Synthesis method of pyrrole[1,2-a]quinoxaline derivative

A synthesis method, 2-a technology, applied in chemical instruments and methods, compounds containing periodic table Group 3/13 elements, organic compounds/hydrides/coordination complex catalysts, etc., and can solve the scope of substrate application It is not wide enough, limited the scope of substrate application, and reduces the yield of brominated products, and achieves the effect of simple and green preparation method, excellent selectivity, and stable physical and chemical properties.

Active Publication Date: 2021-03-09
SHANGHAI INST OF TECH
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Problems solved by technology

As reported in 2008, pyrrole[1,2-a]quinoxaline derivatives were synthesized by CuI-catalyzed coupling reaction, which requires the hydrolysis of trifluoroacetyl groups and the formation of intermolecular amino compounds; in 2010, the Reeves group reported A copper-catalyzed synthesis of pyrrole[1,2-a]quinoxaline was developed. This system avoids the use of complex substrates, but the reaction requires a higher temperature (130°C), and the structure of the ligand used in the reaction is complex. , expensive; the Valerie group used iron-catalyzed reduction of aryl nitro groups and aerobic oxidation of ethanol to construct pyrrole[1,2-a]quinoxaline derivatives; this system requires nitrobenzene with pyrrole substituents in the ortho position The participation of this complex substrate; the scope of substrate application is not wide enough; in 2013; Ma Chen group reported the use of copper acetate in the air to catalyze N-sulfonyl-2-haloaniline compounds with 2-(chloromethyl)- Synthesis of pyrrole[1,2-a]quinoxaline derivatives from 1H-benzo[d]imidazole compounds; this system is only suitable for haloaniline compounds with sulfonyl groups, which limits the scope of substrate application; in addition The method of 2-halogenated aniline and pyrrole formaldehyde compounds catalyzed by CuI has also been developed, but this method requires the participation of ligands, and the reaction still requires a high temperature environment of 110 ° C, and the substrate can only be used and the price is relatively expensive. Only the 2-iodoaniline can obtain higher yield, and the yield is greatly reduced when using bromide

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  • Synthesis method of pyrrole[1,2-a]quinoxaline derivative
  • Synthesis method of pyrrole[1,2-a]quinoxaline derivative
  • Synthesis method of pyrrole[1,2-a]quinoxaline derivative

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preparation example Construction

[0034] The preparation method of this cuprous complex comprises the following steps:

[0035] (1) At -80°C, add the n-BuLi n-hexane solution to the m-carborane tetrahydrofuran solution, then continue stirring for 35 minutes; warm up to room temperature, and continue the reaction for 30 minutes;

[0036] (2) Add 3-chloromethylpyridine, and react at room temperature for 5h;

[0037] (3) Add CuI and react at room temperature for 2 hours. After the reaction, stand and filter, and drain the solvent under reduced pressure to obtain a crude product, and then separate the crude product by column chromatography to obtain the cuprous complex. Wherein, during the column chromatography separation process, the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is 10:1. The molar ratio of n-BuLi, m-carborane, 3-chloromethylpyridine and CuI was 2.1:1:2:1.

[0038] The cuprous complex II can be used to catalyze the one-p...

Embodiment 1

[0056] Use cuprous complex I as a catalyst to catalyze the synthesis of pyrrole[1,2-a]quinoxaline derivatives: 2-bromoaniline (1mmol), aldehydes (1mmol), K 2 CO 3 (1.5mmol) and cuprous complex Cu (0.01mmol) were dissolved in 3mL of toluene, and reacted at 50°C for 6 hours. After the end, the concentrated reaction solution was directly separated by silica gel column chromatography, dried until the mass remained constant, and the corresponding product C 11 h 8 N 2 (productive rate 93%), its reaction formula is:

[0057]

[0058] 1 H NMR (400MHz, CDCl 3 ,25℃):δ=8.79(s,1H),7.95(d,J=7.0Hz,1H),7.83(s,1H),7.80(d,J=7.5Hz,1H),7.50-7.45(m ,1H), 7.43-7.38(m,1H), 6.89-6.85(m,2H). Elemental analysis: C 78.55, H 4.79, N 16.66 (theoretical); C 78.61, H 4.78, N 16.69 (actual).

Embodiment 2

[0060] Use cuprous complex I as a catalyst to catalyze the synthesis of pyrrole[1,2-a]quinoxaline derivatives: 2-bromoaniline (1mmol), aldehydes (1mmol), K 2 CO 3 (1.5mmol) and cuprous complex Cu (0.01mmol) were dissolved in 3mL of toluene, and reacted at 50°C for 6 hours. After the end, the concentrated reaction solution was directly separated by silica gel column chromatography, dried until the mass remained constant, and the corresponding product C 17 h 12 N 2 (productive rate 95%), its reaction formula is:

[0061]

[0062] 1 H NMR (400MHz, CDCl 3 ,25℃):δ=8.70(s,1H),7.82(d,J=7.0Hz,1H),7.40-7.36(m,5H),7.28(d,J=7.5Hz,1H),7.22(t , J=7.5Hz, 1H), 6.99 (t, J=8.0Hz, 1H), 6.83 (d, J=5.0Hz, 1H), 6.64 (d, J=4.0Hz, 1H). Elemental analysis: C 83.58, H4.95, N 11.47 (theoretical); C 83.55, H4.98, N 11.40 (actual).

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Abstract

The invention relates to a synthesis method of a pyrrole [1,2a] quinoxaline derivative. The method comprises the steps: dissolving a cuprous complex, 2-bromoaniline, a pyrrole formaldehyde compound and an alkali in an organic solvent, carrying out a reaction, and carrying out separation and purification to obtain the pyrrole[1,2a] quinoxaline derivative, wherein the molar ratio of the cuprous complex to the 2-bromoaniline to the pyrrole formaldehyde compound to the alkali is (0.01-0.03): 1.0: 1.0: 1.5, the reaction temperature is 50-65 DEG C, and the reaction time is 6-8 hours. Compared with the prior art, the method has the advantages of mild reaction conditions, high yield, high substrate universality, less waste and the like.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a synthesis method of pyrrole [1,2-a] quinoxaline derivatives. Background technique [0002] Pyrrole[1,2-a]quinoxaline is the backbone structure of many natural product molecules and bioactive molecules, and is widely used in biochemistry, medicinal chemistry, and materials science. [0003] With the continuous development of the field of transition metal catalysis, research on copper catalysts has attracted the most attention. As reported in 2008, pyrrole[1,2-a]quinoxaline derivatives were synthesized by CuI-catalyzed coupling reaction, which requires the hydrolysis of trifluoroacetyl groups and the formation of intermolecular amino compounds; in 2010, the Reeves group reported A copper-catalyzed synthesis of pyrrole[1,2-a]quinoxaline was developed. This system avoids the use of complex substrates, but the reaction requires a higher temperature (130°C), and the structure of the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02B01J31/22C07D487/04
CPCC07F5/05B01J31/1815B01J31/1616C07D487/04B01J2531/16
Inventor 姚子健包涵
Owner SHANGHAI INST OF TECH
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