Preparation method of halogenated dibenzofuran

Abstract

The invention belongs to the technical field of organic compound preparation, and particularly relates to a preparation method of halogenated dibenzofuran. According to the preparation method provided by the invention, methoxy hydroxylation and ring closing steps are completed in one step, the synthetic route of halogenated dibenzofuran is shortened, the method is green and environment-friendly, the synthetic route of direct ring closing of methoxy is widened, the product yield is increased and is 70% or above, generation of impurities is reduced, the purity is 99.96% or above, and the production cost is reduced. According to the method, harmful reagents such as boron tribromide and dichloromethane are not used, three wastes are greatly reduced, and the process safety is improved. The preparation method provided by the invention has good ecological benefits, social benefits and economic benefits, has conditions for industrial large-scale application, and has a wide development prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound preparation, and specifically relates to a method for preparing halogenated dibenzofuran. Background Art

[0002] Halogenated dibenzofurans are often used to prepare liquid crystal compounds and compositions thereof. The prepared liquid crystal compounds and compositions thereof have high birefringence, a wide liquid crystal phase temperature range, high chemical and optical stability, high compatibility between liquid crystal molecules and optically active doping, low driving voltage, high contrast, and high white light reflectivity, and can improve the reflection efficiency, contrast and reflective wavelength range of reflective liquid crystal displays.

[0003] At present, there are two main methods for preparing halogenated dibenzofuran: the first is to directly halogenate with a halogen element, taking 2-bromodibenzofuran as an example:

[0004]

[0005] Liquid bromine is slowly dripped into a warm solution of dibenzofuran in glacial acetic acid, the reaction mixture is stirred at room temperature and reacted overnight, after the reaction, a yellow solid is filtered and separated, washed with acetic acid and water, and then the crude product is purified by vacuum sublimation to obtain 2-bromodibenzofuran. However, dibenzofurans at unconventional sites are currently more widely used, and this method can only halogenate the 2-position of dibenzofuran, and cannot modify other sites, so only 2-bromodibenzofuran can be prepared, and the process applicability is very poor; and halogens are highly volatile, and long-term and large-scale inhalation of bromine by the human body can cause neurasthenia and endanger the health of operators.

[0006] The second is a preparation method of brominated dibenzofuran disclosed in Chinese patent CN 116496238A, and the main synthesis route is as follows:

[0007]

[0008] This method obtains brominated dibenzofuran through coupling reaction, demethylation reaction and ring-closing reaction, wherein the coupling reaction conditions are mild and there is no strong base or strong stimulation environment. However, its demethylation reaction uses boron tribromide, which is an air-sensitive compound. When used, a large amount of aerosol will emerge, which increases the difficulty of operation and safety hazards. In addition, the concentration of boron tribromide will affect the reaction rate and effect. Too low a concentration may cause the reaction rate to be too slow. Secondly, not all substrates are suitable for demethylation reaction with boron tribromide. In addition, boron tribromide is generally reacted with dichloromethane, which is a restricted or controlled hazardous chemical.

[0009] In summary, the currently commonly used preparation methods of halogenated dibenzofurans have poor applicability and cannot meet the requirements of green development. Summary of the invention

[0010] The purpose of the present invention is to provide a method for preparing halogenated dibenzofuran. The preparation method provided by the present invention has a wide application range and is green and environmentally friendly.

[0011] In order to achieve the above object, the present invention provides the following technical solutions:

[0012] The present invention provides a method for preparing a halogenated dibenzofuran, comprising the following steps:

[0013] Potassium tert-butoxide, an organic solvent and a substrate are mixed to carry out demethylation and ring-closing reactions to obtain halogenated dibenzofuran; the organic solvent comprises one or both of N,N-dimethylformamide and N-methylpyrrolidone; the structure of the substrate is shown in Formula I:

[0014]

[0015] In formula I, R1, R2, R3 and R4 are independently H or halogen, and R5 is benzene, acene or biphenyl.

[0016] Preferably, the molar ratio of potassium tert-butoxide to substrate is 2 to 2.5:1.

[0017] Preferably, the volume ratio of the organic solvent to the substrate is 3.5-4.5:1.

[0018] Preferably, in Formula I, the halogen includes Br or Cl; and the acene includes naphthalene, anthracene or phenanthrene.

[0019] Preferably, the substrate comprises any one of the following compounds:

[0020]

[0021]

[0022] Preferably, the potassium tert-butoxide, the organic solvent and the substrate are mixed as follows: the organic solvent and the potassium tert-butoxide are first mixed to obtain a premix, and the premix and the substrate are second mixed.

[0023] Preferably, the temperature of the first mixing is not higher than 30° C., and the mixing time is 23 to 28 minutes; the first mixing is stirring mixing.

[0024] Preferably, the second mixing temperature is 40-50° C., and the mixing time is 43-48 min.

[0025] Preferably, the demethylation and ring-closure reactions are carried out in a protective atmosphere; the temperature of the demethylation and ring-closure reactions is 40-50° C., and the insulation reaction time is based on the residual amount of the substrate being no higher than 1wt%.

[0026] Preferably, the demethylation and ring-closure reactions further include post-treatment; the post-treatment is: sequentially subjecting the obtained reaction product to crystallization, first solid-liquid separation, crude product purification, first solid drying, pulping, second solid-liquid separation and second solid drying.

[0027] The present invention provides a method for preparing halogenated dibenzofuran. The present invention constructs a reaction system by using potassium tert-butoxide and a specific solvent, utilizes the synergistic effect of potassium tert-butoxide and the specific solvent to promote a demethylation reaction, and then utilizes the alkalinity of potassium tert-butoxide to form a phenolic hydroxyl group, thereby obtaining halogenated dibenzofuran in one step.

[0028] The preparation method provided by the present invention completes the methoxy hydroxylation and ring closure steps in one step, shortens the synthetic route of halogenated dibenzofuran, is green and environmentally friendly, broadens the synthetic route of direct methoxy ring closure, improves the product yield, the yield is above 70%, reduces the generation of impurities, the purity is above 99.96%, and reduces the production cost. The present invention avoids the use of harmful reagents such as boron tribromide and dichloromethane, greatly reduces the three wastes, and improves the process safety. The preparation method provided by the present invention has good ecological benefits, social benefits and economic benefits at the same time, has the conditions for industrial-scale application, and has broad development prospects.

[0029] Furthermore, the demethylation and ring-closing reactions are carried out in a protective atmosphere; the temperature of the demethylation and ring-closing reactions is 40-50° C., and the insulation reaction time is based on the residual amount of the substrate being no more than 1wt%. The preparation method provided by the present invention has mild reaction conditions, further improving the safety, stability and reliability of the process. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0031] Figure 1 The schematic diagram of the preparation method of the halogenated dibenzofuran provided by the present invention;

[0032] Figure 2 This is the NMR spectrum of the halogenated dibenzofuran prepared in Example 1 of the present invention;

[0033] Figure 3 This is the NMR spectrum of the halogenated dibenzofuran prepared in Example 2 of the present invention;

[0034] Figure 4 This is the NMR spectrum of the halogenated dibenzofuran prepared in Example 3 of the present invention. DETAILED DESCRIPTION

[0035] The present invention provides a method for preparing a halogenated dibenzofuran, comprising the following steps:

[0036] Potassium tert-butoxide, an organic solvent and a substrate are mixed to carry out demethylation and ring-closing reactions to obtain halogenated dibenzofuran; the organic solvent comprises one or both of N,N-dimethylformamide and N-methylpyrrolidone; the structure of the substrate is shown in Formula I:

[0037]

[0038] In formula I, R1, R2, R3 and R4 are independently H or halogen, and R5 is benzene, acene or biphenyl.

[0039] In the present invention, in Formula I, the R5 connected The site relationship is preferably adjacent.

[0040] In the present invention, the molar ratio of potassium tert-butoxide to substrate is preferably 2 to 2.5:1, specifically 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1 or 2.5:1.

[0041] In the present invention, the organic solvent is preferably N,N-dimethylformamide (DMF).

[0042] In the present invention, the volume ratio of the organic solvent to the substrate is preferably 3.5 to 4.5:1, specifically 3.5:1, 3.7:1, 4:1, 4.2:1 or 4.5:1.

[0043] In the present invention, in Formula I, the halogen preferably includes Br or Cl; the acene preferably includes naphthalene, anthracene or phenanthrene.

[0044] In the present invention, the substrate preferably includes any one of the following compounds:

[0045]

[0046]

[0047] In the present invention, the demethylation and ring-closure reactions are preferably carried out in a protective atmosphere; the protective atmosphere is preferably nitrogen.

[0048] In the present invention, the potassium tert-butoxide, organic solvent and substrate are preferably mixed in the following manner: the organic solvent and potassium tert-butoxide are mixed (referred to as the first mixing) to obtain a premix, and the premix and substrate are mixed (referred to as the second mixing).

[0049] In the present invention, the temperature of the first mixing is preferably not higher than 30°C, specifically 20°C, 25°C or 30°C, the mixing time is preferably 23 to 28 minutes, specifically 25 minutes; the first mixing is preferably stirring mixing. During the first mixing process, the organic solvent and potassium tert-butoxide will complex to form a complex.

[0050] In the present invention, the second mixing temperature is preferably 40-50° C., specifically 40° C., 42° C., 44° C., 46° C., 48° C. or 50° C., and the mixing time is preferably 43-48 min, specifically 45 min. During the second mixing process, the complex formed by the organic solvent and potassium tert-butoxide will begin to undergo demethylation and ring-closure reactions with the substrate to generate halogenated dibenzofuran.

[0051] In the present invention, the temperature of the demethylation and ring-closure reaction is preferably 40-50°C, specifically 40°C, 42°C, 44°C, 46°C, 48°C or 50°C, and the insulation reaction time (starting from the end of mixing) is preferably based on the residual amount of substrate not higher than 1wt%, preferably 4-14h, specifically 4h, 8h, 12h or 14h.

[0052] In the present invention, the demethylation and ring-closure reactions preferably further include post-treatment; the post-treatment preferably includes: sequentially subjecting the obtained reaction product to crystallization, solid-liquid separation (referred to as the first solid-liquid separation), crude product purification, solid drying (referred to as the first solid drying), pulping, solid-liquid separation (referred to as the second solid-liquid separation) and solid drying (referred to as the second solid drying).

[0053] In the present invention, the crystallization is preferably: the reaction product is added dropwise into water with stirring; the temperature of the water is preferably not higher than 10°C, specifically 1°C, 3°C, 5°C, 7°C or 10°C; the stirring time is preferably 2 to 3h, specifically 2h, 2.3h, 2.7h or 3h.

[0054] In the present invention, the first solid-liquid separation is preferably suction filtration. In the present invention, the crude halogenated dibenzofuran is obtained by suction filtration.

[0055] In the present invention, the crude product purification is preferably performed by mixing the crude halogenated dibenzofuran product with n-heptane (referred to as mixed C) to obtain a mixed solution, passing the mixed solution through a silica gel column, and then rinsing the silica gel column with n-heptane. The present invention obtains a filtrate containing halogenated dibenzofuran by purifying the crude product.

[0056] In the present invention, the temperature of the mixture C is preferably 28-35°C, specifically 28°C, 30°C, 32°C, 34°C or 35°C; the silica gel content in the silica gel column is preferably 30g.

[0057] In the present invention, the first solid drying is preferably vacuum distillation; the temperature of the vacuum distillation is preferably 60-75°C, specifically 60°C, 65°C, 70°C or 75°C, and the vacuum degree is preferably 0.8-1 atmospheres, specifically 0.9 atmospheres.

[0058] In the present invention, the beating is preferably: mixing the dried solid and methanol for beating; the mass ratio of the dried solid to methanol is preferably 1:0.8-1.0, specifically 1:0.8, 1:0.86, 1:0.9, 1:0.95 or 1:1.

[0059] In the present invention, the second solid-liquid separation is preferably suction filtration. The present invention obtains a large amount of solid products by filtration.

[0060] In the present invention, the second solid drying is preferably oven drying; the drying temperature is preferably 50-65°C, specifically 50°C, 55°C, 60°C or 65°C, and the heat preservation and drying time is preferably 12-24h, specifically 12h, 16h, 20h or 24h.

[0061] The preparation method of halogenated dibenzofuran provided by the present invention takes potassium tert-butoxide and DMF as an example, and the reaction mechanism is as follows Figure 1 As shown in the figure: DMF complexes with potassium tert-butoxide, increasing the alkalinity of the oxygen anion of potassium tert-butoxide, allowing it to directly attack the oxygen atom of the methoxy group on the benzene ring and remove the methyl group; at this time, the lonely electron of the cation is donated to DMF (K + ), DMF reaches electrical neutrality and is released to form a theoretical potassium alcohol group (unstable). At this time, the potassium ion is in a free state in the solution and is continuously complexed by DMF, exposing the oxygen anion, which then attacks the F-position carbon atom of the adjacent benzene ring to form a stable furan ring.

[0062] In order to further illustrate the present invention, the scheme of the present invention is described in detail below in conjunction with the accompanying drawings and embodiments, but they should not be understood as limiting the protection scope of the present invention.

[0063] Example 1

[0064] In this example, 1-bromodibenzofuran was prepared, and the reaction scheme is shown below:

[0065]

[0066] This embodiment prepares 1-bromodibenzofuran, comprising the following steps:

[0067] (1) Take a clean, dry 1L four-necked bottle, purge it with nitrogen, add 400mL of DMF (the volume ratio to the substrate is 4:1), then add 71.28g of potassium tert-butoxide (the molar ratio to the substrate is 2:1), and stir at room temperature (≤30°C) for 28 minutes to obtain a complex.

[0068] (2) Adding 100 g of the substrate A11 compound to the complex in batches, controlling the reaction temperature during the batch addition process to be 50° C. and the addition time to be 48 min. After the batch addition is completed, keeping the reaction warm for 12 h, taking samples for HPLC analysis, and terminating the reaction until the content of the A11 compound is ≤1% to obtain a reaction solution.

[0069] (3) 800 mL of water was added to a 2 L bottle, and the temperature was lowered to 5° C. The reaction solution was added dropwise to the water to precipitate the material. During this process, the temperature of the reaction solution was controlled to be ≤10° C. The crystallization was stirred for 2 h, and the mixture was filtered to obtain a crude product of compound A12.

[0070] (4) Take a clean, dry 2L three-necked flask, add 1L of n-heptane, then add the crude A12 compound, completely dissolve at 28°C, pass through a silica gel column (silica gel: 30g), rinse the silica gel column with 200mL of n-heptane, and distill the obtained filtrate to dryness at 60°C under reduced pressure (vacuum degree is 0.8 atmospheres) to obtain a solid.

[0071] (5) A clean, dry 200 mL three-necked flask was added with the solid and 70 mL of methanol for slurrying. A large amount of solid was precipitated. The solid was collected by suction filtration and dried at 65 °C for 12 h to obtain A12 compound with a purity of 99.97% and a mass of 64.32 g as a white solid. The yield was 73.1%.

[0072] Example 2

[0073] In this example, 1-chloro-8-phenyldibenzo[b,d]furan was prepared, and the reaction scheme is shown below:

[0074]

[0075] This embodiment prepares 1-chloro-8-phenyldibenzo[b,d]furan, comprising the following steps:

[0076] (1) Take a clean, dry 1L four-necked bottle, purge it with nitrogen, add 400mL of DMF (the volume ratio to the substrate is 4:1), then add 71.75g ​​of potassium tert-butoxide (the molar ratio to the substrate is 2:1), and stir at room temperature (≤30°C) for 23 minutes to obtain a complex.

[0077] (2) Adding 100 g of the substrate A21 compound to the complex in batches, controlling the reaction temperature during the batch addition process to be 40° C., and the addition time to be 43 min. After the batch addition is completed, the reaction is kept warm for 12 h, and a sample is taken for HPLC measurement. When the content of the A21 compound is ≤1%, the reaction is terminated to obtain a reaction solution.

[0078] (3) 800 mL of water was added to a 2 L bottle, and the temperature was lowered to 5° C. The reaction solution was added dropwise to the water to precipitate the material. During this process, the temperature of the reaction solution was controlled to be ≤10° C. The crystallization was stirred for 2 h, and the mixture was filtered to obtain a crude product of compound A22.

[0079] (4) Take a clean, dry 2L three-necked flask, add 1L of n-heptane, then add the crude A22 compound, completely dissolve at 35°C, pass through a silica gel column (silica gel: 30g), rinse the silica gel column with 200mL of n-heptane, and distill the obtained filtrate to dryness at 65°C under reduced pressure (vacuum degree is 0.9 atmospheres) to obtain a solid.

[0080] (5) A clean, dry 200 mL three-necked flask was added with the solid and 70 mL of methanol for slurrying. A large amount of solid was precipitated. The solid was collected by suction filtration and dried at 50 °C for 24 h to obtain A22 compound with a purity of 99.96% and a mass of 64.25 g as a white solid. The yield was 72.1%.

[0081] Example 3

[0082] This example prepares 3-bromonaphtho[2,3-b]benzofuran, and the reaction scheme is as follows:

[0083]

[0084] This embodiment prepares 3-bromonaphtho[2,3-b]benzofuran, comprising the following steps:

[0085] (1) Take a clean, dry 1L four-necked bottle, purge it with nitrogen, add 400mL of DMF (the volume ratio to the substrate is 4:1), then add 67.76g of potassium tert-butoxide (the molar ratio to the substrate is 2:1), and stir at room temperature (≤30°C) for 25 minutes to obtain a complex.

[0086] (2) Adding 100 g of the substrate A31 compound to the complex in batches, controlling the reaction temperature during the batch addition process to be 45° C. and the addition time to be 45 min. After the batch addition is completed, keeping the reaction warm for 4 h, taking samples for HPLC analysis, and terminating the reaction when the content of the A31 compound is ≤1% to obtain a reaction solution.

[0087] (3) 800 mL of water was added to a 2 L bottle, the temperature was lowered to 5°C, and the reaction solution was added dropwise to the water to precipitate the material. During this process, the temperature of the reaction solution was controlled to be ≤10°C. The crystallization was stirred for 2 h and filtered to obtain a crude product of compound A32.

[0088] (4) Take a clean, dry 2L three-necked flask, add 1L of n-heptane, then add the crude A32 compound, completely dissolve at 32°C, pass through a silica gel column (silica gel: 30g), rinse the silica gel column with 200mL of n-heptane, and distill the obtained filtrate to dryness at 75°C under reduced pressure (vacuum degree is 1 atmosphere) to obtain a solid.

[0089] (5) A clean, dry 200 mL three-necked flask was added with the solid and 70 mL of methanol for slurrying. A large amount of solid was precipitated. The solid was collected by suction filtration and dried at 50 °C for 24 h to obtain A32 compound with a purity of 99.97% and a mass of 64.81 g as a white solid. The yield was 72.23%.

[0090] The halogenated dibenzofurans of Examples 1 to 3 were subjected to nuclear magnetic resonance detection, and the results were as follows: Figures 2 to 4 As shown. Figures 2 to 4 It can be seen that the present invention successfully synthesizes various halogenated dibenzofurans.

[0091] It can be seen from the above examples that the preparation method provided by the present invention is green and environmentally friendly, broadens the synthetic route of direct methoxy ring closure, improves the product yield, the yield is above 70%, the purity is above 99.96%, and avoids the use of harmful reagents such as boron tribromide and dichloromethane.

[0092] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing a halogenated dibenzofuran, characterized in that: The following steps are involved: Potassium tert-butoxide, an organic solvent and a substrate are mixed to carry out demethylation and ring-closing reactions to obtain halogenated dibenzofuran; the organic solvent comprises one or both of N,N-dimethylformamide and N-methylpyrrolidone; the structure of the substrate is shown in Formula I: In formula I, R1, R2, R3 and R4 are independently H or halogen, and R5 is benzene, acene or biphenyl.

2. The preparation method according to claim 1, characterized in that: The molar ratio of the potassium tert-butoxide to the substrate is 2 to 2.5:

1.

3. The preparation method according to claim 1 or 2, characterized in that: The volume ratio of the organic solvent to the substrate is 3.5-4.5:

1.

4. The preparation method according to claim 1, characterized in that: In Formula I, the halogen includes Br or Cl; and the acene includes naphthalene, anthracene or phenanthrene.

5. The preparation method according to claim 1 or 4, characterized in that: The substrate includes any one of the following compounds:

6. The preparation method according to claim 1, characterized in that: The potassium tert-butoxide, the organic solvent and the substrate are mixed as follows: the organic solvent and the potassium tert-butoxide are first mixed to obtain a premix, and the premix and the substrate are secondly mixed.

7. The preparation method according to claim 6, characterized in that: The temperature of the first mixing is not higher than 30° C., and the mixing time is 23 to 28 minutes; the first mixing is stirring mixing.

8. The preparation method according to claim 6 or 7, characterized in that: The second mixing temperature is 40-50° C., and the mixing time is 43-48 min.

9. The preparation method according to claim 1, characterized in that: The demethylation and ring-closure reactions are carried out in a protective atmosphere; the temperature of the demethylation and ring-closure reactions is 40-50° C., and the insulation reaction time is based on the residual amount of the substrate being no higher than 1wt%.

10. The preparation method according to claim 1 or 9, characterized in that: The demethylation and ring-closure reactions also include post-treatment; the post-treatment is: sequentially subjecting the obtained reaction product to crystallization, first solid-liquid separation, crude product purification, first solid drying, pulping, second solid-liquid separation and second solid drying.

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