1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9h-carbazole and a method for its synthesis

Abstract

This invention discloses a 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)- 9H -Carbazole and its synthetic method. The method uses 3-nitrophthalic acid as a starting material, reacting it with trichloroisocyanuric acid and liquid bromine to obtain 1,2-dibromo-3-nitrobenzene, which is then reduced by stannous chloride to obtain 2,3-dibromoaniline. This is followed by diazotization to obtain 2,3-dibromophenylhydrazine, which is then reacted with p-tert-butylcyclohexanone and dehydrogenated using 2,3-dichloro-5,6-dicyanobenzoquinone to obtain 1,2-dibromo-6-tert-butyl- 9H -Carbazole, which finally reacts with 4-tert-butyliodobenzene to give 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)- 9H -Carbazole. The 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)- 9H The presence of the bromine functional group on the -carbazole makes the further transformation of this compound scalable, and it can be used as a material / drug molecule precursor in fields such as organic light-emitting semiconductors and medicinal chemistry.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis chemistry technology, and relates to a 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole and its synthesis method. Background Technology

[0002] Carbazole and its derivatives are a class of widely used substances. The carbazole skeleton is a component of many natural bioactive substances and drug molecules, and carbazole-based organic fluorescent molecules are also important main materials in materials chemistry fields such as polymer light-emitting diodes (PLEDs) and organic light-emitting devices (OLEDs). Due to the wide range of applications of these molecules in the medical and materials fields, the synthesis, preparation, and structural modification of carbazole and its derivatives are of significant research value.

[0003] Since the first discovery of carbazole, numerous synthetic methods for the carbazole molecule have been developed. The Fischer-Borsche synthesis is a classic method for carbazole synthesis, characterized by its simplicity, mild conditions, low cost, and high yield, making it highly valuable for industrial production. In 1883, Fischer and Jourdan first reported its application to the synthesis of indole ring systems (Fischer E, Jourdan F. Berichte. Der. Deutschen. Chemischen. Gesellschaft., 1883, 16, 2241-2245.). This reaction uses phenylhydrazine and aldehyde / ketone as starting materials, and under acid catalysis, a rearrangement under heating eliminates one molecule of ammonia, yielding 2- or 3-substituted indole compounds. Subsequently, in 1908, Borsche pointed out that the Fischer indole synthesis reaction could be applied to carbazole synthesis and reported on this (Borsche W. Justus. Liebigs. Annalen. Der. Chemie., 1908, 359, 49-80.). They synthesized various tetrahydrocarbazoles by replacing one of the reaction substrates, an aldehyde / ketone, with cyclohexanone, thus verifying the feasibility of the reaction and the universality of the substrates. The resulting tetrahydrocarbazole can then be oxidatively dehydrogenated to yield carbazole compounds.

[0004] The difference between polyhalogenated carbazoles and ordinary carbazoles lies in the fact that multiple hydrogen atoms in the carbazole skeleton are replaced by halogen atoms. The presence of halogen atoms allows the compound to be further transformed, thus exhibiting reactivity scalability; in addition, halogen atoms are often present in various drugs to enhance their pharmacological activity (Voskressensky L, Golansov N, Maharramov A. Synthesis., 2016, 48, 615-643.). However, reports on the synthesis of polyhalogenated carbazoles are relatively rare.

[0005] In 2015, Humme and Lokhande developed a simple, efficient, and direct one-pot method for the iodination of tetrahydrocarbazole (Naykode MS, Humme VT, Lokhande P DJOrg. Chem., 2015, 80, 2392-2396.). The reaction uses molecular iodine in DMSO as a solvent and is carried out at 110 °C. This reaction is applicable to various electron-deficient and electron-rich groups, yielding the desired iodocarbazole with excellent yield and good regioselectivity. Researchers successfully obtained mixed-substituted iodine and chloride carbazoles using tetrahydrocarbazole with chlorine-containing substituents. However, this method is limited by the reactivity of hydrogen atoms at different positions on the carbazole, and can only yield carbazoles iodinated at specific highly active sites.

[0006] In 2016, Zhou and Shi et al. reported a highly efficient intramolecular CH arylation reaction catalyzed by the bimetallic catalytic system Pd(OAc)2 / CuI for the synthesis of fluorocarbazole from corresponding N-phenyl-2-haloaniline derivatives (Kong X, Zhang H, Cao C, et al. Bioorg. Med. Chem., 2016, 24: 1376-1383.). In 2019, the same research group synthesized a series of new compounds with two fluorine substituents at the 2 and 4 positions of carbazole based on this method, and also evaluated the antibacterial activity of these compounds (Zhou SL, Tang HL, Yao M, et al. Chem. Pap., 2019, 73, 2477-2484.). This method requires the use of the precious metal palladium, resulting in high synthesis costs. The fluorine atom substitution position of the synthesized polyfluorocarbazole depends on the substitution position of the fluorine atom in the reaction substrate, which limits the ability of this method to synthesize carbazoles with specific substitution positions (such as 1,2-difluorocarbazole). Summary of the Invention

[0007] The present invention aims to provide 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole and its synthesis method. The method uses readily available and inexpensive 3-nitrophthalic acid as a starting material. 1,2-dibromo-3-nitrobenzene is obtained by reacting trichloroisocyanuric acid with liquid bromine, followed by reduction with stannous chloride to 2,3-dibromoaniline. This is then diazotized to obtain 2,3-dibromophenylhydrazine, which is further reacted with p-tert-butylcyclohexanone and dehydrogenated with 2,3-dichloro-5,6-dicyanobenzoquinone to obtain 1,2-dibromo-6-tert-butyl-9H-carbazole. Finally, it is reacted with 4-tert-butyliodobenzene to yield 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole.

[0008] The technical solution for achieving the objective of this invention is as follows:

[0009] 1,2-Dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole, its structural formula is:

[0010] The synthetic route for 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole is as follows:

[0011]

[0012] Includes the following steps:

[0013] (1) Using trichlorobromomethane as solvent, 3-nitrophthalic acid (I), trichloroisocyanuric acid and liquid bromine as reaction reagents, free radical reaction was carried out under white light and blue light irradiation to synthesize 1,2-dibromo-3-nitrobenzene (II);

[0014] (2) Using methanol as a solvent and hydrochloric acid solution of 1,2-dibromo-3-nitrobenzene and stannous chloride as a reaction reagent, 2,3-dibromoaniline (III) was obtained by reduction.

[0015] (3) After 2,3-dibromoaniline reacts with hydrochloric acid to form a salt, it undergoes a diazotization reaction with an aqueous solution of sodium nitrite, and is then reduced with a hydrochloric acid solution of stannous chloride to obtain 2,3-dibromophenylhydrazine (IV).

[0016] (4) Using methanol as solvent, 2,3-dibromophenylhydrazine and p-tert-butylcyclohexanone as reaction reagents, and concentrated hydrochloric acid with a mass concentration of 35-38% as catalyst, the reaction was refluxed to obtain 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole (V).

[0017] (5) Using toluene as a solvent, 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole and 2,3-dichloro-5,6-dicyanobenzoquinone as reaction reagents, dehydrogenation was performed to obtain 1,2-dibromo-6-tert-butyl-9H-carbazole (VI).

[0018] (6) Using p-xylene as solvent, 1,2-dibromo-6-tert-butyl-9H-carbazole, 4-tert-butyliodobenzene, and potassium carbonate as reagents, and cuprous iodide as catalyst, reflux reaction under an inert atmosphere yielded 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole (VII).

[0019] Preferably, in step (1), the reaction temperature is 115-130℃, the reaction time is 60-72 hours, and the molar ratio of 3-nitrophthalic acid, trichloroisocyanuric acid, and liquid bromine is 1:2-2.5:4-6.

[0020] Preferably, in step (1), the post-reaction treatment method is as follows: after the reaction solution is cooled to room temperature, the reaction is quenched with saturated sodium sulfite solution, the organic phase is collected by separation, the aqueous phase is extracted with dichloromethane, the organic phases are combined, extracted with saturated brine, the organic phase is collected and dried with anhydrous sodium sulfate, filtered, the organic phase is collected, and the crude product is concentrated by rotary evaporation under reduced pressure. Finally, the crude product is purified by column chromatography with ethyl acetate / petroleum ether = 1:9 as the eluent to obtain 1,2-dibromo-3-nitrobenzene.

[0021] Preferably, step (2) specifically involves: dissolving 1,2-dibromo-3-nitrobenzene in methanol, dissolving stannous chloride in concentrated hydrochloric acid with a mass concentration of 35-38%, and then slowly adding the hydrochloric acid solution of stannous chloride to the methanol solution of 1,2-dibromo-3-nitrobenzene under stirring in an ice-water bath. The reaction is carried out at room temperature for 2.5-4 hours, with the molar ratio of 1,2-dibromo-3-nitrobenzene, stannous chloride, and hydrochloric acid being 1:2.5-4:12.4-20, and the mass concentration of concentrated hydrochloric acid being 35-38%.

[0022] Preferably, in step (2), the post-reaction treatment method is as follows: the reaction solution is concentrated by rotary evaporation under reduced pressure to remove methanol, the pH of the remaining reaction solution is adjusted to neutral using saturated sodium hydroxide solution, then extracted with ethyl acetate, the organic phase is dried with anhydrous sodium sulfate, the organic phase is collected by filtration, the crude product is concentrated by rotary evaporation under reduced pressure, and finally separated and purified by column chromatography with ethyl acetate / petroleum ether = 1:9 as the eluent to obtain 2,3-dibromoaniline.

[0023] Preferably, step (3) specifically involves: mixing 2,3-dibromoaniline and hydrochloric acid with a mass concentration of 15-25% and stirring continuously until a white slurry is formed; then slowly adding sodium nitrite solution dropwise in an ice-water bath until the reaction solution is clear; dissolving stannous chloride in concentrated hydrochloric acid with a mass fraction of 35-38%; adding the hydrochloric acid solution of stannous chloride dropwise to the clear reaction solution in an ice-water bath; reacting at room temperature for 2-4 hours; and the molar ratio of 2,3-dibromoaniline, sodium nitrite, and stannous chloride being 1:1-1.1:2-2.5.

[0024] Preferably, in step (3), the post-reaction treatment method is as follows: extract the reaction solution with ethyl acetate, retain the aqueous phase, then adjust the pH to neutral with saturated sodium hydroxide solution, extract with ethyl acetate, retain the organic phase, dry the organic phase with anhydrous sodium sulfate after extraction, filter and collect the organic phase, and concentrate under reduced pressure by rotary evaporation to obtain 2,3-dibromophenylhydrazine.

[0025] Preferably, in step (4), the reflux reaction temperature is 80-100°C and the reflux reaction time is 2.5-4 hours.

[0026] Preferably, in step (4), the post-reaction treatment method is as follows: after the reaction solution is cooled to room temperature, it is concentrated by rotary evaporation under reduced pressure, dissolved in ethyl acetate, and then extracted with saturated sodium carbonate solution and saturated brine solution respectively. After extraction, the organic phase is dried with anhydrous sodium sulfate, filtered and collected, and concentrated by rotary evaporation under reduced pressure to obtain the crude product 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole.

[0027] Preferably, step (5) specifically involves dissolving 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole and 2,3-dichloro-5,6-dicyanobenzoquinone in toluene, and adding the toluene solution of 2,3-dichloro-5,6-dicyanobenzoquinone dropwise to the toluene solution of 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole under an ice-water bath. The reaction is then carried out at room temperature for 3 to 5 hours. The molar ratio of 2,3-dibromophenylhydrazine, p-tert-butylcyclohexanone, and 2,3-dichloro-5,6-dicyanobenzoquinone is 1:1 to 1.2:2 to 2.5.

[0028] Preferably, in step (5), the post-reaction treatment method is as follows: filter the insoluble matter in the reaction solution with short silica gel, wash with ethyl acetate, concentrate the filtrate by rotary evaporation under reduced pressure, and then purify by column chromatography with dichloromethane / petroleum ether = 1:9 as the eluent to obtain 1,2-dibromo-6-tert-butyl-9H-carbazole.

[0029] Preferably, in step (6), the reflux reaction temperature is 140-160°C, the reflux reaction time is 24-48 hours, the inert atmosphere is nitrogen, and the molar ratio of 1,2-dibromo-6-tert-butyl-9H-carbazole, 4-tert-butyliodobenzene, potassium carbonate, and cuprous iodide is 1:4-6:3-5:0.2-0.5.

[0030] Preferably, in step (6), the post-reaction treatment method is as follows: after the reaction solution is cooled to room temperature, the insoluble matter is filtered through short silica gel, washed with ethyl acetate, the filtrate is concentrated by rotary evaporation under reduced pressure, and then purified by column chromatography and pulping. The eluent is dichloromethane / petroleum ether = 1:9, and the mixed solvent used for pulping is composed of dichloromethane and methanol to obtain 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole.

[0031] Compared with the prior art, the present invention has the following advantages:

[0032] (1) The 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole of the present invention is a novel compound. The presence of the bromine functional group on the molecule facilitates subsequent transformation and has potential value for application in the synthesis of pharmaceutical and organic optoelectronic materials. For example, the compound can be coupled with 1,3,5,7,8-pentamethyl-2,6-diethyl-4,4-difluoro-4-boron-(3a,4a)-diaza-s-indadiene (CAS:1394861-86-9) via the Sonogashira reaction to obtain a fluorescent molecule for use in OLED materials or biomedical imaging. Alternatively, the compound can be further modified to synthesize organometallic luminescent materials.

[0033] (2) The synthetic route of the present invention does not use a noble metal catalyst, which significantly saves costs. The carbazole bromide obtained by synthesis is at positions 1 and 2, which have low reactivity and are difficult to react.

[0034] (3) The present invention adopts a six-step synthesis reaction. Each step of the reaction is stable and reliable, and each step of the reaction can be scaled up to the gram scale. The products are easy to obtain and purify, which shows the practicality of the synthesis route and lays the foundation for further scale-up synthesis of the synthesis route. Attached Figure Description

[0035] Figure 1 For compound II 1 H NMR spectrum.

[0036] Figure 2 For compound II 13 C10 NMR spectrum.

[0037] Figure 3 For compound III 1 H NMR spectrum.

[0038] Figure 4 For compound IV 1 H NMR spectrum.

[0039] Figure 5 For compound IV 13 C10 NMR spectrum.

[0040] Figure 6 For compound VI 1 H NMR spectrum.

[0041] Figure 7 For compound VI 13 C10 NMR spectrum.

[0042] Figure 8 For compound VII 1 H NMR spectrum.

[0043] Figure 9 For compound VII 13 C10 NMR spectrum. Detailed Implementation

[0044] The present invention will be further described in detail below with reference to specific embodiments.

[0045] Example 1

[0046] (1) Synthesis of 1,2-dibromo-3-nitrobenzene:

[0047]

[0048] In a 500 mL round-bottom flask, a magnetic stir bar, 3-nitrophthalic acid (I) (70 mmol, 1 eq.), and trichloroisocyanuric acid (2 eq.) were added. Trichlorobromomethane (140 mL) was added as a solvent to dissolve the precipitate, and finally liquid bromine (4 eq.) was added. The mixture was refluxed using a Graham condenser and irradiated with two light sources: a blue and a white 45W LED. The reaction was carried out at 120 °C for 60 hours in a heating module. After the reaction was completed, the mixture was cooled to room temperature. The reaction was quenched using saturated sodium sulfite solution. The organic phase was collected by separation, and the aqueous phase was extracted with dichloromethane. The organic phases were combined, extracted with saturated brine, and then dried over anhydrous sodium sulfate. The mixture was filtered, and the organic phase was collected and concentrated by rotary evaporation under reduced pressure to obtain the crude product. The crude product was then purified by column chromatography (eluent: ethyl acetate / petroleum ether = 1:9) to give a white solid product, 1,2-dibromo-3-nitrobenzene (II), in 33% yield.

[0049] 1 H NMR (500MHz, CDCl3) δ7.84 (dd, J=8.1, 1.5Hz, 1H), 7.63 (dd, J=8.1, 1.5Hz, 1H), 7.34 (t, J=8.0Hz, 1H). 13 C NMR (126MHz, CDCl3) δ152.22,136.53,128.89,128.05,123.46,117.34.

[0050] (2) Synthesis of 2,3-dibromoaniline:

[0051]

[0052] In a 100 mL round-bottom flask, a magnetic stir bar was added. 1,2-Dibromo-3-nitrobenzene (II) (30 mmol, 1 eq.) was dissolved in methanol (15 mL), and stannous chloride (3 eq.) was dissolved in concentrated hydrochloric acid (12.4 eq.) with a mass concentration of 38%. The stannous chloride hydrochloric acid solution was slowly added dropwise to the stirred methanol solution of 1,2-dibromo-3-nitrobenzene in an ice-water bath. After the addition was complete, the ice-water bath was removed, and the reaction was allowed to proceed at room temperature for 3 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure by rotary evaporation to remove methanol. The pH of the remaining reaction solution was adjusted to neutral using saturated sodium hydroxide solution, and the solution was extracted with ethyl acetate. After extraction, the organic phase was dried over anhydrous sodium sulfate. The organic phase was collected by filtration and concentrated under reduced pressure by rotary evaporation to obtain the crude product. This crude product was then purified by column chromatography (eluent: ethyl acetate / petroleum ether = 1:9) to give a white solid 2,3-dibromoaniline (III) in 87% yield.

[0053] 1 H NMR (500MHz, CDCl3) δ7.01 (dd, J=7.9, 1.6Hz, 1H), 6.95 (t, J=7.9Hz, 1H), 6.68 (dd, J=7.9, 1.5Hz, 1H), 4.07 (br, 2H).

[0054] (3) Synthesis of 2,3-dibromophenylhydrazine:

[0055]

[0056] First, in a 50 mL round-bottom flask, add a magnetic stir bar, 10 mmol of 2,3-dibromoaniline (III), and 10 mL of 18% hydrochloric acid. Stir continuously until the reaction solution becomes a white, homogeneous slurry. Dissolve 10 mmol of sodium nitrite in 10 mL of water. Slowly add the sodium nitrite solution dropwise to the reaction solution in an ice-water bath. After the addition is complete, wait until the reaction solution is clear before proceeding to the second step of the reaction. Dissolve 20 mmol of stannous chloride in 6 mL of 38% concentrated hydrochloric acid to prepare a solution. Add the stannous chloride solution dropwise to the reaction solution from the first step in an ice-water bath. After the addition is complete, remove the ice-water bath and incubate the reaction at a constant temperature for 2 hours. After the reaction is complete, extract the reaction solution with ethyl acetate, retaining the aqueous phase. Adjust the pH of the solution to neutral using saturated sodium hydroxide solution. Extract again with ethyl acetate, retaining the organic phase. After extraction, dry the organic phase with anhydrous sodium sulfate. The organic phase was collected by filtration and concentrated by rotary evaporation under reduced pressure to obtain a white solid, 2,3-dibromophenylhydrazine (IV). When exposed to air, it gradually oxidizes to a yellow color, with a yield of 74%.

[0057] 1H NMR(500MHz, CDCl3)δ7.12(t,J=7.9Hz,1H),7.05(m,2H),5.88(br,1H),3.66(br,2H).13C NMR (126MHz, CDCl3) δ149.52,128.96,125.45,122.98,110.57,109.63.

[0058] (4) Synthesis of 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole:

[0059]

[0060] In a 100 mL round-bottom flask, a magnetic stir bar was added, along with 2,3-dibromophenylhydrazine (IV) (15 mmol, 1 eq.) and p-tert-butylcyclohexanone (1.1 eq.), dissolved in methanol (30 mL). Then, 38% concentrated hydrochloric acid (1 eq.) was added, and the mixture was refluxed using a condenser. The flask was placed in a heating element and reacted at 100 °C for 2.5 hours. After the reaction was complete, the mixture was cooled to room temperature. The reaction solution was concentrated by rotary evaporation under reduced pressure, dissolved in ethyl acetate, and extracted with saturated sodium carbonate solution and saturated brine, respectively. After extraction, the organic phase was dried over anhydrous sodium sulfate. The organic phase was collected by filtration and concentrated by rotary evaporation under reduced pressure to obtain the crude product 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole (V), which could be used in the next step without further separation.

[0061] (5) Synthesis of 1,2-dibromo-6-tert-butyl-9H-carbazole:

[0062]

[0063] Crude 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1H-carbazole (V) was dissolved in a suitable amount of toluene in a 100 mL round-bottom flask (with a magnetic stir bar). 1 eq. was calculated based on the 15 mmol molar amount of 2,3-dibromophenylhydrazine added in step (4). 2 eq. of 2,3-dichloro-5,6-dicyanobenzoquinone was weighed and dissolved in toluene. The toluene solution of 2,3-dichloro-5,6-dicyanobenzoquinone was added dropwise to the round-bottom flask while reacting under ice-water bath conditions. After the addition was complete, the ice-water bath was removed, and the reaction was allowed to proceed at room temperature for 3.5 hours. The total amount of toluene used was ensured to be 30 mL. After the reaction was complete, the insoluble matter in the reaction solution was filtered through a short silica gel filter, washed with ethyl acetate, and the filtrate was concentrated by rotary evaporation under reduced pressure. The product was then purified by column chromatography (eluent: dichloromethane / petroleum ether = 1:9) to obtain a white solid product 1,2-dibromo-6-tert-butyl-9H-carbazole (VI). The overall yield of the two steps (4) and (5) was 97%.

[0064] 1 H NMR (500MHz, CDCl3) δ8.21(br,1H),8.01(s,1H),7.87(d,J=8.2Hz,1H),7.56(dd,J=8.6,1.8Hz,1H),7.44(m,2H),1.44(s,9H). 13 C NMR (126MHz, CDCl3) δ143.71,139.75,137.45,124.99,123.96,123.46,123.25,120.63,119.98,116.82,110.69,106.65,34.81,31.94.

[0065] (6) Synthesis of 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole:

[0066]

[0067] In a 250 mL round-bottom flask, a magnetic stir bar was added, along with 1,2-dibromo-6-tert-butyl-9H-carbazole (VI) (15 mmol, 1 eq.), 4-tert-butyliodobenzene (4 eq.), cuprous iodide (20 mol%) as catalyst, potassium carbonate (4 eq.) as base, and p-xylene (75 mL) as solvent. A condenser was installed, and after purging with nitrogen, a cooling water circulation system was started. The flask was placed in a heating module and reacted at 150 °C for 24 hours. After the reaction was complete, the mixture was cooled to room temperature. The insoluble matter in the reaction solution was filtered through a short silica gel filter, washed with ethyl acetate, and the filtrate was concentrated by rotary evaporation under reduced pressure. The filtrate was then purified by column chromatography (eluent: dichloromethane / petroleum ether = 1:9) and pulping (dichloromethane / methanol) to obtain the white solid product 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-9H-carbazole (VII) in 92% yield. 1 H NMR(500MHz, CDCl3)δ8.06(d,J=1.5Hz,1H),7.96(d,J=8.2Hz,1H),7.53(m,3H),7.47(dd, J=8.7,1.8Hz,1H),7.29(d,J=8.4Hz,2H),7.01(d,J=8.7Hz,1H),1.43(s,9H),1.42(s,9H). 13CNMR (126MHz, CDCl3) δ151.93,144.02,141.93,139.55,135.31,129.41,125.85,125.19,12 4.90,124.51,123.65,121.54,119.85,115.95,110.67,106.61,34.91,34.81,31.97,31.56.

[0068] Comparative Example 1

[0069] This comparative example is basically the same as Example 1, except that carbon tetrachloride is used as the solvent in step (1). The yield is less than 10%.

[0070] Comparative Example 2

[0071] This comparative example is basically the same as Example 1, except that chloroform is used as the solvent in step (1). The yield is less than 10%.

[0072] Comparative Example 3

[0073] This comparative example is basically the same as Example 1, except that only white light irradiation is used in step (1). The yield is 23%.

[0074] Comparative Example 4

[0075] This comparative example is basically the same as Example 1, except that in step (2), ethanol (30 mL) is used as the solvent, and reduced iron powder (3 eq.) and concentrated hydrochloric acid (1.24 eq.) with a mass concentration of 38% are used as the reaction reagents. The reaction is carried out under reflux at 85°C for 2 hours. The yield is 50%.

[0076] Comparative Example 5

[0077] This comparative example is basically the same as Example 1, except that acetic acid is used as a solvent in step (4), and hydrochloric acid is not added as a catalyst. The combined yield of the two steps after the dehydrogenation reaction of 2,3-dichloro-5,6-dicyanobenzoquinone is 26%.

[0078] Comparative Example 6

[0079] This comparative example is essentially the same as Example 1, except that acetic acid is used as the solvent in step (4). The combined yield of the two steps after the dehydrogenation reaction of 2,3-dichloro-5,6-dicyanobenzoquinone was 62%.

[0080] Comparative Example 7

[0081] This comparative example is essentially the same as Example 1, except that 1,2-dichloroethane is used as the solvent in step (4). The combined yield of the two steps after the dehydrogenation reaction of 2,3-dichloro-5,6-dicyanobenzoquinone is 45%.

[0082] Comparative Example 8

[0083] This comparative example is essentially the same as Example 1, except that cesium carbonate is used as the base in step (6), and the reaction is carried out for 12 hours, yielding 4-tert-butyliodobenzene (1.5 eq.). The yield is less than 5%.

[0084] Comparative Example 9

[0085] This comparative example is basically the same as Example 1, except that potassium tert-butoxide is used as the base in step (6), and the reaction is carried out for 12 hours, yielding 4-tert-butyliodobenzene (1.5 eq.). The yield is 34%.

[0086] Comparative Example 10

[0087] This comparative example is essentially the same as Example 1, except that sodium bicarbonate is used as the base in step (6), and the reaction is carried out for 12 hours with 4-tert-butyliodobenzene (1.5 eq.). The yield is less than 5%.

[0088] Comparative Example 11

[0089] This comparative example is basically the same as Example 1, except that the reaction time in step (6) is 12 hours, with 4-tert-butyliodobenzene (1.5 eq.). The yield is 50%.

[0090] Comparative Example 12

[0091] This comparative example is basically the same as Example 1, except that in step (6), the reaction is carried out in an air atmosphere for 12 hours, yielding 4-tert-butyliodobenzene (1.5 eq.). The yield is 45%.

[0092] Comparative Example 13

[0093] This comparative example is basically the same as Example 1, except that the 4-tert-butyliodobenzene equivalent in step (6) is changed to 1.5 eq. The yield is 53%.

[0094] Comparative Example 14

[0095] This comparative example is basically the same as Example 1, except that the 4-tert-butyliodobenzene equivalent in step (6) is changed to 2 eq. The yield is 66%.

Claims

1. 1,2-Dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-carbazole 9H Process for the synthesis of 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-carbazole, characterized in that, Comprise the following steps: (1) with trichlorobromomethane as solvent, with 3-nitrophthalic acid, trichloroisocyanuric acid and liquid bromine as reaction reagent, under the irradiation of white light and blue light, free radical reaction is carried out, and 1,2-dibromo-3-nitrobenzene is synthesized; (2) with methanol as solvent, with 1,2-dibromo-3-nitrobenzene and stannous chloride hydrochloride solution as reaction reagent, reduction is carried out to obtain 2,3-dibromoaniline; (3) after 2,3-dibromoaniline is reacted with hydrochloric acid to form salt, diazotization reaction is carried out with sodium nitrite aqueous solution, and then reduction is carried out with stannous chloride hydrochloride solution to obtain 2,3-dibromo phenyl hydrazine, and step (3) is specifically as follows: 2,3-dibromoaniline and 15-25% hydrochloric acid are mixed and continuously stirred until white paste is obtained, then sodium nitrite solution is slowly added into the white paste in an ice water bath, and the reaction is carried out until the reaction solution is clear;Stannous chloride is dissolved in 35-38% concentrated hydrochloric acid, and the stannous chloride hydrochloride solution is added into the clear reaction solution in an ice water bath, and the reaction is carried out at room temperature for 2-4 hours; (4) using methanol as a solvent, 2,3-dibromophenylhydrazine and p-tert-butyl cyclohexanone as reaction reagents, and concentrated hydrochloric acid with a mass concentration of 35-38% as a catalyst, refluxing to obtain 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro- 1H -carbazole; (5) 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1 H-carbazole was prepared by using toluene as solvent, 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro-1 H-carbazole as reactant, and dehydrogenation with carbazole and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as reaction reagent to obtain 1,2-dibromo-6-tert-butyl-1,2-dihydrocarbazole; 1H 9H carbazole;​ (6) 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)-carbazole was obtained by using p-xylene as solvent, 1,2-dibromo-6-tert-butyl-carbazole, 4-tert-butyl iodobenzene, potassium carbonate as reaction reagents, cuprous iodide as catalyst, and refluxing under inert atmosphere. 9H 9H ;​​ In step (4), the reflux reaction temperature is 80-100 DEG C, and the reflux reaction time is 2.5-4 hours; In step (5), the room temperature reaction is carried out for 3-5 hours; In step (6), the reflux reaction temperature is 140-160 DEG C, and the reflux reaction time is 24-48 hours.

2. The method of synthesis according to claim 1, wherein, In step (1), the reaction temperature is 115-130 DEG C, the reaction time is 60-72 hours, and the molar ratio of 3-nitrophthalic acid, trichloroisocyanuric acid and liquid bromine is 1:2-2.5:4-6.

3. The method of synthesis of claim 1, wherein, In step (1), after the reaction, the reaction liquid is cooled to room temperature, saturated sodium sulfite solution is used to quench the reaction, the organic phase is collected by liquid separation, the water phase is extracted with dichloromethane, the organic phases are combined, saturated brine is used for extraction, then the organic phase is collected, dried with anhydrous sodium sulfate, filtered, the organic phase is collected, concentrated by rotary evaporation under reduced pressure to obtain the crude product, finally, column chromatography is used for separation and purification, the eluent is ethyl acetate / petroleum ether=1:9, and 1,2-dibromo-3-nitrobenzene is obtained.

4. The method of synthesis of claim 1, wherein, Step (2) is specifically as follows: 1,2-dibromo-3-nitrobenzene is dissolved in methanol, stannous chloride is dissolved in 35-38% concentrated hydrochloric acid, then the stannous chloride hydrochloride solution is slowly added into the methanol solution of 1,2-dibromo-3-nitrobenzene under stirring in an ice water bath, the reaction is carried out at room temperature for 2.5-4 hours, the molar ratio of 1,2-dibromo-3-nitrobenzene, stannous chloride and hydrochloric acid is 1:2.5-4:12.4-20, and the mass concentration of concentrated hydrochloric acid is 35-38%.

5. The method of synthesis of claim 1, wherein, In step (2), after the reaction, the reaction liquid is concentrated by rotary evaporation under reduced pressure to remove methanol, saturated sodium hydroxide solution is used to adjust the pH of the remaining reaction liquid to neutral, then the reaction liquid is extracted with ethyl acetate, the organic phase is dried with anhydrous sodium sulfate, the organic phase is collected by filtration, concentrated by rotary evaporation under reduced pressure to obtain the crude product, finally, column chromatography is used for separation and purification, the eluent is ethyl acetate / petroleum ether=1:9, and 2,3-dibromoaniline is obtained.

6. The method of synthesis of claim 1, wherein, In step (3), the molar ratio of 2,3-dibromoaniline, sodium nitrite and stannous chloride is 1:1~1.1:2~2.5; the post-reaction treatment method is: extracting the reaction solution with ethyl acetate, retaining the aqueous phase, then adjusting the pH to neutral with saturated sodium hydroxide solution, extracting with ethyl acetate, retaining the organic phase, drying the organic phase with anhydrous sodium sulfate after extraction, collecting the organic phase by filtration, and concentrating under reduced pressure to obtain 2,3-dibromo phenylhydrazine.

7. The method of synthesis of claim 1, wherein, In step (4), the reaction work-up method is as follows: after the reaction solution is cooled to room temperature, it is concentrated under reduced pressure by rotary evaporation, dissolved in ethyl acetate, and extracted with saturated sodium carbonate solution and saturated brine respectively, and then the organic phase is dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro- 1H -carbazole.

8. The method of synthesis of claim 1, wherein, Step (5) is specifically: 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro- carbazole and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone are dissolved in toluene, the toluene solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is added dropwise into the toluene solution of 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro- carbazole under ice water bath, then the reaction is carried out at room temperature for 3-5 hours, the molar ratio of 2,3-dibromo phenylhydrazine, p-tert-butyl cyclohexanone, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is 1:1-1.2:2-2.5; the post-treatment method of the reaction is: the insoluble substances in the reaction solution are filtered by short silica gel, then the filter liquor is washed by ethyl acetate, then the filter liquor is concentrated by rotary evaporation under reduced pressure, then the concentrated solution is separated and purified by column chromatography, the eluent is dichloromethane / petroleum ether=1:9, to obtain 1,2-dibromo-6-tert-butyl- carbazole. 1H 1H 9H Step (5) is specifically: 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro- carbazole and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone are dissolved in toluene, the toluene solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is added dropwise into the toluene solution of 7,8-dibromo-3-(tert-butyl)-2,3,4,9-tetrahydro- carbazole under ice water bath, then the reaction is carried out at room temperature for 3-5 hours, the molar ratio of 2,3-dibromo phenylhydrazine, p-tert-butyl cyclohexanone, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is 1:1-1.2:2-2.5; the post-treatment method of the reaction is: the insoluble substances in the reaction solution are filtered by short silica gel, then the filter liquor is washed by ethyl acetate, then the filter liquor is concentrated by rotary evaporation under reduced pressure, then the concentrated solution is separated and purified by column chromatography, the eluent​​ 9. The method of synthesis of claim 1, wherein, In step (6), the inert atmosphere is nitrogen atmosphere, the molar ratio of 1,2-dibromo-6-tert-butyl- 9H carbazole, 4-tert-butyl iodobenzene, potassium carbonate, cuprous iodide is 1:4~6:3~5:0.2~0.5; the reaction post-processing method is: after the reaction solution is cooled to room temperature, insoluble substances are filtered through short silica gel, and then the filter liquor is washed with ethyl acetate, concentrated under reduced pressure, and then separated and purified by column chromatography and slurry, the eluent is dichloromethane / petroleum ether = 1:9, and the mixed solvent used for slurry is composed of dichloromethane and methanol, to obtain 1,2-dibromo-6-tert-butyl-9-(4-tert-butylphenyl)- 9H carbazole.

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