Preparation method of 5-bromonaphtho [1, 2-b] benzofuran

Abstract

The invention discloses a preparation method of 5-bromonaphthalene [1, 2-b] benzofuran, relates to the technical field of synthesis of dibenzofuran compounds, and aims to solve the problem that the existing synthesis method of 5-bromonaphthalene [1, 2-b] benzofuran cannot meet the requirements of simplicity, economy, greenness and high efficiency. The preparation method comprises the following steps: reacting 1-naphthol with N-bromosuccinimide to prepare 4-bromo-1-naphthol; the preparation method comprises the following steps: carrying out C-O coupling and C-C coupling cascade reaction on 4-bromo-1-naphthol and o-bromo iodobenzene or o-chloro iodobenzene under the action of a copper salt and nickel salt composite catalyst, a pyridine-2-formamidine ligand and alkali to prepare 5-bromo-naphtho [1, 2-b] benzofuran; sodium iodide or potassium iodide is also added into reactants of the cascade reaction as an additive for improving the selectivity and the yield of the reaction; the method is simple in preparation process, high in reaction total yield, low in preparation raw material cost, economical and environment-friendly, and a novel preparation method is provided for synthesizing the 5-bromonaphtho [1, 2-b] benzofuran.

Description

Technical Field

[0001] The invention relates to the technical field of synthesis of dibenzofuran compounds, in particular to a method for preparing 5-bromonaphtho[1,2-b]benzofuran. Background Art

[0002] Organic luminescence is the phenomenon that organic materials produce light under the stimulation of electric current or electric field. Organic light-emitting diodes (OLEDs), as a current-type organic light-emitting device, can achieve electroluminescence through the injection and recombination of carriers. As a new display technology, OLED has the advantages of wide viewing angle, ultra-thinness, fast response, high luminous efficiency, and flexible display. It is called a "dreamlike display" and is recognized worldwide as the next generation mainstream display after liquid crystal. At the same time, OLED has the characteristics of large-area film formation and low power consumption. It is an ideal planar light source and has broad application prospects in the future energy-saving and environmentally friendly lighting field.

[0003] Derivative compounds containing a dibenzofuran skeleton are a class of oxygen-containing condensed-ring aromatic compounds with a structure similar to that of nitrogen-containing carbazole compounds. They have good thermal stability, photostability and device luminescence performance, and can effectively improve the efficiency and life of OLED devices. Therefore, they have important applications in the preparation of organic light-emitting devices such as organophosphorus light-emitting diodes (PhOLEDs).

[0004] 5-bromonaphtho[1,2-b]benzofuran is a dibenzofuran chemical intermediate with excellent optical and electrical properties. It is widely used as a synthetic intermediate for organic semiconductors such as organic / polymer light-emitting diodes (OLED / PLED). Aromatic compounds containing dibenzofuran skeletons prepared by further modification have important applications in OLED as luminescent host and guest materials, hole transport materials, luminescent auxiliary layer materials and exciton blocking materials. It has been widely studied and applied in recent years. Therefore, studying the synthesis of 5-bromonaphtho[1,2-b]benzofuran is of great significance to the development of the OLED industry. According to existing literature reports, there are three main types of 5-bromonaphtho[1,2-b]benzofuran:

[0005] Route 1: First synthesize naphtho[1,2-b]benzofuran, and then brominate it to prepare 5-bromonaphtho[2,1-b]benzofuran. For example, patent CN201180056093.4 reports a method for preparing 5-bromonaphtho[2,1-b]benzofuran, which uses 1-naphthol and 1,3-cyclohexadiene as starting materials, first reacts with 1,3-cyclohexadiene under the catalysis of p-toluenesulfonic acid to prepare 7,8,9,10-tetrahydrobenzo[b]naphtho[2,1-d]furan, then undergoes an oxidative cyclization reaction under the action of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to prepare naphtho[1,2-b]benzofuran, and finally naphtho[2,1-b]benzofuran is subjected to a bromination reaction with N-bromosuccinimide (NBS) to prepare 5-bromonaphtho[1,2-b]benzofuran, and the total yield of the three-step reaction is 12.3%;

[0006]

[0007] Route 2: Preparation of 5-bromonaphtho[1,2-b]benzofuran by intramolecular dehydrogenation ring-closure reaction of phenolic hydroxyl intermediates catalyzed by transition metals. For example, patent CN201710157722.1 reported a method for preparing 5-bromonaphtho[1,2-b]benzofuran, which uses 4-bromo-2-phenyl-1-ol as a starting material and prepares 5-bromonaphtho[1,2-b]benzofuran by intramolecular dehydrogenation ring-closure reaction of phenolic hydroxyl under the catalysis of palladium acetate / 3-nitropyridine, with a reaction yield of 45%;

[0008]

[0009] Route 3: Intramolecular nucleophilic substitution cyclization reaction to construct a dibenzofuran ring structure to prepare 5-bromonaphtho[1,2-b]benzofuran. For example, patent CN202110961441.8 reports a method for preparing 5-bromonaphtho[1,2-b]benzofuran, which uses 2-iodoanisole and 4-bromo-1-fluoronaphthalene-2-boric acid as starting materials, and uses 2-iodoanisole and 4-bromo-1-fluoronaphthalene-2-boric acid as starting materials to prepare 5-bromonaphtho[1,2-b]benzofuran through Suzuki coupling reaction, demethylation, and intramolecular nucleophilic substitution cyclization reaction. The total yield of the three-step reaction is 22.4%;

[0010]

[0011] In the above-mentioned synthetic routes, in route 1, 1-naphthol and 1,3-cyclohexadiene are used as starting materials to prepare 7,8,9,10-tetrahydrobenzo[b]naphtho[2,1-d]furan. However, due to the high price of 1,3-cyclohexadiene, the raw material cost is high, the reaction selectivity is poor, the purification is difficult, and the reaction yield is low. The equivalent p-toluenesulfonic acid catalytic post-treatment process is seriously polluted. In the three-step reaction to prepare 5-bromonaphtho[1,2-b]benzofuran, the total reaction yield is low, resulting in high preparation cost. Therefore, this route has the disadvantages of low total reaction yield, high raw material price, high production cost, and many wastes. Route 2 uses 4-bromo-2-phenyl-1-ol as a starting material to prepare 5-bromonaphtho[1,2-b]benzofuran. The reaction conditions are mild and the preparation steps are short. However, the starting material 4-bromo-2-phenyl-1-ol itself is expensive and requires multiple steps to prepare. It also requires expensive hexafluorobenzene as a reaction solvent, 1,3-dimethyl-2-imidazolidinone as another reaction solvent and two equivalents of tert-butyl perbenzoate as an oxidant. In the post-treatment process, it causes environmental problems such as a lot of waste, heavy pollution, etc., and the post-treatment purification is difficult and the reaction yield is insufficient. Therefore, this route has the defects of high raw material prices, great difficulty in post-treatment purification, and heavy pollution. Route 3 uses 2-iodoanisole and 4-bromo-1-fluoronaphthalene-2-boric acid as starting materials, and adopts common intramolecular substitution reaction to form intramolecular CO bond to construct dibenzofuran skeleton structure to prepare 5-bromonaphtho[1,2-b]benzofuran. However, its initial raw material 4-bromo-1-fluoronaphthalene-2-boric acid is expensive and requires multiple steps of reaction preparation. The total yield of the three steps of the preparation process is only 22.4%. It also has the disadvantages of expensive raw materials, low total reaction yield, high production cost, and poor atom utilization.

[0012] In summary, the existing synthesis methods generally have the disadvantages of expensive and difficult to obtain reaction raw materials, poor reaction selectivity and atom economy, low total reaction yield, high production cost, prominent environmental problems, etc., which do not meet the development requirements of green chemistry and synthetic economy, and seriously restrict their industrial application in the preparation of 5-bromonaphtho[1,2-b]benzofuran. Therefore, a preparation method of 5-bromonaphtho[1,2-b]benzofuran is urgently needed to solve these problems. Summary of the invention

[0013] The object of the present invention is to provide a method for preparing 5-bromonaphtho[1,2-b]benzofuran, so as to solve the problem that the existing method for synthesizing 5-bromonaphtho[1,2-b]benzofuran cannot meet the requirements of being simple, economical, green and efficient.

[0014] To achieve the above object, the present invention provides the following technical solution: a method for preparing 5-bromonaphtho[1,2-b]benzofuran, comprising the following steps:

[0015] Step 1: 1-naphthol is reacted with N-bromosuccinimide to prepare 4-bromo-1-naphthol;

[0016] Step 2: The 4-bromo-1-naphthol prepared in step 1 is reacted with o-bromoiodobenzene or o-chloroiodobenzene in the presence of a copper salt and nickel salt composite catalyst, a pyridine-2-carboxamidine ligand and a base to prepare 5-bromonaphtho[1,2-b]benzofuran through a CO coupling and CC coupling tandem reaction; sodium iodide or potassium iodide is also added to the reactants of the tandem reaction as an additive to improve the selectivity and yield of the reaction.

[0017] Preferably, in the above step 1, the preparation process of 4-bromo-1-naphthol comprises: adding 1-naphthol and an organic solvent to a reaction vessel under protective gas conditions, stirring evenly and completely dissolving, adding N-bromosuccinimide under conditions that ensure that the temperature does not rise suddenly, reacting completely at room temperature, removing impurities and purifying to obtain 4-bromo-1-naphthol; wherein the organic solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, dichloromethane, 1,2-dichloroethane or N,N-dimethylformamide, and the molar ratio of 1-naphthol to N-bromosuccinimide is 1:(0.95-1.05).

[0018] Preferably, in the above step 2, the composite catalyst consists of catalyst A and catalyst B, catalyst A is a copper salt selected from one or more of cuprous oxide, cuprous bromide, cuprous iodide, and cuprous chloride, and catalyst B is a nickel salt selected from one or more of nickel iodide, (1,1'-bis(diphenylphosphino)ferrocene)nickel dichloride, and bis(triphenylphosphine)nickel dichloride; the molar ratio of 4-bromo-1-naphthol to catalyst A and catalyst B is 1:(0.01-0.20):(0.005-0.05).

[0019] In the above preferred embodiments, preferably, catalyst A is cuprous oxide and / or cuprous iodide.

[0020] Preferably, in the above step 2, the pyridine-2-carboxamidine ligand is selected from one or more of 4-methoxypyridine-2-carboxamidine, 5-methoxypyridine-2-carboxamidine, 4-isopropylpyridine-2-carboxamidine, 4-ethylpyridine-2-carboxamidine, and pyridine-2,6-dicarboxamidine, and the molar ratio of 4-bromo-1-naphthol to the ligand is 1:(0.01~0.10).

[0021] Preferably, in the above step 2, the molar ratio of 4-bromo-1-naphthol to the additive is 1:(0.10-0.20).

[0022] Preferably, in the above step 2, the base is selected from one or more of potassium phosphate, cesium carbonate, cesium acetate, sodium hydroxide, sodium tert-butoxide, and potassium tert-butoxide, and the molar ratio of 4-bromo-1-naphthol to the base is 1:(2.50-4.00).

[0023] Preferably, in the above step 2, the tandem reaction temperature is 130-170° C., and the reaction time is 24-36 h.

[0024] Preferably, in the above step 2, after the cascade reaction is completed, unreacted o-bromoiodobenzene is recovered by distillation under reduced pressure, water and an extraction solvent are added to the residue cooled to room temperature, and the organic layer is subjected to column chromatography, desolventization, and recrystallization to obtain 5-bromonaphtho[1,2-b]benzofuran.

[0025] In the preferred embodiment, the extraction solvent is selected from one or more of butyl acetate, ethyl acetate, dichloromethane, tetrahydrofuran, and 1,2-dichloroethane, and the recrystallization solvent is one or more of ethyl acetate, dichloromethane, o-xylene, methanol, ethanol, petroleum ether, n-hexane, tetrahydrofuran, and acetonitrile.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] 1. The preparation method of 5-bromonaphtho[1,2-b]benzofuran comprises the following steps: firstly using 1-naphthol as a starting material to synthesize 4-bromo-1-naphthol, and then subjecting the 1-naphthol to a series reaction of CO coupling and CC coupling under nickel / copper synergistic catalysis with o-bromoiodobenzene or o-chloroiodobenzene, to prepare 5-bromonaphtho[1,2-b]benzofuran in one pot. The method has the characteristics of simple process preparation flow, high total reaction yield, low preparation raw material cost, economy and environmental protection, and provides a new preparation method for synthesizing 5-bromonaphtho[1,2-b]benzofuran, is conducive to large-scale production, has industrial feasibility, and expands the synthesis method of 5-bromonaphtho[1,2-b]benzofuran for material design in the fields of optics and medicine.

[0028] 2. The method for preparing 5-bromonaphtho[1,2-b]benzofuran adopts a nickel / copper bimetallic synergistic catalytic tandem reaction of 4-bromo-1-naphthol and o-bromoiodobenzene or o-chloroiodobenzene to prepare 5-bromonaphtho[1,2-b]benzofuran, which has the advantages of high reaction selectivity and simple post-treatment purification operation, and can obtain a higher yield of 5-bromonaphtho[1,2-b]benzofuran.

[0029] 3. The method for preparing 5-bromonaphtho[1,2-b]benzofuran uses o-bromoiodobenzene or o-chloroiodobenzene as both a reactant and a reaction solvent during the reaction process. After the reaction is completed, the o-bromoiodobenzene or o-chloroiodobenzene can be separated from 5-bromonaphtho[1,2-b]benzofuran by vacuum distillation and the o-bromoiodobenzene or o-chloroiodobenzene can be recovered. The method has simple operation, high economic effect and is environmentally friendly.

[0030] 4. The preparation method of 5-bromonaphtho[1,2-b]benzofuran adopts sodium iodide or potassium iodide as an additive to promote the reaction, improve the selectivity and yield of the reaction, and help reduce the generation of by-products. DETAILED DESCRIPTION

[0031] Based on the problems mentioned in the above background technology, the inventors of the present invention need to find raw materials and steps different from the existing synthetic routes, rather than adjusting the existing routes, so the development difficulty increases sharply. Starting from the target product, reverse deconstruction, after a large number of ideas and assumptions, a large number of theoretically feasible schemes are formulated, but most of them cannot meet the requirements of simplicity, economy and greenness, and after meeting these requirements, it is difficult to achieve a satisfactory yield and industrial application, so the development progress is stagnant; the inventors re-hypothesized the possible synthetic route of the target product, screened out the synthetic route with economical raw materials and shorter steps, and then improved the raw materials and replaced them with greener schemes. After a large number of experimental attempts, the schemes with a yield higher than 20% are retained as feasible schemes, and then the raw materials are re-examined according to the reaction mechanism, and the promoting supplementary materials that may affect the reaction selectivity are supplemented. Finally, it is accidentally discovered that the scheme of the present invention can well meet the preparation requirements of simplicity, economy, greenness and high efficiency at the same time. A preparation method of 5-bromonaphtho[1,2-b]benzofuran of the present invention comprises the following steps:

[0032] Step 1: 1-naphthol is reacted with N-bromosuccinimide to prepare 4-bromo-1-naphthol. The reaction formula is as follows:

[0033]

[0034] Specifically, under protective gas conditions, 1-naphthol and an organic solvent are added to a reaction container, stirred evenly and completely dissolved, N-bromosuccinimide is added under conditions that ensure that the temperature does not rise suddenly, and after the reaction is completed at room temperature, 4-bromo-1-naphthol is purified by impurity removal; wherein, according to testing, the organic solvent can be one or more of tetrahydrofuran, 2-methyltetrahydrofuran, dichloromethane, 1,2-dichloroethane or N,N-dimethylformamide, and in order not to waste raw materials, the molar ratio of 1-naphthol to N-bromosuccinimide is preferably controlled to be 1:(0.95-1.05).

[0035] Step 2: 4-bromo-1-naphthol prepared in step 1 is reacted with o-bromoiodobenzene or o-chloroiodobenzene in the presence of a copper salt and nickel salt composite catalyst, a pyridine-2-carboxamidine ligand and a base to prepare 5-bromonaphtho[1,2-b]benzofuran through a CO coupling and CC coupling tandem reaction; sodium iodide or potassium iodide is also added to the reactants of the tandem reaction as an additive to improve the selectivity and yield of the reaction; for reference, the tandem reaction temperature can be 130 to 170° C., and the reaction time can be 24 to 36 hours; the reaction formula is as follows:

[0036]

[0037] Specifically, under protective gas conditions, all raw materials (including 4-bromo-1-naphthol, o-bromoiodobenzene or o-chloroiodobenzene, catalyst, ligand, base, additives) are added into a reaction container, the temperature is raised and the stirring speed is 550 rpm, and the temperature is kept for reaction. After the reaction is completed, purification and impurity removal can be carried out.

[0038] In the above step 2, the composite catalyst is composed of catalyst A and catalyst B, catalyst A is a copper salt, for reference, can be selected from one or more of cuprous oxide, cuprous bromide, cuprous iodide, cuprous chloride, more preferably cuprous oxide and / or cuprous iodide, catalyst B is a nickel salt, for reference, can be selected from one or more of nickel iodide, (1,1'-bis(diphenylphosphino)ferrocene) nickel dichloride, bis(triphenylphosphine) nickel dichloride; further optionally, the molar ratio of 4-bromo-1-naphthol to catalyst A and catalyst B is preferably 1:(0.01-0.20):(0.005-0.05); pyridine-2-carboxamidine ligands can be One or more selected from 4-methoxypyridine-2-carboxamidine, 5-methoxypyridine-2-carboxamidine, 4-isopropylpyridine-2-carboxamidine, 4-ethylpyridine-2-carboxamidine, pyridine-2,6-dicarboxamidine, further optionally, the molar ratio of 4-bromo-1-naphthol to the ligand is 1:(0.01-0.10); the molar ratio of 4-bromo-1-naphthol to the additive can be 1:(0.10-0.20); the base can be selected from one or more of potassium phosphate, cesium carbonate, cesium acetate, sodium hydroxide, sodium tert-butoxide, potassium tert-butoxide, further optionally, the molar ratio of 4-bromo-1-naphthol to the base is preferably 1:(2.50-4.00).

[0039] In a preferred embodiment, purification and impurity removal can be specifically carried out in the following manner: unreacted o-bromoiodobenzene is recovered by vacuum distillation, water and an extraction solvent are added to the residue cooled to room temperature, and the organic layer is subjected to column chromatography, desolventization, and recrystallization to obtain 5-bromonaphtho[1,2-b]benzofuran. For reference, the extraction solvent can be selected from one or more of butyl acetate, ethyl acetate, dichloromethane, tetrahydrofuran, and 1,2-dichloroethane, and the recrystallization solvent can be one or more of ethyl acetate, dichloromethane, o-xylene, methanol, ethanol, petroleum ether, n-hexane, tetrahydrofuran, and acetonitrile.

[0040] In order to make the purpose, technical solutions and advantages of the present invention clearer, the above contents of the present invention are further described in detail below in conjunction with embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments.

[0041] Embodiment 1:

[0042] (1) Preparation of 4-bromo-1-naphthol: Under nitrogen protection, 1-naphthol (99%, 144.2 g, 1.0 mol) and 1000 mL of dichloromethane were added to a reaction flask, stirred evenly and completely dissolved, and N-bromosuccinimide (99%, 178.0 g, 1.0 mol) was added to the reaction flask in batches at 0°C, and the temperature was naturally raised to room temperature and the reaction was continued for 4 hours. After monitoring the complete reaction of 1-naphthol, 250 mL of water was added to the reaction system and stirred for 1 hour, and the liquid was separated, and then the organic phase was washed twice with water and once with saturated brine, dried, concentrated under reduced pressure, added with n-hexane, stirred evenly, and filtered to obtain 212.0 g of 4-bromo-1-naphthol;

[0043] (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 1343.8 g of o-bromoiodobenzene (99%, 4.75 mol), 36.2 g of cuprous iodide (99%, 0.19 mol), 14.8 g of nickel iodide (99%, 47.5 mmol), 14.4 g of 4-methoxypyridine-2-carboximidamide (99%, 95.0 mmol), 28.5 g of sodium iodide (99%, After the addition of the materials, the temperature was raised to 150°C, the stirring speed was 550 rpm, and the reaction was kept warm for 36 hours. After the reaction was completed, unreacted o-bromoiodobenzene was recovered by vacuum distillation, and the residue was cooled to room temperature, and water and butyl acetate were added to extract the residue. The organic layer was subjected to silica gel column chromatography and desolventization to obtain a crude product, which was crystallized with a mixed solvent of petroleum ether / ethyl acetate to obtain 165.3 g of 5-bromonaphtho[1,2-b]benzofuran. Based on 1-naphthol as the starting material, the total yield of the reaction was 55.6%.

[0044] Embodiment 2:

[0045] (1) Preparation of 4-bromo-1-naphthol: Under nitrogen protection, 1-naphthol (99%, 144.2 g, 1.0 mol) and 1000 mL of tetrahydrofuran were added to a reaction flask, stirred evenly and completely dissolved, and N-bromosuccinimide (99%, 187.0 g, 1.05 mol) was added to the reaction flask in batches at 0°C, and the temperature was naturally raised to room temperature and the reaction was continued for 4 hours. After monitoring the complete reaction of 1-naphthol, 250 mL of water was added to the reaction system and stirred for 1 hour, and the liquid was separated, and then the organic phase was washed twice with saturated brine, and the aqueous phase was washed once with dichloromethane. The organic liquids were combined, dried, concentrated under reduced pressure, and n-hexane was added and stirred evenly, and then filtered to obtain 200.8 g of 4-bromo-1-naphthol;

[0046] (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 200.8 g of 4-bromo-1-naphthol (99%, 0.90 mol), 1273.0 g of o-bromoiodobenzene (99%, 4.5 mol), 34.3 g of cuprous iodide (99%, 0.18 mol), 30.5 g of (1,1'-bis(diphenylphosphino)ferrocene) nickel dichloride (99%, 45.0 mmol), 13.6 g of 5-methoxypyridine-2-carboximidamide (99%, 90.0 mmol), 27.0 g of iodine were added into the reaction flask. 99%, 0.18 mol of sodium iodide and 573.0 g of potassium phosphate (99%, 2.7 mol) were added. The temperature was raised to 150°C and the stirring speed was 550 rpm. The reaction was kept warm for 36 hours. After the reaction, unreacted o-bromoiodobenzene was recovered by vacuum distillation. The residue was cooled to room temperature and extracted with water and dichloromethane. The organic layer was subjected to silica gel column chromatography and desolventization to obtain a crude product. The crude product was crystallized with a petroleum ether / dichloromethane mixed solvent to obtain 175.4 g of 5-bromonaphtho[1,2-b]benzofuran. The total yield of the reaction was 59.0% based on 1-naphthol as the starting material.

[0047] Embodiment 3:

[0048] Step (1) is the same as in Example 1; (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 806.3 g of o-bromoiodobenzene (99%, 2.85 mol), 27.2 g of cuprous oxide (99%, 0.19 mol), 31.1 g of bis(triphenylphosphine)nickel dichloride (99%, 47.5 mmol), 14.2 g of 4-ethylpyridine-2-carboximidamide (99%, 95.0 mmol), 28.5 g of iodine were added to the reaction flask. After the addition of the materials, the temperature was raised to 170°C, the stirring speed was 550rpm, and the reaction was kept warm for 36 hours. After the reaction, unreacted o-bromoiodobenzene was recovered by vacuum distillation, and the residue was cooled to room temperature, and water and 2-methyltetrahydrofuran were added to extract the organic layer. The crude product was obtained by silica gel column chromatography and desolventization. 156.7 g of 5-bromonaphtho[1,2-b]benzofuran was obtained by crystallization with a mixed solvent of petroleum ether / tetrahydrofuran. Based on 1-naphthol as the starting material, the total yield of the reaction was 52.7%.

[0049] Embodiment 4:

[0050] Step (1) is the same as in Example 1; (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 806.3 g of o-bromoiodobenzene (99%, 2.85 mol), 18.1 g of cuprous iodide (99%, 95.0 mmol), 12.9 g of (1,1'-bis(diphenylphosphino)ferrocene)nickel dichloride (99%, 19.0 mmol), 8.2 g of pyridine-2,6-dicarboximidamide (99%, 47.5 mmol), 2 8.6 g of sodium iodide (99%, 0.19 mol) and 504.2 g of potassium phosphate (99%, 2.375 mol) were added, the temperature was raised to 170°C, the stirring speed was 550 rpm, and the reaction was kept warm for 36 hours. After the reaction was completed, unreacted o-bromoiodobenzene was recovered by vacuum distillation, and water and dichloromethane were added to the residue to cool to room temperature for extraction. The organic layer was subjected to silica gel column chromatography and desolventization to obtain a crude product, which was crystallized with a petroleum ether / dichloromethane mixed solvent to obtain 185.1 g of 5-bromonaphtho[1,2-b]benzofuran. Based on 1-naphthol as the starting material, the total reaction yield was 62.3%.

[0051] Embodiment 5:

[0052] Step (1) is the same as in Example 1; (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 1812.2 g of o-chloroiodobenzene (99%, 7.6 mol), 18.1 g of cuprous iodide (99%, 95.0 mmol), 12.9 g of (1,1'-bis(diphenylphosphino)ferrocene) nickel dichloride (99%, 19.0 mmol), 8.2 g of pyridine-2,6-dicarboximidamide (99%, 47.5 mmol), 2 8.6 g of sodium iodide (99%, 0.19 mol) and 504.2 g of potassium phosphate (99%, 2.375 mol) were added, the temperature was raised to 170°C, the stirring speed was 550 rpm, and the reaction was kept warm for 36 hours. After the reaction was completed, unreacted o-bromoiodobenzene was recovered by vacuum distillation, and water and dichloromethane were added to the residue to cool to room temperature for extraction. The organic layer was subjected to silica gel column chromatography and desolventization to obtain a crude product, which was crystallized with a petroleum ether / dichloromethane mixed solvent to obtain 167.8 g of 5-bromonaphtho[1,2-b]benzofuran. Based on 1-naphthol as the starting material, the total reaction yield was 56.5%.

[0053] Comparative Example 1:

[0054] The difference from the embodiment is that the reaction system in step (2) uses 1,2-dibromobenzene as the reaction raw material

[0055] Step (1) is the same as in Example 1; (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 1120.5 g of 1,2-dibromobenzene (99%, 4.75 mol), 18.1 g of cuprous iodide (99%, 95.0 mmol), 12.9 g of (1,1'-bis(diphenylphosphino)ferrocene) nickel dichloride (99%, 19.0 mmol), 8.2 g of 2,6-dicarboximidamide (99%, 47.5mmol), 28.6g of sodium iodide (99%, 0.19mol), 504.2g of potassium phosphate (99%, 2.375mol), after adding the materials, the temperature was raised to 170°C, the stirring speed was 550rpm, and the reaction was kept warm for 36 hours; after the reaction was completed, 1,2-dibromobenzene was recovered by vacuum distillation, and the residue was cooled to room temperature, water and dichloromethane were added to extract, and the organic layer was analyzed by GC-MS, and the content of 5-bromonaphtho[1,2-b]benzofuran was <1%.

[0056] Comparative Example 2:

[0057] The difference from the embodiment is that the reaction system in step (2) uses 2-bromochlorobenzene as the reaction raw material

[0058] Step (1) is the same as in Example 1; (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 909.4 g of 2-bromochlorobenzene (99%, 4.75 mol), 18.1 g of cuprous iodide (99%, 95.0 mmol), 12.9 g of (1,1'-bis(diphenylphosphino)ferrocene) nickel dichloride (99%, 19.0 mmol), 8.2 g of Pyridine-2,6-dicarboximidamide (99%, 47.5mmol), 28.6g of sodium iodide (99%, 0.19mol), 504.2g of potassium phosphate (99%, 2.375mol), after adding the materials, the temperature was raised to 170°C, the stirring speed was 550rpm, and the reaction was kept warm for 36h; after the reaction was completed, 2-bromochlorobenzene was recovered by vacuum distillation, and the residue was cooled to room temperature and extracted with water and dichloromethane. The organic layer was analyzed by GC-MS, and the content of 5-bromonaphtho[1,2-b]benzofuran was less than 1%.

[0059] Comparative Example 3:

[0060] Step (1) is the same as in Example 1; (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 1132.6 g of o-chloroiodobenzene (99%, 4.75 mol), 27.2 g of cuprous oxide (99%, 0.19 mol), 14.8 g of nickel iodide (99%, 47.5 mmol), 15.5 g of 4-isopropylpyridine-2-carboximidamide (99%, 95.0 mmol) were added to the reaction flask. l), 547.0g of cesium acetate (99%, 2.85mol), after adding the materials, the temperature was raised to 140°C, the stirring speed was 550rpm, and the reaction was kept warm for 24h; after the reaction, unreacted o-chloroiodobenzene was recovered by vacuum distillation, and the residue was cooled to room temperature, and water and dichloromethane were added to extract the residue. The organic layer was subjected to silica gel column chromatography and desolventization to obtain a crude product, which was crystallized with a petroleum ether / dichloromethane mixed solvent to obtain 100.6g of 5-bromonaphtho[1,2-b]benzofuran. Based on 1-naphthol as the starting material, the total yield of the reaction was 33.8%.

[0061] Comparative Example 4:

[0062] Step (1) is the same as in Example 1; (2) Preparation of 5-bromonaphtho[1,2-b]benzofuran: Under nitrogen protection, 212.0 g of 4-bromo-1-naphthol (99%, 0.95 mol), 679.6 g of o-chloroiodobenzene (99%, 2.85 mol), 1.81 g of cuprous iodide (99%, 9.5 mmol), 1.48 g of nickel iodide (99%, 4.75 mmol), 1.55 g of pyridine-2,6-dicarboximidamide (99%, 9.5 mmol) were added to the reaction flask. , 773.8g of cesium carbonate (99%, 2.375mol), after the addition of the materials, the temperature was raised to 170°C, the stirring speed was 550rpm, and the reaction was kept warm for 36h; after the reaction, unreacted o-bromoiodobenzene was recovered by vacuum distillation, and the residue was cooled to room temperature and extracted with water and dichloromethane. The organic layer was subjected to silica gel column chromatography and desolventization to obtain a crude product, which was crystallized with a petroleum ether / dichloromethane mixed solvent to obtain 78.2g of 5-bromonaphtho[1,2-b]benzofuran. Taking 1-naphthol as the starting material, the total yield of the reaction was 26.3%.

[0063] It can be seen from Comparative Examples 1 and 2 that 4-bromo-1-naphthol and o-bromoiodobenzene or o-chloroiodobenzene in the present invention react well without other solvents, but if the reaction raw materials are replaced with o-dibromobenzene or o-chlorobromobenzene of similar structure, the reaction cannot proceed; 4-bromo-1-naphthol as a reaction raw material is greatly affected by the bromine at the 4th position, and cannot react with o-dibromobenzene or o-chlorobromobenzene to generate 5-bromonaphtho[1,2-b]benzofuran during the reaction, but two molecules of 4-bromo-1-naphthol will undergo CO coupling reaction with themselves, generating by-products that hinder the formation of the target product; Comparative Examples 3 and 4 do not add additives, and their reaction selectivity changes, and the total reaction yield is directly affected.

[0064] The above are only a few of the numerous embodiments of the present invention, but not all of them. However, the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope defined by the claims.

[0065] The matters not described in detail in the present invention are all known technologies to those skilled in the art.

Claims

1. A method for preparing 5-bromonaphtho[1,2-b]benzofuran, characterized in that: The following steps are involved: Step 1: 1-naphthol is reacted with N-bromosuccinimide to prepare 4-bromo-1-naphthol; Step 2: The 4-bromo-1-naphthol prepared in step 1 is reacted with o-bromoiodobenzene or o-chloroiodobenzene in the presence of a copper salt and nickel salt composite catalyst, a pyridine-2-carboxamidine ligand and a base to prepare 5-bromonaphtho[1,2-b]benzofuran through a CO coupling and CC coupling tandem reaction; sodium iodide or potassium iodide is also added to the reactants of the tandem reaction as an additive to improve the selectivity and yield of the reaction.

2. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 1, characterized in that: In the step 1, the preparation process of 4-bromo-1-naphthol comprises: adding 1-naphthol and an organic solvent to a reaction vessel under protective gas conditions, stirring evenly and completely dissolving, adding N-bromosuccinimide under conditions that ensure that the temperature does not rise suddenly, reacting completely at room temperature, removing impurities and purifying to obtain 4-bromo-1-naphthol; wherein the organic solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, dichloromethane, 1,2-dichloroethane or N,N-dimethylformamide, and the molar ratio of 1-naphthol to N-bromosuccinimide is 1:(0.95-1.05).

3. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 1, characterized in that: In the step 2, the composite catalyst is composed of catalyst A and catalyst B, catalyst A is a copper salt selected from one or more of cuprous oxide, cuprous bromide, cuprous iodide, and cuprous chloride, and catalyst B is a nickel salt selected from one or more of nickel iodide, (1,1'-bis(diphenylphosphino)ferrocene) nickel dichloride, and bis(triphenylphosphine) nickel dichloride; the molar ratio of 4-bromo-1-naphthol to catalyst A and catalyst B is 1:(0.01-0.20):(0.005-0.05).

4. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 3, characterized in that: The catalyst A is cuprous oxide and / or cuprous iodide.

5. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 1, characterized in that: In step 2, the pyridine-2-carboxamidine ligand is selected from one or more of 4-methoxypyridine-2-carboxamidine, 5-methoxypyridine-2-carboxamidine, 4-isopropylpyridine-2-carboxamidine, 4-ethylpyridine-2-carboxamidine, and pyridine-2,6-dicarboxamidine, and the molar ratio of 4-bromo-1-naphthol to the ligand is 1:(0.01-0.10).

6. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 1, characterized in that: In the step 2, the molar ratio of 4-bromo-1-naphthol to the additive is 1:(0.10-0.20).

7. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 1, characterized in that: In step 2, the base is selected from one or more of potassium phosphate, cesium carbonate, cesium acetate, sodium hydroxide, sodium tert-butoxide, and potassium tert-butoxide, and the molar ratio of 4-bromo-1-naphthol to the base is 1:(2.50-4.00).

8. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 1, characterized in that: In step 2, the tandem reaction temperature is 130-170° C., and the reaction time is 24-36 hours.

9. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 1, characterized in that: In the step 2, after the cascade reaction is completed, unreacted o-bromoiodobenzene is recovered by vacuum distillation, and water and an extraction solvent are added to the residue cooled to room temperature. The organic layer is subjected to column chromatography, desolventization, and recrystallization to obtain 5-bromonaphtho[1,2-b]benzofuran.

10. The method for preparing 5-bromonaphtho[1,2-b]benzofuran according to claim 9, characterized in that: The extraction solvent is selected from one or more of butyl acetate, ethyl acetate, dichloromethane, tetrahydrofuran, and 1,2-dichloroethane, and the recrystallization solvent is one or more of ethyl acetate, dichloromethane, o-xylene, methanol, ethanol, petroleum ether, n-hexane, tetrahydrofuran, and acetonitrile.

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