Preparation method of halogenated carbazole
The synthesis steps of bromocarbazole are simplified by the one-pot method, the complexity and low yield problems in the prior art are solved, and the preparation of 2-bromocarbazole with high purity and high yield is achieved, which is suitable for industrial production.
Patent Information
- Application Number
- CN202510458758.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-14
- Publication Date
- 2025-07-11
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
In the prior art, the method of synthesizing single-substituted bromocarbazole is complex and has low yields, making it difficult to achieve industrial mass production.
By using the one-pot method of coupling first and then cyclic bonding, 1-bromo-3-fluoro-4-iodobenzene and 2-aminobenzene boric acid were reacted in the presence of an inorganic base and a palladium catalyst by the Suzuki-Miyaura coupling reaction, and 2-bromocarbazole was then prepared by the ring-combination reaction.
The synthesis steps are simplified, impurity generation is reduced, yield is improved, and it is suitable for industrial production.
Smart Images
Figure CN120289348A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of new materials, and particularly relates to a preparation method of halogenated carbazole. Background Art
[0002] Carbazole and its derivatives have unique electrical, electrochemical, and photophysical properties, so they can be used as good hole-transporting materials, and carbazole derivatives are widely used in the field of polymer materials. The continuous reports of luminescent materials formed by various substituents have proved the importance of carbazole and its derivatives in the field of photoconductive materials. In addition, its anion recognition has important applications in the fields of environment, biology, and medical research. Moreover, it also has antibacterial, anti-tumor, anti-Alzheimer's, anti-diabetic and other effects clinically. Brominated carbazole is an important intermediate for organic photoconductive materials and medicines. For example, 3-bromocarbazole is an intermediate for synthesizing the photoconductor sensitizer bis(6-bromo-9-ethyl-carbazol-3-yl)tolyliodonium salt, and 3,6-dibromocarbazole is an intermediate for the immunomodulator 3,6-dibromocarbazole-N-acetic acid, etc. People use the strong photosensitization ability and low melting point of brominated carbazole to make many organic photoconductive materials.
[0003] There are various methods for synthesizing brominated carbazole, but there are not many methods to obtain single-substituted brominated carbazole. The existing synthesis methods are as follows: 1) The method of mixing potassium bromide and potassium bromate generally obtains a mixture of carbazoles with different degrees of substitution; 2) The diazonium salt method and the chloranil dehydrogenation method. It has been reported that 3-bromocarbazole was prepared by these two methods, and the disadvantages are many reaction steps and low final yield; 3) The sulfonation method. The difficulty of preparing carbazole-3-sulfonic acid in this method has exceeded the difficulty of bromination, and it is the most complex among all the methods for synthesizing brominated carbazole; 4) The NBS method. The reaction time of this method is long. When preparing polysubstituted carbazole, a polysubstituted mixture is obtained; 5) The direct bromination method is the simplest method. This method can prepare carbazoles with different substitutions, but the reaction conditions need to be strictly controlled. Therefore, it is necessary to develop a preparation method of brominated carbazole that is simple, has few impurities, generates less waste, and is convenient for industrial mass production. Summary of the Invention
[0004] To solve the deficiencies mentioned in the above background art, the purpose of the present invention is to provide a preparation method of halogenated carbazole. 2-bromocarbazole is prepared by a one-pot method of first coupling and then cyclizing, with few impurities, a simple overall preparation method, less waste generation, and is convenient for industrial mass production.
[0005] The purpose of the present invention can be achieved by the following technical solutions: A preparation method of halogenated carbazole, the halogenated carbazole is 2-bromocarbazole, and its preparation method includes the following steps: Step 1: Mix raw material 1-bromo-3-fluoro-4-iodobenzene, 2-aminophenylboronic acid, inorganic base, dimethyl sulfoxide, and tetrakis(triphenylphosphine)palladium, and carry out the Suzuki-Miyaura coupling reaction: Step 2: Then continue to raise the temperature to carry out the ring-closure reaction to obtain 2-bromocarbazole; .
[0006] Preferably, the inorganic base is one or more of sodium hydroxide, potassium hydroxide, sodium tert-butoxide, and potassium tert-butoxide.
[0007] Preferably, the molar ratio of raw material 1-bromo-3-fluoro-4-iodobenzene to 2-aminophenylboronic acid is 1:1 to 1.1.
[0008] Preferably, the molar ratio of raw material 1-bromo-3-fluoro-4-iodobenzene to the inorganic base is 1:2 to 2.2.
[0009] Preferably, the molar ratio of raw material 1-bromo-3-fluoro-4-iodobenzene to tetrakis(triphenylphosphine)palladium is 1:0.003 to 0.005.
[0010] Preferably, in Step 1, the reaction temperature of the coupling reaction is 80-85 °C, and the reaction time is 3-5 h.
[0011] Preferably, in Step 2, the reaction temperature of the ring-closure reaction is 105-110 °C, and the reaction time is 10-12 h.
[0012] Advantages of the present invention: The preparation method of 2-bromocarbazole in this application is a one-pot method, which is synthesized by the method of amino cyclization to prepare a carbazole ring. Compared with the prior art (first coupling, then treating the intermediate, and then carrying out nitro cyclization reaction), the preparation method of the present invention has a lower reaction difficulty, uses a weaker catalyst, has a better selectivity in the coupling reaction, and almost no multi-coupling intermediate impurities are generated under the conditions of controlling the palladium catalyst and the base, so the yield is higher. At the same time, the preparation method of the present invention is convenient to operate, adopts a one-step reaction, does not need to treat the intermediate, and after the coupling reaction is completed, the temperature can be continuously raised to carry out the second-step cyclization reaction. Description of the Drawings
[0013] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, for those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative efforts.
[0014] Figure 1 It is the nuclear magnetic characterization result of 2-bromocarbazole prepared in Example 3 of the present invention; Figure 2This is the gas chromatography - mass spectrometry characterization result of 2 - bromocarbazole prepared in Example 3 of the present invention. Detailed implementation manners
[0015] Next, in combination with the embodiments of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.
[0016] Example 1 A preparation method of a halogenated carbazole, the halogenated carbazole is 2 - bromocarbazole, and its preparation method includes the following steps: Step 1: Add 200 g of raw material 1 - bromo - 3 - fluoro - 4 - iodobenzene into a 2 - L three - necked flask, add 1.5 L of dimethyl sulfoxide, start stirring, then add 91 g of raw material 2 - aminophenylboronic acid, 74.6 g of potassium hydroxide, add 2.3 g of tetrakis(triphenylphosphine)palladium under nitrogen protection, raise the temperature of the reaction solution to 80 °C, and keep stirring for 3 h; Step 2: Raise the temperature of the reaction solution to 110 °C, keep stirring for 11 h, quench the reaction solution by adding 0.6 L of water, then extract the product with 1.2 L of ethyl acetate, separate the liquid, concentrate the organic phase, then add 1.2 L of n - heptane and stir for 1 h, filter by suction to obtain a light yellow crude product, and then recrystallize with 110 ml of toluene and 50 ml of n - heptane to obtain 127 g of white solid 2 - bromocarbazole, HPLC = 99.7%, and the yield is 77%.
[0017] Example 2 A preparation method of a halogenated carbazole, the halogenated carbazole is 2 - bromocarbazole, and its preparation method includes the following steps: Step 1: Add 150 g of raw material 1 - bromo - 3 - fluoro - 4 - iodobenzene into a 2 - L three - necked flask, add 1.2 L of dimethyl sulfoxide, start stirring, then add 68 g of raw material 2 - aminophenylboronic acid, 40 g of potassium hydroxide, add 1.73 g of tetrakis(triphenylphosphine)palladium under nitrogen protection, raise the temperature of the reaction solution to 85 °C, and keep stirring for 5 h; Step 2: Raise the temperature of the reaction solution to 105 °C, keep stirring for 12 h, quench the reaction solution by adding 0.4 L of water, then extract the product with 0.8 L of ethyl acetate, separate the liquid, concentrate the organic phase, then add 0.8 L of n - heptane and stir for 1 h, filter by suction to obtain a light yellow crude product, and then recrystallize with 90 ml of toluene and 50 ml of n - heptane to obtain 99 g of white solid 2 - bromocarbazole, HPLC = 99.6%, and the yield is 80%.
[0018] Example 3 A preparation method of a halogenated carbazole, the halogenated carbazole is 2 - bromocarbazole, and its preparation method includes the following steps: Step 1: Add 175 g of raw material 1-bromo-3-fluoro-4-iodobenzene into a 2 L three-necked flask, add 1.35 L of dimethyl sulfoxide, start stirring, then add 80 g of raw material 2-aminophenylboronic acid and 57.2 g of potassium hydroxide. Under nitrogen protection, add 2.02 g of tetrakis(triphenylphosphine)palladium. Heat the reaction solution to 82 °C and stir at a constant temperature for 4 h. Step 2: Heat the reaction solution to 108 °C and stir at a constant temperature for 12 h. Quench the reaction solution by adding 0.5 L of water, then extract the product with 1 L of ethyl acetate. Separate the layers, concentrate the organic phase, then add 1 L of n-heptane and stir for 1 h. Filter by suction to obtain a pale yellow crude product. Then add 100 ml of toluene and 50 ml of n-heptane for recrystallization to obtain 113 g of white solid 2-bromocarbazole, HPLC = 99.8%, and the yield is 82%.
[0019] Perform NMR characterization and GC-MS characterization on the 2-bromocarbazole prepared in Example 3, and the results are as Figure 1 、 Figure 2 shown. It can be seen from Figure 1 that the number of H atoms and the relative chemical shift of the product are highly consistent with those of 2-bromocarbazole. It can be seen from Figure 2 that the molecular weight and fragment molecular weight of the product are highly consistent with those of 2-bromocarbazole.
[0020] Comparative Example 1 Comparative Example 1 uses the current mainstream method for preparing 2-bromocarbazole. First, perform coupling, and then synthesize the carbazole ring through nitro ring closure. The specific synthesis route is as follows: .
[0021] The above method for preparing 2-bromocarbazole includes the following steps: Step 1: Add 138 g of o-nitroaniline, 188.4 g of bromobenzene, and 1 L of dichloromethane into a 2 L reaction flask. Cool down to 0 °C, slowly dropwise add 91.5 g of tert-butyl nitrite, control the reaction temperature at 0 - 5 °C for 30 min, then slowly heat the mixture in the reaction flask to reflux and react for 5 h. Then add 0.5 L of water, let it stand for separation. Wash the dichloromethane layer with 100 ml of 10% hydrochloric acid. Concentrate the organic phase under reduced pressure to dryness, then add 1 L of ethanol, heat to reflux, and finally cool down to 20 °C. After filtration and drying, obtain white solid 4-bromo-2'-nitrobiphenyl. Step 2: Add 500 g of triethyl phosphite and 202 g of 4-bromo-2'-nitrobiphenyl obtained in Step 1 into a 2 L reaction flask, heat to 160 °C, react for 2 h, then cool to 20 °C, add 300 ml of concentrated hydrochloric acid with a concentration of 35%, heat to reflux and react for 1 h, then cool to 30 °C to precipitate a white solid. Finally, after filtration and drying, 136.6 g of white solid 2-bromocarbazole is obtained, HPLC = 99.9%, and the yield is 67.6%.
[0022] Compared with Comparative Example 1, Examples 1 to 3 show that by measuring the content of 2-bromocarbazole in the product by high performance liquid chromatography, the purity of 2-bromocarbazole prepared by the preparation method of halogenated carbazole of the present invention is not much different from that of the existing mainstream methods, but the yield is greatly increased, and the operation is more convenient at the same time.
[0023] In the description of this specification, the description with reference to terms such as "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.
[0024] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments, and the above embodiments and the description in the specification only illustrate the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed.
Claims
1. A method for preparing a halogenated carbazole, characterized in that, The halogenated carbazole is 2-bromocarbazole, and its preparation method comprises the following steps: Step 1: Mix raw material 1-bromo-3-fluoro-4-iodobenzene, 2-aminophenylboronic acid, inorganic base, dimethyl sulfoxide, and tetrakis(triphenylphosphine)palladium for a Suzuki-Miyaura coupling reaction; Step 2: Then continue to raise the temperature for a cyclization reaction to obtain 2-bromocarbazole; 。 2. The preparation method of the halogenated carbazole according to claim 1, wherein The inorganic base is one or more of sodium hydroxide, potassium hydroxide, sodium tert-butoxide, and potassium tert-butoxide.
3. The preparation method of the halogenated carbazole according to claim 1, characterized in that, The molar ratio of the raw material 1-bromo-3-fluoro-4-iodobenzene to 2-aminophenylboronic acid is 1:1 to 1.
1.
4. The preparation method of the halogenated carbazole according to claim 1, wherein, The molar ratio of the raw material 1-bromo-3-fluoro-4-iodobenzene to the inorganic base is 1:2 to 2.
2.
5. The preparation method of the halogenated carbazole according to claim 1, wherein, The molar ratio of the raw material 1-bromo-3-fluoro-4-iodobenzene to tetrakis(triphenylphosphine)palladium is 1:0.003 to 0.
005.
6. The preparation method of the halogenated carbazole according to claim 1, wherein In Step 1, the reaction temperature of the coupling reaction is 80 to 85 °C, and the reaction time is 3 to 5 h.
7. The preparation method of the halogenated carbazole according to claim 1, characterized in that, In Step 2, the reaction temperature of the cyclization reaction is 105 to 110 °C, and the reaction time is 10 to 12 h.