CN112675919A - Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzylbenzofuran compounds - Google Patents
Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzylbenzofuran compounds Download PDFInfo
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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(CH3)C(CH3)NR`]C}Br2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。The invention discloses the application of nitrogen heterocyclic carbene-based mixed nickel (II) complex in synthesizing α-benzyl benzofuran compounds. The invention uses an air-stable mixed nickel (II) complex Ni[P(OEt) 3 ]{[R`NC(CH 3 )C(CH 3 )NR`]C}Br 2 as a catalyst, wherein R` is 2,4,6-trimethylphenyl, and in the presence of an organic base, α-benzyl benzofuran compounds are synthesized through the hydrogen heteroarylation reaction of aryl vinyl compounds and benzofuran compounds, The operability and substrate applicability of the catalyst are obviously better than those of the prior art, and at the same time, the nickel-based catalyst has more practical application value because of its air stability and easier synthesis.
Description
Technical Field
The invention belongs to the technical field of organic synthesis and preparation, and particularly relates to an application of a nitrogen heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compounds.
Background
Benzofuran and its derivatives are not only widely present in natural products and biologically active molecules, but also are common building blocks for the construction of drug molecules (see Horton, D.A.; Bourne, G.T.; Smythe, M.L.).Chem. Rev.2003, 103, 893). In benzofuran-based derivatives, alkylation at the beta position on the benzofuran skeleton can now be achieved by Lewis acid or Bronsted acid catalysis (see Rueping, M.; Nachtsheim, B.J.). Beilstein J. Org. Chem.2010, 6, 6). However, the methods for alkylation of the alpha position on the benzofuran skeleton are currently relatively few and have significant limitations. For example, the Yoshiaki group achieved the hydroarylation of styrene with benzofuran using air-sensitive zero-valent nickel catalysts, but only in this case, no development of the substrate was seen (see Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T).Angew. Chem.,Int. Ed.2010, 49, 4451）。
Disclosure of Invention
The invention aims to provide a novel method for synthesizing alpha-benzylbenzofuran compounds, namely, air-stable mixed nickel (II) complex Ni [ P (OEt)3]{[R`NC(CH3)C(CH3)NR`]C}Br2In the presence of organic alkali, aryl ethylene compound and benzofuran compound are subjected to hydro-heteroaromatic reaction to synthesize alpha-benzyl benzofuran compound in the presence of catalyst (R' is 2,4, 6-trimethylphenyl), and the operability and substrate applicability of the catalyst are obviously superior to those of the prior art.
The invention adopts the following technical scheme:
the application of the N-heterocyclic carbene-based mixed nickel (II) complex as a catalyst in the reaction of synthesizing alpha-benzyl benzofuran compounds; the application comprises the following steps of reacting a mixed catalyst, an organic base, a benzofuran compound, an aryl ethylene compound and a solvent in an inert gas atmosphere to obtain the alpha-benzyl benzofuran compound.
Specifically, the method for synthesizing the alpha-benzylbenzofuran compound comprises the step of reacting a benzofuran compound and an aryl ethylene compound serving as raw materials in a solvent in the presence of a catalyst and an organic base in an inert gas atmosphere to obtain the alpha-benzylbenzofuran compound.
In the invention, the catalyst is a nitrogen heterocyclic carbene group mixed nickel (II) complex, and the chemical structural formula is as follows:
r' has the following structural formula:
in the technical scheme, after the reaction is finished, conventional purification is carried out to obtain the alpha-benzyl benzofuran compound; for example, after the reaction is finished, the reaction is stopped by water, the reaction product is extracted by ethyl acetate, and the product is separated and purified by column chromatography to obtain the product, and the yield can be quantitatively analyzed.
In the technical scheme, the reaction temperature is 100-130 ℃, and the reaction time is 36-60 hours; preferably, the reaction temperature is 110 ℃ and the reaction time is 48 hours.
In the technical scheme, 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, preferably sodium tert-butoxide.
In the technical scheme, the molar ratio of the catalyst, the organic base, the benzofuran compound and the aryl ethylene compound is (0.08-0.11): (0.8-1.2): 1: 1.5, preferably 0.10: 1: 1.5. In a preferred embodiment, the amount of the arylvinyl compound is 1.5 times of the amount of the benzofuran compound, the amount of the organic base is 1 time of the amount of the benzofuran compound, and the amount of the catalyst is 10% of the molar amount of the benzofuran compound.
In the present invention, the benzofuran compound is represented by the following chemical structural formula:
wherein R is1Is hydrogen or alkyl, R2Is hydrogen, methyl or methoxy.
In the invention, the chemical structural formula of the aryl ethylene compound is as follows:
ar is a group having an aromatic ring; specifically, the arylethenyl compound comprises styrene, o-methoxystyrene, m-methylstyrene, p-methoxystyrene, p-fluorostyrene, p-trimethylsilylstyrene, p-diphenylaminostyrene, 1-vinylnaphthalene, 2-vinylnaphthalene, 4-vinylbiphenyl, p-morpholinostyrene or 2-vinylbenzothiophene.
In the invention, the chemical structural formula of the alpha-benzyl benzofuran compound is as follows:
wherein R is1、R2From benzofuran compounds and Ar from aryl vinyl compounds.
The technical scheme of the invention can be expressed as follows:
IMesMeis [ R' NC (CH)3)C(CH3)NR`]C, wherein R' is 2,4, 6-trimethylphenyl having the following structural formula:
due to the application of the technical scheme, the invention has the following advantages:
1. the invention takes the air-stable N-heterocyclic carbene-based mixed nickel (II) complex as the catalyst, realizes the hydrogen heteroaromatic reaction of aryl ethylene compounds and benzofuran compounds in the presence of organic base, and provides a new synthetic method for alpha-benzyl benzofuran compounds.
2. The preparation method disclosed by the invention has better substrate applicability, and has more practical application value because of the air stability and easier synthesis of the nickel catalyst.
Detailed Description
All the raw materials are conventional products, and the related specific operation method is a conventional method; in the inert gas atmosphere, benzofuran compounds and aryl ethylene compounds are used as raw materials and react in a solvent in the presence of a catalyst and organic base to obtain alpha-benzyl benzofuran compounds; no other raw materials or additives are needed. The invention is further described below with reference to the following examples:
the first embodiment is as follows: ni [ P (OEt)3]{[R`NC(CH3)C(CH3)NR]C}Br2Synthesis of (R' = 2,4, 6-trimethylphenyl)
Under the protection of argon, N-heterocyclic carbene [ R' NC (CH)3)C(CH3)NR`]C (0.3325 g, 1.0 mmol) was added to a tetrahydrofuran solution of nickel (II) dibromide (0.5508 g, 1.0 mmol) bis (triethyl phosphite), reacted at room temperature for 2 hours, the solvent was removed in vacuo, the residue was washed with n-hexane, the obtained residue was extracted with toluene, the supernatant was transferred and the solvent toluene was removed to obtain a red solid as heteroleptic nickel (II) complex with a yield of 85%, which was used as a catalyst in the following examples to catalyze arylethene compounds and benzofuranThe hydro-heteroaromatization of the compound is carried out to prepare the product alpha-benzyl benzofuran compound; and the catalyst does not change color in the air for two days, which proves that the catalyst of the invention has good stability in the air.
Elemental analysis of the product was performed and the results are shown in table 1:
the product was characterized by nuclear magnetism and the results are shown below:
the product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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。
the chemical structural formula of the product mixed type nickel (II) complex is as follows:
r' has the following structural formula:
example Didivalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of styrene and benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), styrene (86 μ l, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110 ml of wateroC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent), wherein the yield is 92%, and the structural formula of the product is as follows:
the product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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)。
the sodium tert-butoxide was replaced with lithium tert-butoxide, potassium tert-butoxide, sodium methoxide and potassium methoxide in equimolar amounts, respectively, and the yields of the remaining components were 80%, 60% and 68%, respectively.
The reaction conditions were changed to 130 ℃ for 6 hours, and the rest was unchanged, resulting in a product yield of 85%.
Example Tri-divalent Nickel (II) Complex as catalyst for the Hydroheteroaromatization of o-methoxystyrene and benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), o-methoxystyrene (100 μ l, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110 ml of wateroC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 90%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example Tetradivalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of m-methylstyrene with benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), m-methoxystyrene (98 μ l, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110 ml of wateroC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 85 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example penta-divalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of P-methoxystyrene and benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), p-methoxystyrene (100 μ l, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110 ml of wateroC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 92 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example Hexadivalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of p-fluorostyrene and benzofuran
Under the protection of argon, reactingThe catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55. mu.l, 0.5 mmol), p-fluorostyrene (89. mu.l, 0.75 mmol), toluene (1.5 ml) were added in succession to the flask as solvent, and the mixture was dissolved in 110 ml of solventoC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 90%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3):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).
example heptadivalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of Trimethylsilylstyrene and benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), p-trimethylsilylstyrene (154 μ l, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as solvent, and the mixture was dissolved in 110 ml of wateroC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 95%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example Octadivalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of P-Diphenylaminostyrene and benzofuran
Under argon protection, a reaction flask was charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), and benzofuran (b)55 microliters, 0.5 mmol), p-diphenylaminostyrene (271 mg, 0.75 mmol), toluene (1.5 ml) as a solvent in 110 microlitersoC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 85 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3):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).
example nonadivalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of 1-Vinylnaphthalene and benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), 1-vinylnaphthalene (154 mg, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110oC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 94 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example a Nickel (II) Ten-valent complex as a catalyst for catalyzing the hydroaromatic reaction of 2-vinylnaphthalene and benzofuran
Under argon protection, the catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), 2-vinylnaphthalene (E-benzol-naphthalene) were added to the flask in this order154 mg, 0.75 mmol) and toluene (1.5 ml) as solvent in 110oC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 90%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example eleven divalent Nickel (II) Complex as catalyst for the Hydroheteroaromatization of para-4-Vinylbiphenyl and benzofuran
Under argon protection, a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), 4-vinylbiphenyl (135 mg, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110oC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 94 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example dodeca-divalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of P-2-Vinylbenzothiophene and benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), 2-vinylbenzothiophene (170 mg, 0.75 mmol), toluene (1.5 ml) were added in succession to a reaction flask as solvent, in 130 mloC, reacting for 60 hours, stopping the reaction by using water, and reacting the reaction product by using BExtracting with ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) with the yield of 85%.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example thirteen-divalent Nickel (II) Complex as catalyst for catalyzing Hydroheteroaromatization of para-Morpholinostyrene and benzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55 μ l, 0.5 mmol), p-morpholinostyrene (142 mg, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110 ml of wateroC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 92 percent.
The product was dissolved in CDCl3Medium (about 40 mg), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature:1H NMR (400 MHz, CDCl3): 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).
example tetradecyl divalent nickel (II) complex as catalyst for catalyzing hydroheteroaromatization of styrene and 3-methylbenzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 3-methylbenzofuran (63. mu.l, 0.5 mmol), styrene (86. mu.l, 0.75 mmol), toluene (1.5 ml) were added in this order as solvents to a reaction flask, and the mixture was dissolved in 100 ml of wateroReacting for 36 hours under the condition of C, stopping the reaction by using water, and reacting products by usingExtraction with ethyl acetate, purification by column chromatography (using petroleum ether as developing solvent) and 93% yield.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature: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).
example fifteen divalent Nickel (II) Complex as catalyst for Hydroheteroaromatization of styrene and 5-methylbenzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 5-methylbenzofuran (63. mu.l, 0.5 mmol), styrene (86. mu.l, 0.75 mmol), toluene (1.5 ml) were added in this order as solvents to a reaction flask, and the mixture was dissolved in 110 ml of wateroReacting for 36 hours at the temperature of C, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 93 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), sealed, characterized by measurement on a Unity Inova-400 NMR instrument at room temperature: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).
example sixteen divalent Nickel (II) Complex as catalyst, catalyzing the Hydroheteroaromatization of styrene and 5-Methoxybenzofuran
Under argon protection, catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), 5-methoxybenzofuran (74 mg, 0.5 mmol), styrene (86. mu.l, 0.75 mmol), toluene (1.5 ml) were added in order to a reaction flask as a solvent, and the mixture was dissolved in 110 ml of wateroReacting for 36 hours at the temperature of C, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by column chromatography (using petroleum ether as a developing agent) to obtain the yield of 93 percent.
The product was dissolved in CDCl3Medium (about 0.4 mL), seal tube, at room temperature at Unity IMeasurement and characterization on a nova-400 type NMR instrument: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).
example seventeen other divalent Nickel (II) complexes as catalysts for Hydroheteroaromatization of styrene and benzofuran
Under the protection of argon, a catalyst (0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55. mu.l, 0.5 mmol), styrene (86. mu.l, 0.75 mmol), toluene (1.5 ml) were added in this order as solvents to a reaction flask, and the mixture was dissolved in 110 ml of wateroC, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, and separating and purifying by using column chromatography (using petroleum ether as a developing agent) to obtain a yield of 31 percent;
the catalyst is Ni [ IMes ]][P(OEt)3]Br2IMes is [ (R 'NCHCHNR') C](R' is 2,4, 6-trimethylphenyl) having the following structural formula:
the catalyst has the following structural formula:
r' is the following structural formula:
the method utilizes the stable divalent nickel (II) complex in the air as the catalyst to realize the hydrogen heteroaromatic reaction of a series of aryl ethylene compounds and benzofuran compounds, has originality, can provide a new synthetic method with good substrate applicability for alpha-benzyl benzofuran compounds, and has obvious innovation and potential practical application value.
Claims (10)
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| WO2022155981A1 (en) * | 2021-01-25 | 2022-07-28 | 苏州大学 | USE OF N-HETEROCYCLIC CARBENE-BASED COMPOUNDED NICKEL (II) COMPLEX IN SYNTHESIS OF α-BENZYL BENZOFURAN COMPOUND |
| CN115974788A (en) * | 2022-07-31 | 2023-04-18 | 苏州大学 | Method for synthesizing alpha-linear alkyl substituted heteroarene |
| WO2024026596A1 (en) * | 2022-07-31 | 2024-02-08 | 苏州大学 | METHOD FOR SYNTHESIZING α-LINEAR ALKYL SUBSTITUTED HETEROARENE |
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| WO2024026596A1 (en) * | 2022-07-31 | 2024-02-08 | 苏州大学 | METHOD FOR SYNTHESIZING α-LINEAR ALKYL SUBSTITUTED HETEROARENE |
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