CN107935913B - Carbazole compound and synthesis method and application thereof - Google Patents

Carbazole compound and synthesis method and application thereof Download PDF

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CN107935913B
CN107935913B CN201711046112.0A CN201711046112A CN107935913B CN 107935913 B CN107935913 B CN 107935913B CN 201711046112 A CN201711046112 A CN 201711046112A CN 107935913 B CN107935913 B CN 107935913B
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iodine salt
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CN107935913A (en
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姜雪峰
王明
范巧玲
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East China Normal University
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    • 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
    • C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • 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
    • 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

Abstract

The invention discloses a carbazole compound shown in a formula (2) and a synthesis method thereof, which take high-iodine salt as a reaction raw material, and react in a solvent under the action of an inorganic nitrogen reagent, an additive, alkali and a metal catalyst at the temperature of 80-150 ℃ to obtain various carbazole compounds. The invention avoids the incompatibility of the nitrogen heterocyclic ring to the reaction conditions of metal catalysts and the like in the early reaction by introducing nitrogen atoms in the later period; in addition, the full utilization of the two aryl groups in the high-iodine salt fully shows the atom economy of the method. The carbazole compound prepared by the method can be further applied to the synthesis of the non-steroidal anti-inflammatory drug carprofen.

Description

Carbazole compound and synthesis method and application thereof
Technical Field
The invention belongs to the technical field of synthesis and application of organic compounds, and relates to a novel method for synthesizing carbazole compounds and application thereof, in particular to synthesis of functionalized carbazole compounds and application thereof in preparation of non-steroidal anti-inflammatory drug Carprofen (Carprofen).
Background
Carbazole compounds are a very important compound, and are particularly widely applied to material molecules and drug molecules, as shown in formula (C) antihypertensive drug catalol (Carazolol), formula (D) antihypertensive drug Carvedilol (Carvedilol) and formula (E) anti-inflammatory drug Carprofen (Carprofen). Therefore, it is very important to develop a method for synthesizing carbazole compounds with high efficiency, environmental protection and good compatibility.
Figure BDA0001452290850000011
The traditional method for synthesizing carbazole compounds is mainly prepared by intramolecular coupling of aryl halides and arylamines or oxidative coupling of diarylamines. The traditional method is to introduce nitrogen in the early stage, while nitride has complexation effect on metal catalyst in the later reaction and is incompatible with oxidant; at the same time, the protection and deprotection of the nitrogen-containing compound is not favorable for the simplification of the reaction steps; on the other hand, high-iodine salts are widely used as arylating reagents as a class of easily prepared and stable compounds, and when the traditional high-iodine salts are used as arylating reagents, only one aryl group is generally utilized, so that the atom economy of the high-iodine salts is poor. Therefore, there is a trend in recent years to develop efficient utilization of the two aryl groups in high iodine salts.
Disclosure of Invention
The invention overcomes the defects in the prior art, and innovatively provides a method for efficiently constructing carbazole compounds by directly introducing nitrogen atoms at the later stage and applying high-iodine salt with atom economy. The synthesis method adopts high-iodine salt as a reaction raw material, and synthesizes the carbazole compound under the action of an inorganic nitrogen reagent, a metal catalyst, alkali and an additive. The synthesis method has the advantages of cheap and easily-obtained raw materials, wide substrate universality and better yield.
The invention provides a synthesis method of carbazole compounds, which takes high-iodine salt shown in formula (1) as a reaction raw material, and the carbazole compounds shown in formula (2) are obtained by reaction in a solvent under the action of an inorganic nitrogen reagent, alkali, a metal catalyst and an additive. The reaction process is shown in the following reaction formula (A).
Figure BDA0001452290850000021
Wherein the content of the first and second substances,Ar1、Ar2is aryl or aryl heterocycle with various substituents;
preferably, it is 2-methoxyphenyl, 2-acetamidophenyl, 2-tert-butylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-trifluoromethylphenyl, 3-chlorophenyl, 4-methylphenyl, 4-chlorophenyl, naphthyl, 2-bromo-6-chlorophenyl, 5-methyl-2-methylbiphenyl or 2-biphenyl.
X-Is an anion of a high iodine salt selected from a p-toluenesulfonic acid anion, a trifluoromethanesulfonic acid anion, a tetrafluoroboric acid anion, a hexafluorophosphoric acid anion, an iodide anion, a bromide anion or a chloride anion; preferably, p-toluenesulfonic acid anion and trifluoromethanesulfonic acid anion.
In the present invention, specifically, the carbazole-based compound includes carbazole, 2-methoxycarbazole, 2-acetaminocarbazole, 2-tert-butylcarbazole, 2-fluorocarbazole, 2-chlorocarbazole, 2-bromocarbazole, 2-trifluoromethylcarbazole, 3-chlorocarbazole, 4-methylcarbazole, 4-chlorocarbazole, 7H-benzo [ c ] carbazole, 2-bromo-6-chlorocarbazole, 5-methyl-2-o-tolylcarbazole, and 2-phenylcarbazole.
In the invention, the reaction temperature is 80-150 ℃; preferably, it is 100 ℃.
In the invention, the reaction time is 6-15 hours; preferably, it is 12 hours.
In the present invention, the solvent is selected from one or more of dimethylsulfoxide, N-dimethylformamide, N-dimethylacetamide DMA, N-methylpyrrolidone, and the like; preferably, it is N, N-dimethylacetamide.
In the invention, the inorganic nitrogen reagent is a reaction nitrogen source and is selected from one or more of sodium azide, potassium azide and the like; preferably, sodium azide.
In the invention, the dosage molar ratio of the high-iodine salt to the inorganic nitrogen reagent is 1 (1-5); preferably, the molar ratio of the high iodine salt to the inorganic nitrogen reagent is 1: 2.
In the present invention, the base is selected from one or more of potassium phosphate, dipotassium hydrogen phosphate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, sodium hydroxide, potassium hydroxide, triethylamine, diisopropylethylamine, DBU (1, 8-diazacyclo [5,4,0] undecene-7), and the like; preferably, it is potassium phosphate.
In the invention, the molar ratio of the high-iodine salt to the alkali is 1 (1-5); preferably, the molar ratio of the high-iodine salt to the base is 1: 2.
In the invention, the metal catalyst is selected from one or more of cuprous thiophene-2-carboxylate (CuTc), copper trifluoromethanesulfonate, copper acetylacetonate, cuprous iodide, copper acetate, copper sulfate and the like; preferably, it is cuprous thiophene-2-carboxylate (CuTc).
In the invention, the molar ratio of the high-iodine salt to the metal catalyst is 1 (0.05-1); preferably, the molar ratio of the high-iodine salt to the metal catalyst is 1: 0.1.
In the present invention, the additive is selected from triphenylphosphine (PPh)3) One or more of tris (2-methylphenyl) phosphine, tris (4-methylphenyl) phosphine, tris (2-methoxyphenyl) phosphine, tris (4-methoxyphenyl) phosphine, and the like; preferably, triphenylphosphine (PPh)3)。
In the invention, the molar ratio of the high-iodine salt to the additive is 1 (1-5); preferably, the molar ratio of the high-iodine salt to the additive is 1: 1.5.
In the present invention, the reaction is preferably carried out under nitrogen protection.
In the present invention, when the inorganic nitrogen reagent is sodium azide NaN3Firstly, carrying out anion exchange on sodium azide and high-iodine salt 1 to obtain an intermediate 3, reducing and eliminating the intermediate 3 to obtain an intermediate 4, forming a nitrogen-phosphorus compound intermediate 5 by the intermediate 4 under the action of triphenylphosphine, forming a trivalent copper intermediate 6 by the intermediate 5 under the action of a copper catalyst, namely the cuprous thiophene-2-carboxylate, and reducing and eliminating the intermediate 6 under the action of water to obtain a carbazole compound 2.
Figure BDA0001452290850000031
The invention also provides a carbazole compound shown in the formula (2),
Figure BDA0001452290850000041
wherein Ar is1、Ar2Is aryl or aryl heterocycle with various substituents;
preferably, it is 2-methoxyphenyl, 2-acetamidophenyl, 2-tert-butylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-trifluoromethylphenyl, 3-chlorophenyl, 4-methylphenyl, 4-chlorophenyl, naphthyl, 2-bromo-6-chlorophenyl, 5-methyl-2-methylbiphenyl, or 2-biphenyl.
In the present invention, specifically, the carbazole-based compound includes carbazole, 2-methoxycarbazole, 2-acetaminocarbazole, 2-tert-butylcarbazole, 2-fluorocarbazole, 2-chlorocarbazole, 2-bromocarbazole, 2-trifluoromethylcarbazole, 3-chlorocarbazole, 4-methylcarbazole, 4-chlorocarbazole, 7H-benzo [ c ] carbazole, 2-bromo-6-chlorocarbazole, 5-methyl-2-o-tolylcarbazole, and 2-phenylcarbazole.
The invention also provides the carbazole compound shown in the formula (2) prepared by the synthesis method.
The invention also provides application of the carbazole compound in preparation of non-steroidal anti-inflammatory drug Carprofen (2- (6-chlorocarbazole-2-yl) propionic acid).
The invention has the beneficial effects that: the invention provides a method for preparing carbazole compounds by introducing nitrogen atoms at a later stage, which avoids incompatibility of nitrogen heterocyclic rings to reaction conditions such as metal catalysts and the like in the early-stage reaction; in addition, the full utilization of the two aryl groups in the high-iodine salt fully shows the atom economy of the method. Compared with the traditional method for preparing the carbazole compound by coupling and cyclizing, the method simplifies the operation steps.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, but the present invention is not limited to the following examples. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited. The data given in the examples below include specific operating and reaction conditions and products. The purity of the product was identified by nuclear magnetism.
In examples 1 to 16, the reaction temperature was 100 ℃.
In example 16, the carbazole-based compound obtained can be further converted to obtain Carprofen (2- (6-chlorocarbazol-2-yl) propionic acid), which is a non-steroidal anti-inflammatory drug.
The synthesis reaction of the carbazole compound comprises the following steps: under the protection of nitrogen, high-iodine salt (0.1mmol) and NaN are added3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. And (3) after the reaction is stirred for a specified time at a specified temperature, cooling to room temperature, adding 10mL of water into the system for dilution, adding ethyl acetate (10mL of 3) for extraction, drying by anhydrous sodium sulfate, filtering, concentrating, and carrying out column chromatography separation to obtain a purified target product.
Example 1
Synthesis of compound 2 a:
Figure BDA0001452290850000051
under the protection of nitrogen, high-iodine salt 1a (42.8mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. The reaction is stirred for 12h at 100 ℃, then cooled to room temperature, and 10mL of water is added into the system for dilution, and thenExtraction was performed by adding ethyl acetate (10mL × 3), dried over anhydrous sodium sulfate, filtered, concentrated, and isolated by column chromatography to give colorless oil 2a (12.6mg, 89%).1H NMR(400MHz,CDCl3)8.13-8.02(m,3H),7.47-7.39(m,4H),7.28-7.20(m,2H)；13C NMR(100MHz,CDCl3)139.5,125.8,123.3,120.3,119.4,110.6；MS(EI)m/z＝167(100).
Example 2
Synthesis of compound 2 b:
Figure BDA0001452290850000052
under the protection of nitrogen, high-iodine salt 1b (45.8mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10mL × 3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to isolate white solid 2b (14.8mg, 75%).1H NMR(400MHz,d6-DMSO)11.11(s,1H),7.97(t,J＝8.6Hz,2H),7.41(d,J＝8.0Hz,1H),7.27(t,J＝7.6Hz,1H),7.10(t,J＝7.3Hz,1H),6.96(d,J＝2.1Hz,1H),6.76(dd,J＝8.5,2.2Hz,1H),3.84(s,3H)；13C NMR(100MHz,d6-DMSO)158.5,141.1,139.7,124.1,122.6,120.9,119.2,118.5,116.2,110.6,107.7,94.4,55.2；IR(KBr)ν3399,2924,2856,1729,1607,1460,1376,1303,1165,1153,1030,798,751cm-1；HRMS(EI)for C13H11NO Calculated:197.0841,found:197.0840.
Example 3
Synthesis of compound 2 c:
Figure BDA0001452290850000061
under the protection of nitrogen, high-iodine salt 1c (48.5mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10mL × 3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2c (10.1mg, 45%) as a white solid.1H NMR(500MHz,d6-acetone)8.22(d,J＝1.7Hz,1H),8.01(d,J＝7.8Hz,1H),7.97(d,J＝8.4Hz,1H),7.46(d,J＝8.1Hz,1H),7.35-7.28(m,1H),7.19(dd,J＝8.4,1.8Hz,1H),7.14(t,J＝7.5Hz,1H),2.13(s,3H)；13C NMR(126MHz,d6-acetone)168.8,141.4,141.1,138.6,125.6,124.0,120.9,120.3,119.7,112.0,111.4,102.1,24.4；IR(KBr)ν2925,2859,1666,1601,1543,1459,1375,1253,1164,1030,727cm-1；HRMS(EI)for C14H12N2O Calculated:224.0950,found:224.0955.
Example 4
Synthesis of compound 2 d:
Figure BDA0001452290850000071
under the protection of nitrogen, high-iodine salt 1d (48.5mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12h, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10mL × 3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2d (21.7mg, 97%) as a white solid.1H NMR(400MHz,CDCl3)8.07-7.91(m,3H),7.46-7.35(m,3H),7.32(dd,J＝8.3,1.6Hz,1H),7.25-7.17(m,1H),1.43(s,9H)；13C NMR(100MHz,CDCl3)149.6,139.8,139.7,125.3,123.4,120.9,120.1,119.8,119.3,117.5,110.4,107.1,35.1,31.8；IR(KBr)ν3422,2924,2856,1629,1460,1376,1249,816,736cm-1；HRMS(EI)for C16H17N Calculated:223.1361,found:223.1363.
Example 5
Synthesis of compound 2 e:
Figure BDA0001452290850000072
under the protection of nitrogen, high-iodine salt 1e (44.6mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10 mL. times.3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2e (15.4mg, 83%) as a white solid.1H NMR(400MHz,d6-acetone)10.46(brs,1H),8.14-8.02(m,2H),7.51(d,J＝8.1Hz,1H),7.41-7.33(m,1H),7.28-7.16(m,2H),7.05-6.86(m,1H)；13C NMR(100MHz,d6-acetone)164.0,161.6,141.7,141.6,126.2,123.6,122.1/122.0(J＝10.6Hz),120.6,120.2,111.8,107.7/107.4(J＝24.4Hz),98.3/98.0(J＝26.4Hz)；19F NMR(376MHz,CDCl3)59.8；IR(KBr)ν3421,2885,1487,1306,1261,592,508cm-1；HRMS(EI)for C12H8FN Calculated:185.0641,found:185.0642.
Example 6
Synthesis of compound 2 f:
Figure BDA0001452290850000081
under the protection of nitrogen, high-iodine salt 1f (46.3mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10 mL. times.3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to isolate 2f (14.9mg, 74%) as a white solid.1H NMR(400MHz,d6-DMSO)11.39(s,1H),8.12(d,J＝8.3Hz,2H),7.55-7.47(m,2H),7.45-7.35(m,1H),7.22-7.11(m,2H)；13C NMR(100MHz,d6-DMSO)140.3,140.1,129.8,125.9,121.8,121.5,121.3,120.3,119.0,118.6,111.2,110.6；IR(KBr)ν3393,2923,2854,1602,1454,1325,1263,1067,852,808,753cm-1；HRMS(EI)for C12H8ClN Calculated:201.0345,found:201.0347.
Example 7
Synthesis of Compound 2 g:
Figure BDA0001452290850000091
under the protection of nitrogen, 1g (50.7mg,0.1mmol) of high-iodine salt, NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, the reaction mixture was cooled to room temperature, and 10mL of water was added to the reaction mixture to dilute the reaction mixture, followed by addition of ethyl acetate (10 mL. times.3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to obtain 2g (15.5mg, 63%) of a white solid.1H NMR(400MHz,d6-acetone)10.51(brs,1H),8.12(d,J＝7.7Hz,1H),8.06(d,J＝8.3Hz,1H),7.71(d,J＝1.7Hz,1H),7.53(d,J＝8.2Hz,1H),7.45-7.39(m,1H),7.32(dd,J＝8.3,1.7Hz,1H),7.24-7.16(m,1H)；13C NMR(100MHz,d6-acetone)141.9,141.2,127.0,123.3,123.1,122.6,122.4,121.0,120.3,119.3,114.6,112.0；IR(KBr)ν3396,2925,2111,1600,1438,1324,1238,1053,854,811,750cm-1；HRMS(EI)for C12H8BrN Calculated:244.9840,found:244.9841.
Example 8
Synthesis of compound 2 h:
Figure BDA0001452290850000092
high-iodine salt is added for 1h (49.6mg,0.1mmol) and NaN under the protection of nitrogen3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12h, it was cooled to room temperature, and 10mL of water was added to dilute the reaction, followed by addition of ethyl acetate (10 mL. times.3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give a white solid for 2h (15.3mg, 65%).1H NMR(400MHz,d6-DMSO)11.65(brs,1H),8.34(d,J＝8.1Hz,1H),8.23(d,J＝7.8Hz,1H),7.82(s,1H),7.59(d,J＝8.2Hz,1H),7.52-7.42(m,2H),7.24(t,J＝7.5Hz,1H)；13C NMR(100MHz,d6-DMSO)140.8,138.7,127.0,125.7,125.3,123.7,121.4,121.1,121.0,119.3,114.8(q,J＝3.3Hz),111.5,108.0(q,J＝4.2Hz),；19F NMR(376MHz,d6-DMSO)-59.2；IR(KBr)ν3423,1442,1340,1168,1105,825,731cm-1；HRMS(EI)for C13H8F3N Calculated:235.0609,found:235.0611.
Example 9
Synthesis of compound 2 i:
Figure BDA0001452290850000101
under the protection of nitrogen, high-iodine salt 1i (46.3mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10mL × 3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to isolate 2i (12.1mg, 60%) as a white solid.1H NMR(400MHz,d6-acetone)10.48(brs,1H),8.17-8.12(m,2H),7.57-7.49(m,2H),7.45-7.34(m,2H),7.21(t,J＝7.5Hz,1H)；13C NMR(100MHz,d6-acetone)141.7,139.4,127.3,126.3,125.3,124.7,123.1,121.3,120.6,120.1,113.1,112.0；IR(KBr)ν3404,2924,2854,1718,1601,1445,1266,1185,1074,970,877,748,695cm-1；HRMS(EI)for C12H8ClN Calculated:201.0345,found:201.0343.
Example 10
Synthesis of compound 2 j:
Figure BDA0001452290850000111
under the protection of nitrogen, high-iodine salt 1j (44.2mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10mL × 3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2j (12.0mg, 66%) as a colorless oil.1H NMR(400MHz,CDCl3)8.10(d,J＝7.9Hz,1H),7.96(brs,1H),7.37-7.30(m,2H),7.27-7.12(m,3H),6.94(d,J＝7.0Hz,1H),2.80(s,3H)；13C NMR(100MHz,CDCl3)139.5(0),139.4(8),133.4,125.7,125.2,124.0,122.6,121.9,120.9,119.4,110.3,108.1,20.8；IR(KBr)ν3385,3054,2925,2853,1600,1453,1390,1326,1258,1214,1079,724cm-1；HRMS(EI)for C13H11N Calculated:181.0891,found:181.0890.
Example 11
Synthesis of compound 2 k:
Figure BDA0001452290850000112
under the protection of nitrogen, high-iodine salt 1k (46.3mg,0.1mmol) and NaN are added3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, the reaction was cooled to room temperature, and 10mL of water was added to the reaction system to dilute the reaction, followed by addition of ethyl acetate (10mL × 3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to obtain 2k (8.5mg, 42%) as a white solid.1H NMR(400MHz,CDCl3)8.52(d,J＝8.0Hz,1H),8.08(brs,1H),7.48-7.34(m,2H),7.32-7.08(m,4H)；13C NMR(100MHz,CDCl3)140.5,139.5,128.8,126.4,126.1,123.1,122.3,120.7,120.3,119.9,110.3,108.9；IR(KBr)ν3412,3059,2924,1899,1602,1490,1451,1389,1325,1283,1228,1177,940,749,718cm-1；HRMS(EI)for C12H8ClN Calculated:201.0345,found:201.0348.
Example 12
Synthesis of compound 2 l:
Figure BDA0001452290850000121
under the protection of nitrogen, 1l (47.8mg,0.1mmol) of high-iodine salt, NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to dilute the reaction, followed by addition of ethyl acetate (10 mL. times.3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2l (12.2mg, 56%) of a white solid.1H NMR(500MHz,CDCl3)8.79(brs,1H),8.18-8.10(m,3H),8.02(d,J＝8.0Hz,1H),7.67(d,J＝8.6Hz,1H),7.63-7.52(m,3H),7.48-7.42(m,1H),7.32(t,J＝7.5Hz,1H)；13C NMR(126MHz,CDCl3)138.5,134.9,132.4,129.0,125.5,125.2,124.9,124.2,121.1,120.5,120.2,120.0,119.9,119.3,118.4,111.0；IR(KBr)ν3409,1478,1402,845,483cm-1；HRMS(EI)for C16H11N Calculated:217.0891,found:217.0894.
Example 13
Synthesis of compound 2 m:
Figure BDA0001452290850000122
Figure BDA0001452290850000131
under the protection of nitrogen, high-iodine salt 1m (54.2mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to dilute the reaction, followed by addition of ethyl acetate (10 mL. times.3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2m (12.6mg, 45%) of a white solid.1H NMR(400MHz,CDCl3)8.08(brs,1H),7.98(d,J＝1.8Hz,1H),7.85(d,J＝8.3Hz,1H),7.56(d,J＝1.5Hz,1H),7.41-7.31(m,3H)；13C NMR(100MHz,CDCl3)140.7,137.8,126.4,125.5,124.0,123.1,121.6,121.5,120.1,113.9,111.7；IR(KBr)ν3401,1599,1445,1265,1050,890,810,736cm-1；HRMS(EI)for C12H7BrClN Calculated:278.9450,found:278.9453.
Example 14
Synthesis of compound 2 n:
Figure BDA0001452290850000132
under the protection of nitrogen, high-iodine salt 1n (53.2mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12 hours, it was cooled to room temperature, and 10mL of water was added to dilute the reaction, followed by addition of ethyl acetate (10 mL. times.3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2n (25.9mg, 90%) as a colorless oil.1H NMR(400MHz,CDCl3)8.18-8.09(m,2H),7.48(d,J＝8.3Hz,1H),7.42-7.27(m,7H),7.03(d,J＝6.5Hz,1H),2.86(s,3H),2.36(s,3H)；13C NMR(100MHz,CDCl3)142.9,139.9,138.4,135.8,133.4,133.3,130.4,130.3,126.9,126.6,125.8,125.7,123.8,123.1,122.0,121.0,109.8,108.2,20.9,20.7；IR(KBr)ν3065,2982,1728,1614,1471,1989,1913,1245,1116,936,781cm-1；HRMS(EI)for C14H9NS Calculated:223.0456,found:223.0455.
Example 15
Synthesis of compound 2 o:
Figure BDA0001452290850000141
under the protection of nitrogen, high-iodine salt 1o (50.4mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100 ℃ for 12h, it was cooled to room temperature, and 10mL of water was added to the reaction system to dilute it, followed by addition of ethyl acetate (10mL × 3) for extraction, drying over anhydrous sodium sulfate, filtration, concentration, and column chromatography to give 2o (14.1mg, 58%) as a white solid.1H NMR(400MHz,DMSO)11.33(brs,1H),8.15(dd,J＝20.5,7.9Hz,2H),7.79-7.68(m,3H),7.53-7.44(m,4H),7.38(q,J＝7.4Hz,2H),7.17(t,J＝7.4Hz,1H)；13C NMR(100MHz,DMSO)141.2,140.4,140.3,137.8,129.0,127.1,127.0,125.7,122.2,121.8,120.6,120.3,118.7,117.8,111.0,108.9；IR(KBr)ν3402,2924,2854,1711,1601,1460,1262,1020,805,750,697cm-1；HRMS(EI)for C18H13N Calculated:243.1048,found:243.1046.
Example 16
Synthesis of compound 2 p:
Figure BDA0001452290850000142
under the protection of nitrogen, high-iodine salt 1p (56.3mg,0.1mmol), NaN3(7.8mg,0.12mmol)，PPh3(39.3mg,0.15mmol)，NaHCO3(42.5mg,0.2mmol), CuTc (1.9mg,0.01mmol) and dry DMA (1mL) were added to a dry Schlenk reaction tube. Stirring reaction at 100 deg.C for 4h, cooling to room temperature, diluting with 10mL water, extracting with ethyl acetate (10mL x 3), drying with anhydrous sodium sulfate, filtering, concentrating, and performing column chromatographyWhite solid 2 p' (17.2mg, 57%) was isolated.1H NMR(400MHz,CDCl3)8.19(brs,1H),7.96-7.87(dd,J＝17.0,4.8Hz,2H),7.33-7.23(m,3H),7.16(dd,J＝8.1,1.3Hz,1H),4.24-4.04(m,2H),3.85(q,J＝7.1Hz,1H),1.56(d,J＝7.2Hz,3H),1.20(t,J＝7.1Hz,3H)；13C NMR(100MHz,CDCl3)174.9,140.3,139.3,138.0,125.7,124.8,124.2,121.5,120.5,119.9,119.6,111.5,109.5,60.9,45.9,18.9,14.1；HRMS(EI)for C16H14ClNO2 Calculated:287.0713,found:287.0712.
2M aqueous NaOH (1mL) was added to a solution of 2 p' (15.1mg,0.05mmol) in methanol (1mL), stirred at room temperature for 8 h, and the reaction quenched with 1M HCl (2mL) and diluted with dichloromethane. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, concentrated, and the concentrated crude product was subjected to column chromatography to give 2p (12.5mg, 91%) as a white solid.
The synthesis method can achieve the technical effects at the temperature of 80-150 ℃.
The synthesis method of the invention can realize the technical effects when the inorganic nitrogen reagent is potassium azide.
The synthesis method of the invention can also realize the technical effects when other bases are adopted, such as one or more of cesium carbonate, sodium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium hydroxide, potassium hydroxide, triethylamine, diisopropylethylamine and DBU 1, 8-diazacyclo [5,4,0] undecene-7.
The synthesis method of the invention can also realize the technical effects when other metal catalysts are adopted, such as one or more of copper trifluoromethanesulfonate, copper acetylacetonate, cuprous iodide, copper acetate and copper sulfate.
The protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected.

Claims (5)

1. A synthesis method of carbazole compounds is characterized in that high-iodine salt shown in a formula (1) is used as a reaction raw material, and the carbazole compounds shown in a formula (2) are obtained by reaction in a solvent under the action of an inorganic nitrogen reagent, an additive, alkali and a metal catalyst; wherein, the inorganic nitrogen reagent is selected from one or two of sodium azide and potassium azide; the solvent is selected from one or more of dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide and N-methylpyrrolidone; the alkali is selected from one or more of cesium carbonate, sodium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine, diisopropylethylamine and DBU 1, 8-diazacyclo [5,4,0] undecene-7; the metal catalyst is selected from one or more of thiophene-2-cuprous carboxylate, copper trifluoromethanesulfonate, copper acetylacetonate, cuprous iodide, copper acetate and copper sulfate; the additive is selected from one or more of triphenylphosphine, tri (2-methylphenyl) phosphine, tri (4-methylphenyl) phosphine, tri (2-methoxyphenyl) phosphine and tri (4-methoxyphenyl) phosphine;
the reaction process is shown as the following reaction formula (A):
Figure FDA0002664584950000011
wherein Ar is1、Ar2Is phenyl, 2-methoxyphenyl, 2-acetamidophenyl, 2-tert-butylphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-trifluoromethylphenyl, 3-chlorophenyl, 4-methylphenyl, 4-chlorophenyl, naphthyl, 2-bromo-6-chlorophenyl, 5-methyl-2-methylbiphenyl or 2-biphenyl, X-Is the anion of high iodine salt, such as p-toluenesulfonic acid anion, trifluoromethanesulfonic acid anion, tetrafluoroboric acid anion, hexafluorophosphoric acid anion, iodine anion, bromine anion or chlorine anion.
2. The synthesis method of claim 1, wherein the molar ratio of the high-iodine salt to the inorganic nitrogen reagent is 1 (1-5).
3. The synthesis method of claim 1, wherein the molar ratio of the high-iodine salt to the base is 1 (1-5).
4. The synthesis method of claim 1, wherein the molar ratio of the high-iodine salt to the metal catalyst is 1 (0.05-1).
5. The synthesis method of claim 1, wherein the molar ratio of the high-iodine salt to the additive is 1 (1-5).
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