CN112521328A - Preparation method of 3-bromocarbazole - Google Patents
Preparation method of 3-bromocarbazole Download PDFInfo
- Publication number
- CN112521328A CN112521328A CN202011243774.9A CN202011243774A CN112521328A CN 112521328 A CN112521328 A CN 112521328A CN 202011243774 A CN202011243774 A CN 202011243774A CN 112521328 A CN112521328 A CN 112521328A
- Authority
- CN
- China
- Prior art keywords
- bromocarbazole
- carbazole
- added
- reaction
- organic solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a preparation method of 3-bromocarbazole, belonging to the technical field of organic synthesis. The method uses carbazole as raw material, adopts organic solvent containing stabilizer 2, 6-di-tert-butyl-p-cresol, adds phase transfer catalyst, and uses Br‑/O2 2‑Synthesizing 3-bromocarbazole through oxidation bromination reaction in the system. The invention adopts a phase transfer catalyst in Br‑/O2 2‑In the system, by controlling the solubility of carbazole in an organic phase-aqueous phase solution, the defects of poor carbazole solubility, long reaction time, incomplete conversion and the like in the existing bromination method are effectively overcome, so that the purity and the yield of 3-bromocarbazole are remarkably improved; meanwhile, the purposes of reducing cost and protecting environment are achieved, and feasible technical support is provided for large-scale industrial production.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of high-purity 3-bromocarbazole.
Background
Bromocarbazole has strong photosensitization ability and low melting point, and is an important intermediate of organic photoelectric materials and medicines. For example, 3-bromocarbazole is an intermediate for synthesizing a sensitizer for photoconductors, such as bis (6-bromo-9-ethyl-carbazol-3-yl) tolyl iodonium salt, and is also useful as a raw material for synthesizing an intermediate for organic photoelectric materials, such as carbazole-3-boronic acid and N-phenylcarbazole-3-boronic acid; the 3, 6-dibromocarbazole is an intermediate for synthesizing an immunomodulator, namely 3, 6-dibromocarbazole-N-acetic acid. Direct bromination reaction of C-H bonds at positions C3 and C6 of carbazole is the simplest and most economical method for obtaining 3-and 6-brominated carbazole. The C3 and C6 positions of carbazole with the same electron cloud density are likely to have electrophilic bromination reaction, and the method for synthesizing dibrominated carbazole and polybrominated carbazole is relatively mature; there are not many methods for obtaining high-purity 3-bromocarbazole due to problems such as bromination selectivity.
The most commonly used brominating reagents such as bromine, NBS, dibromohydantoin and the like in the direct bromination reaction of carbazole C3 have the defects of high cost, low atom utilization rate, serious pollution, poor selectivity, complex post-treatment and the like. In 2015, Jianghui et al published an article named "Green synthetic New Process research of 3-bromocarbazole" in Guangzhou chemistry (2015, volume 40, No. 1, pages 37-41), summarizing the five existing synthetic methods of 3-bromocarbazole (i.e.: potassium bromide and potassium bromate mixing method; di-azoate method and chloranil dehydrogenation method; tri-sulfonation method; tetra-NBS method; and tetra-direct bromination method) and pointing out the disadvantages of various methods. Acetyl is introduced at the 9-position of carbazole as a protective group, and high-purity 3-bromocarbazole is prepared through bromination and deacetylation. Although the method obtains high-purity 3-bromocarbazole with high yield (the total yield is 83.8%), the method has the disadvantages of long steps, complex operation and high production cost, and the bromination process still has the possibility of selectivity problems and does not have atom economy.
Therefore, it is necessary to improve the existing synthesis method of 3-bromocarbazole, and on the basis of ensuring high product purity and high yield, a synthesis method with high atom utilization rate, green economy, simple operation steps and post-treatment process and easy industrialization is provided, so as to meet the increasing demand of various fields of the market for the product.
Disclosure of Invention
1. Problems to be solved
Aiming at the problems of poor solubility and bromination reaction selectivity of the existing carbazole, the invention provides a method for synthesizing 3-bromocarbazole through direct bromination reaction of carbazole, and provides a novel method for synthesizing 3-bromocarbazole through carbazole oxidative bromination reaction, which has mild reaction conditions, high selectivity, high atom utilization rate, environmental friendliness and is green, economical and environment-friendly.
2. Technical scheme
In order to solve the problems, the technical scheme adopted by the invention is as follows:
the preparation method of the high-purity 3-bromocarbazole takes carbazole as a raw material, and the carbazole is reacted in Br-/O2 2-Synthesizing 3-bromocarbazole through oxidation bromination reaction under the system. Compared with the reported method, the method has the characteristics of low cost of a bromine source system, high atom utilization rate, high selectivity, simple post-treatment purification process and environmental friendliness, and provides a new method for obtaining high-purity 3-bromocarbazole.
Compared with carbazole, the electron cloud density at the C6 position of 3-bromocarbazole is reduced, and the bromination reaction activity of the carbazole is reduced; the generation of 3, 6-dibromo carbazole can be effectively controlled by strictly controlling the conditions such as bromine source equivalent, reaction temperature and the like. Meanwhile, the carbazole has poor solubility in most organic solvents, and the carbazole cannot be completely dissolved and participates in bromination reaction, so that the carbazole and the product 3-bromocarbazole are included, and the conversion rate of the carbazole is influenced; if a large amount of carbazole remains in the reaction, it is difficult to remove it by recrystallization or the like due to poor solubility thereof, and it is difficult to obtain high-purity 3-bromocarbazole; if a large excess of bromine source is added, the conversion rate of carbazole can be improved, but the generation of corresponding 3, 6-dibromo carbazole is increased to influence the selectivity of reaction; therefore, the key to obtain high-purity 3-bromocarbazole is to solve the problems of carbazole solubility, bromination reaction selectivity and the like.
Carbazole in the inventionIn Br-/O2 2-The method for synthesizing high-purity 3-bromocarbazole through oxidation bromination reaction under the system solves the problem that the solubility of carbazole, the control of the equivalent number of bromine sources and the like are critical to the reaction. The small amount of phase transfer catalyst in the invention can greatly accelerate the reaction speed and well solve the problem that the carbazole is included in the product due to poor solubility and can not be completely converted; the reaction temperature, the dosage of brominating agent/oxidant, the addition speed and other conditions are strictly controlled, so that the selectivity of carbazole oxybromination reaction can be improved, and the generation of 3, 6-dibromocarbazole can be reduced; lower reaction temperatures and small amounts of BHT can greatly reduce the acidic hydrolysis and oxidative decomposition of the solvent.
The reaction formula for synthesizing 3-bromocarbazole through carbazole oxybromination reaction is shown as follows:
the invention relates to a method for preparing high-purity 3-bromocarbazole by oxidizing bromination reaction of carbazole, which comprises the following steps:
under the condition of room temperature, carbazole is dissolved in an organic solvent (containing stabilizer BHT) and is uniformly stirred, a small amount of phase transfer catalyst is added, the temperature of a reaction system is controlled to be 0 ℃, brominating agent is added in batches, the reaction system is stirred for 25-35 minutes at low temperature after the brominating agent is added, quantitative oxidant is added in batches at the constant temperature of 0 ℃, the system continues to react for 6-10 hours under the condition of 0-20 ℃ after the adding is finished, and the stirring is stopped when the conversion rate of carbazole is detected to be more than or equal to 99.5% by a liquid phase. And after the reaction is finished, adding 10-15% of sodium carbonate aqueous solution to enable the reaction system to be neutral, extracting an organic layer, washing with water for at least 3 times, washing with inorganic layer ethyl acetate for at least 3 times, performing rotary evaporation to recover the organic solvent to obtain a crude product, and performing repeated recrystallization, purification and vacuum drying on the crude product to obtain the high-purity 3-bromocarbazole.
Preferably, the organic solvent is selected from one or a mixed solution of dichloromethane, 1, 2-dichloroethane, tetrahydrofuran, 2-methyltetrahydrofuran, methoxycyclopentane, dioxane, N-dimethylformamide, dimethyl sulfoxide and the like.
Preferably, the phase transfer catalyst is a PTC compound selected from polyethylene glycol, 18-crown-6, tetrabutylammonium bromide or benzyltriethylammonium chloride.
Preferably, the brominating agent is selected from hydrobromic acid, potassium bromide, sodium bromide, ammonium bromide or lithium bromide.
Preferably, the oxidant is selected from hydrogen peroxide, sodium peroxide, potassium persulfate or magnesium peroxide.
Preferably, the mass fraction ratio of the stabilizer BHT to the organic solvent is (0.01-1.00%): 1, the molar ratio of the brominating agent to the carbazole is (1.05-1.15): 1, the molar ratio of the oxidant to the carbazole is (1.05-1.20): 1, the molar ratio of the phase transfer catalyst to the carbazole is (0.01-5.00): 1.
preferably, the solvent for recrystallization is selected from one or a mixed solution of ethanol, ethyl acetate, dichloromethane, xylene, tetrahydrofuran, and the like.
Preferably, the structure of the stabilizer 2, 6-di-tert-butyl-p-cresol (BHT) is as follows:
BHT was chosen as the stabilizer: (1) BHT is a stabilizer for common organic solvents, especially tetrahydrofuran as the solvent; (2) the product has the advantages of simple structure, strong stability, good alcohol solubility, easy removal, no influence on product quality, low price, economic benefit and environmental protection, and can be used as a food additive.
3. Advantageous effects
Compared with the prior art, the invention has the beneficial effects that:
(1) the invention adopts a phase transfer catalyst in Br-/O2 2-In the system, by controlling the solubility of carbazole in an organic phase-aqueous phase solution, the defects of poor carbazole solubility, long reaction time, incomplete conversion and the like in the existing bromination method are effectively overcome, so that the purity and the yield of 3-bromocarbazole are remarkably improved; simultaneously, the purposes of reducing cost and protecting environment are realized, and the method is suitable for large-scale industrial productionThe feasible technical support is provided;
(2) the 3-bromocarbazole preparation method provided by the invention uses cheap and easily-obtained Br-/O2 2-The system is used as a bromine source, and the defects of low utilization rate of bromine atoms, poor bromination reaction selectivity, serious environmental pollution and the like in the existing method are effectively overcome by controlling reaction conditions such as system temperature, bromine source amount and the like; meanwhile, the method has the advantages of low bromine source cost, simple operation steps and post-treatment purification, high atom utilization rate and reaction selectivity, economy, environmental protection, greenness and the like, has industrial feasibility, and is beneficial to large-scale industrial production.
Drawings
FIG. 1 is an HPLC chromatogram of high purity 3-bromocarbazole of example 1 of the present invention;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of 3-bromocarbazole in example 1 of the present invention;
FIG. 3 is a NMR spectrum of 3-bromocarbazole in example 1 of the present invention;
FIG. 4 is an HPLC chromatogram of 3-bromocarbazole of comparative example 1 of the present invention.
Detailed Description
Exemplary embodiments of the present invention are described in detail below. Although these exemplary embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, it should be understood that other embodiments may be realized and that various changes to the invention may be made without departing from the spirit and scope of the present invention. The following more detailed description of the embodiments of the invention is not intended to limit the scope of the invention, as claimed, but is presented for purposes of illustration only and not limitation to describe the features and characteristics of the invention, to set forth the best mode of carrying out the invention, and to sufficiently enable one skilled in the art to practice the invention. Accordingly, the scope of the invention is to be limited only by the following claims.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of 2-methyltetrahydrofuran (containing 0.5% BHT) and 3.3g of 18-crown-6 (99%, 12.50mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 55.6g of hydrobromic acid (40%, 0.275mol and 40.3mL) are added dropwise under the condition of 0 ℃ and stirred for 30 minutes at low temperature, 31.2g of hydrogen peroxide (30%, 0.275mol and 28.1mL) are added dropwise in three parts, after the dropwise addition is completed, the system is stirred continuously (the rotating speed is 700rpm) under the condition that the solvent is partially hydrolyzed or participates in the reaction under the acidic condition when the temperature is higher than 20 ℃ so as to cause safety hazards, meanwhile, the generation of 3, 6-dibromocarbazole is increased so as to cause separation difficulty, the yield of 3-bromocarbazole is lower, and the solid is precipitated in the system when the temperature is lower than 0 ℃ so as to affect the conversion rate of the reaction) for 10 hours, and (5) stopping stirring when the conversion rate of carbazole reaches 99.5% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and carrying out three-time tetrahydrofuran reflux recrystallization and decoloration on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours provides 42.3g of white crystalline high-purity 3-bromocarbazole, the content is 99.8% by HPLC detection as shown in figure 1, and the yield is 68.8%.
FIG. 2 shows the NMR spectrum of 3-bromocarbazole of this example, in which1H NMR(400MHz,DMSO-d6):δ＝7.17(td,J＝8.0,4.0Hz,1H),7.51-7.39(m,4H),8.16(d,J＝8.0Hz,1H),8.35(s,1H),11.41(s,1H)。
FIG. 3 shows the NMR carbon spectrum of 3-bromocarbazole of this example, in which13C NMR(151MHz,DMSO-d6):δ＝111.0,111.6,113.3,119.4,121.2,121.9,123.2,124.8,126.8,128.3,138.8,140.6。
Example 2
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of tetrahydrofuran (containing 1.0% of BHT) and 1.6g of tetrabutylammonium bromide (99%, 5.0mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 53.1g of hydrobromic acid (40%, 262.50mmol and 38.5mL) are added dropwise at the condition of 0 ℃ and stirred for 30 minutes at low temperature, 29.8g of hydrogen peroxide (30%, 262.50mmol and 26.8mL) are added dropwise in three parts on average, the system is stirred continuously (rotating speed of 700rpm) for 8 hours at the condition of 20 ℃ after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.6% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 4 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing reflux recrystallization on the crude product by using ethanol for three times to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours provides 46.1g of white crystalline high-purity 3-bromocarbazole (the content is 99.8 percent by HPLC), and the yield is 74.9 percent.
Example 3
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of 1, 2-dichloroethane (containing 0.5% of BHT) and 5.0g of polyethylene glycol-400 (99%, 12.50mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 53.1g of hydrobromic acid (40%, 262.50mmol and 38.5mL) are added dropwise at 0 ℃ and stirred for 30 minutes at low temperature, 34.0g of hydrogen peroxide (30%, 0.30mol and 30.6mL) is added dropwise in three parts, the system is stirred continuously (rotating speed of 700rpm) for 6 hours at 10 ℃ after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing tertiary ethyl acetate reflux recrystallization on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 47.7g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC), and the yield is 77.5 percent.
Example 4
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 100mL of N, N-dimethylformamide (containing 1.0% BHT) and 0.80g of tetrabutylammonium bromide (99%, 2.5mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 55.6g of hydrobromic acid (40%, 0.275mol and 40.3mL) are added dropwise at the condition of 0 ℃ and stirred for 30 minutes at low temperature, 29.8g of hydrogen peroxide (30%, 262.50mmol and 26.8mL) are added dropwise in three parts on average, the system is stirred continuously (rotating speed of 700rpm) for 10 hours at the condition of 20 ℃ after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% by liquid phase detection. After the reaction, 12% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing reflux recrystallization on the crude product by using dichloromethane for three times to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying for 3 hours under the condition of 0.095MPa to obtain 42.9g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 69.7 percent.
Example 5
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of 1, 4-dioxane (containing 0.5% of BHT) and 1.14g of benzyltriethylammonium chloride (99%, 5.0mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 58.2g of hydrobromic acid (40%, 287.50mmol and 42.2mL) are added dropwise at 0 ℃ and stirred continuously at low temperature for 30 minutes, 31.2g of hydrogen peroxide (30%, 0.275mol and 28.1mL) is added dropwise in three parts, the system is stirred continuously at 10 ℃ for 8 hours (rotating speed of 700rpm) after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% by liquid phase detection. After the reaction, 15% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 4 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and carrying out three-time tetrahydrofuran reflux recrystallization and decoloration on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 43.8g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 71.2 percent.
Example 6
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of dichloromethane (containing 0.50% of BHT) and 3.2g of tetrabutylammonium bromide (99%, 10.0mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 59.2g of sodium bromide aqueous solution (50%, 287.50mmol) is added dropwise under the condition of 0 ℃ and stirred for 35 minutes continuously at low temperature, 34.0g of hydrogen peroxide (30%, 0.30mol and 30.6mL) is added dropwise in three parts averagely, the stirring is continued under the condition of 0 ℃ for 10 hours (rotating speed of 700rpm) after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% under the liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing reflux recrystallization on the crude product by using ethanol for three times to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying for 3 hours under the condition of 0.095MPa to obtain 40.9g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 66.5 percent.
Example 7
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of tetrahydrofuran (containing 0.50% of BHT) and 1.6g of tetrabutylammonium bromide (99%, 5.0mmol) are added into a 500mL four-neck round-bottom flask and uniformly stirred, 53.9g of ammonium bromide aqueous solution (50%, 0.275mol) is dropwise added under the condition of 0 ℃ and continuously stirred at low temperature for 25 minutes, 31.2g of hydrogen peroxide (30%, 0.275mol and 28.1mL) is evenly divided into three parts and gradually and dropwise added, the system is continuously stirred under the condition of 10 ℃ for 8 hours (rotating speed of 700rpm), and the stirring is stopped when the conversion rate of carbazole is up to 99.5% through liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing tertiary xylene reflux recrystallization on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 42.7g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 69.4 percent.
Example 8
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of 2-methyltetrahydrofuran (containing 1.0% BHT) and 3.2g of tetrabutylammonium bromide (99%, 10.0mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 58.2g of hydrobromic acid (40%, 287.50mmol and 42.2mL) are added dropwise at 0 ℃ and stirred for 30 minutes at low temperature, 21.4g of sodium peroxide (99%, 0.275mol) are added in three parts in an average manner, the stirring is continued at 0 ℃ for 6 hours (rotating speed 700rpm) after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.8% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and carrying out three-time tetrahydrofuran reflux recrystallization and decoloration on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 41.6g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 67.6 percent.
Example 9
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 150mL of N, N-dimethylformamide (containing 0.50% BHT) and 5.0g of polyethylene glycol-400 (99%, 12.5mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 55.6g of hydrobromic acid (40%, 0.275mol and 40.3mL) are added dropwise at 0 ℃ and stirred for 30 minutes at low temperature, 14.8g of magnesium peroxide (99%, 262.5mmol) are added in three parts in an average manner, the system is stirred continuously at 10 ℃ for 10 hours at the rotating speed of 700rpm after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing reflux recrystallization on the crude product by using dichloromethane for three times to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 45.0g of white crystalline high-purity 3-bromocarbazole (the HPLC detection content is more than or equal to 99 percent), and the yield is 73.1 percent.
Example 10
Under the condition of room temperature, 41.8g of carbazole (99 percent, 0.25mol), 250mL of tetrahydrofuran (containing 1.0 percent of BHT) and 1.6g of tetrabutylammonium bromide (99 percent, 5.0mmol) are added into a 500mL four-mouth round-bottom flask and stirred uniformly, 59.2g of sodium bromide aqueous solution (50 percent, 287.50mmol) is added dropwise under the condition of 0 ℃ and stirred for 30 minutes at low temperature, 14.8g of magnesium peroxide (99 percent, 262.5mmol) is added in three parts in an average way, the system is stirred continuously (rotating speed of 700rpm) for 10 hours under the condition of 0 ℃ after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5 percent under the liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and carrying out three-time tetrahydrofuran reflux recrystallization and decoloration on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying for 3 hours under the condition of 0.095MPa to obtain 40.5g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 65.8 percent.
Example 11
Under the condition of room temperature, 83.6g of carbazole (99%, 0.5mol), 500mL of tetrahydrofuran (containing 0.50% of BHT) and 3.2g of tetrabutylammonium bromide (99%, 10.0mmol) are added into a 1000mL four-neck round-bottom flask and stirred uniformly, 106.2g of hydrobromic acid (40%, 0.525mol and 77.0mL) are added dropwise under the condition of 0 ℃ and stirred for 30 minutes at low temperature, 62.4g of hydrogen peroxide (30%, 0.550mol and 56.2mL) are added dropwise in three parts on average, the system is stirred continuously (rotating speed of 700rpm) for 8 hours under the condition of 0 ℃ after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% under the liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing tertiary xylene reflux recrystallization on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 98.7g of white crystalline high-purity 3-bromocarbazole (the HPLC detection content is more than or equal to 99 percent), and the yield is 80.2 percent.
Example 12
Under the condition of room temperature, 83.6g of carbazole (99%, 0.5mol), 500mL of 1, 2-dichloroethane (containing 1.0% of BHT) and 4.0g of tetrabutylammonium bromide (99%, 12.5mmol) are added into a 1000mL four-neck round-bottom flask and stirred uniformly, 116.3g of hydrobromic acid (40%, 0.575mol and 84.3mL) are added dropwise at 0 ℃ and stirred continuously at low temperature for 30 minutes, 68.0g of hydrogen peroxide (30%, 0.60mol and 61.3mL) are added dropwise in three parts, the system is stirred continuously (rotating speed of 700rpm) for 10 hours at 10 ℃ after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing three-time tetrahydrofuran reflux recrystallization on the crude product to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 96.5g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 78.4 percent.
Example 13
Under the condition of room temperature, 83.6g of carbazole (99%, 0.5mol), 500mL of 1, 4-dioxane (containing 0.50% of BHT) and 3.2g of tetrabutylammonium bromide (99%, 10.0mmol) are added into a 1000mL four-neck round-bottom flask and stirred uniformly, 106.2g of hydrobromic acid (40%, 0.525mol and 77.0mL) are added dropwise at 0 ℃ and stirred continuously at low temperature for 30 minutes, 68.0g of hydrogen peroxide (30%, 0.60mol and 61.3mL) are added dropwise in three parts on average, the system is stirred continuously (rotating speed of 700rpm) for 10 hours at 15 ℃ after the dropwise addition is finished, and the stirring is stopped when the conversion rate of carbazole reaches 99.5% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 3 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing reflux recrystallization on the crude product by using ethanol for three times to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying for 3 hours under the condition of 0.095MPa to obtain 102.3g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 83.1 percent.
Comparative example 1
This comparative example is essentially the same as example 2 except that no phase transfer catalyst was added.
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol) and 250mL of tetrahydrofuran (containing 1.0% BHT) are added into a 500mL four-mouth round-bottom flask and stirred uniformly, 53.1g of hydrobromic acid (40%, 262.50mol and 38.5mL) are added dropwise at 0 ℃ and stirred at low temperature for 30 minutes, 29.8g of hydrogen peroxide (30%, 262.50mol and 26.8mL) are added dropwise in three parts evenly, stirring is continued at 20 ℃ for 8 hours (rotating speed of 700rpm) after the addition is finished, and stirring is stopped when the conversion rate of carbazole reaches 99.6% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 4 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing reflux recrystallization on the crude product by using ethanol for three times to obtain a white crystalline solid.
Placing the white solid in a vacuum drying oven at 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours provides 26.15g of white crystalline high-purity 3-bromocarbazole, and the content is 99.2% by HPLC detection and the yield is 42.5% as shown in figure 4.
Comparative example 2
This comparative example is essentially the same as example 2 except that the molar ratio of the added phase transfer catalyst (tetrabutylammonium bromide) to carbazole was increased from (2 mol%: 1) to (5 mol%: 1).
Under the condition of room temperature, 41.8g of carbazole (99%, 0.25mol), 250mL of tetrahydrofuran (containing 1.0% of BHT) and 4.0g of tetrabutylammonium bromide (99%, 12.5mmol) are added into a 500mL four-neck round-bottom flask and stirred uniformly, 53.1g of hydrobromic acid (40%, 262.50mmol and 38.5mL) are added dropwise at the condition of 0 ℃ and stirred for 30 minutes at low temperature, 29.8g of hydrogen peroxide (30%, 262.50mmol and 26.8mL) are added dropwise in three parts on average, the system is stirred continuously at the condition of 20 ℃ for 8 hours (the rotating speed is 700rpm), and the stirring is stopped when the conversion rate of carbazole reaches 99.6% by liquid phase detection. After the reaction, 10% sodium carbonate aqueous solution was added to make the reaction system neutral, the organic layer was extracted and washed with water 4 times, and the inorganic layer was washed with ethyl acetate 3 times. And (4) recovering the organic solvent by rotary evaporation to obtain a crude product, and performing reflux recrystallization on the crude product by using ethanol for three times to obtain a white crystalline solid.
Placing the white solid in a vacuum drying ovenAt medium temperature of 100 ℃ and PTrueDrying under the condition of 0.095MPa for 3 hours to obtain 46.9g of white crystalline high-purity 3-bromocarbazole (the content is more than or equal to 99 percent by HPLC detection), and the yield is 76.2 percent.
Carbazole in Br in the invention-/O2 2-The method for synthesizing high-purity 3-bromocarbazole through oxidation bromination reaction under the system solves the problem that the solubility of carbazole, the control of the equivalent number of bromine sources and the like are critical to the reaction. The small amount of phase transfer catalyst in the invention can greatly accelerate the reaction speed and well solve the problem that the carbazole is included in the product due to poor solubility and can not be completely converted; the reaction temperature, the dosage of brominating agent/oxidant, the addition speed and other conditions are strictly controlled, so that the selectivity of carbazole oxybromination reaction can be improved, and the generation of 3, 6-dibromocarbazole can be reduced; lower reaction temperatures and small amounts of BHT can greatly reduce the acidic hydrolysis and oxidative decomposition of the solvent.
The structure and the implementation of the present invention are explained by using the specific embodiments, and the above description of the embodiments is only used to help understand the core idea of the present invention. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
Claims (10)
1. A process for preparing 3-bromocarbazole features that carbazole is used as raw material, organic solvent containing 2, 6-ditert-butyl-p-cresol as stabilizer is used, phase transfer catalyst is added, and Br is added-/O2 2-Synthesizing 3-bromocarbazole through oxidation bromination reaction in the system.
2. The preparation method of 3-bromocarbazole according to claim 1, characterized by comprising the following specific steps:
(1) under the condition of room temperature, carbazole is dissolved in an organic solvent containing a stabilizer 2, 6-di-tert-butyl-p-cresol and is uniformly stirred, a small amount of phase transfer catalyst is added, a brominating agent is added in batches at the temperature of 0 ℃ by controlling the temperature of a reaction system, and the reaction system is stirred for 25-35 minutes at low temperature after the brominating agent is added;
(2) adding quantitative oxidant in batches at a constant temperature of 0 ℃, continuously reacting for 6-10 hours at a temperature of 0-20 ℃ after the addition of the oxidant, and stopping stirring when the conversion rate of carbazole is more than or equal to 99.5% by liquid phase detection;
(3) and after the reaction is finished, adding 10-15% of sodium carbonate aqueous solution to enable the reaction system to be neutral, extracting an organic layer, washing with water for at least 3 times, washing with inorganic layer ethyl acetate for at least 3 times, performing rotary evaporation to recover the organic solvent to obtain a crude product, and performing repeated recrystallization, purification and vacuum drying on the crude product to obtain the high-purity 3-bromocarbazole.
3. The method for producing 3-bromocarbazole according to claim 2, wherein the organic solvent is one or a mixed solution selected from dichloromethane, 1, 2-dichloroethane, tetrahydrofuran, 2-methyltetrahydrofuran, methoxycyclopentane, dioxane, N-dimethylformamide, dimethylsulfoxide, and the like.
4. The method of claim 2, wherein the phase transfer catalyst is a PTC compound selected from polyethylene glycol, 18-crown-6, tetrabutylammonium bromide, and benzyltriethylammonium chloride.
5. The method for producing 3-bromocarbazole according to claim 2, wherein the brominating agent is selected from hydrobromic acid, potassium bromide, sodium bromide, ammonium bromide or lithium bromide.
6. The method for preparing 3-bromocarbazole according to claim 2, wherein the oxidizing agent is selected from hydrogen peroxide, sodium peroxide, potassium persulfate or magnesium peroxide.
7. The preparation method of 3-bromocarbazole according to claim 2, wherein the mass fraction ratio of the stabilizer 2, 6-di-tert-butyl-p-cresol to the organic solvent is (0.01% to 1.00%): 1, or the molar ratio of the brominating agent to carbazole is (1.05-1.15): 1.
8. the preparation method of 3-bromocarbazole according to claim 2, wherein the molar ratio of the oxidant to carbazole is (1.05-1.20): 1, or the molar ratio of the phase transfer catalyst to the carbazole is (0.01-5.00): 1.
9. the method for producing 3-bromocarbazole according to claim 2, wherein the solvent for recrystallization is one or a mixed solution selected from ethanol, ethyl acetate, dichloromethane, xylene, tetrahydrofuran, and the like.
10. The method of claim 2, wherein the stabilizer 2, 6-di-tert-butyl-p-cresol has the following structure:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011243774.9A CN112521328A (en) | 2020-11-10 | 2020-11-10 | Preparation method of 3-bromocarbazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011243774.9A CN112521328A (en) | 2020-11-10 | 2020-11-10 | Preparation method of 3-bromocarbazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112521328A true CN112521328A (en) | 2021-03-19 |
Family
ID=74979990
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011243774.9A Pending CN112521328A (en) | 2020-11-10 | 2020-11-10 | Preparation method of 3-bromocarbazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112521328A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113480470A (en) * | 2021-08-11 | 2021-10-08 | 山东瑞辰新材料有限公司 | Preparation method of 3-bromo-N-phenylcarbazole |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772269A (en) * | 2014-01-27 | 2014-05-07 | 南京邮电大学 | Controllable preparation method of carbazole bromo-compound |
-
2020
- 2020-11-10 CN CN202011243774.9A patent/CN112521328A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772269A (en) * | 2014-01-27 | 2014-05-07 | 南京邮电大学 | Controllable preparation method of carbazole bromo-compound |
Non-Patent Citations (6)
| Title |
|---|
| D. BOGDAL等: "Halogenation of carbazole and other aromatic compounds with hydrohalic acids and hydrogen peroxide under microwave irradiation", 《GREEN CHEM 》 * |
| HONG-YI ZHAO等: "Cu-mediated selective bromination of aniline derivatives and preliminary mechanism study", 《SYNTHETIC COMMUNICATIONS》 * |
| JIHAD DAKKA等: "Quaternary Ammonium Salts as Bifunctional Catalysts in the Oxybromination of Aromatic Compounds by Aqueous Hydrogen BromidelHydrogen Peroxide", 《JOURNAL OF THE CHEMICAL SOCIETY，CHEMICAL COMMUNICATIONS》 * |
| 张国富等: "芳香化合物氧化溴化研究进展", 《有机化学》 * |
| 李雄辉等: "《杂环化学与杂环化合物》", 30 June 2017, 江西科学技术出版社 * |
| 陶友田等: "《高效有机电致磷光双极主体材料的合成与性能》", 31 May 2015, 知识产权出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113480470A (en) * | 2021-08-11 | 2021-10-08 | 山东瑞辰新材料有限公司 | Preparation method of 3-bromo-N-phenylcarbazole |
| CN113480470B (en) * | 2021-08-11 | 2023-09-26 | 山东瑞辰新材料有限公司 | Preparation method of 3-bromo-N-phenylcarbazole |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104402909B (en) | A kind of synthetic method of cefoxitin acid | |
| CN112521328A (en) | Preparation method of 3-bromocarbazole | |
| CN113549048B (en) | Preparation method of ethylene sulfite | |
| CN113072436A (en) | Preparation method of benzyl aryl ether | |
| KR101583851B1 (en) | Method for producing 3-methyl-2-thiophenecarboxylic acid | |
| CN113387971B (en) | Synthesis method of clenbuterol | |
| CN114478611B (en) | Synthesis method of tetraethylene silane | |
| CN113416142A (en) | Preparation method of 5-ALA intermediate 5-bromolevulinate | |
| CN111072450B (en) | Synthesis method of allyl alcohol derivative | |
| CN100368375C (en) | 3- alkoxy -4-carbalkoxyphenylacetate and 3-alkoxy-4-carbalkoxyphenylacetic acid synthesis method | |
| CN103387584A (en) | Synthetic method of 7-amino-3-chloro-3-cephem-4-carboxylic acid | |
| CN108084077B (en) | Synthetic method of zafirlukast intermediate | |
| CN102127061B (en) | One prepares improving one's methods of fluoro-3, the 4-dihydro-2 H-1-benzopyran-2-epoxy ethanes of 6- | |
| CN112811974B (en) | Novel aryl trifluoroethylene synthesized by arylation reagent and preparation method thereof | |
| CN110452139B (en) | Preparation method of 2-methyl-3-bromo-6-methylsulfonyl benzonitrile | |
| CN115974737B (en) | Preparation method of photoelectric material monomer, photoelectric material monomer and application | |
| CN110467529B (en) | Synthesis method of ester | |
| CN112624898B (en) | Synthetic method of aryl trifluoroethylene compound | |
| CN114805015A (en) | Synthesis process of 2, 4-dichloro-9, 9-dimethyl-9H-fluorene | |
| CN112159416B (en) | Preparation method of 4, 6-dibromo-thienofuran-1, 3-dione | |
| CN102417451B (en) | Method for synthesizing (R,S)1-bromoethyl acetate | |
| CN114163312B (en) | Synthesis method of fluorine-containing terephthalyl diether compound | |
| CN115108922B (en) | Method for one-step synthesis of pyribenzoxim by taking 2, 3-dichloro-6-nitroaniline as raw material | |
| CN111635368B (en) | Preparation method of amine compound | |
| CN102786511B (en) | Improved method for preparing fupentixol dihydrochloride intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210319 |
|
| RJ01 | Rejection of invention patent application after publication |