Preparation method of 3, 4-benzocoumarin compound
By using carbon-carbon coupling-cyclization reaction of CO2 and 2-bromophenylboric acid and inexpensive copper catalysts under normal pressure, the problems of high costs and environmental pollution in the existing coumarin synthesis methods are solved, and low costs are achieved. Environmentally friendly 3,4-benzocoumarin preparation.
Patent Information
- Application Number
- CN202411317351.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-20
- Publication Date
- 2024-12-27
AI Technical Summary
Existing coumarin synthesis methods require valuable transition metal catalysts or high pressure conditions, resulting in high costs and unfriendly environment.
3,4-benzocoumarin was prepared by carbon-carbon coupling-cyclization reaction under normal pressure using CO2 and 2-bromophenylboric acid as the reaction raw material, and the copper catalyst and nitrogen were used to combine. The body forms a complex and promotes the reaction.
The low-cougarin preparation of 3,4-benzocoumarin under mild conditions is achieved, reducing its environmental impact and avoiding the use of high pressure and precious metals.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of coumarin compound synthesis, and particularly relates to a method for preparing a 3,4-benzocoumarin compound. Background Art
[0002] Coumarin compounds are a class of natural carboxylic acid lactone compounds with a wide range of biological and pharmacological activities. They can be used as plant fungicides and herbicides because of their anti-tumor, anti-cancer, antibacterial, antioxidant and anti-proliferative activities. For example, Agata N, Nogi H, Milhollen M, et al. 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic Acid, a Small Molecule Isocoumarin, Potentiates Dexamethasone-Induced Apoptosis of Human Multiple Myeloma Cells [J]. Cancer research, 2004, 64 (23): 8512-8516. It is pointed out that 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid (NM-3) can resist human multiple myeloma (human multiple myeloma, MM) cells. In addition, NM-3 can also enhance the apoptosis of MM1.S cells induced by dexamethasone; for example, Zhao Y, Liu D, Proksch P, et al. Isocoumarin Derivatives from the Sponge-Associated Fungus Peyronellaea glomerata with Antioxidant Activities [J]. Chemistry & Biodiversity, 2016, 13 (9): 1186-1193. pointed out that isopentanylcoumarin A, B and D played an effective ARE activation role in HepG2C8 cells.
[0003] In addition to their uses in the biological field, coumarin compounds are also widely used in organic light-emitting materials, such as Kumar S, Puttaraju B, Patil SA Deep-Blue Electroluminescent Device Based on a Coumarin Derivative. [J]. ChemPlusChem, 2016, 814:, 384-390. The design and synthesis of 7-(9H-carbazole-9-yl)-4-methylcoumarin (Cz-Cm) for blue organic light-emitting diodes, which includes a carbazole donor part and a 4-methylcoumarin acceptor unit, exhibits deep blue emission and high photoluminescence quantum yield in both solution and doped matrix; such as Li Y, Yu T, Su W, et al. Polycyclic aromatichydrocarbon-bridged coumarin derivatives for organic light-emitting devices [J]. Arabian Journal of Chemistry, 2020, 13(2): 4126-4133. The article points out that three polycyclic aromatic hydrocarbon dicoumarin derivatives (CAn-C, C-Py-C and C-DBC-C) synthesized are used as luminescent materials in organic light-emitting devices, among which the dicoumarin compound (C-Py-C) with pyrene as the bridge group exhibits better photoluminescence and electroluminescence properties.
[0004] In recent years, excessive CO2 emissions have led to an imbalance in natural ecosystems, causing environmental problems such as the greenhouse effect. CO2 is widely distributed, non-toxic and renewable, and can be used as a C1 resource. CO2 can be converted into high-value-added chemicals, thereby effectively controlling the CO2 content in the atmosphere. In particular, CO2 is used as a carbonyl source to cyclize lactone compounds. As more and more functions of coumarin compounds are discovered, exploring methods to synthesize coumarin compounds with biological and optical significance through CO2 has become one of the research hotspots for chemists.
[0005] At present, there are many methods for synthesizing coumarin compounds, which use CO2 as a C1 resource for synthesis. Due to the thermodynamic and kinetic inertness of CO2, the structure is generally constructed by catalysis of transition metals such as Pd and Rh, but these methods still have many shortcomings. For example, some reactions require precious transition metals as catalysts, or high pressure conditions are required to activate CO2 to react smoothly. Based on this, the present invention develops a method using CO2 and 2-bromophenylboronic acid as reaction raw materials, using cheap and easily available transition metal copper as a catalyst, and obtaining 3,4-benzocoumarin by carbon-carbon coupling-cyclization reaction in a one-step process at normal pressure. Summary of the invention
[0006] The invention provides a method for preparing a 3,4-benzocoumarin compound. CO2 and 2-bromophenylboronic acid are used as reaction raw materials, and cheap copper is used as a catalyst. The addition amount is 0.1 equiv., and the amount used is small. CO2 is activated under normal pressure in a one-step method to obtain 3,4-benzocoumarin through carbon-carbon coupling-cyclization. The conditions are mild, the cost is low, and it is environmentally friendly.
[0007] The present invention solves the above technical problems through the following technical solutions.
[0008] The object of the present invention is to provide a method for preparing a 3,4-benzocoumarin compound, comprising the following steps: using a 2-bromophenylboronic acid compound as a reaction substrate, adding a ligand and dissolving the ligand in a solvent, and carrying out a one-step carbon-carbon coupling-cyclization reaction at normal pressure under a CO2 atmosphere under the action of an alkali and a copper catalyst to obtain a 3,4-benzocoumarin compound; the ligand is a 1,10-phenanthroline compound, a 2,2′-bipyridine compound, a 2,2′-biquinoline or a 2,2′,6′,2″-terpyridine; and the synthesis route is as follows:
[0009]
[0010] In a preferred embodiment, the molar ratio of the 2-bromophenylboronic acid compound to the copper catalyst is 1:0.1-0.2.
[0011] In a preferred embodiment, the copper catalyst is cuprous bromide, cuprous iodide, cuprous chloride, cupric chloride, cupric chloride, cupric chloride monohydrate, cupric acetate monohydrate, copper phosphate, copper oxalate or copper chloride [1,3-bis (2,6-diisopropylphenyl) imidazole-2-ylidene].
[0012] In a preferred embodiment, the molar ratio of the 2-bromophenylboronic acid compound to the ligand is 1:0.1-0.2.
[0013] In a preferred embodiment, the molar ratio of the 2-bromophenylboronic acid compound to the base is 1:1-3.
[0014] In a preferred embodiment, the carbon-carbon coupling-cyclization reaction temperature is 20° C. to 100° C., and the reaction time is 6 hours.
[0015] In a preferred embodiment, the 1,10-phenanthroline compound is 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 5-nitro-1,10-phenanthroline or 4-methyl-1,10-phenanthroline; the 2,2′-bipyridine compound is 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine or 5-bromo-2,2'-bipyridine.
[0016] In a preferred embodiment, the base is potassium carbonate, sodium carbonate, cesium carbonate, cesium fluoride, potassium phosphate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene or potassium methoxide.
[0017] In a preferred embodiment, the solvent is dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, 1,4-dioxane, toluene, 1,3-dimethyl-2-imidazolidinone, acetone, tetrahydrofuran or acetonitrile.
[0018] In a preferred embodiment, after the reaction is completed, the reaction solution is quenched, then extracted with ethyl acetate, and the solvent is evaporated under reduced pressure to obtain a crude 3,4-benzocoumarin compound, which is then chromatographically separated to obtain a 3,4-benzocoumarin compound; the eluent for the chromatographic separation is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 100:1.
[0019] Compared with the prior art, the present invention has the following beneficial effects:
[0020] The invention provides a preparation method of a 3,4-benzocoumarin compound. CO2 and 2-bromophenylboronic acid are used as reaction raw materials, 1,10-phenanthroline compound, 2,2′-bipyridine compound, 2,2′-biquinoline or 2,2′,6′,2″-terpyridine is used as a ligand, dissolved in a solvent, and cheap copper is used as a catalyst. The addition amount is 0.1 equiv., and the amount is small. 3,4-benzocoumarin is obtained by a one-step method of activating CO2 under normal pressure through carbon-carbon coupling-cyclization. The reaction mechanism is that the copper catalyst and the nitrogen ligand form a complex A, the complex A forms B under the action of a base, then 2-bromophenylboronic acid reacts with B to form an intermediate I, CO2 inserts between the C-Cu bonds to form an intermediate II, the base induces another molecule of 2-bromophenylboronic acid to form an aryl alkyne C, the intermediate II and the aryl alkyne undergo a nucleophilic addition reaction to form an intermediate III, and the intermediate III generates 3,4-benzocoumarin under the action of a base. The conditions are mild, the reaction process is simple, the cost is low, and it is environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 The hydrogen NMR spectrum of the 3,4-benzocoumarin compound of the present invention.
[0022] Figure 2 The carbon-NMR spectrum of the 3,4-benzocoumarin compound of the present invention. DETAILED DESCRIPTION
[0023] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0024] It should be noted that the professional terms used in the present invention are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention. Unless otherwise specifically stated, the various raw materials, reagents, instruments and equipment used in the following embodiments of the present invention can be purchased from the market or prepared by existing methods.
[0025] There are many known methods for synthesizing 3,4-benzocoumarin derivatives. Generally, the structure is constructed by catalysis of transition metals such as Pd and Rh. For example, Sasano K, Takaya J, Iwasawa N. Palladium (II)-Catalyzed Direct Carboxylation of Alkenyl C–H Bonds with CO2 [J]. Journal of the American Chemical Society, 2013, 45 (30): 10954-10957. This paper points out that coumarin compounds were synthesized under 1 atm CO2 atmosphere at 100 °C using 2-hydroxystyrene as the reaction substrate, palladium acetate as the catalyst, cesium carbonate as the base, and diethylene glycol dimethyl ether as the solvent. For example, Lei F, Shangda L, Zhihua C, et al. Ligand-enabled site-selectivity in a versatile rhodium(ii)-catalysed aryl C–H carboxylation with CO2[J]. Nature Catalysis, 2018, 1(6): 469-478. pointed out that coumarin compounds were obtained under the conditions of 90℃~150℃ using 2-arylphenol as reaction substrate, 1atm CO2 atmosphere, dimerized rhodium acetate as catalyst, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl or tricyclohexylphosphine as ligand, and potassium tert-butoxide as base. For example, Yoo WJ, Nguyen TVQ, Kobayashi S. Synthesis of isocoumarins through three-component couplings of arynes, terminal alkynes, and carbon dioxide catalyzed by an NHC-copper complex [J]. Angewandte Chemie, 2014, 126 (38): 10377-10381. pointed out that isocoumarins were obtained under the conditions of 90 °C with terminal alkynes and 2-(trimethylsilyl)aryl trifluorates as substrates under the catalysis of azacarbene copper, 15 atm CO2 atmosphere, cesium carbonate as base, cesium fluoride as additive, acetonitrile / tetrahydrofuran (volume ratio 1:1) as solvent.
[0026] However, in the above-mentioned synthesis method, due to the thermodynamic and kinetic inertness of CO2, precious transition metals are required as catalysts or high pressure conditions are required to activate CO2 for the reaction to proceed smoothly.
[0027] Based on this, the present invention provides a method for preparing a 3,4-benzocoumarin compound, comprising the following steps: using a 2-bromophenylboronic acid compound as a reaction substrate, adding a ligand and dissolving the ligand in a solvent, and performing a one-step carbon-carbon coupling-cyclization reaction at normal pressure under a CO2 atmosphere under the action of an alkali and a copper catalyst to obtain a 3,4-benzocoumarin compound; the ligand is a 1,10-phenanthroline compound, a 2,2′-bipyridine compound, a 2,2′-biquinoline or a 2,2',6',2"-terpyridine; and the synthesis route is as follows:
[0028]
[0029] The present invention uses CO2 and 2-bromophenylboronic acid as reaction raw materials, uses 1,10-phenanthroline compound, 2,2′-bipyridine compound, 2,2′-biquinoline or 2,2',6',2"-terpyridine as ligand, which are dissolved in a solvent, uses cheap copper as a catalyst, and the addition amount is 0.1 equiv., which is a small amount. The CO2 is activated under normal pressure in a one-step method to obtain 3,4-benzocoumarin through carbon-carbon coupling-cyclization. The reaction mechanism is as follows: taking cuprous chloride in a copper catalyst as an example, first, cuprous chloride and nitrogen ligand form complex A, and complex A forms B under the action of a base, then 2-bromophenylboronic acid and B react to form intermediate I, CO2 inserts between C-Cu bonds to form intermediate II, the base induces another molecule of 2-bromophenylboronic acid to form aryl yne C, intermediate II and aryl yne undergo nucleophilic addition reaction to generate intermediate III, intermediate III generates 3,4-benzocoumarin under the action of the base, and regenerates B to carry out the next cycle.
[0030]
[0031] In a specific embodiment, in order to improve the purity of the 3,4-benzocoumarin compound, more specifically, a one-step method is carried out under normal pressure at 20°C to 100°C under a CO2 atmosphere for 6 hours of carbon-carbon coupling-cyclization reaction, and the reaction is detected by a thin layer chromatography plate. After the reaction stops, the mixed solution is cooled to room temperature, water is added to quench the reaction, and then extracted three times with ethyl acetate, the organic phase is collected and dried over anhydrous magnesium sulfate, filtered, and the filtrate is evaporated to remove the solvent under reduced pressure, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as an eluent, and the eluate containing the target compound is collected, and the solvent is evaporated to obtain the purified product 3,4-benzocoumarin.
[0032] In a specific embodiment, the molar ratio of the 2-bromophenylboronic acid compound to the copper catalyst is 1:0.1-0.2. The copper catalyst is cuprous bromide, cuprous iodide, cuprous chloride, cupric chloride, cupric chloride, cupric chloride monohydrate, cupric acetate monohydrate, copper phosphate, cupric oxalate or chloro[1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene]copper. As a preferred embodiment of the present invention, the copper catalyst is cuprous chloride, and the molar ratio of the 2-bromophenylboronic acid compound to cuprous chloride is 1:0.1. The copper catalyst coordinates with the ligand to stabilize the metal catalyst, improve the reaction activity of the catalyst, and adjust the catalytic performance of the catalyst.
[0033] In a specific embodiment, the molar ratio of the 2-bromophenylboronic acid compound to the ligand is 1:0.1-0.2. The ligand is a 1,10-phenanthroline compound, a 2,2′-bipyridine compound, a 2,2′-biquinoline or a 2,2',6',2"-terpyridine; the 1,10-phenanthroline compound is 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 5-nitro-1,10-phenanthroline or 4-methyl-1,10-phenanthroline; the 2,2′-bipyridine compound is 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine or 5-bromo-2,2'-bipyridine. As a preferred embodiment of the present invention, the ligand is 1,10-phenanthroline, and the molar ratio of 1,10-phenanthroline to cuprous chloride is 1:1.
[0034] In a specific embodiment, the molar ratio of the 2-bromophenylboronic acid compound to the base is 1:1-3. The base is potassium carbonate, sodium carbonate, cesium carbonate, cesium fluoride, potassium phosphate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene or potassium methoxide. As a preferred embodiment of the present invention, the base is potassium carbonate, the base promotes metal transfer, the base removes boric acid, etc.
[0035] In a specific embodiment, the solvent is dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, 1,4-dioxane, toluene, 1,3-dimethyl-2-imidazolidinone, acetone, tetrahydrofuran or acetonitrile. As a preferred embodiment of the present invention, the solvent is dimethyl sulfoxide.
[0036] The invention is further described below through specific examples.
[0037] Example 1
[0038] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0039] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium carbonate (K2CO3) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50° C. at normal pressure for 6 h under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC.
[0040] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 28%. Its synthetic route is as follows:
[0041]
[0042] Example 2
[0043] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0044] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboronic acid and 2 mmol of cesium carbonate (Cs2CO3) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 50°C for 6 h under normal pressure in a one-step method. The reaction system was carried out under CO2 atmosphere throughout the process and the reaction was detected by TLC plate.
[0045] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 24.5%. Its synthetic route is as follows:
[0046]
[0047] Example 3
[0048] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0049] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboronic acid and 2 mmol of potassium carbonate (K2CO3) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 75°C for 6 h under normal pressure in a one-step method. The reaction system was carried out under CO2 atmosphere throughout the process. The reaction was detected by TLC plate.
[0050] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 22%. Its synthetic route is as follows:
[0051]
[0052] Example 4
[0053] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0054] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium methoxide CH3OK were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0055] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 21%. Its synthetic route is as follows:
[0056]
[0057] Example 5
[0058] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0059] S1. 0.1 mmol of cuprous iodide CuI, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium methoxide CH3OK were added sequentially into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0060] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected and dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 20%. Its synthetic route is as follows:
[0061]
[0062] Example 6
[0063] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0064] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of sodium bicarbonate NaHCO3 were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate;
[0065] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 19%. Its synthetic route is as follows:
[0066]
[0067] Example 7
[0068] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0069] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of sodium carbonate Na2CO3 were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate;
[0070] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 18.4%. Its synthetic route is as follows:
[0071]
[0072] Example 8
[0073] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0074] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 4-methyl-1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium methoxide CH3OK were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0075] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 14%. Its synthetic route is as follows:
[0076]
[0077] Example 9
[0078] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0079] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 5-nitro-1,10-phenanthroline, 1 mmol of 2-bromophenylboronic acid and 2 mmol of potassium methoxide CH3OK were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0080] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 13%. Its synthetic route is as follows:
[0081]
[0082] Example 10
[0083] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0084] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium carbonate (K2CO3) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 100°C for 6 h under normal pressure in a one-step method under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process and the reaction was detected by TLC plate.
[0085] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 13%. Its synthetic route is as follows:
[0086]
[0087] Embodiment 11
[0088] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0089] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 3 mmol of potassium carbonate (K2CO3) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 50°C for 6 h under normal pressure in a one-step method. The reaction system was carried out under CO2 atmosphere throughout the process and the reaction was detected by TLC plate.
[0090] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 12%. Its synthetic route is as follows:
[0091]
[0092] Example 12
[0093] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0094] S1. 0.1 mmol of copper oxalate CuC2O4, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium methoxide CH3OK were added sequentially into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0095] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 11%. Its synthetic route is as follows:
[0096]
[0097] Embodiment 13
[0098] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0099] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 5,5'-dimethyl-2,2'-bipyridine, 1 mmol of 2-bromophenylboronic acid and 2 mmol of potassium methoxide CH3OK were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0100] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 10%. Its synthetic route is as follows:
[0101]
[0102] Embodiment 14
[0103] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0104] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 1 mmol of potassium carbonate (K2CO3) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 50°C for 6 h under normal pressure in a one-step method. The reaction system was carried out under CO2 atmosphere throughout the process. The reaction was detected by TLC plate.
[0105] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 10%. Its synthetic route is as follows:
[0106]
[0107] Embodiment 15
[0108] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0109] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 5-bromo-2,2'-bipyridine, 1 mmol of 2-bromophenylboronic acid and 2 mmol of potassium methoxide CH3OK were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0110] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 9%. Its synthetic route is as follows:
[0111]
[0112] Example 16
[0113] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0114] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium hydroxide (KOH) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 50°C for 6 h under normal pressure in a one-step method. The reaction system was carried out under CO2 atmosphere throughout the process. The reaction was detected by TLC plate.
[0115] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 9%. Its synthetic route is as follows:
[0116]
[0117] Embodiment 17
[0118] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0119] S1. 0.1 mmol of cuprous chloride (CuCl), 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of sodium hydroxide (NaOH) were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide (DMSO) was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 50°C for 6 h under normal pressure in a one-step method. The reaction system was carried out under CO2 atmosphere throughout the process and the reaction was detected by TLC plate.
[0120] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 8.5%. Its synthetic route is as follows:
[0121]
[0122] Embodiment 18
[0123] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0124] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 2,2'-bipyridine, 1 mmol of 2-bromophenylboronic acid and 2 mmol of potassium methoxide CH3OK were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0125] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 8%. Its synthetic route is as follows:
[0126]
[0127] Embodiment 19
[0128] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0129] S1. 0.1 mmol of cuprous bromide CuBr, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium methoxide CH3OK were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate.
[0130] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 7%. Its synthetic route is as follows:
[0131]
[0132] Embodiment 20
[0133] The preparation method of 3,4-benzocoumarin compound comprises the following steps:
[0134] S1. 0.1 mmol of copper chloride monohydrate CuCl2·H2O, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium methoxide CH3OK were added in sequence to a dry 25 mL reaction tube equipped with a magnetic stirrer. The 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube. The process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent dimethyl sulfoxide DMSO was added to the system under CO2 atmosphere. The cyclization reaction was carried out at 50°C for 6 h under normal pressure in a one-step method. The reaction system was carried out under CO2 atmosphere throughout the process and the reaction was detected by TLC plate.
[0135] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 4.5%. Its synthetic route is as follows:
[0136]
[0137] Embodiment 21
[0138] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0139] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium carbonate K2CO3 were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent N,N-dimethylformamide DMF was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate;
[0140] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 4%. Its synthetic route is as follows:
[0141]
[0142] Embodiment 22
[0143] A method for preparing a 3,4-benzocoumarin compound comprises the following steps:
[0144] S1. 0.1 mmol of cuprous chloride CuCl, 0.1 mmol of 1,10-phenanthroline, 1 mmol of 2-bromophenylboric acid and 2 mmol of potassium carbonate K2CO3 were sequentially added into a dry 25 mL reaction tube equipped with a magnetic stirrer, and the 25 mL reaction tube was evacuated and replaced with CO2 using a double-row tube, and the process was repeated three times to fill the 25 mL reaction tube with CO2 gas. 3 mL of solvent N,N-dimethylacetamide DMA was added to the system under CO2 atmosphere, and a one-step cyclization reaction was carried out at 50°C for 6 h at normal pressure under CO2 atmosphere. The reaction system was carried out under CO2 atmosphere throughout the process, and the reaction was detected by TLC plate;
[0145] S2. After the reaction stops, the mixed solution is cooled to room temperature, 5 mL of water is added to quench the reaction, and then extracted three times with 5 mL of ethyl acetate, the organic phase is collected, dried with anhydrous magnesium sulfate, filtered, and the filtrate is decompressed to remove the solvent, and then separated by silica gel column chromatography, using a mixed solution of petroleum ether / ethyl acetate in a volume ratio of 100:1 as the eluent, collecting the eluate containing the target compound, and evaporating the solvent to obtain the purified white solid product 3,4-benzocoumarin, with an isolation yield of 2%. Its synthetic route is as follows:
[0146]
[0147] The structures of the products 3,4-benzocoumarin prepared in Examples 1-22 were characterized by nuclear magnetic resonance spectroscopy (NMR).
[0148] H NMR 1 HNMR (400MHz) spectral data and carbon NMR spectrum 13 The C NMR (101 MHz) spectral data were recorded by a Bruker Ascend nuclear magnetic resonance instrument from Switzerland, and the deuterated reagent dimethyl sulfoxide (DMSO-d6) was used as the internal standard solvent.
[0149] Since the products 3,4-benzocoumarin prepared in Examples 1-22 have the same structure, the H NMR spectrum 1 H NMR and C NMR spectroscopy 13 C NMR is basically the same, therefore, the product 3,4-benzocoumarin prepared in Example 1 was subjected to hydrogen nuclear magnetic resonance spectroscopy. 1 HNMR and C NMR spectroscopy 13 CNMR Description, Nuclear Magnetic Hydrogen Spectroscopy 1 HNMR spectrum Figure 1 As shown, the NMR carbon spectrum 13 CNMR spectrum Figure 2 shown.
[0150] The characterization data of the product 3,4-benzocoumarin are:
[0151] 1 H NMR (400MHz, DMSO-d6) δ8.46(d,J=8.1Hz,1H),8.38(d,J=8.0Hz,1H),8.26(d,J=7.9Hz,1H) ,7.96(t,J=7.8Hz,1H),7.70(t,J=7.6Hz,1H),7.58(t,J=7.8Hz,1H),7.42(t,J=8.9Hz,2H).
[0152] 13 C NMR (101MHz, DMSO-d6) δ160.69,151.20,135.82,134.77,131.22,130.21,129.79,125.25,124.13,123.08,121.08,118.17,117.72.
[0153] It was confirmed that the white solid product was 3,4-benzocoumarin.
[0154] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.
[0155] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.
Claims
1. A method for preparing a 3,4-benzocoumarin compound, characterized in that: The method comprises the following steps: using 2-bromophenylboronic acid compounds as reaction substrates, adding ligands and dissolving the ligands in a solvent, and carrying out a one-step carbon-carbon coupling-cyclization reaction at normal pressure under a CO2 atmosphere under the action of alkali and copper catalysts to obtain 3,4-benzocoumarin compounds; the ligands are 1,10-phenanthroline compounds, 2,2′-bipyridine compounds, 2,2′-biquinoline or 2,2',6',2"-terpyridine; and the synthesis route is as follows:
2. The method for preparing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The molar ratio of the 2-bromophenylboronic acid compound to the copper catalyst is 1:0.1-0.
2.
3. The method for preparing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The copper catalyst is cuprous bromide, cuprous iodide, cuprous chloride, cupric chloride, cupric chloride, cupric chloride monohydrate, cupric acetate monohydrate, cupric phosphate, cupric oxalate or copper chloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloride.
4. The method for preparing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The molar ratio of the 2-bromophenylboronic acid compound to the ligand is 1:0.1-0.
2.
5. The method for synthesizing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The molar ratio of the 2-bromophenylboronic acid compound to the base is 1:1-3.
6. The method for synthesizing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The carbon-carbon coupling-cyclization reaction temperature is 20° C. to 100° C., and the reaction time is 6 hours.
7. The method for synthesizing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The 1,10-phenanthroline compound is 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 5-nitro-1,10-phenanthroline or 4-methyl-1,10-phenanthroline; the 2,2′-bipyridine compound is 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine or 5-bromo-2,2'-bipyridine.
8. The method for synthesizing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The base is potassium carbonate, sodium carbonate, cesium carbonate, cesium fluoride, potassium phosphate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene or potassium methoxide.
9. The method for synthesizing the 3,4-benzocoumarin compound according to claim 1, characterized in that: The solvent is dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, 1,4-dioxane, toluene, 1,3-dimethyl-2-imidazolidinone, acetone, tetrahydrofuran or acetonitrile.
10. The method for synthesizing 3,4-benzocoumarin compounds according to claim 1, characterized in that: After the reaction is completed, the reaction solution is quenched, and then extracted with ethyl acetate, and the solvent is evaporated under reduced pressure to obtain a crude 3,4-benzocoumarin compound, which is then separated by chromatography to obtain a 3,4-benzocoumarin compound; the eluent for the chromatographic separation is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 100:1.