A process for the preparation of 2-bromo-9-phenyl-9H-carbazole

Abstract

The application belongs to the technical field of synthesis of organic light-emitting material intermediates, and particularly relates to a preparation method of 2-bromo-9-phenyl-9H-carbazole, which comprises the following steps: under inert gas, 2-nitroaniline and a bromine reagent are subjected to an electrophilic aromatic substitution reaction to generate an intermediate A-1; under acidic conditions, sodium nitrite and the intermediate A-1 are subjected to a diazotization reaction to generate a diazonium salt, and then under alkaline conditions, the diazonium salt is coupled with benzene to generate an intermediate A-2; the intermediate A-2 and triphenylphosphine are subjected to a reaction to generate a carbene, and then the carbene is subjected to a ring-closing reaction to generate an intermediate A-3; and the intermediate A-3 and bromobenzene are subjected to an Ullmann reaction to obtain 2-bromo-9-phenyl-9H-carbazole. The new method has the advantages of cheap and readily available raw materials, simple process, high yield, high continuous degree of reaction, short production cycle, low production cost and suitability for industrial production.

Description

Technical Field

[0001] This invention specifically relates to a method for preparing 2-bromo-9-phenyl-9H-carbazole, an intermediate for organic light-emitting materials, and belongs to the field of synthesis technology of organic light-emitting material intermediates. Background Technology

[0002] Organic light-emitting diodes (OLEDs) are a novel display technology. Due to their advantages such as self-illumination, wide viewing angle, high resolution, vibrant colors, fast response speed, low power consumption, good thermal stability, and thinness, flexibility, and bendability, they have been widely used in the display field in recent years, especially in small-sized screens such as smartwatches, mobile phones, automotive dashboards, tablets, televisions, and VR wearable devices. OLEDs are multilayered structures, with organic light-emitting materials being the key core component. Phosphorescent materials, which serve as the main light-emitting materials, mostly contain carbazole groups. Carbazole and its derivatives are important nitrogen-containing aromatic heterocyclic compounds. Due to their large conjugated system and strong intramolecular electron transfer, they possess excellent photoelectric properties and charge transport capabilities. Among these, light-emitting materials containing N-phenylcarbazole structural units are the most abundant organic compounds in phosphorescent materials, and 2-bromo-9-phenyl-9H-carbazole is an important substrate for synthesizing this type of intermediate and material.

[0003] The existing methods for synthesizing 2-bromo-9-phenyl-9H-carbazole have many technical problems, such as low yield, expensive raw materials leading to high costs, and the generation of impurities during the reaction process, making purification difficult, all of which are not conducive to industrial production.

[0004] Currently, the synthesis of 2-bromo-9-phenyl-9H-carbazole mainly employs the following methods:

[0005] Patent application CN103703003A discloses a synthetic route using 2-nitroiodobenzene and 4-bromophenylboronic acid as starting materials. First, 2-nitro-4-bromobiphenyl is obtained via Suzuki coupling, then cyclized by reflux with triethyl phosphite as solvent to obtain 2-bromocarbazole. Finally, 2-bromocarbazole and iodobenzene undergo an Ullmam reaction under cuprous iodide catalysis to yield 2-bromo-9-phenyl-9H-carbazole. The starting materials and precious metal catalysts used in this route are expensive, resulting in high costs. The yield of 2-bromocarbazole synthesized by the triethyl phosphite method is too low, only 44.38%, leading to an overall yield of only 31.4%, which is not conducive to industrial mass production. Furthermore, the Ullmam reaction between 2-bromocarbazole and iodobenzene is prone to side reactions such as iodobromine ion exchange, which leads to the formation of the byproduct 2-iodo-9-phenyl-9H-carbazole, and the byproduct 2'-bromo-9-phenyl-9H-2,9'-bicarbazole formed by the Ullmam reaction with 2-bromocarbazole. This increases the separation cost of 2-bromo-9-phenyl-9H-carbazole and makes purification difficult.

[0006] Therefore, it is of great significance to develop a new method for synthesizing 2-bromo-9-phenyl-9H-carbazole that is low-cost, simple in process, high in yield, highly continuous in reaction, short in production cycle, and suitable for industrial production. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides a method for preparing the organic light-emitting material intermediate 2-bromo-9-phenyl-9H-carbazole. The preparation method uses inexpensive and readily available raw materials, has a simple process, high yield, high degree of continuous reaction, short production cycle, and low production cost, making it more suitable for industrial production.

[0008] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a method for preparing 2-bromo-9-phenyl-9H-carbazole, wherein the preparation method is as follows:

[0009] Under S1 and inert gas conditions, 2-nitroaniline undergoes an electrophilic aromatic substitution reaction with a brominating agent to generate intermediate A-1, which is 4-bromo-2-nitroaniline.

[0010] S2. Under inert gas conditions, sodium nitrite reacts with intermediate A-1 in an acidic environment to form a diazonium salt. Then, under alkaline conditions and with the help of a catalyst, a 4-bromo-2-nitrobenzene free radical is generated, which is then coupled with benzene to form intermediate A-2, which is 4-bromo-2-nitrobenzene.

[0011] Under S3 and inert gas conditions, intermediate A-2 reacts with triphenylphosphine to form carbene, which then cyclizes to form intermediate A-3, which is 2-bromocarbazole.

[0012] Under S4 and an inert gas atmosphere, intermediate A-3 undergoes a Ullmann reaction with bromobenzene to yield 2-bromo-9-phenyl-9H-carbazole.

[0013] Furthermore, after step S2, intermediate A-2 is extracted using bromobenzene, and the bromobenzene solution containing intermediate A-2 directly enters step S3. The reaction solution after step S3 directly enters step S4.

[0014] Furthermore, in step S1, the reaction temperature is 10-20℃ and the reaction time is 1-3h.

[0015] Furthermore, in step S1, the brominating agent is at least one of NBS, bromine, and dibromohydantoin, wherein the brominating agent is added to the reaction in batches, and the molar ratio of 2-nitroaniline to the brominating agent is 1:(1.0-1.2).

[0016] Furthermore, in step S2, the diazotization reaction is carried out at a temperature of 0-5℃ for 2-4 hours, and the coupling reaction is carried out at a temperature of 5-20℃ for 1.5-3 hours.

[0017] Furthermore, in step S2, the acidic conditions are provided using an inorganic acid, and the alkaline conditions have a pH of 8-9.

[0018] Furthermore, in step S2, the catalyst is at least one of copper powder, cuprous chloride, and cuprous oxide; in step S4, the Ullman reaction catalytic system uses cuprous oxide, crown ether, and potassium carbonate working together.

[0019] Further, in step S2, the molar ratio of intermediate A-1, acid, sodium nitrite, benzene, and catalyst is 1:(2-6):(1-1.2):(2-8):(0.1-0.5); in step S3, the molar ratio of intermediate A-2 and triphenylphosphine is 1:(2-5); in step S4, the molar ratio of intermediate A-3:cuprous oxide:crown ether:potassium carbonate is 1:(0.05-0.3):(0.05-0.3):(1-3), and the ratio of intermediate A-3 to bromobenzene is 1g:(4-10)mL.

[0020] Furthermore, in step S3, the reaction process is a reflux reaction with a reaction time of 10-14 h; in step S4, the Ullmann reaction is a reflux reaction with a reaction time of 5-8 h.

[0021] Furthermore, in step S1, the solvent used in the reaction system is at least one of tetrahydrofuran, dichloromethane, N,N-dimethylformamide, and acetic acid; in step S2, the solvent used in the reaction system is a mixed solvent of benzene and water; in step S3, the solvent used in the reaction system is bromobenzene; and in step S4, the solvent used in the reaction system is bromobenzene.

[0022] The beneficial effects of this invention are:

[0023] (1) The preparation method described in this invention is to synthesize the intermediate 2-bromo-9-phenyl-9H-carbazole by benzene radical method. This method avoids the use of precious metal palladium catalyst and can effectively reduce the cost of raw materials.

[0024] (2) The preparation method described in this invention uses inexpensive and readily available 2-nitroaniline as the starting material. The intermediate steps hardly require purification, the intermediate product loss is small, the product yield is high, and the total yield can reach more than 75%, thereby greatly reducing the production cost.

[0025] (3) The preparation method described in this invention achieves efficient utilization of solvents. The solvent benzene used in the second step reaction is both a raw material and a reaction solvent, and can be recycled after the reaction is completed, with a high recovery rate, even reaching 85%; the solvent bromobenzene used in the post-treatment of the second step reaction is both a solvent in the third step reaction and a solvent and raw material in the fourth step reaction, and can also be recycled after the reaction is completed, with a recovery rate of over 91%. This can greatly reduce the generation of waste liquid and reduce the cost of using solvents.

[0026] (4) The preparation method described in this invention achieves continuous reaction. The first step reaction only requires simple water precipitation and filtration before being fed into the next step. The organic phase after water washing in the second step reaction does not require further treatment and can be used for the third step reaction. After the third step reaction is completed, no post-treatment is required; only cooling and the addition of other raw materials are needed to carry out the fourth step reaction. This greatly simplifies the production process, shortens the production cycle, and is more conducive to industrial production.

[0027] (5) In the last step of the preparation method described in this invention, bromobenzene is used instead of iodobenzene as the raw material and solvent for the Ullmam reaction, which can effectively avoid side reactions such as iodine-bromine ion exchange during the reaction process, thereby greatly reducing the generation of impurities, reducing the difficulty of product purification, and further achieving the goal of saving costs. Attached Figure Description

[0028] Figure 1 The 1H NMR spectrum of 2-bromo-9-phenyl-9H-carbazole in Example 1;

[0029] Figure 2 The image shows the liquid chromatogram of 2-bromo-9-phenyl-9H-carbazole in Example 1. Detailed Implementation

[0030] The specific embodiments of the present invention will be described in detail below. The present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the invention. Therefore, the present invention is not limited to the specific embodiments disclosed.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used is for describing particular embodiments only and is not intended to limit the invention.

[0032] A method for preparing 2-bromo-9-phenyl-9H-carbazole, wherein the preparation method comprises:

[0033] Under S1 and inert gas conditions, 2-nitroaniline undergoes an electrophilic aromatic substitution reaction with a brominating agent to generate intermediate A-1, which is 4-bromo-2-nitroaniline.

[0034] S2. Under inert gas conditions, sodium nitrite reacts with intermediate A-1 in an acidic environment to form a diazonium salt. Then, under alkaline conditions and with the help of a catalyst, a 4-bromo-2-nitrobenzene free radical is generated, which is then coupled with benzene to form intermediate A-2, which is 4-bromo-2-nitrobenzene.

[0035] Under S3 and inert gas conditions, intermediate A-2 reacts with triphenylphosphine to form carbene, which then cyclizes to form intermediate A-3, which is 2-bromocarbazole.

[0036] Under S4 and an inert gas atmosphere, intermediate A-3 undergoes a Ullmann reaction with bromobenzene to yield 2-bromo-9-phenyl-9H-carbazole.

[0037] The process principle of the preparation method of the 2-bromo-9-phenyl-9H-carbazole is as follows:

[0038] .

[0039] Specifically, after step S2, intermediate A-2 is extracted using bromobenzene. The bromobenzene solution containing intermediate A-2 directly enters step S3. The reaction solution after S3 does not require post-processing and directly enters step S4.

[0040] Specifically, in step S1, the solvent used in the reaction system is at least one of tetrahydrofuran, dichloromethane, N,N-dimethylformamide, and acetic acid.

[0041] More specifically, in this embodiment of the invention, the solvent used in step S1 is tetrahydrofuran.

[0042] Specifically, in step S2, the solvent used in the reaction system is a mixture of benzene and water, wherein in this embodiment of the invention, the amount of water is twice the mass of concentrated sulfuric acid; in step S3, the solvent used in the reaction system is bromobenzene; in step S4, the solvent used in the reaction system is bromobenzene.

[0043] Specifically, in step S1, the reaction temperature is 10-20℃ and the reaction time is 1-3h, preferably 2h.

[0044] Specifically, in step S1, the brominating agent is at least one of NBS, bromine, and dibromohydantoin. The brominating agent is added to the reaction in batches, and the molar ratio of 2-nitroaniline to the brominating agent is 1:(1.0-1.2), preferably 1:1.1.

[0045] More specifically, in this embodiment of the invention, the brominating reagent is added to the reaction in 10 batches, with a total addition time of 3 hours. The brominating reagent used is NBS.

[0046] More specifically, the specific operation of step S1 is as follows: under nitrogen protection, 2-nitroaniline and tetrahydrofuran are added to a three-necked flask. After stirring and dissolving at room temperature, the temperature is lowered to 10-20℃. The brominating reagent is added to the reaction flask in batches at a rate of once every 18 minutes, for a total addition time of 8 hours. After the addition is completed, the temperature is kept at 10-20℃ for reaction. After the reaction is completed, the reaction solution is poured into 900mL of ice water to settle, filtered and dried to obtain the intermediate.

[0047] Specifically, in step S2, the diazotization reaction is carried out at a temperature of 0-5℃ for 2-4 hours, and the coupling reaction is carried out at a temperature of 5-20℃ for 1.5-3 hours.

[0048] Specifically, in step S2, the acidic conditions are provided using inorganic acids, and the alkaline conditions have a pH of 8-9.

[0049] More specifically, the acid used in the embodiments of the present invention is concentrated sulfuric acid (mass fraction of 98%), and the alkaline conditions are adjusted by sodium carbonate.

[0050] Specifically, in step S2, the catalyst is at least one of copper powder, cuprous chloride, and cuprous oxide, preferably cuprous oxide.

[0051] Specifically, in step S2, the molar ratio of intermediate A-1, acid, sodium nitrite, benzene, and catalyst is 1:(2-6):(1-1.2):(2-8):(0.1-0.5), preferably 1:4:1.1:5.6:0.2.

[0052] More specifically, step S2 is performed as follows: Under nitrogen protection, intermediate A-1, benzene, and water are added to a three-necked flask. Concentrated sulfuric acid is added dropwise while stirring. After the concentrated sulfuric acid is added, the mixture is stirred at room temperature until it is completely dissolved. The temperature is then lowered to 0-5°C, and sodium nitrite aqueous solution (sodium nitrite dissolved in water, with a mass concentration of 20%) is added dropwise. After the addition is complete, the reaction is timed. Cuprous oxide is added to the system, and sodium carbonate is slowly added at 5-20°C to adjust the pH of the system to 8-9. The reaction is then maintained at this temperature. Post-reaction procedures are as follows: Benzoate is recovered under reduced pressure, and then bromobenzene is added and stirred for 30 minutes. The insoluble matter is filtered out, and the filtrate is collected and allowed to stand for separation. The organic phase is collected, washed with water until neutral, heated to reflux to remove low-boiling substances, and then cooled to room temperature to obtain a bromobenzene solution of intermediate A-2, which is directly added to step S3.

[0053] Specifically, in step S3, the molar ratio of intermediate A-2 to triphenylphosphine is 1:(2-5), preferably 1:2.3; the reaction process is a reflux reaction, the reaction time is 10-14h, after the reaction is completed, the temperature is lowered to room temperature, and no post-treatment is required for the reaction solution, which is then directly added to step S4.

[0054] Specifically, in step S4, the Ullman reaction catalytic system uses cuprous oxide, crown ether, and potassium carbonate working together. The molar ratio of intermediate A-3:cuprous oxide:crown ether:potassium carbonate is 1:(0.05-0.3):(0.05-0.3):(1-3), preferably 1:0.15:0.15:1.5. The ratio of intermediate A-3 to bromobenzene is 1g:(4-10)mL, preferably 1g:6mL.

[0055] Specifically, in step S4, the Ullman reaction is a reflux reaction with a reaction time of 5-8 hours.

[0056] Specifically, the molar ratio of anhydrous zinc chloride to intermediate A-3 used in the post-treatment is 1:(0.5-2), with 1:0.5 being preferred.

[0057] More specifically, after the reaction in step S4 is completed, the post-processing operation is as follows: (1) Cool the reaction solution to -10-0℃, keep it warm and stir, filter to obtain filter cake and filtrate; (2) Wash the filter cake with bromobenzene, and dry the filter cake under reduced pressure, and collect the bromobenzene washing liquid; (3) Desolvate the filtrate collected in steps (1) and (2) under reduced pressure to recover bromobenzene and obtain crude product 1 of concentrate; (4) Dissolve the crude product 1 obtained in (3) under reflux with a mixed solution of ethanol and toluene, cool it to 35-45℃, add anhydrous zinc chloride, keep it warm and stir; (5) Filter, collect the filtrate, desolvate the filtrate under reduced pressure to obtain crude product 2; (6) Recrystallize crude product 2 with toluene to obtain the target product.

[0058] In this embodiment of the invention, the volume ratio of ethanol to toluene in step (4) above is 3:1. However, this does not constitute a limitation on the technical solution of the present invention, as long as the crude product 1 can be refluxed and dissolved.

[0059] Example 1

[0060] Synthesis of S1, 4-bromo-2-nitroaniline (intermediate A-1):

[0061] Under nitrogen protection, 1.09 mol (150 g) of 2-nitroaniline and 450 mL of tetrahydrofuran were added to a three-necked flask. After stirring and dissolving at room temperature, the mixture was cooled to 15 °C. 1.20 mol (212.33 g) of NBS was added to the reaction flask in 10 batches over 3 hours at a rate of once every 18 minutes. After the addition was complete, the mixture was kept at 15 °C for 2 hours. The reaction solution was poured into 900 mL of ice water to settle, filtered, and dried. The wet weight was 280 g. Based on the dry weight being equal to the theoretical weight, intermediate A-1 was obtained: 1.09 mol (235.7 g), with a yield of 100% and a purity of 96%. The product did not require drying and was directly used in the next step.

[0062] Synthesis of S2, 4-bromo-2-nitrobenzene (intermediate A-2):

[0063] Under nitrogen protection, 1.09 mol (235.7 g) of intermediate A-1, 544 mL of benzene, and 872 mL of water were added to a three-necked flask. 436 g of concentrated sulfuric acid was added dropwise with stirring. After the addition was complete, the mixture was stirred at room temperature until completely dissolved. The temperature was lowered to 3°C, and an aqueous solution of sodium nitrite (1.2 mol (82.4 g) of sodium nitrite dissolved in 330 mL of water) was added dropwise. After the addition was complete, the reaction was timed for 3 hours. 0.22 mol (31.1 g) of cuprous oxide was then added to the system. Sodium carbonate was slowly added at 10°C to adjust the pH of the system to 8. -9, keep the reaction at the temperature for 2 hours, desolventize under reduced pressure to recover 380 mL of solvent benzene, with a benzene recovery rate of 85%, then add 900 mL of bromobenzene and stir for 30 minutes. Filter the insoluble matter, collect the filtrate, let it stand and separate the liquid, collect the organic phase, wash the organic phase with water until neutral, heat to reflux to remove low-boiling substances, and cool to room temperature. Calculated by theoretical weight, a bromobenzene solution of 1.09 mol (302.1 g) of intermediate A-2 is obtained, with a yield of 100% and a purity of 92%.

[0064] Synthesis of S3, 2-bromocarbazole (intermediate A-3):

[0065] Under nitrogen protection, a bromobenzene solution containing 1.09 mol (302.1 g) of intermediate A-2 and 2.5 mol (655.3 g) of triphenylphosphine were added to a three-necked flask. The mixture was heated to reflux for 12 h and then cooled to room temperature. Based on theoretical weight, 1.09 mol (267.3 g) of intermediate A-3 was obtained with a yield of 100% and a purity of 90%. The reaction solution was not treated and was directly added to S4.

[0066] S4. Synthesis of the target compound (2-bromo-9-phenyl-9H-carbazole):

[0067] Under nitrogen protection, 0.163 mol (23.3 g) of cuprous oxide, 1.635 mol (225.5 g) of potassium carbonate, 0.163 mol (43.1 g) of crown ether, and 900 mL of bromobenzene were added to the reaction solution of intermediate A-3. The mixture was heated to reflux and the water was separated for 6 h.

[0068] Post-processing: (1) Cool the reaction solution to -10-0℃, keep it warm and stir for 4h, filter to obtain filter cake and filtrate; (2) Wash the filter cake with 600mL bromobenzene, and dry the filter cake under reduced pressure, and collect the bromobenzene washing liquid; (3) Desolvate the filtrate collected in steps (1) and (2) under reduced pressure to recover 2100mL of bromobenzene, with a bromobenzene recovery rate of 91.7%, and obtain crude product 1 of concentrate; (4) Use 1933mL ethanol and 644mL methanol to treat crude product 1 obtained in (3). The mixed solution of benzene was heated and refluxed to dissolve it. After cooling to 35-45℃, 0.545mol (74g) of anhydrous zinc chloride was added, and the mixture was stirred for 4h. (5) The mixture was filtered, the filtrate was collected, and the filtrate was dried under reduced pressure to obtain crude product 2. (6) Crude product 2 was recrystallized with toluene to obtain 0.84mol (269.5g) of the target compound (2-bromo-9-phenyl-9H-carbazole), with a yield of 77% and a purity of 99.5%. The detection data of liquid chromatography are as follows, and the detection spectrum is as follows. Figure 2 As shown. The 1H NMR spectrum is as follows. Figure 1 As shown, hydrogen spectrum analysis: 1 H NMR (CDCl3, 500 MHz, Chloroform- d ) δ8.16 (s, 1H), 8.11 (s, 1H), 7.85 (s, 1H), 7.50 (d, J = 6.6 Hz, 2H), 7.39 (s,1H), 7.25 – 7.29 (m, 3H), 7.19 – 7.15 (m, 2H), 7.15 – 7.10 (m, 1H).

[0069] Table 1. Liquid Chromatography Detection Data

[0070]

[0071] Example 2

[0072] Synthesis of S1, 4-bromo-2-nitroaniline (intermediate A-1):

[0073] Under nitrogen protection, 1.09 mol (150 g) of 2-nitroaniline and 450 mL of tetrahydrofuran were added to a three-necked flask. After stirring and dissolving at room temperature, the mixture was cooled to 10 °C. 1.09 mol (192.86 g) of NBS was added to the reaction flask in 10 batches over 3 hours at a rate of once every 18 minutes. After the addition was complete, the mixture was kept at 10 °C for 1 hour. The reaction solution was poured into 900 mL of ice water to settle, filtered, and dried. The wet weight was 280 g. Based on the dry weight being equal to the theoretical weight, 1.09 mol (235.7 g) of intermediate A-1 was obtained, with a yield of 100% and a purity of 97%. The product did not require drying and was directly used in the next step.

[0074] Synthesis of S2, 4-bromo-2-nitrobenzene (intermediate A-2):

[0075] Under nitrogen protection, 1.09 mol (235.7 g) of intermediate A-1, 194 mL of benzene, and 436 mL of water were added to a three-necked flask. 218 g of concentrated sulfuric acid was added dropwise with stirring. After the addition was complete, the mixture was stirred at room temperature until dissolved. The temperature was lowered to 0°C, and sodium nitrite aqueous solution (1.09 mol (75.19 g) of sodium nitrite dissolved in 300 mL of water) was added dropwise. After the addition was complete, the reaction was timed for 4 hours. 0.11 mol (7 g) of copper powder was added to the system. Sodium carbonate was slowly added at 5°C to adjust the pH of the system to 8-9. The reaction was maintained at this temperature. After 3 hours, 83 mL of solvent benzene was recovered under reduced pressure, with a benzene recovery rate of 85.6%. Then, 900 mL of bromobenzene was added and stirred for 30 minutes. The insoluble matter was filtered off, and the filtrate was collected and allowed to stand for separation. The organic phase was collected, washed with water until neutral, heated to reflux to remove low-boiling substances, and cooled to room temperature to obtain 1.08 mol (299 g) and 1.09 mol (302.1 g) of intermediate A-2, with a yield of 100% and a purity of 92%. This was directly used in the next step.

[0076] Synthesis of S3, 2-bromocarbazole (intermediate A-3):

[0077] Under nitrogen protection, a bromobenzene solution containing 1.08 mol (299 g) of intermediate A-2 and 2.16 mol (566.1 g) of triphenylphosphine were added to a three-necked flask. The mixture was heated to reflux for 14 h and then cooled to room temperature to obtain 1.08 mol (264.5 g) of intermediate A-3 with a yield of 100% and a purity of 90%. The reaction solution was not treated and was directly added to S4.

[0078] S4. Synthesis of the target compound (2-bromo-9-phenyl-9H-carbazole):

[0079] Under nitrogen protection, 0.054 mol (7.73 g) of cuprous oxide, 1.08 mol (148.9 g) of potassium carbonate, 0.054 mol (14.28 g) of crown ether, and 800 mL of bromobenzene were added to the reaction solution of intermediate A-3. The mixture was heated to reflux and the water was separated and reacted for 5 h.

[0080] Post-processing: (1) Cool the reaction solution to -10-0℃, keep it warm and stir for 4h, filter to obtain filter cake and filtrate; (2) Rinse the filter cake with 260mL of bromobenzene, and dry the filter cake under reduced pressure, and collect the bromobenzene eluent; (3) Desolvate the filtrate collected in steps (1) and (2) under reduced pressure to recover 1680mL of bromobenzene, with a bromobenzene recovery rate of 91.1%, and obtain crude product 1 of concentrate; (4) Use 1920mL of ethyl acetate to desolvate the crude product 1 obtained in (3). The mixture of alcohol and 640 mL of toluene was heated and refluxed to dissolve the alcohol. After cooling to 35-45 °C, 1.08 mol (147 g) of anhydrous zinc chloride was added and stirred for 4 h. (5) The mixture was filtered, the filtrate was collected, and the filtrate was dried under reduced pressure to obtain crude product 2. (6) Crude product 2 was recrystallized with toluene to obtain 0.82 mol (263.2 g) of the target compound (2-bromo-9-phenyl-9H-carbazole), with a yield of 76% and a purity of 98.6%. 1 H NMR (CDCl3, 500 MHz, Chloroform- d ) δ 8.16 (s, 1H), 8.11 (s, 1H), 7.85 (s, 1H),7.50 (d, J = 6.6 Hz,2H), 7.39 (s, 1H), 7.25 – 7.29 (m, 3H), 7.19 – 7.15 (m, 2H), 7.15 – 7.10 (m,1H).

[0081] Example 3

[0082] Synthesis of S1, 4-bromo-2-nitroaniline (intermediate A-1):

[0083] Under nitrogen protection, 1.09 mol (150 g) of 2-nitroaniline and 450 mL of tetrahydrofuran were added to a three-necked flask. After stirring and dissolving at room temperature, the mixture was cooled to 20 °C. 0.654 mol (187 g) of dibromohydantoin was added to the reaction flask in 10 batches over 3 hours at a rate of once every 18 minutes. After the addition was complete, the mixture was kept at 20 °C for 2 hours. The reaction solution was poured into 900 mL of ice water to settle, filtered, and dried. The wet weight was 280 g. Based on the dry weight being equal to the theoretical weight, 1.09 mol (235.7 g) of intermediate A-1 was obtained, with a yield of 100% and a purity of 96%. The product did not require drying and was directly used in the next step.

[0084] Synthesis of S2, 4-bromo-2-nitrobenzene (intermediate A-2):

[0085] Under nitrogen protection, 1.09 mol (235.7 g) of intermediate A-1, 777 mL of benzene, and 1308 mL of water were added to a three-necked flask. 654 g of concentrated sulfuric acid was added dropwise with stirring. After the addition was complete, the mixture was stirred at room temperature until completely dissolved. The temperature was lowered to 5°C, and an aqueous solution of sodium nitrite (1.308 mol (90.23 g) of sodium nitrite dissolved in 361 mL of water) was added dropwise. After the addition was complete, the reaction was timed for 2 hours. 0.55 mol (54.5 g) of cuprous chloride was added to the system, and sodium carbonate was slowly added at 20°C to adjust the pH to 8. 9. After reacting at a constant temperature for 1.5 h, 580 mL of solvent benzene was recovered under reduced pressure, with a benzene recovery rate of 85.3%. Then, 900 mL of bromobenzene was added and stirred for 30 min. The insoluble matter was filtered out, and the filtrate was collected and allowed to stand for separation. The organic phase was collected and washed with water until neutral. The organic phase was heated to reflux to remove low-boiling substances. The separated mixed solution was collected and cooled to room temperature to obtain 1.09 mol (302.1 g) of intermediate A-2 with a yield of 100% and a purity of 92%. This was directly added to the next step.

[0086] Synthesis of S3, 2-bromocarbazole (intermediate A-3):

[0087] Under nitrogen protection, a bromobenzene solution containing 1.09 mol (302.1 g) of intermediate A-2 and 5.45 mol (1428.4 g) of triphenylphosphine were added to a three-necked flask. The mixture was heated to reflux for 10 h and then cooled to room temperature to obtain 1.09 mol (267.3 g) of intermediate A-3 with a yield of 100% and a purity of 89%. The reaction solution was not treated and was directly added to S4.

[0088] S4. Synthesis of the target compound (2-bromo-9-phenyl-9H-carbazole):

[0089] Under nitrogen protection, 0.33 mol (47.2 g) of cuprous oxide, 3.27 mol (451 g) of potassium carbonate, 0.327 mol (86.47 g) of crown ether, and 1500 mL of bromobenzene were added to the reaction solution of intermediate A-3. The mixture was heated to reflux and the water was separated and reacted for 8 h.

[0090] Post-processing: (1) Cool the reaction solution to -10-0℃, keep it warm and stir for 4h, filter to obtain filter cake and filtrate; (2) Rinse the filter cake with 1100mL of bromobenzene, and dry the filter cake under reduced pressure, and collect the bromobenzene eluent; (3) Desolvate the filtrate collected in steps (1) and (2) under reduced pressure to recover 3100mL of bromobenzene, with a bromobenzene recovery rate of 91.6%, and obtain crude product 1 of concentrate; (4) Use 1950mL of ethyl acetate to desolvate the crude product 1 obtained in (3). The mixture of alcohol and 650 mL of toluene was heated and refluxed to dissolve the alcohol. After cooling to 35-45 °C, 2.18 mol (297 g) of anhydrous zinc chloride was added and stirred for 4 h. (5) The mixture was filtered, the filtrate was collected, and the filtrate was dried under reduced pressure to obtain crude product 2. (6) Crude product 2 was recrystallized with toluene to obtain 0.85 mol (272.9 g) of the target compound (2-bromo-9-phenyl-9H-carbazole), with a yield of 78% and a purity of 98.8%. 1 H NMR (CDCl3, 500 MHz, Chloroform- d ) δ 8.16 (s, 1H), 8.11 (s, 1H), 7.85 (s, 1H),7.50 (d, J = 6.6 Hz,2H), 7.39 (s, 1H), 7.25 – 7.29 (m, 3H), 7.19 – 7.15 (m, 2H), 7.15 – 7.10 (m,1H).

[0091] Comparative Example 1

[0092] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that in this comparative example, the amount of NBS used in step S1 was reduced, and 0.98 mol (173.40 g) of NBS was added, with 2-nitroaniline:NBS = 1:0.9 (lower than the amount of NBS specified in this invention).

[0093] In this comparative example, after the reaction in step S1, the purity of 4-bromo-2-nitroaniline (intermediate A-1) was detected to be 87%. After proceeding with steps S2, S3 and S4, 0.75 mol (240.75 g) of the target compound (2-bromo-9-phenyl-9H-carbazole) was finally obtained in S4, with a yield of 69% and a purity of 95%.

[0094] The results from Comparative Example 1 and Example 1 show that in step S1, reducing the amount of NBS significantly reduced the yield of the target compound (2-bromo-9-phenyl-9H-carbazole). This is because the reduction in the amount of NBS leads to incomplete reaction of the raw materials in step S1, ultimately resulting in a decrease in the yield of the target product.

[0095] Comparative Example 2

[0096] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that: in this comparative example, the amount of NBS added in step S1 was 1.635 mol (289.30 g) of NBS, and the ratio of 2-nitroaniline to NBS was 1:1.5 (higher than the amount of NBS specified in this invention).

[0097] In this comparative example, after the reaction in step S1, the purity of 4-bromo-2-nitroaniline (intermediate A-1) was detected to be 79%; the final yield of the target compound (2-bromo-9-phenyl-9H-carbazole) was 0.654 mol (209.93 g), with a yield of 60% and a purity of 94%.

[0098] The results from Comparative Example 2 and Example 1 show that in step S1, increasing the amount of NBS significantly reduced the purity of 4-bromo-2-nitroaniline, and also reduced the yield and purity of the final product 2-bromo-9-phenyl-9H-carbazole. This is because increasing the amount of NBS leads to the generation of dibromo-containing impurities during the reaction in step S1, which ultimately reduces the yield of the target product and affects its purity.

[0099] Comparative Example 3

[0100] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that the reaction temperature in step S1 was reduced in Comparative Example 3, and the reaction was carried out at 5°C.

[0101] In this comparative example, after increasing the reaction time from 2 h to 4 h in step S1, the starting material reacted completely. After the reaction in step S1 was completed, the purity of 4-bromo-2-nitroaniline (intermediate A-1) was detected to be 96%. Finally, 0.84 mol (269.5 g) of the target compound (2-bromo-9-phenyl-9H-carbazole) was obtained, with a yield of 77% and a purity of 99%.

[0102] The results from Comparative Example 3 and Example 1 show that in step S1, lowering the temperature has no effect on the yield and purity of 4-bromo-2-nitroaniline, but it will prolong the reaction time of S1 and affect the production efficiency. This is because lowering the temperature will slow down the reaction rate, thereby prolonging the reaction.

[0103] Comparative Example 4

[0104] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that the reaction temperature of S1 was increased in Comparative Example 4, and the reaction was carried out at 25°C.

[0105] In this comparative example, after the reaction in step S1, the purity of 4-bromo-2-nitroaniline (intermediate A-1) was detected to be 83%; the target compound (2-bromo-9-phenyl-9H-carbazole) was finally obtained in 0.71 mol (227.91 g), with a yield of 65% and a purity of 94%.

[0106] The results from Comparative Example 4 and Example 1 show that increasing the temperature in step S1 affects the purity of 4-bromo-2-nitroaniline. Specifically, increasing the reaction temperature decreases the purity, and also reduces the yield and purity of the final product, 2-bromo-9-phenyl-9H-carbazole. This is because increasing the temperature leads to the formation of dibromo-containing impurities during the reaction in step S1, resulting in a decrease in the final product yield and affecting its purity.

[0107] Comparative Example 5

[0108] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that in Comparative Example 5, the diazotization reaction temperature was increased during step S2, and the diazotization reaction was controlled at 10°C.

[0109] In this comparative example, after the reaction in step S2, the purity of 4-bromo-2-nitrobiphenyl (intermediate A-2) was detected to be 85%; the final yield of the target compound (2-bromo-9-phenyl-9H-carbazole) was 0.763 mol (244.92 g), with a yield of 70% and a purity of 97%.

[0110] The results from Comparative Example 5 and Example 1 show that increasing the reaction temperature of the diazotization reaction leads to a decrease in the purity of 4-bromo-2-nitrobiphenyl, and a decrease in the yield and purity of the final product 2-bromo-9-phenyl-9H-carbazole. This is because increasing the temperature causes the obtained diazonium salt to decompose, thereby affecting the product yield.

[0111] Comparative Example 6

[0112] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that in Comparative Example 6, the coupling reaction temperature was increased during step S2, and the coupling reaction was controlled at 30°C.

[0113] In this comparative example, after the reaction in step S2, the purity of 4-bromo-2-nitrobiphenyl (intermediate A-2) was detected to be 79%; the final yield of the target compound (2-bromo-9-phenyl-9H-carbazole) was 0.71 mol (227.91 g), with a yield of 65% and a purity of 95%.

[0114] The results from Comparative Example 6 and Example 1 show that increasing the reaction temperature of the coupling reaction leads to a decrease in the yield of 4-bromo-2-nitrobiphenyl, and a decrease in the yield and purity of the final product 2-bromo-9-phenyl-9H-carbazole. This is because increasing the coupling temperature causes the obtained diazonium salt to decompose. Under higher temperature conditions, the decomposition rate of the diazonium salt will be accelerated, which will affect the product yield.

[0115] Comparative Example 7

[0116] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that in step S2 of Comparative Example 7, sodium carbonate was used to adjust the pH of the system to 5-6 (below the pH range for coupling reaction defined in this invention).

[0117] In this comparative example, the coupling reaction required incubation for 6 hours to complete. After the reaction in step S2, the purity of 4-bromo-2-nitrobiphenyl (intermediate A-2) was detected to be 76%. Finally, 0.68 mol (218.28 g) of the target compound (2-bromo-9-phenyl-9H-carbazole) was obtained, with a yield of 62% and a purity of 94%.

[0118] The results from Comparative Example 7 and Example 1 show that during the coupling reaction, an acidic system leads to a decrease in the reaction rate of step S2, resulting in a decrease in the yield and purity of the final product 2-bromo-9-phenyl-9H-carbazole. This is because if the system is acidic during the coupling reaction, the reaction rate will be significantly reduced under acidic conditions, and the reaction will be incomplete, thus affecting the product yield.

[0119] Comparative Example 8

[0120] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 1, except that in step S2 of Comparative Example 8, sodium carbonate was used to adjust the pH of the system to 10-11 (higher than the pH range for coupling reactions defined in this invention).

[0121] In this comparative example, after the reaction in step S2, the purity of 4-bromo-2-nitrobiphenyl (intermediate A-2) was detected to be 87%, and the target compound (2-bromo-9-phenyl-9H-carbazole) was finally obtained in 0.779 mol (250.2 g), with a yield of 71.5% and a purity of 95.8%.

[0122] The results from Comparative Example 8 and Example 1 show that if the system is too alkaline during the coupling reaction, the purity of 4-bromo-2-nitrobiphenyl will decrease, and the yield and purity of the final product 2-bromo-9-phenyl-9H-carbazole will also decrease. This is because an alkaline system will cause the diazonium salt to decompose, which in turn will affect the product yield.

[0123] Comparative Example 9

[0124] The target compound (2-bromo-9-phenyl-9H-carbazole) was prepared using the same method as in Example 3, except that more concentrated sulfuric acid was added in step S2 of Comparative Example 9. The amount of concentrated sulfuric acid added in Comparative Example 9 was 872g, and the molar ratio of intermediate A-1 to concentrated sulfuric acid was 1:8.

[0125] In this comparative example, the purity of 4-bromo-2-nitrobenzene (intermediate A-2) was 92% after the reaction in step S2. However, more sodium carbonate was needed to adjust the pH of the system. The final yield of the target compound (2-bromo-9-phenyl-9H-carbazole) was 0.85 mol (272.9 g), with a yield of 78% and a purity of 98.8%.

[0126] The results from Comparative Example 9 and Example 3 show that adding more concentrated sulfuric acid does not affect the yield and purity of the product, but it requires more sodium carbonate to adjust the pH of the system in the subsequent reaction process, resulting in resource waste and increased costs.

[0127] Comparative Example 10

[0128] The target compound (2-bromo-9-phenyl-9H-carbazole) was treated using the same method as in Example 1, except that in Comparative Example 10, NBS was added to the reaction flask in 10 batches every 10 minutes in S1.

[0129] In this comparative example, after the reaction in step S1, the purity of 4-bromo-2-nitroaniline (intermediate A-1) was detected to be 95%; the target compound (2-bromo-9-phenyl-9H-carbazole) was finally obtained in 0.763 mol (244.92 g), with a yield of 70% and a purity of 93%.

[0130] The results from Comparative Example 10 and Example 1 show that adding NBS too quickly reduces the purity of 4-bromo-2-nitrobiphenyl, and consequently reduces the yield and purity of the final product 2-bromo-9-phenyl-9H-carbazole. This is because adding NBS too quickly can cause side reactions, ultimately leading to a decrease in product yield and affecting product purity.

[0131] In summary, the yield and purity data of the intermediates and target products in the examples and comparative examples are shown in Table 2.

[0132] Table 2 Yield and purity data from the examples and comparative examples

[0133]

[0134] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are exhaustively listed. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0135] For those skilled in the art, various modifications and improvements can be made without departing from the concept of the present invention, and these modifications and improvements are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the appended claims.

Claims

1. A method for preparing 2-bromo-9-phenyl-9H-carbazole, characterized in that, The preparation method is as follows: S1. Under inert gas, 2-nitroaniline reacts with a brominating reagent in an electrophilic aromatic substitution reaction to generate intermediate A-1, which is 4-bromo-2-nitroaniline. The reaction temperature is 10-20℃, and the brominating reagent is added to the reaction in batches. The molar ratio of 2-nitroaniline to the brominating reagent is 1:(1.0-1.2). S2. Under inert gas conditions and in acidic conditions, sodium nitrite reacts with intermediate A-1 in a diazotization reaction to form a diazonium salt. Then, under alkaline conditions (pH 8-9), a 4-bromo-2-nitrobenzene free radical is generated under the action of a catalyst. This free radical is then coupled with benzene to form intermediate A-2, which is 4-bromo-2-nitrobenzene. The diazotization reaction temperature is 0-5℃, the coupling reaction temperature is 5-20℃, and the molar ratio of intermediate A-1, acid, sodium nitrite, benzene, and catalyst is 1:(2-6):(1-1.2):(2-8):(0.1-0.5). Under S3 and inert gas conditions, intermediate A-2 reacts with triphenylphosphine to generate carbene, which then cyclizes to generate intermediate A-3, which is 2-bromocarbazole. The molar ratio of intermediate A-2 to triphenylphosphine is 1:(2-5). S4. Under inert gas, intermediate A-3 undergoes a Ullmann reaction with bromobenzene to give 2-bromo-9-phenyl-9H-carbazole. The catalytic system uses cuprous oxide, crown ether, and potassium carbonate in combination. The molar ratio of intermediate A-3:cuprous oxide:crown ether:potassium carbonate is 1:(0.05-0.3):(0.05-0.3):(1-3), and the ratio of intermediate A-3 to bromobenzene is 1g:(4-10)mL. After step S2, intermediate A-2 is extracted with bromobenzene. The bromobenzene solution containing intermediate A-2 directly enters step S3. The reaction solution after step S3 directly enters step S4. In step S1, the solvent used in the reaction system is tetrahydrofuran; In step S4, the solvent used in the reaction system is bromobenzene; The process principle of the preparation method of the 2-bromo-9-phenyl-9H-carbazole is as follows: 。 2. The method for preparing 2-bromo-9-phenyl-9H-carbazole according to claim 1, characterized in that, In step S1, the reaction time is 1-3 hours.

3. The method for preparing 2-bromo-9-phenyl-9H-carbazole according to claim 1, characterized in that, In step S1, the brominating agent is at least one of NBS, bromine, and dibromohydantoin.

4. The method for preparing 2-bromo-9-phenyl-9H-carbazole according to claim 1, characterized in that, In step S2, the reaction time is 2-4 hours, and the coupling reaction time is 1.5-3 hours.

5. The method for preparing 2-bromo-9-phenyl-9H-carbazole according to claim 1, characterized in that, In step S2, the acidic conditions are provided using an inorganic acid.

6. The method for preparing 2-bromo-9-phenyl-9H-carbazole according to claim 1, characterized in that, In step S2, the catalyst is at least one of copper powder, cuprous chloride, and cuprous oxide.

7. The method for preparing 2-bromo-9-phenyl-9H-carbazole according to claim 1, characterized in that, In step S3, the reaction process is a reflux reaction; in step S4, the Ullman reaction is a reflux reaction.

Images