Carbazole compound and its synthesis method and application

A synthesis method and compound technology, which are applied in the preparation of non-steroidal anti-inflammatory drug carprofen, and the field of synthesis of functionalized carbazole compounds, can solve the problem of unfavorable protection and deprotection of nitrogen-containing compounds and atoms of periodic salts Problems such as poor economy, simplified reaction steps, etc., to avoid incompatibility, good yield, and simplified operation steps

Active Publication Date: 2020-11-27
EAST CHINA NORMAL UNIV
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  • Abstract
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Problems solved by technology

The traditional method is to introduce nitrogen in the early stage, while nitrides have a complexing effect on metal catalysts and are incompatible with oxidants in the late reaction; at the same time, the protection and deprotection of nitrogen-containing compounds are not conducive to the simplification of the reaction steps; on the other hand, high As a class of easily prepared and stable compounds, iodine salts are widely used as arylation reagents, while when traditional periododium salts are used as arylation reagents, only one of the aryl groups is usually used, which makes periodonium Salts have poor atom economy

Method used

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  • Carbazole compound and its synthesis method and application
  • Carbazole compound and its synthesis method and application
  • Carbazole compound and its synthesis method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Synthesis of Compound 2a:

[0040]

[0041] Under the protection of nitrogen, periodinium salt 1a (42.8mg, 0.1mmol), NaN 3 (7.8mg, 0.12mmol), PPh 3 (39.3mg, 0.15mmol), NaHCO 3(42.5 mg, 0.2 mmol), CuTc (1.9 mg, 0.01 mmol) and dry DMA (1 mL) were added to a dry Schlenk reaction tube. The reaction was stirred at 100°C for 12 hours, cooled to room temperature, diluted with 10 mL of water, extracted with ethyl acetate (10 mL*3), dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography to obtain a colorless Oil 2a (12.6 mg, 89%). 1 H NMR (400MHz, CDCl 3 )δ8.13-8.02(m,3H),7.47-7.39(m,4H),7.28-7.20(m,2H); 13 C NMR (100MHz, CDCl 3 )δ139.5, 125.8, 123.3, 120.3, 119.4, 110.6; MS(EI) m / z=167(100).

Embodiment 2

[0043] Synthesis of compound 2b:

[0044]

[0045] Under the protection of nitrogen, periodinium salt 1b (45.8mg, 0.1mmol), NaN 3 (7.8mg, 0.12mmol), PPh 3 (39.3mg, 0.15mmol), NaHCO 3 (42.5 mg, 0.2 mmol), CuTc (1.9 mg, 0.01 mmol) and dry DMA (1 mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100°C for 12 hours, it was lowered to room temperature, 10 mL of water was added to the system for dilution, and ethyl acetate (10 mL*3) was added for extraction, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography to obtain a white solid 2b (14.8 mg, 75%). 1 H NMR (400MHz, d 6 -DMSO) δ11.11(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); 13 C NMR (100MHz, d 6 -DMSO)δ158.5,141.1,139.7,124.1,122.6,120.9,119.2,118.5,116.2,110.6,107.7,94.4,55.2; IR(KBr)ν3399,2924,2856,1729,1607,1460,1376,13503,...

Embodiment 3

[0047] Synthesis of compound 2c:

[0048]

[0049] Under the protection of nitrogen, periodinium salt 1c (48.5mg, 0.1mmol), NaN 3 (7.8mg, 0.12mmol), PPh 3 (39.3mg, 0.15mmol), NaHCO 3 (42.5 mg, 0.2 mmol), CuTc (1.9 mg, 0.01 mmol) and dry DMA (1 mL) were added to a dry Schlenk reaction tube. After the reaction was stirred at 100°C for 12 hours, it was lowered to room temperature, 10 mL of water was added to the system for dilution, and ethyl acetate (10 mL*3) was added for extraction, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography to obtain a white solid 2c (10.1 mg, 45%). 1 H NMR (500MHz, d 6 -acetone) δ8.22(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); 13 C NMR (126MHz, d 6 -acetone)δ168.8,141.4,141.1,138.6,125.6,124.0,120.9,120.3,119.7,112.0,111.4,102.1,24.4; IR(KBr)ν2925,2859,1666,1601,1543,1459,1...

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Abstract

The invention discloses a carbazole compound represented by a formula (2) and a synthesis method of the compound. A high-iodine salt is taken as a reaction raw material, and under the action of an inorganic nitrogen reagent, an additive, a base and a metal catalyst, a reaction is carried out in a solvent under a condition of 80-150 DEG C to obtain various carbazole compounds. According to the method provided by the invention, nitrogen atoms are introduced in a later period, so that the non-compatibility of nitrogen heterocyclic rings to the reaction conditions such as the metal catalyst and the like in an early reaction period is avoided. In addition, two aryl groups in the high-iodine salt are fully utilized, so that the atomic economic efficiency of the method provided by the present invention is fully exhibited. The carbazole compound prepared by the method provided by the invention can be further applied to the synthesis of non-steroidal anti-inflammatory drug carprofen.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis and application, relates to a new method for synthesizing carbazole compounds and its application, in particular to the synthesis of functionalized carbazole compounds, and in the preparation of non-steroidal anti-inflammatory drug carprofen ( Carprofen). Background technique [0002] Carbazole compounds are a class of very important compounds, especially widely used in material molecules and drug molecules, such as the antihypertensive drug Carazolol (Carazolol) of formula (C), the antihypertensive drug of formula (D) Shown in the drug carvedilol (Carvedilol) and the anti-inflammatory drug carprofen (Carprofen) of formula (E). Therefore, it is particularly important to develop efficient, environmentally friendly, and compatible methods for the synthesis of carbazole compounds. [0003] [0004] The traditional method of synthesizing carbazoles is mainly through the intramo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/86C07D209/88C07D209/80
CPCC07D209/80C07D209/86C07D209/88
Inventor 姜雪峰王明范巧玲
Owner EAST CHINA NORMAL UNIV
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