CN112675919B - Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compound - Google Patents
Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compound Download PDFInfo
- Publication number
- CN112675919B CN112675919B CN202110098677.3A CN202110098677A CN112675919B CN 112675919 B CN112675919 B CN 112675919B CN 202110098677 A CN202110098677 A CN 202110098677A CN 112675919 B CN112675919 B CN 112675919B
- Authority
- CN
- China
- Prior art keywords
- compound
- benzofuran
- catalyst
- mmol
- complex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses an application of an N-heterocyclic carbene-based mixed nickel (II) complex in synthesizing an alpha-benzyl benzofuran compound. The invention uses air-stable compound nickel (II) complex Ni [ P (OEt) 3 ]{[R`NC(CH 3 )C(CH 3 )NR`]C}Br 2 The catalyst is characterized in that R' is 2,4, 6-trimethylphenyl, the alpha-benzylbenzofuran compound is synthesized through the hydrogen heteroaryl reaction of aryl vinyl compound and benzofuran compound in the presence of organic base, the operability and substrate applicability of the catalyst are obviously superior to those of the prior art, and meanwhile, the nickel catalyst has practical application value because of the air stability and easier synthesis.
Description
Technical Field
The invention belongs to the technical field of organic synthesis and preparation, and particularly relates to application of an N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compounds.
Background
Benzofuran and its derivatives are not only widely found in natural products and bioactive molecules, but also in general building blocks for constructing pharmaceutical molecules (see Horton, d.a.; bourne, g.t.; smythe, m.l).Chem. Rev.2003, 103, 893). In benzofuran-based derivatives, alkylation of the beta position on the benzofuran skeleton is currently achieved by Lewis acid or Bronsted acid catalysis (see ruuping, M.; nachtsheim, B.J.. Beilstein J. Org. Chem.2010, 6, 6). However, the methods for alkylation at the α position on the benzofuran skeleton are currently relatively few and have significant limitations. For example, the Yoshiaki group has achieved the hydroheteroarylation of styrene with benzofuran using an air-sensitive zero-valent nickel catalyst, but only this example, no substrate expansion 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-benzyl benzofuran compounds, namely, air-stable compound nickel (II) complex Ni [ P (OEt) 3 ]{[R`NC(CH 3 )C(CH 3 )NR`]C}Br 2 In the presence of organic base, the catalyst (R' is 2,4, 6-trimethylphenyl) is synthesized into the alpha-benzyl benzofuran compound through the hydrogen heteroaryl reaction of aryl vinyl compound and benzofuran compound, 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 compound 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, organic base, benzofuran compounds, aryl vinyl compounds and a solvent in an inert gas atmosphere to obtain the alpha-benzyl benzofuran compounds.
Specifically, the method for synthesizing the alpha-benzyl benzofuran compounds comprises the steps of reacting benzofuran compounds and aryl vinyl compounds serving as raw materials in an inert gas atmosphere in the presence of a catalyst and an organic base in a solvent to obtain the alpha-benzyl benzofuran compounds.
In the invention, the catalyst is an N-heterocyclic carbene-based compound type nickel (II) complex, and the chemical structural formula is as follows:
r' has the following structural formula:
in the technical scheme, conventional purification is carried out after the reaction is finished, and the alpha-benzyl benzofuran compounds are obtained; for example, after the reaction is finished, the reaction is stopped by using water, the reaction product is extracted by using ethyl acetate, and the product is obtained through column chromatography separation and purification, 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 temperature of the reaction is 110℃and the time of the reaction is 48 hours.
In the above 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 to the organic base to the benzofuran compound to the aryl vinyl compound is (0.08-0.11) to (0.8-1.2) to 1:1.5, and is preferably 0.10:1:1:1.5. In the preferred technical scheme, the dosage of the aryl vinyl compound is 1.5 times of that of the benzofuran compound, the dosage of the organic base is 1 time of that of the benzofuran compound, and the dosage of the catalyst is 10% of that of the benzofuran compound in terms of mass.
In the present invention, the benzofuran compound is represented by the following chemical structural formula:
wherein R is 1 Is hydrogen or alkyl, R 2 Is hydrogen, methyl or methoxy.
In the present invention, the chemical structural formula of the arylvinyl compound is as follows:
ar is a group with an aromatic ring; specifically, the aryl vinyl compound comprises styrene, o-methoxystyrene, m-methylstyrene, p-methoxystyrene, p-fluorostyrene, p-trimethylsilyl styrene, p-diphenylamino styrene, 1-vinylnaphthalene, 2-vinylnaphthalene, 4-vinylbiphenyl, p-morpholino styrene or 2-vinylbenzothiophene.
In the invention, the chemical structural formula of the alpha-benzyl benzofuran compound is as follows:
wherein R is 1 、R 2 From benzofurans, ar from arylethylenes.
The technical scheme of the invention can be expressed as follows:
IMes Me is [ R' ] NC (CH 3 )C(CH 3 )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 compound nickel (II) complex as a catalyst, realizes the hydrogen heteroaryl reaction of aryl vinyl compounds and benzofuran compounds in the presence of organic alkali, and provides a novel synthesis method for alpha-benzyl benzofuran compounds.
2. The preparation method disclosed by the invention has better substrate applicability, and meanwhile, the nickel-based catalyst has higher practical application value because of air stability and easier synthesis.
Detailed Description
All raw materials of the invention are conventional products, and the related specific operation method is a conventional method; in the invention, in inert gas atmosphere, benzofuran compounds and aryl vinyl compounds are used as raw materials, and the alpha-benzyl benzofuran compounds are obtained by reaction in a solvent in the presence of a catalyst and organic base; no other raw materials or additives are needed. The invention is further described below with reference to examples:
embodiment one: ni [ P (OEt) 3 ]{[R`NC(CH 3 )C(CH 3 )NR]C}Br 2 Synthesis of (R' =2, 4, 6-trimethylphenyl)
Under the protection of argon, N-heterocyclic carbene [ R' ] NC (CH 3 )C(CH 3 )NR`]C (0.3325 g,1.0 mmol) was added to a solution of nickel (II) bis (triethyl phosphite) dibromide (0.5508 g,1.0 mmol) in tetrahydrofuran, 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 a mixed nickel (II) complex in 85% yield, which was used as a catalyst in the following examples to catalyze the hydroheteroarylation of an arylvinyl compound with a benzofuran compound to prepare a product α -benzylbenzofuran compound; and the catalyst does not change color in the air for two days, so that the catalyst has good stability in the air.
Elemental analysis of the product was performed and the results are shown in table 1:
the products were subjected to nuclear magnetic characterization, the results are shown below:
the product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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。
the chemical structural formula of the product compound nickel (II) complex is as follows:
r' has the following structural formula:
example Nickel (II) Di-valent complexes as catalysts for the hydroheteroarylation of styrene with benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), styrene (86. Mu.l, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was heated to 110 o C, reacting for 48 hours, stopping the reaction by using water, extracting a reaction product by using ethyl acetate, separating and purifying by column chromatography (using petroleum ether as a developing agent), and obtaining 92% yield, wherein the structural formula of the product is as follows:
dissolving the productIn CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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)。
the sodium tert-butoxide is respectively replaced by equimolar amounts of lithium tert-butoxide, potassium tert-butoxide, sodium methoxide and potassium methoxide, and the yields of the products are respectively 80%, 60% and 68%.
The reaction conditions are changed to 130 ℃ for 6 hours, the rest is unchanged, and the yield of the product is 85%.
Example Nickel (II) Tribivalent Complex as catalyst for catalyzing Hydrogen heteroarylation reaction of O-methoxystyrene and benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), o-methoxystyrene (100. Mu.l, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was heated to 110 o The reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 90% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example tetradivalent Nickel (II) Complex as catalyst, catalytic Hydrogen heteroaryl reaction of Methylstyrene and benzofuran
Under the protection of argon, a reaction flask was charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), and m-butanol in this orderMethoxystyrene (98. Mu.l, 0.75 mmol), toluene (1.5 ml) as solvent at 110 o The reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 85% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example pentadivalent Nickel (II) Complex as catalyst, catalyzing Hydrogen heteroarylation of para-methoxystyrene and benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), p-methoxystyrene (100. Mu.l, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was heated to 110 o The reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 92% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example Hexadivalent Nickel (II) Complex as catalyst, catalyzing the Hydrogen heteroarylation of para-fluorostyrene with benzofuran
Under argon, a reaction flask was charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium tert-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), and p-fluorostyrene (89. Mu.l)Liter, 0.75 mmol), toluene (1.5 ml) as solvent, at 110 o The reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 90% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example seven Nickel (II) Complex as catalyst for the Hydrogen heteroarylation of p-trimethylsilylstyrene with benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), p-trimethylsilyl styrene (154. Mu.l, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was heated to 110 o The reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 95% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example octadivalent Nickel (II) Complex as catalyst, catalyzing Hydrogen heteroaryl reaction of para-diphenylamino styrene and benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), p-diphenylamino styrene (271 mg, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was heated to 110 o C for 48 hours, water is usedThe reaction was terminated, the reaction product was extracted with ethyl acetate, and purified by column chromatography (petroleum ether as developing agent) in 85% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
EXAMPLE nine Nickel (II) Complex as catalyst, catalyzing Hydrogen heteroarylation of 1-vinyl naphthalene and benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), 1-vinylnaphthalene (154 mg, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was stirred under a vacuum atmosphere to obtain a mixture of two or more of 110 and o the reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 94% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example deca-nickel (II) Complex as catalyst for the Hydrogen-heteroarylation of 2-vinylnaphthalene with benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), 2-vinylnaphthalene (154 mg, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was stirred under a vacuum atmosphere to obtain a mixture of a catalyst and a solvent, and the mixture was heated to 110 o The reaction was stopped with water after 48 hours under C, and the reaction product was quenched with ethyl acetateThe ester is extracted, and the product is separated and purified by column chromatography (petroleum ether is used as developing agent), and the yield is 90 percent.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example eleven Nickel (II) Complex as catalyst, catalyzing Hydrogen heteroarylation of 4-vinylbiphenyl with benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), 4-vinylbiphenyl (135 mg, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was stirred under a vacuum atmosphere to obtain a mixture of two or more of 110 o The reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 94% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example dodecanickel (II) Complex as catalyst, catalyzing the Hydrogen heteroarylation of 2-vinylbenzothiophene with benzofuran
Under the protection of argon, a reaction flask was charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), 2-vinylbenzothiophene (170 mg, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was stirred in the flask under a vacuum atmosphere to give a mixture of sodium tert-butoxide and sodium tert-butoxide (48 mg, 0.5 mmol) as a solvent, and the mixture was stirred in a vacuum atmosphere to give a mixture of sodium tert-butoxide and sodium tert-butoxide (170 mg, 0.75 mmol) and toluene (1.5 ml) as a solvent o The reaction was stopped with water after 60 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 85% yield.
Will produceDissolving in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example thirteen Nickel (II) Complex as catalyst, catalyzing Hydrogen heteroaryl reaction of p-morpholinyl styrene and benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), p-morpholinophenylstyrene (142 mg, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was stirred under a vacuum atmosphere to prepare a mixture of a catalyst and sodium t-butoxide (48 mg, 0.5 mmol), and p-morpholinophenylstyrene (142 mg, 0.75 mmol) and toluene (1.5 ml) as a solvent o The reaction was stopped with water after 48 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 92% yield.
The product was dissolved in CDCl 3 In (about 40 mg), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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).
example fourteen Nickel (II) Complex as catalyst for Hydrogen heteroaryl reaction of styrene and 3-methylbenzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-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) as a solvent, and the mixture was stirred under a vacuum atmosphere to obtain a mixture of 100 o The reaction was stopped with water after 36 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 93% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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 Nickel (II) Complex as catalyst, catalytic Hydrogen heteroarylation of styrene with 5-methylbenzofuran
Under the protection of argon, a reaction flask was charged with a catalyst (35.9 mg, 0.05 mmol, 10 mol%), sodium t-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) as a solvent, and the mixture was stirred under a vacuum atmosphere to prepare a mixture of 110 o The reaction was stopped with water after 36 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 93% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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 Nickel (II) Complex as catalyst for catalyzing Hydrogen heteroarylation reaction of styrene and 5-methoxybenzofuran
Under the protection of argon, a reaction flask was charged with a 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) as a solvent in this order, at 110 o The reaction was stopped with water after 36 hours under C, and the reaction product was extracted with ethyl acetate and purified by column chromatography (petroleum ether as developing agent) in 93% yield.
The product was dissolved in CDCl 3 (about 0.4. 0.4 mL), tube sealed, characterization measured on a Unity Inova-400 NMR instrument at room temperature: 1 H 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 Nickel (II) complexes as catalysts for the Hydrogen heteroarylation of styrene with benzofuran
Under the protection of argon, a reaction flask was sequentially charged with a catalyst (0.05 mmol, 10 mol%), sodium t-butoxide (48 mg, 0.5 mmol), benzofuran (55. Mu.l, 0.5 mmol), styrene (86. Mu.l, 0.75 mmol), toluene (1.5 ml) as a solvent, and the mixture was stirred at a temperature of 110 o C, 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 31 percent of yield;
the catalyst is Ni [ IMes ]][P(OEt) 3 ]Br 2 IMes 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 invention uses the stable divalent nickel (II) complex in the air as the catalyst to realize the hydrogen heteroaryl reaction of a series of aryl vinyl compounds and benzofuran compounds, has originality, can provide a novel synthesis method with good substrate applicability for alpha-benzyl benzofuran compounds, and has obvious innovation and potential practical application value.
Claims (8)
1. The application of the N-heterocyclic carbene-based compound nickel (II) complex in synthesizing alpha-benzyl benzofuran compounds is characterized in that in an inert gas atmosphere, the benzofuran compounds and aryl vinyl compounds are used as raw materials, the N-heterocyclic carbene-based compound nickel (II) complex is used as a catalyst, and the alpha-benzyl benzofuran compounds are obtained by reacting in a solvent in the presence of organic alkali; the organic base is sodium tert-butoxide, lithium tert-butoxide, potassium tert-butoxide, sodium methoxide or potassium methoxide; the chemical structural formula of the N-heterocyclic carbene-based compound type nickel (II) complex is as follows:
2. The use according to claim 1, wherein the synthesis is carried out at a temperature of 100 to 130 ℃ for a time of 36 to 60 hours.
3. The use according to claim 1, wherein the molar ratio of catalyst, organic base, benzofuran compound, arylvinyl compound is (0.08-0.11) to (0.8-1.2) to 1:1.5.
4. The use according to claim 1, wherein the inert gas is argon; the solvent is alkylbenzene solvent.
5. The use according to claim 1, wherein the benzofuran compound is represented by the following chemical formula:
6. Use according to claim 1, characterized in that the chemical formula of the arylvinyl compound is as follows:
7. The use according to claim 6, wherein the aryl vinyl compound is styrene, o-methoxystyrene, m-methylstyrene, p-methoxystyrene, p-fluorostyrene, p-trimethylsilylstyrene, p-dianiline styrene, 4-vinylbiphenyl, p-morpholino styrene or 2-vinylbenzothiophene.
8. The use according to claim 1, characterized in that the purification is carried out after the end of the reaction to obtain the α -benzylbenzofuran compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110098677.3A CN112675919B (en) | 2021-01-25 | 2021-01-25 | Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110098677.3A CN112675919B (en) | 2021-01-25 | 2021-01-25 | Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112675919A CN112675919A (en) | 2021-04-20 |
| CN112675919B true CN112675919B (en) | 2023-06-13 |
Family
ID=75459122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110098677.3A Active CN112675919B (en) | 2021-01-25 | 2021-01-25 | Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112675919B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN114380824B (en) * | 2022-01-30 | 2023-04-07 | 苏州大学 | Method for synthesizing 2-phenyl-5-benzyl-imidazo [1,2-a ] pyridine compound |
| WO2024026596A1 (en) * | 2022-07-31 | 2024-02-08 | 苏州大学 | METHOD FOR SYNTHESIZING α-LINEAR ALKYL SUBSTITUTED HETEROARENE |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0189596A1 (en) * | 1984-12-28 | 1986-08-06 | Shionogi & Co., Ltd. | Benzofuran and benzothiophene derivatives |
| CA2630714A1 (en) * | 2005-11-23 | 2007-05-31 | Epix Delaware, Inc. | S1p receptor modulating compounds and use thereof |
| CN101412702A (en) * | 2008-03-20 | 2009-04-22 | 上海交通大学 | Method for preparing chiral dihydrobenzofuran compounds and catalyst used thereby |
| CN101628904A (en) * | 2009-04-02 | 2010-01-20 | 苏州大学 | Synthesis method of 2-nitro-3-aryl-2,3,5,7-tetrahydrobenzofuran-4-one derivative |
| CN102584512A (en) * | 2011-12-22 | 2012-07-18 | 北京师范大学 | Method for synthesizing benzofuran derivatives in one pot process |
| CN105712960A (en) * | 2014-12-05 | 2016-06-29 | 中国石油化工股份有限公司 | Barium dibenzofuran formate compound and preparation method and cationic initiating system thereof, and preparation method of conjugated diene polymer |
| CN106279297A (en) * | 2016-08-08 | 2017-01-04 | 苏州大学 | Mixed matching nickel (II) coordination compound based on phosphite ester and unsaturated nitrogen heterocycle carbine, its preparation method and application |
| CN109503477A (en) * | 2019-01-04 | 2019-03-22 | 湖南大学 | A kind of triarylmethane class compound and its efficient catalytic synthetic method |
| CN110330535A (en) * | 2019-07-28 | 2019-10-15 | 苏州大学 | N-heterocyclic carbine base mixed matching nickel (II) complex and its application |
-
2021
- 2021-01-25 CN CN202110098677.3A patent/CN112675919B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0189596A1 (en) * | 1984-12-28 | 1986-08-06 | Shionogi & Co., Ltd. | Benzofuran and benzothiophene derivatives |
| CA2630714A1 (en) * | 2005-11-23 | 2007-05-31 | Epix Delaware, Inc. | S1p receptor modulating compounds and use thereof |
| CN101412702A (en) * | 2008-03-20 | 2009-04-22 | 上海交通大学 | Method for preparing chiral dihydrobenzofuran compounds and catalyst used thereby |
| CN101628904A (en) * | 2009-04-02 | 2010-01-20 | 苏州大学 | Synthesis method of 2-nitro-3-aryl-2,3,5,7-tetrahydrobenzofuran-4-one derivative |
| CN102584512A (en) * | 2011-12-22 | 2012-07-18 | 北京师范大学 | Method for synthesizing benzofuran derivatives in one pot process |
| CN105712960A (en) * | 2014-12-05 | 2016-06-29 | 中国石油化工股份有限公司 | Barium dibenzofuran formate compound and preparation method and cationic initiating system thereof, and preparation method of conjugated diene polymer |
| CN106279297A (en) * | 2016-08-08 | 2017-01-04 | 苏州大学 | Mixed matching nickel (II) coordination compound based on phosphite ester and unsaturated nitrogen heterocycle carbine, its preparation method and application |
| CN109503477A (en) * | 2019-01-04 | 2019-03-22 | 湖南大学 | A kind of triarylmethane class compound and its efficient catalytic synthetic method |
| CN110330535A (en) * | 2019-07-28 | 2019-10-15 | 苏州大学 | N-heterocyclic carbine base mixed matching nickel (II) complex and its application |
Non-Patent Citations (4)
| Title |
|---|
| 2-芳基苯并呋喃类化合物及双黄酮类化合物的合成研究;时志春;《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》;20121115(第11期);第B014-23页 * |
| Palladium-Catalyzed Regioselective C-2 Arylation of;Jun Cao et al.;《Eur. J. Org. Chem.》;20181231;第2774-2779页 * |
| 基于钯催化C―H键活化的多米诺反应;沈金海等;《化学进展》;20120724;第24卷(第07期);第1324-1336页 * |
| 镍催化合成 2-取代苯并呋喃化合物的研究;周蓉等;《广东化工》;20170415;第44卷(第7期);第57-58页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112675919A (en) | 2021-04-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112675919B (en) | Application of N-heterocyclic carbene-based mixed nickel (II) complex in synthesis of alpha-benzyl benzofuran compound | |
| CN110330535B (en) | N-heterocyclic carbene-based mixed nickel (II) complex and application thereof | |
| CN112979400A (en) | Method for preparing 2-iodo aryl ether under action of alkali metal hydride | |
| CN112645909A (en) | Method for synthesizing alpha-benzyl benzofuran compound | |
| CN108129287B (en) | Preparation method of 1, 2-dihydronaphthalene derivative | |
| Ma et al. | Phosphine-catalyzed [4+ 2] annulation of γ-benzyl allenoates: facile synthesis of benzothieno [3, 2-b] pyran derivatives | |
| WO2012090888A1 (en) | Organoboron compound and method for manufacturing the same | |
| CN111468191A (en) | Synthetic method of ruthenium carbene catalyst | |
| JP4550413B2 (en) | Novel transition metal complexes and their use in transition metal-catalyzed reactions | |
| CN110615811B (en) | Method for preparing chiral sulfinamide monophosphine ligand in large scale | |
| CN111646964A (en) | Novel method for synthesizing 2H-pyran-2-one derivative by base catalysis | |
| CN111662147B (en) | Process for preparing diynes and analogues thereof | |
| CN111217847B (en) | Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction | |
| WO2022155980A1 (en) | METHOD FOR SYNTHESIZING α-BENZYL BENZOFURAN COMPOUND | |
| WO2022155981A1 (en) | USE OF N-HETEROCYCLIC CARBENE-BASED COMPOUNDED NICKEL (II) COMPLEX IN SYNTHESIS OF α-BENZYL BENZOFURAN COMPOUND | |
| CN114380824B (en) | Method for synthesizing 2-phenyl-5-benzyl-imidazo [1,2-a ] pyridine compound | |
| JP2014528911A (en) | Process for the production of palladium (I) tri-t-butylphosphine bromide dimer and process using it in isomerization reactions | |
| JP2013519519A (en) | A novel phosphine-based catalyst useful for short-chain polymerization of butadiene | |
| JP5493346B2 (en) | Ferrocene derivatives and uses thereof | |
| CN113845550B (en) | Flexible large-steric-hindrance N-heterocyclic carbene palladium complex containing halogenated benzene ring, preparation method and application thereof | |
| CN115108932B (en) | Preparation method of aromatic amide compound | |
| CN111732541B (en) | Method for efficiently synthesizing 6-alkenyl phenanthridine derivative through ruthenium-catalyzed C-H activation/cyclization reaction | |
| WO2024026596A1 (en) | METHOD FOR SYNTHESIZING α-LINEAR ALKYL SUBSTITUTED HETEROARENE | |
| CN110467556B (en) | Nucleophilic reaction method for catalyzing imine ions and acetophenone by nickel | |
| WO2023142128A1 (en) | Method for synthesizing 2-phenyl-5-benzyl-imidazo[1,2-a]pyridine compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |