solvent, react at 80 o C for 13 hours, The reaction was terminated with water, and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of
  • Embodiment 4 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is a catalyst, and catalyzes the reaction of m-methylstyrene and 2-phenylimidazo[1,2-a]pyridine Hydrogen heteroarylation reaction: under the protection of argon, add catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenylimidazole in sequence in the reaction flask And[1,2-a]pyridine (97mg, 0.5mmol), m-methylstyrene (100 ⁇ l, 0.75mmol), toluene (1.5ml) as solvent, react at 90 o C for 16 hours, The reaction was terminated with water, and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petrole
  • Example 5 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is used as a catalyst to catalyze p-methoxystyrene and 2-phenylimidazo[1,2-a]pyridine Hydrogen heteroarylation reaction: under the protection of argon, the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenyl Imidazo[1,2-a]pyridine (97 mg, 0.5 mmol), p-methoxystyrene (100 microliters, 0.75 mmol), toluene (1.5 ml) were used as solvents, and reacted at 80 o C for 10 Hours, the reaction was terminated with water, and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum
  • Example 6 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is a catalyst to catalyze the hydrogenation of p-fluorostyrene and 2-phenylimidazo[1,2-a]pyridine Heteroarylation reaction: under the protection of argon, the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenylimidazo [1,2-a]pyridine (97mg, 0.5mmol), p-fluorostyrene (89 ⁇ l, 0.75mmol), toluene (1.5ml) as solvent, react at 120 o C for 20 hours, terminate with water Reaction, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:2 as the developing solvent), and the yield was 89%.
  • Example 7 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is used as a catalyst to catalyze p-tert-butylstyrene and 2-phenylimidazo[1,2-a]pyridine Hydrogen heteroarylation reaction: under the protection of argon, the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenyl Imidazo[1,2-a]pyridine (97 mg, 0.5 mmol), p-tert-butylstyrene (137 microliters, 0.75 mmol), toluene (1.5 ml) were used as solvents, and reacted at 90 o C for 15 Hours, the reaction was terminated with water, and the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate
  • Example 8 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is used as a catalyst to catalyze p-trimethylsilylstyrene and 2-phenylimidazo[1,2-a ] Hydroheteroarylation reaction of pyridine: Under the protection of argon, the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2- Phenylimidazo[1,2-a]pyridine (97 mg, 0.5 mmol), p-trimethylsilylstyrene (154 ⁇ l, 0.75 mmol), toluene (1.5 ml) as solvent, at 100 o C for 18 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and separate and purify it by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:2 as
  • Example 9 The divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is used as a catalyst to catalyze 2,4,6-trimethylstyrene and 2-phenylimidazo[1, 2-a] Hydroheteroarylation of pyridine: under the protection of argon, add the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol) in sequence in the reaction flask , 2-phenylimidazo[1,2-a]pyridine (97 mg, 0.5 mmol), 2,4,6-trimethylstyrene (121 ⁇ l, 0.75 mmol), toluene (1.5 mL) As a solvent, react at 110 o C for 18 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and separate and purify it by column chromatography (using a mixed solvent of ethyl acetate/petrole
  • Example 11 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is used as a catalyst to catalyze 1-vinylnaphthalene and 2-phenylimidazo[1,2-a]pyridine Hydrogen heteroarylation reaction: under the protection of argon, the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenyl Imidazo[1,2-a]pyridine (97 mg, 0.5 mmol), 1-vinylnaphthalene (111 ⁇ l, 0.75 mmol), toluene (1.5 ml) were used as solvents, and reacted at 110 o C for 18 hours , the reaction was terminated with water, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:2 as the developing solvent),
  • Example 12 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is a catalyst, catalyzing 4-vinylbiphenyl and 2-phenylimidazo[1,2-a] Hydroheteroarylation reaction of pyridine: Under argon protection, add catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-benzene Imidazo[1,2-a]pyridine (97mg, 0.5mmol), 4-vinylbiphenyl (135mg, 0.75mmol), toluene (1.5ml) were used as solvents, and reacted at 110 o C for 16 Hours, the reaction was terminated with water, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:2 as the developing solvent), and
  • Example 13 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is used as a catalyst to catalyze 2-vinylthiophene and 2-phenylimidazo[1,2-a]pyridine Hydrogen heteroarylation reaction: under the protection of argon, the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 2-phenyl Imidazo[1,2-a]pyridine (97 mg, 0.5 mmol), 2-vinylthiophene (79 ⁇ l, 0.75 mmol), toluene (1.5 ml) were used as solvents, and reacted at 120 o C for 15 hours , the reaction was terminated with water, the reaction product was extracted with ethyl acetate, and separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:2 as the developing
  • Example 14 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is a catalyst, catalyzing 2-vinyl-N-methylpyrrole and 2-phenylimidazo[1, 2-a] Hydroheteroarylation of pyridine: under the protection of argon, add the catalyst (18 mg, 0.025 mmol, 5 mol%), sodium tert-butoxide (48 mg, 0.5 mmol) in sequence in the reaction flask , 2-phenylimidazo[1,2-a]pyridine (97 mg, 0.5 mmol), 2-vinyl-N-methylpyrrole (90 ⁇ l, 0.75 mmol), toluene (1.5 ml) Solvent, react at 100 o C for 15 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and separate and purify it by column chromatography (the mixed solvent of ethyl acetate/petroleum ether with a volume
  • Example 15 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is a catalyst, catalyzing styrene and 2-(4-methoxyphenyl) imidazo[1,2 -a] Heteroarylation reaction of pyridine: Under argon protection, Ni[P(OEt)3](IMesMe)Br2 catalyst (18 mg, 0.025 mmol, 5 mol%), t- Sodium butoxide (48 mg, 0.5 mmol), 2-(4-methoxyphenyl)imidazo[1,2-a]pyridine (112 mg, 0.5 mmol), styrene (86 ⁇ l, 0.75 mmol), toluene (1.5 ml) as solvent, reacted at 120°C for 18 hours, terminated the reaction with water, extracted the reaction product with ethyl acetate, separated and purified by column chromatography (the volume ratio of ethyl acetate
  • Embodiment 16 Divalent nickel (II) complex Ni[P(OEt) 3 ](IMes Me )Br 2 is a catalyst, catalyzes styrene and 2-(4-trifluoromethylphenyl) imidazo[1, 2-a] Heteroarylation reaction of pyridine: Under argon protection, Ni[P(OEt)3](IMesMe)Br2 catalyst (18 mg, 0.025 mmol, 5 mol%), Sodium tert-butoxide (48 mg, 0.5 mmol), 2-(4-trifluoromethylphenyl)imidazo[1,2-a]pyridine (131 mg, 0.5 mmol), styrene (86 ⁇ l , 0.75 mmol), toluene (1.5 ml) as solvent, reacted at 110°C for 15 hours, terminated the reaction with water, extracted the reaction product with ethyl acetate, separated and purified by column chromatography (according to the

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Abstract

本发明公开了一种合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶化合物的方法，通过使用分子式为Ni[P(OEt) 3]{[RNC(CH 3)C(CH 3)NR]C}Br 2（R为2,4,6-三甲基苯基）的混配型镍(II)配合物为催化剂、在叔丁醇钠存在下通过芳基乙烯类化合物与2-苯基咪唑并[1,2-a]吡啶类化合物的氢杂芳基化反应合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物。本发明提供了一种基于镍系催化剂的新型氢杂芳基化反应，为2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物提供了新合成方法，这是由镍系催化剂实现的、通过芳基乙烯类化合物与2-苯基咪唑并[1,2-a]吡啶类化合物的氢杂芳基化反应制备2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的第一例。

Description

一种合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法 技术领域
本发明属于有机合成制备技术领域，具体涉及到一种合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法。
 背景技术
2-苯基咪唑并[1,2-a]吡啶是一种重要的含氮杂环结构单元，存在于许多天然产物、药物分子中以及光电功能材料中，因此，对这一骨架进行修饰是具有重要应用价值的（参见Yu, Y.; Su, Z.; Cao, H. Chem. Rec. 2019, 19, 2105），现有技术对这一骨架进行各种烷基化修饰已经有很多的文献报道，但是以烯烃作为烷基化试剂的报道很少。现有技术报道了β-硝基苯乙烯类化合物和2-苯基咪唑并[1,2-a]吡啶类化合物在叔丁醇中的付-克烷基化反应；还报道了Mn(CO) 5Br/醋酸铵体系催化的马来酰亚胺类化合物与2-苯基咪唑并[1,2-a]吡啶类化合物在2,2,2-三氟乙醇中的反应；还报道了以FeCl 2为催化剂、曙红Y为光敏剂，实现了芳基乙烯、2-苯基咪唑并[1,2-a]吡啶类化合物和硅烷的三组份光反应（参见Li, K.; Zhu, X.-J.; Lu, S.; Zhou, X.-Y.; Xu, Y.; Hao, X.-Q.; Song, M.-P. Synlett 2016, 27, 387；Ghosh, S.; Khandelia, T.; Patel, B. K. Org. Lett. 2021, 23, 7370；Neogi, S.; Ghosh, A. K.; Mandal, S.; Ghosh, D.; Ghosh, S.; Hajra, A. Org. Lett. 2021, 23, 6510）。现有技术都可以实现2-苯基咪唑并[1,2-a]吡啶骨架的烷基化，但是制备方法以及原料还需改善。
技术问题
本发明的目的是提供一种合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的新方法，即以空气稳定的混配型镍(II)配合物：Ni[P(OEt) 3]{[RNC(CH 3)C(CH 3)NR]C}Br 2为催化剂（R为2,4,6-三甲基苯基，分子式可简化为Ni[P(OEt) 3](IMes Me)Br 2），在叔丁醇钠存在下，通过芳基乙烯类化合物与2-苯基咪唑并[1,2-a]吡啶类化合物的烷基化反应来合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物。
技术解决方案
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2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物中的应用。
一种合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法，包括以下步骤，在惰性气体气氛中，混合氮杂环卡宾基混配型镍(II)配合物、添加剂、2-苯基咪唑并[1,2-a]吡啶类化合物、芳基乙烯类化合物和溶剂，反应得到2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物。
本发明中，氮杂环卡宾基混配型镍(II)配合物为Ni(IMes Me)[P(OEt) 3]Br 2，其化学结构式如下： 。
R为以下结构式：  。
上述技术方案中，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。
上述技术方案中，添加剂为叔丁醇盐，优选的，叔丁醇盐为叔丁醇钠、叔丁醇钾或者叔丁醇锂。
上述技术方案中，所述反应的温度为80～120℃，时间为10～20小时。优选的；反应的温度是110℃，反应的时间为18小时。
上述技术方案中，所述惰性气体为氩气或者氮气；所述溶剂为苯类溶剂、醚类溶剂等，比如甲苯、四氢呋喃、甲基四氢呋喃。
上述技术方案中，氮杂环卡宾基混配型镍(II)配合物、添加剂、2-苯基咪唑并[1,2-a]吡啶类化合物、芳基乙烯类化合物的摩尔比为（0.02～0.06）∶（0.8～1）∶1∶（1～1.6）。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2-苯基咪唑并[1,2-a]吡啶类化合物的1.5倍，叔丁醇钠的用量是2-苯基咪唑并[1,2-a]吡啶类化合物的1倍，催化剂的用量是2-苯基咪唑并[1,2-a]吡啶类化合物的5 %。
本发明中，2-苯基咪唑并[1,2-a]吡啶类化合物由下列化学结构式表达： 。
R 1为氢、甲氧基或三氟甲基中的一种；芳基乙烯类化合物的化学结构式如下： 。
具体的，芳基乙烯类化合物包括苯乙烯、对甲基苯乙烯、间甲基苯乙烯、对甲氧基苯乙烯、对氟苯乙烯、对叔丁基苯乙烯、对三甲基硅基苯乙烯、2,4,6-三甲基苯乙烯、对二苯胺基苯乙烯、1-乙烯基萘、4-乙烯基联苯、2-乙烯基噻吩或者2-乙烯基-N-甲基吡咯。
本发明的技术方案可表示如下： R 1为氢、甲氧基或三氟甲基中的一种；Ar来自芳基乙烯类化合物，为芳香基团或者杂环芳香基团，包括苯基、对甲基苯基、间甲基苯基、对甲氧基苯基、对氟苯基、对叔丁基苯基、对三甲基硅基苯基、2,4,6-三甲基苯基、对二苯胺基苯基、萘基、联苯基、噻吩基或者N-甲基吡咯基。
有益效果
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混配型镍(II)配合物为催化剂，在叔丁醇钠的存在下实现了芳基乙烯类化合物与2-苯基咪唑并[1,2-a]吡啶类化合物的氢杂芳基化反应，可以对2-苯基咪唑并[1,2-a]吡啶骨架的5位进行烷基化修饰，合成了2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物。
2. 本发明公开的制备方法反应条件温和，具有较好的底物适用性，同时因为二价镍(II)配合物具有空气稳定和较易合成的特点，因此具有实际应用价值。
 本发明的实施方式
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]{[RNC(CH 3)C(CH 3)NR]C}Br 2（R = 2,4,6-三甲基苯基）的合成为现有技术，可参见发明人公开的文献或者专利文件。在此概述为，在氩气保护下，氮杂环卡宾[RNC(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3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，得红色固体为二价镍(II)配合物，称为Ni[P(OEt) 3](IMes Me)Br 2，其化学结构式如下： R具有以下结构式：  。
以Ni[P(OEt) 3](IMes)Br 2为对比，其化学结构式如下： 。
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2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入Ni[P(OEt) 3](IMes Me)Br 2催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97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℃下反应18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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率91%。
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 7.89 (d, J = 7.4 Hz, 2H), 7.65 (d, J = 9.0 Hz, 1H), 7.62 (s, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.32 (d, J = 7.3 Hz, 3H), 7.28 – 7.21 (m, 4H), 6.85 (d, J = 7.0 Hz, 1H), 4.36 (q, J = 7.0 Hz, 1H), 1.77 (d, J = 7.1 Hz, 3H)。
在上述苯乙烯与2-苯基咪唑并[1,2-a]吡啶的反应的基础上做单因素变化，结果如下。
。
。
a 反应条件：2-苯基咪唑并[1,2-a]吡啶（0.5 mmol），苯乙烯（0.75 mmol），镍催化剂（5 mol%），添加剂（0.5 mmol），甲苯（1.5 mL），18 h，产物的收率以正十二烷作为内标通过气相确定。 b 分离收率。
在实施例二基础上，溶剂从甲苯调整为2-MeTHF，其余不变，产物气相收率为84%。
实施例三 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化对甲基苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、对甲基苯乙烯（99微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于80 oC下反应13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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），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 7.86 (dd, J = 8.3, 1.2 Hz, 2H), 7.60 – 7.55 (m, 2H), 7.36 (t, J = 7.6 Hz, 2H), 7.28 – 7.17 (m, 2H), 7.05 (s, 4H), 6.76 (d, J = 7.0 Hz, 1H), 4.25 (q, J = 7.0 Hz, 1H), 2.25 (s, 3H), 1.67 (d, J = 7.1 Hz, 3H)。
实施例四 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化间甲基苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、间甲基苯乙烯（100微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于90 oC下反应16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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率89%。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 7.93 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 11.4 Hz, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 7.28 – 7.18 (m, 2H), 7.03 (dd, J = 17.0, 8.0 Hz, 3H), 6.82 (d, J = 7.0 Hz, 1H), 4.29 (q, J = 6.9 Hz, 1H), 2.30 (s, 3H), 1.73 (d, J = 7.1 Hz, 3H)。
实施例五 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化对甲氧基苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，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80 oC下反应10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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率91%。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 7.98 – 7.88 (m, 2H), 7.62 (t, J = 4.4 Hz, 2H), 7.40 (t, J = 7.6 Hz, 2H), 7.29 (t, J = 7.4 Hz, 1H), 7.23 (dd, J = 9.0, 7.1 Hz, 1H), 7.10 (d, J = 8.7 Hz, 2H), 6.80 (dd, J = 20.3, 7.8 Hz, 3H), 4.27 (q, J = 7.0 Hz, 1H), 3.72 (s, 3H), 1.69 (d, J = 7.1 Hz, 3H)。
实施例六 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化对氟苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，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120 oC下反应20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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率89%。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 7.90 (d, J = 8.1 Hz, 2H), 7.63 (d, J = 9.0 Hz, 1H), 7.55 (s, 1H), 7.40 (t, J = 7.4 Hz, 2H), 7.32 – 7.27 (m, 1H), 7.23 (t, J = 8.0 Hz, 1H), 7.17 – 7.09 (m, 2H), 6.97 (t, J = 8.2 Hz, 2H), 6.77 (d, J = 7.0 Hz, 1H), 4.28 (q, J = 6.9 Hz, 1H), 1.68 (d, J = 7.0 Hz, 3H)。
实施例七 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化对叔丁基苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、对叔丁基苯乙烯（137微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于90 oC下反应15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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率89%。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 7.95 (d, J = 7.5 Hz, 2H), 7.69 – 7.62 (m, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.37 – 7.28 (m, 3H), 7.26 – 7.20 (m, 1H), 7.15 (d, J = 8.2 Hz, 2H), 6.79 (d, J = 6.9 Hz, 1H), 4.31 (q, J = 6.7 Hz, 1H), 1.72 (d, J = 7.0 Hz, 3H), 1.31 (s, 9H)。
实施例八 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化对三甲基硅基苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，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100 oC下反应18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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率91%。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 7.94 – 7.87 (m, 2H), 7.64 (d, J = 10.2 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.32 (dd, J = 10.8, 7.3 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 6.86 (d, J = 7.0 Hz, 1H), 4.38 (q, J = 6.9 Hz, 1H), 1.79 (d, J = 7.1 Hz, 3H), 0.27 (s, 9H)。
实施例九 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化2,4,6-三甲基苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、2,4,6-三甲基苯乙烯（121微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110 oC下反应18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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），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 7.94 (d, J = 7.6 Hz, 2H), 7.73 (s, 1H), 7.55 (d, J = 9.0 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.29 (t, J = 7.3 Hz, 1H), 7.13 (dd, J = 8.9, 7.0 Hz, 1H), 6.86 (s, 2H), 6.58 (d, J = 6.9 Hz, 1H), 3.13 – 3.06 (m, 2H), 3.01 – 2.94 (m, 2H), 2.24 (s, 9H)。
实施例十 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化对二苯胺基苯乙烯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、对二苯胺基苯乙烯（204毫克，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于120 oC下反应20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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率78%。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 7.89 (d, J = 7.4 Hz, 2H), 7.67 – 7.54 (m, 2H), 7.39 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 7.4 Hz, 1H), 7.23 – 7.19 (m, 2H), 7.16 (d, J = 7.8 Hz, 3H), 7.00 (ddd, J = 24.5, 7.8, 5.1 Hz, 10H), 6.77 (d, J = 7.0 Hz, 1H), 4.26 (q, J = 6.9 Hz, 1H), 1.71 (d, J = 7.0 Hz, 3H)。
实施例十一 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化1-乙烯基萘与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、1-乙烯基萘（111微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于110 oC下反应18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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），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, CDCl 3) δ 8.16 (d, J = 8.2 Hz, 1H), 7.96 (d, J = 7.7 Hz, 1H), 7.79 (t, J = 8.8 Hz, 3H), 7.63 (ddd, J = 17.2, 11.8, 8.7 Hz, 3H), 7.45 (s, 1H), 7.41 – 7.28 (m, 4H), 7.27 – 7.23 (m, 1H), 7.14 (d, J = 7.1 Hz, 1H), 6.83 (d, J = 7.0 Hz, 1H), 5.12 (q, J = 6.9 Hz, 1H), 1.87 (d, J = 7.0 Hz, 3H)。
实施例十二 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化4-乙烯基联苯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，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16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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率88%。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 7.95 (d, J = 7.3 Hz, 2H), 7.68 (d, J = 6.2 Hz, 2H), 7.57 (t, J = 8.0 Hz, 4H), 7.44 (t, J = 7.6 Hz, 4H), 7.39 – 7.28 (m, 5H), 6.87 (d, J = 7.0 Hz, 1H), 4.41 (q, J = 6.9 Hz, 1H), 1.80 (d, J = 7.1 Hz, 3H)。
实施例十三 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化2-乙烯基噻吩与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、2-乙烯基噻吩（79微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于120 oC下反应15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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率28%。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 7.95 (d, J = 7.7 Hz, 2H), 7.79 (s, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.27 – 7.18 (m, 2H), 6.98 – 6.92 (m, 1H), 6.88 (d, J = 3.3 Hz, 1H), 6.78 (d, J = 7.0 Hz, 1H), 4.70 (q, J = 7.0 Hz, 1H), 1.87 (d, J = 7.0 Hz, 3H)。
实施例十四 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化2-乙烯基-N-甲基吡咯与2-苯基咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-苯基咪唑并[1,2-a]吡啶（97毫克，0.5毫摩尔）、2-乙烯基-N-甲基吡咯（90微升，0.75毫摩尔）、甲苯（1.5毫升）作溶剂，于100 oC下反应15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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率88%。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 7.99 (d, J = 7.4 Hz, 2H), 7.92 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.4 Hz, 1H), 7.07 (dd, J = 8.9, 7.2 Hz, 1H), 6.59 (s, 1H), 6.26 (d, J = 7.0 Hz, 1H), 6.20 – 6.10 (m, 2H), 4.41 – 4.29 (m, 1H), 3.23 (s, 3H), 1.72 (d, J = 7.0 Hz, 3H)。
实施例十五 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化苯乙烯与2-（4-甲氧基苯基）咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入Ni[P(OEt)3](IMesMe)Br2催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-（4-甲氧基苯基）咪唑并[1,2-a]吡啶（112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120℃下反应18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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率81%。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 (d, J = 8.5 Hz, 2H), 7.62 (d, J = 9.0 Hz, 1H), 7.53 (s, 1H), 7.33 (t, J = 7.3 Hz, 2H), 7.24 (dd, J = 12.4, 7.6 Hz, 4H), 6.95 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 7.0 Hz, 1H), 4.37 (q, J = 6.9 Hz, 1H), 3.84 (s, 3H), 1.78 (d, J = 7.0 Hz, 3H)。
实施例十六 二价镍(II)配合物Ni[P(OEt) 3](IMes Me)Br 2为催化剂，催化苯乙烯与2-（4-三氟甲基苯基）咪唑并[1,2-a]吡啶的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入Ni[P(OEt)3](IMesMe)Br2催化剂（18毫克，0.025毫摩尔，5 mol%）、叔丁醇钠（48毫克，0.5毫摩尔）、2-（4-三氟甲基苯基）咪唑并[1,2-a]吡啶（131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℃下反应15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（以乙酸乙酯/石油醚体积比为1∶2的混合溶剂为展开剂），产率84%。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 7.97 (d, J = 8.1 Hz, 2H), 7.72 – 7.61 (m, 4H), 7.33 (q, J = 8.1, 7.5 Hz, 3H), 7.28 – 7.21 (m, 3H), 6.89 (d, J = 7.0 Hz, 1H), 4.39 (q, J = 7.0 Hz, 1H), 1.80 (d, J = 7.1 Hz, 3H)。

Claims (10)

  1. 氮杂环卡宾基混配型镍(II)配合物作为催化剂在合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物中的应用。
  2. 根据权利要求1所述的应用，其特征在于，氮杂环卡宾基混配型镍(II)配合物为Ni[P(OEt) 3](IMes Me)Br 2。
  3. 根据权利要求1所述的应用，其特征在于，以2-苯基咪唑并[1,2-a]吡啶类化合物、芳基乙烯类化合物为底物，反应合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物。
  4. 根据权利要求3所述的应用，其特征在于，反应在惰性气体中，添加剂以及溶剂存在下进行。
  5. 一种合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法，其特征在于，包括以下步骤，在惰性气体气氛中，混合氮杂环卡宾基混配型镍(II)配合物、添加剂、2-苯基咪唑并[1,2-a]吡啶、芳基乙烯类化合物和溶剂，反应得到2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物。
  6. 根据权利要求5所述合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法，其特征在于，2-苯基咪唑并[1,2-a]吡啶类化合物由下列化学结构式表达：
    芳基乙烯类化合物的化学结构式如下：
    Ar为芳香基团或者杂环芳香基团。
  7. 根据权利要求5所述合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法，其特征在于，添加剂为叔丁醇盐；所述惰性气体为氩气或者氮气；所述溶剂为苯类溶剂、醚类溶剂中的一种。
  8. 根据权利要求5所述合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法，其特征在于，所述反应的温度为80～120℃，时间为10～20小时。
  9. 根据权利要求5所述合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法，其特征在于，氮杂环卡宾基混配型镍(II)配合物为Ni[P(OEt) 3](IMes Me)Br 2。
  10. 根据权利要求5所述合成2-苯基-5-苄基-咪唑并[1,2-a]吡啶类化合物的方法，其特征在于，氮杂环卡宾基混配型镍(II)配合物、添加剂、2-苯基咪唑并[1,2-a]吡啶类化合物、芳基乙烯类化合物的摩尔比为（0.02～0.06）∶（0.8～1）∶1∶（1～1.6）。
PCT/CN2022/075264 2022-01-30 2022-01-30 一种合成 2- 苯基 -5- 苄基 - 咪唑并 [1,2-a] 吡啶类化合物的方法 Ceased WO2023142128A1 (zh)

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