CN107235891B - Preparation method of 4-bromocarbazole - Google Patents
Preparation method of 4-bromocarbazole Download PDFInfo
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- CN107235891B CN107235891B CN201710375453.6A CN201710375453A CN107235891B CN 107235891 B CN107235891 B CN 107235891B CN 201710375453 A CN201710375453 A CN 201710375453A CN 107235891 B CN107235891 B CN 107235891B
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Abstract
The invention discloses a preparation method of 4-bromocarbazole, belonging to the field of organic chemical synthesis. The method comprises the following steps: (1) carrying out condensation reaction on 1, 3-cyclohexanedione and aniline to prepare 3-aniline-cyclohexene-2-ketone; (2) the 3-aniline-cyclohexene-2-ketone is subjected to cyclization reaction to prepare 1,2,3, 9-tetrahydrocarbazole-4-ketone; (3) reducing the 1,2,3, 9-tetrahydrocarbazole-4-ketone to prepare 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole; (4) preparing 4-bromo-1, 2,3, 9-tetrahydrocarbazole through bromination reaction of the 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole; (5) the 4-bromo-1, 2,3, 9-tetrahydrocarbazole is subjected to dehydrogenation reaction to prepare the 4-bromocarbazole. The method has the advantages of cheap and easily-obtained reaction raw materials, simple reaction operation, less side reaction and high yield; the prepared 4-bromocarbazole has high purity, can be used in the fields of OLED photoelectric materials, medicines and the like, and is an important carbazole intermediate.
Description
Technical Field
The invention relates to the field of organic chemical synthesis, in particular to a preparation method of 4-bromocarbazole.
Background
Carbazole derivatives are a large class of intermediates having a wide range of uses. The carbazole derivative has good photoelectric property, and other derivatives prepared by taking carbazole as a raw material are widely applied to the fields of OLED photoelectric materials, medicines, dyes, pesticides and the like.
The halides at different substituent positions on the carbazole are prepared by different methods. At present, carbazole derivatives such as 3-bromocarbazole, 2-bromocarbazole, 1-bromocarbazole and the like have been widely reported. The derivative is widely applied to the fields of OLED photoelectric materials, medicines, dyes, pesticides and the like. The synthesis method is mainly obtained by direct bromination, the synthesis of many carbazoles and cyclization or the synthesis of the Fisher indole method.
The preparation methods of the 4-bromocarbazole and the derivatives thereof are few in reports, and most of the derivatives are obtained by performing Suzuki coupling on o-nitrobenzeneboronic acid and o-bromoiodobenzene and then cyclizing under the action of triethyl phosphite or triphenylphosphine at high temperature. The raw materials are expensive, wherein triethyl phosphite has a large odor, a large amount of by-products such as triphenyl phosphine oxide and the like are generated in the process of cyclization preparation by triphenylphosphine, and the final product has a dark color and is difficult to purify due to the high-temperature operation of the product.
In addition, the Chinese application CN 103936656A discloses a method for synthesizing 4-bromocarbazole, which takes bromobenzene boric acid as a raw material and obtains 2-bromo-2' -nitrobiphenyl through Suzuki reaction; then 2-bromo-2' -nitrobiphenyl is synthesized into the product 4-bromocarbazole by taking triphenyl phosphite as a reducing agent. It also has the problems of generating a large amount of triphenylphosphine by-product in the ring closing process and difficult purification. Currently, the production process of 4-bromocarbazole needs to be improved in order to meet the increasing product demand.
Disclosure of Invention
In order to solve the problems, the invention provides a novel preparation method of 4-bromocarbazole, which has the advantages of mild reaction conditions, simple post-treatment and purification, high yield and low cost.
The preparation method of the 4-bromocarbazole of the invention has the following synthetic route:
the method comprises the following steps:
(1) carrying out condensation reaction on 1, 3-cyclohexanedione and aniline to prepare 3-aniline-cyclohexene-2-ketone;
(2) the 3-aniline-cyclohexene-2-ketone is subjected to cyclization reaction to prepare 1,2,3, 9-tetrahydrocarbazole-4-ketone;
(3) reducing the 1,2,3, 9-tetrahydrocarbazole-4-ketone to prepare 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
(4) preparing 4-bromo-1, 2,3, 9-tetrahydrocarbazole through bromination reaction of the 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
(5) the 4-bromo-1, 2,3, 9-tetrahydrocarbazole is subjected to dehydrogenation reaction to prepare the 4-bromocarbazole.
According to the preparation method provided by the invention, the reaction conditions (such as reaction temperature, solvent selection, product separation and the like) of each step can be realized by adopting conventional available means in the field, and the requirement that the 4-bromocarbazole can be prepared by the reaction process can be met.
In order to further improve the quality of the preparation route and better achieve the aim of the invention, the invention optimizes the specific conditions of the preparation method as follows:
in the method, in the step (1), the ideal molar charge ratio of the 1, 3-cyclohexanedione to the aniline is 1:0.9-1.05, and preferably 1: 1. Under the condition of the feeding ratio, the two raw materials can fully react, and the method has the advantages of high conversion rate and no other redundant impurities.
In the method of the invention, the catalyst used in the condensation reaction in the step (1) is a metal oxide; preferably, the metal oxide is one of aluminum oxide, magnesium oxide or calcium oxide; more preferably alumina.
Wherein the ideal molar usage of the catalyst is aniline: the catalyst is 1: 0.1-0.2.
In the method of the present invention, the condensation reaction in step (1) is carried out in a solvent; the solvent is preferably toluene, and the ideal dosage of the solvent is aniline solvent 1g:5-15 mL.
In the method, the reaction temperature of the condensation reaction in the step (1) is 100-120 ℃; preferably 108-110 ℃.
Preferably, step (1) further comprises the separation of intermediate products, specifically: washing an organic layer obtained by the condensation reaction with water to be neutral, and then drying and concentrating to obtain the 3-aniline-cyclohexene-2-ketone; the separation step can remove mechanical impurities and catalysts, and is beneficial to the full implementation of the next reaction.
In the method of the present invention, the cyclization reaction in step (2) is carried out in the presence of a palladium catalyst and an inorganic base;
wherein the palladium catalyst is one of palladium acetate, 1' -bis (diphenylphosphino) ferrocene palladium dichloride or tris (dibenzylideneacetone) dipalladium; preferably palladium acetate;
the inorganic base is one of potassium carbonate, sodium carbonate or cesium carbonate; preferably potassium carbonate.
Preferably, the palladium catalyst is used in a molar amount of 3-aniline-cyclohexene-2-one: the palladium catalyst (molar ratio) is 1:0.01 to 1, more preferably 1: 0.02.
And/or the inorganic base is desirably used in an amount of 3-aniline-cyclohexene-2-one to inorganic base (molar ratio) ═ 1:2-3, preferably 1: 2.
In the method, the cyclization reaction in the step (2) is carried out in a solvent, wherein the solvent is DMF, N-dimethylacetamide or NMP; preferably DMF. The ideal dosage of the solvent is 3-aniline-cyclohexene-2-ketone, and the solvent is 1g and 5-15 mL.
In the method, the ideal reaction temperature of the cyclization reaction in the step (2) is 80-140 ℃; preferably 80-100 deg.C.
Preferably, step (2) further comprises the separation of intermediate products, specifically: passing a product obtained by the cyclization reaction through a silica gel column, and then washing and drying an organic phase to obtain the 1,2,3, 9-tetrahydrocarbazole-4-ketone; the purification step can remove mechanical impurities and catalysts, and is beneficial to the next reaction.
According to the method, in the step (3), the 1,2,3, 9-tetrahydrocarbazole-4-ketone and sodium borohydride are subjected to reduction reaction; the molar dosage of the sodium borohydride is 1,2,3, 9-tetrahydrocarbazole-4-ketone: sodium borohydride (molar ratio) is 1:1-3, preferably 1: 2.
In the method of the present invention, in step (3), the reduction reaction is performed in a solvent, and preferably the amount of the solvent is 1,2,3, 9-tetrahydrocarbazole-4-one, 1g of the solvent is 5 to 20 mL;
more preferably, the solvent is tetrahydrofuran.
In the method, the ideal reaction temperature of the reduction reaction in the step (3) is 0-50 ℃; preferably 10-25 deg.c.
Preferably, step (3) further comprises the separation of intermediate products, specifically: adding water to quench the reduction reaction, extracting the obtained product with dichloromethane, washing with water, and drying to obtain the 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole.
According to the method, a bromination reagent adopted in the bromination reaction in the step (4) is hydrobromic acid or tribromooxyphosphorus; preferably hydrobromic acid; the dosage of the bromination reagent is 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole, and the bromination reagent is 1: 1-1.1.
More desirably, when the brominating agent is hydrobromic acid, it is present in solution, suitably at a concentration of 30% to 60%, preferably 48%.
In the method of the present invention, the bromination reaction in the step (4) is performed under the catalysis of a catalyst, and preferably, the catalyst is ferric bromide.
Most preferably, the catalyst is used in an amount of 1,2,3, 9-tetrahydrocarbazol-4-one: iron bromide (molar ratio) 1: 0.1-0.5.
According to the method, the reaction temperature of the bromination reaction in the step (4) is-20-50 ℃; preferably 10 to 20 ℃.
Preferably, step (4) further comprises the separation of intermediate products, specifically: washing the organic phase obtained by the bromination reaction with water, drying and concentrating to obtain the 4-bromo-1, 2,3, 9-tetrahydrocarbazole.
In the preparation method, in the step (5), the 4-bromo-1, 2,3, 9-tetrahydrocarbazole is subjected to dehydrogenation reaction in the presence of tetrachlorobenzoquinone; preferably, the molar ratio of the 4-bromo-1, 2,3, 9-tetrahydrocarbazole to the tetrachlorobenzoquinone is 1: 2-4;
the tetrachlorobenzoquinone is used as a dehydrogenating agent, is low in price and has good solubility, so that the reaction has high conversion rate, and the post-treatment is simple and easy to implement.
In the preparation method of the present invention, the dehydrogenation reaction in step (5) is performed in a solvent, and preferably, the amount of the solvent is 4-bromo-1, 2,3, 9-tetrahydrocarbazole, where the solvent is 1g:5-20 mL; more preferably, the solvent is toluene. The reaction conversion rate under the solvent is high, the post-treatment is simple, and the solvent is convenient to recycle and reuse.
According to the preparation method, the reaction temperature of the dehydrogenation reaction in the step (5) is 90-130 ℃; preferably 100-110 ℃.
Preferably, step (5) further comprises a product separation step, specifically: washing the organic phase obtained by the dehydrogenation reaction with water, drying, passing through a silica gel column, and then recrystallizing to obtain the 4-bromocarbazole.
Preferably, the steps (1) to (5) are all carried out under the protection of inert gas; the inert gas is preferably nitrogen.
Preferably, the preparation method of 4-bromocarbazole of the present invention comprises the following steps under the protection of inert gas:
(1) carrying out condensation reaction on 1, 3-cyclohexanedione and aniline in toluene in the presence of metal oxide to obtain 3-aniline-cyclohexene-2-one;
(2) carrying out cyclization reaction on the 3-aniline-cyclohexene-2-ketone in the presence of a palladium catalyst and inorganic base to prepare 1,2,3, 9-tetrahydrocarbazole-4-ketone;
the palladium catalyst is one of palladium acetate, 1' -bis (diphenylphosphino) ferrocene palladium dichloride or tris (dibenzylideneacetone) dipalladium; the molar usage of the palladium catalyst is 3-aniline-cyclohexene-2-ketone: a palladium catalyst 1: 0.01-1;
and/or the inorganic base is one of potassium carbonate, sodium carbonate or cesium carbonate; the molar amount of the inorganic base is 3-aniline-cyclohexene-2-ketone: inorganic base 1: 2-3;
(3) carrying out reduction reaction on the 1,2,3, 9-tetrahydrocarbazole-4-ketone and sodium borohydride in tetrahydrofuran to prepare 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
the dosage of the sodium borohydride is 1,2,3, 9-tetrahydrocarbazole-4-ketone: sodium borohydride is 1: 1-3;
(4) carrying out bromination reaction on the 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole in the presence of a bromination reagent and a catalyst to prepare 4-bromo-1, 2,3, 9-tetrahydrocarbazole;
the bromination reagent is hydrobromic acid or tribromooxyphosphorus, and the dosage of the bromination reagent is 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole: brominating reagent 1: 1-1.1;
the catalyst is ferric bromide;
(5) carrying out dehydrogenation reaction on the 4-bromo-1, 2,3, 9-tetrahydrocarbazole in toluene in the presence of tetrachlorobenzoquinone to obtain the 4-bromocarbazole; the molar ratio of the 4-bromo-1, 2,3, 9-tetrahydrocarbazole to the tetrachlorobenzoquinone is 1: 2-4.
The invention adopts the conventional raw materials such as 1, 3-cyclohexanedione, aniline and the like with low price to replace expensive raw materials such as o-nitrobenzeneboronic acid, o-bromoiodobenzene and the like, and the obtained intermediate can be directly and simply treated and then directly put into the next step of reaction under the condition of no purification. The post-treatment is simple, the yield is high, the total yield can reach more than 80 percent, and the content of the gas chromatography can reach 99 percent.
The method adopts milder processes of reduction, bromination, dehydrogenation and the like after cyclization to replace high-temperature reactions such as triethyl phosphite, triphenylphosphine and the like, and mildly realizes the preparation of 4-bromocarbazole. The requirements of industrial production on equipment and other conditions are reduced, energy is saved, and the industrial production is facilitated.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. The basic raw materials used in the present invention are all conventional commercial products.
Example 1
The embodiment provides a preparation method of 4-bromocarbazole, specifically, the method includes the following steps:
(1) 18.6g of aniline (molecular weight 93.13, 0.2mol), 22.4g of 1, 3-cyclohexanedione (molecular weight 112.13, 0.2mol), 2.0g of alumina (molecular weight 101.96, 0.02mol) and 224mL of toluene were added to a reaction flask with mechanical stirring, reflux condenser, thermometer and oil bath heating under nitrogen. Heating to 110 ℃, reacting for 4 hours, finishing the reaction, washing the obtained organic phase to be neutral, drying the organic phase for 1 hour by using 20g of sodium sulfate, and then concentrating the organic phase to be dry to obtain 37.3g (molecular weight of 187.24, 0.2mol) of off-white solid 3-aniline-cyclohexene-2-ketone; ms (fab): m/z 187(M +);
(2) under the protection of nitrogen, adding 0.9g (molecular weight of 224.29, 0.004mol) of 3-aniline-cyclohexene-2-ketone prepared in the step (1), 0.9g (molecular weight of 0.004mol) of palladium acetate and 55.2g (molecular weight of 138, 0.4mol) of potassium carbonate into 373mL of DMF, heating to 100 ℃, reacting for 8 hours, ending the reaction, passing the obtained product through 18g of silica gel column, pouring the column-passing liquid into 3740mL of water, carrying out suction filtration, and drying to obtain 36.4g of brown yellow intermediate 1,2,3, 9-tetrahydrocarbazole-4-ketone; ms (fab): m/z 185(M +);
(3) dissolving the intermediate 1,2,3, 9-tetrahydrocarbazole-4-ketone prepared in the step (2) by 364mL of tetrahydrofuran, adding sodium borohydride 15.1g (with the molecular weight of 37.83, 0.4mol) in 3 batches at 15 ℃, reacting for 2 hours at the temperature, adding 36.4mL of water to quench and react, extracting the obtained product by 364mL of dichloromethane, washing by water, and drying by 20g of sodium sulfate to obtain 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
(4) the temperature of the organic phase obtained in step (3) was lowered to 20 ℃ and 33.7g (molecular weight 81, 0.2mol) of HBr solution (48% strength) and 5.9g (molecular weight 295.5, 0.02mol) of ferric bromide were added thereto. Reacting at 20 ℃ for 4 hours, finishing the reaction, washing an organic phase to be neutral, drying the organic phase by using 20g of sodium sulfate, and concentrating the organic phase to be dry to obtain 49g of intermediate 4-bromo-1, 2,3, 9-tetrahydrocarbazole; ms (fab): m/z 250(M +);
(5) and (3) adding the intermediate 4-bromo-1, 2,3, 9-tetrahydrocarbazole obtained in the step (4), 490mL of toluene and tetrachlorobenzoquinone (molecular weight of 245.88, 0.44mol) into a reaction bottle, and reacting at 110 ℃ for 4 hours to finish the reaction. And (3) washing the obtained organic phase to be neutral, drying the organic phase by using 20g of sodium sulfate, then removing color by using 18g of silica gel column, concentrating the column-passing solution until 49mL of the residual solution is obtained, adding 100mL of ethanol into the column-passing solution, crystallizing at 15 ℃, filtering, and drying to obtain 38.8g of white powder 4-bromocarbazole.
The total yield of 4-bromocarbazole prepared by the method described in this example was 78.6%, and the purity was 99.36%.
Melting point of the product: 104.8-105.6 ℃. Ms (fab): m/z 246(M +). Elemental analysis C12H8BrN: 58.51% of theoretical value C; h: 3.25 percent; br: 32.51 percent; n: 5.68 percent. Found C58.53%; h: 3.26 percent; br: 32.5 percent; n: 5.67 percent.
Example 2
The embodiment provides a preparation method of 4-bromocarbazole, specifically, the method includes the following steps:
(1) 18.6g of aniline (molecular weight 93.13, 0.2mol), 22.4g of 1, 3-cyclohexanedione (molecular weight 112.13, 0.2mol), 0.8g of magnesium oxide (molecular weight 40.30, 0.02mol) and 224mL of toluene were placed in a reaction flask with mechanical stirring, reflux condenser, thermometer and oil bath heating under nitrogen. Heating to 110 ℃, reacting for 4 hours, finishing the reaction, washing the obtained organic phase to be neutral, drying the organic phase for 1 hour by using 20g of sodium sulfate, and then concentrating the organic phase to be dry to obtain 37.4g (molecular weight of 187.24, 0.2mol) of off-white solid 3-aniline-cyclohexene-2-ketone;
(2) under the protection of nitrogen, adding 2.92g (molecular weight of 731.71, 0.004mol) of 3-aniline-cyclohexene-2-ketone prepared in the step (1), 2.92g (molecular weight of 0.004mol) of 1,1' -bis-diphenylphosphino ferrocene palladium dichloride and 130.3g (molecular weight of 325.82, 0.4mol) of cesium carbonate into 374mL of N, N-dimethylacetamide, heating to 80 ℃, reacting for 8 hours, ending the reaction, passing the obtained product through 18g of silica gel column, pouring the column-passing liquid into 3740mL of water, filtering, and drying to obtain 36.4g of brown yellow intermediate 1,2,3, 9-tetrahydrocarbazole-4-ketone;
(3) dissolving the intermediate 1,2,3, 9-tetrahydrocarbazole-4-ketone prepared in the step (2) by 364mL of tetrahydrofuran, adding 15.1g (with the molecular weight of 37.83 and 0.4mol) of sodium borohydride in 3 batches at 20 ℃, reacting for 2 hours at the temperature, adding 36.4mL of water to quench and react, extracting the obtained product by 364mL of dichloromethane, washing by water, and drying by 20g of sodium sulfate to obtain 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
(4) the temperature of the organic phase obtained in step (3) was reduced to 15 ℃ and 33.7g (molecular weight 81, 0.2mol) of HBr solution (48% strength) and 5.9g (molecular weight 295.5, 0.02mol) of ferric bromide were added thereto. Reacting at 15 ℃ for 4 hours, finishing the reaction, washing an organic phase to be neutral, drying the organic phase by using 20g of sodium sulfate, and concentrating the organic phase to be dry to obtain 48.9g of intermediate 4-bromo-1, 2,3, 9-tetrahydrocarbazole;
(5) and (3) adding the intermediate 4-bromo-1, 2,3, 9-tetrahydrocarbazole obtained in the step (4), 489mL of diethylbenzene and tetrachlorobenzoquinone (molecular weight of 245.88, 0.44mol) into a reaction bottle, and reacting at 110 ℃ for 4 hours to finish the reaction. Washing the obtained organic phase to be neutral, drying the organic phase by using 20g of sodium sulfate, removing color by using 18g of silica gel column, concentrating the column-passing liquid until the residual 45mL of the organic phase is obtained, adding 150mL of ethanol into the column-passing liquid, crystallizing at 10 ℃, filtering, and drying to obtain 40.2g of white powder 4-bromocarbazole.
The total yield of 4-bromocarbazole prepared by the method of the embodiment is 81.6%, and the purity is 99.1%.
Example 3
The embodiment provides a preparation method of 4-bromocarbazole, specifically, the method includes the following steps:
(1) 18.6g of aniline (molecular weight 93.13, 0.2mol), 22.4g of 1, 3-cyclohexanedione (molecular weight 112.13, 0.2mol), 2.0g of alumina (molecular weight 101.96, 0.02mol) and 224mL of toluene were added to a reaction flask with mechanical stirring, reflux condenser, thermometer and oil bath heating under nitrogen. Heating to 110 ℃, reacting for 4 hours, finishing the reaction, washing the obtained organic phase to be neutral, drying the organic phase for 1 hour by using 20g of sodium sulfate, and then concentrating the organic phase to be dry to obtain 37.4g (molecular weight of 187.24, 0.2mol) of off-white solid 3-aniline-cyclohexene-2-ketone;
(2) under the protection of nitrogen, 3-aniline-cyclohexene-2-ketone prepared in the step (1), 3.66g (molecular weight 915.72, 0.004mol) of tris (dibenzylideneacetone) dipalladium and 55.2g (molecular weight 138, 0.4mol) of potassium carbonate are added into 374mL of NMP, the temperature is increased to 80 ℃, the reaction is finished after 8 hours of reaction, the obtained product passes through 18g of silica gel column, the column passing liquid is poured into 3740mL of water, and 36.4g of brown yellow intermediate 1,2,3, 9-tetrahydrocarbazole-4-ketone is obtained through suction filtration and drying;
(3) dissolving the intermediate 1,2,3, 9-tetrahydrocarbazole-4-ketone prepared in the step (2) by 364mL of tetrahydrofuran, adding 7.6g (with the molecular weight of 37.83 and 0.2mol) of sodium borohydride in 3 batches at 15 ℃, reacting for 2 hours at the temperature, adding 36.4mL of water to quench and react, extracting the obtained product by 364mL of dichloromethane, washing by water, and drying by 20g of sodium sulfate to obtain 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
(4) and (3) cooling the organic phase obtained in the step (3) to 15 ℃, and adding 57.3g (molecular weight 286.69, 0.2mol) of tribromooxyphosphorus to the organic phase. Reacting at 15 ℃ for 4 hours, finishing the reaction, washing an organic phase to be neutral, drying the organic phase by using 20g of sodium sulfate, and concentrating the organic phase to be dry to obtain 49g of intermediate 4-bromo-1, 2,3, 9-tetrahydrocarbazole;
(5) and (3) adding the intermediate 4-bromo-1, 2,3, 9-tetrahydrocarbazole obtained in the step (4), 490mL of xylene and 149.8 (molecular weight 227, 0.66mol) of dichlorodicyanoquinone into a reaction bottle, and reacting at 110 ℃ for 4 hours. Washing the obtained organic phase to be neutral, drying the organic phase by using 20g of sodium sulfate, removing color by using 18g of silica gel column, concentrating the column-passing liquid until the residual 50mL of the organic phase is obtained, adding 200mL of ethanol into the column-passing liquid, crystallizing at 10 ℃, filtering, drying to obtain 39.2g of white powder 4-bromocarbazole.
The total yield of 4-bromocarbazole prepared by the method described in this example was 79.6%, and the purity was 99.22%.
Although the invention has been described in detail above with reference to a general description and specific examples, it will be apparent to one skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (23)
1. The preparation method of 4-bromocarbazole is characterized in that the synthetic route is as follows:
the method comprises the following steps:
(1) carrying out condensation reaction on 1, 3-cyclohexanedione and aniline to prepare 3-aniline-cyclohexene-2-ketone;
(2) the 3-aniline-cyclohexene-2-ketone is subjected to cyclization reaction to prepare 1,2,3, 9-tetrahydrocarbazole-4-ketone;
(3) reducing the 1,2,3, 9-tetrahydrocarbazole-4-ketone to prepare 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
(4) preparing 4-bromo-1, 2,3, 9-tetrahydrocarbazole through bromination reaction of the 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
(5) the 4-bromo-1, 2,3, 9-tetrahydrocarbazole is subjected to dehydrogenation reaction to prepare the 4-bromocarbazole.
2. The method according to claim 1, wherein in the step (1), the molar charge ratio of the 1, 3-cyclohexanedione to the aniline is 1: 0.9-1.05.
3. The method according to claim 2, wherein in the step (1), the molar charge ratio of the 1, 3-cyclohexanedione to the aniline is 1: 1.
4. The process according to claim 1 or 2, wherein the catalyst used in the condensation reaction in step (1) is a metal oxide.
5. The method of claim 4, wherein the metal oxide is one of aluminum oxide, magnesium oxide, or calcium oxide.
6. The method according to any one of claims 1 to 3 and 5, wherein the cyclization reaction in the step (2) is carried out in the presence of a palladium catalyst and an inorganic base; the inorganic base is one of potassium carbonate, sodium carbonate or cesium carbonate.
7. The method of claim 6, wherein the palladium catalyst is one of palladium acetate, 1' -bis-diphenylphosphinoferrocene palladium dichloride, or tris (dibenzylideneacetone) dipalladium.
8. The process according to claim 4, wherein the cyclization reaction in step (2) is carried out in the presence of a palladium catalyst and an inorganic base; the inorganic base is one of potassium carbonate, sodium carbonate or cesium carbonate.
9. The method of claim 8, wherein the palladium catalyst is one of palladium acetate, 1' -bis-diphenylphosphinoferrocene palladium dichloride, or tris (dibenzylideneacetone) dipalladium.
10. The method of claim 6, wherein the molar amount of palladium catalyst is 3-aniline-cyclohexene-2-one: a palladium catalyst 1: 0.01-1; the molar amount of the inorganic base is 3-aniline-cyclohexene-2-ketone: inorganic base 1: 2-3.
11. The method according to any one of claims 1 to 3, 5 and 8 to 10, wherein in the step (3), the 1,2,3, 9-tetrahydrocarbazole-4-one is subjected to a reduction reaction with sodium borohydride.
12. The method according to claim 11, wherein the amount of sodium borohydride is 1,2,3, 9-tetrahydrocarbazol-4-one, sodium borohydride is 1: 1-3.
13. The method of claim 12, wherein the amount of sodium borohydride is 1,2,3, 9-tetrahydrocarbazol-4-one, sodium borohydride is 1: 2.
14. The method according to any one of claims 1 to 3, 5, 8 to 10, 12 and 13, wherein in the step (3), the reduction reaction is performed in a solvent, and the amount of the solvent is 1,2,3, 9-tetrahydrocarbazol-4-one: and 5-20mL of solvent.
15. The method of claim 14, wherein the solvent is tetrahydrofuran.
16. The method according to any one of claims 1 to 3, 5, 8 to 10, 12, 13 and 15, wherein the bromination reaction in the step (4) is carried out by using hydrobromic acid or phosphorus oxybromide; and (4) carrying out bromination reaction under the catalysis of a catalyst.
17. The method of claim 16, wherein the brominating reagent is used in an amount of 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole: brominating reagent ═ 1: 1-1.1.
18. The method of claim 16, wherein the catalyst is ferric bromide.
19. The method according to any one of claims 1 to 3, 5, 8 to 10, 12, 13, 17 and 18, wherein in the step (5), the 4-bromo-1, 2,3, 9-tetrahydrocarbazole is subjected to dehydrogenation reaction in the presence of tetrachlorobenzoquinone; the dehydrogenation reaction in step (5) is carried out in a solvent.
20. The method of claim 19, wherein the molar ratio of 4-bromo-1, 2,3, 9-tetrahydrocarbazole to tetrachlorobenzoquinone is 1: 2-4.
21. The method of claim 19, wherein the solvent is used in an amount of 4-bromo-1, 2,3, 9-tetrahydrocarbazole, solvent 1g:5-20 mL.
22. The method according to claim 21, wherein in the step (5), the solvent is toluene.
23. The method according to claim 1 or 2, characterized in that it comprises the following steps under inert gas protection:
(1) carrying out condensation reaction on 1, 3-cyclohexanedione and aniline in toluene in the presence of metal oxide to obtain 3-aniline-cyclohexene-2-one;
(2) carrying out cyclization reaction on the 3-aniline-cyclohexene-2-ketone in the presence of a palladium catalyst and inorganic base to prepare 1,2,3, 9-tetrahydrocarbazole-4-ketone;
the palladium catalyst is one of palladium acetate, 1' -bis (diphenylphosphino) ferrocene palladium dichloride or tris (dibenzylideneacetone) dipalladium; the molar usage of the palladium catalyst is 3-aniline-cyclohexene-2-ketone: a palladium catalyst 1: 0.01-1; the inorganic base is one of potassium carbonate, sodium carbonate or cesium carbonate; the molar amount of the inorganic base is 3-aniline-cyclohexene-2-ketone, wherein the inorganic base is 1: 2-3;
(3) carrying out reduction reaction on the 1,2,3, 9-tetrahydrocarbazole-4-ketone and sodium borohydride in tetrahydrofuran to prepare 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole;
the dosage of the sodium borohydride is 1,2,3, 9-tetrahydrocarbazole-4-ketone, namely sodium borohydride is 1: 1-3;
(4) carrying out bromination reaction on the 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole in the presence of a bromination reagent and a catalyst to prepare 4-bromo-1, 2,3, 9-tetrahydrocarbazole;
the brominating reagent is hydrobromic acid or tribromooxyphosphorus, and the dosage of the brominating reagent is 4-hydroxy-1, 2,3, 9-tetrahydrocarbazole, wherein the brominating reagent is 1: 1-1.1;
the catalyst is ferric bromide;
(5) carrying out dehydrogenation reaction on the 4-bromo-1, 2,3, 9-tetrahydrocarbazole in toluene in the presence of tetrachlorobenzoquinone to obtain the 4-bromocarbazole; the molar ratio of the 4-bromo-1, 2,3, 9-tetrahydrocarbazole to the tetrachlorobenzoquinone is 1: 2-4.
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