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A sort of n -Preparation method of aryl-substituted heterocyclic compound

A technology of heterocyclic compounds and compounds, applied in the field of organic chemical synthesis, can solve the problems of long-term reaction under harsh conditions, heavy metal pollution, and difficult removal of guiding groups, etc., and achieve the effect of simple synthesis process, rapid reaction and excellent yield

Active Publication Date: 2021-01-05
NANCHANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Although the transition metal-catalyzed Ar-H direct amination reaction is widely used, there are also a series of disadvantages, such as: 1) need to use expensive ligands and catalysts, and sometimes some additives; 2) require harsh conditions (High temperature or long-term reaction); 3) Heavy metal pollution, especially when synthesizing compounds that require high heavy metal content; 4) The removal of the directing group in the reaction substrate is a big problem
Through literature research, we found that the metal-free catalyzed Ar-H and N-H direct coupling CDC reaction is less studied, and there are still great challenges and research value

Method used

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  • A sort of  <i>n</i> -Preparation method of aryl-substituted heterocyclic compound
  • A sort of  <i>n</i> -Preparation method of aryl-substituted heterocyclic compound
  • A sort of  <i>n</i> -Preparation method of aryl-substituted heterocyclic compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: Preparation of 3a-3h.

[0024] Will N -Methylanilines 1a-1h (0.5 mmol), t -BuONa (294 mg, 1.5 mmol), nitrobenzene 2a (184.5 mg, 1.5 mmol), added to 2.0 mL of dimethyl sulfoxide (DMSO), reacted at room temperature for 60 minutes to stop the reaction, quenched with water, dichloro Methane extraction, column chromatography separation (using silica gel column; eluent: petroleum ether / ethyl acetate = 20 / 1), to obtain pure product N -Methyldiphenyl derivatives 3a-3h.

[0025] Its synthetic route is as follows:

[0026]

[0027] N -methyl-4-nitro- N -phenylaniline: 3a

[0028]

[0029] Yellow solid, the yield is 83%; 1 H NMR (400 MHz, CDCl 3 ) δ 7.98 -7.92 (m, 2H), 7.36(t, J = 7.8 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.16 -7.11 (m, 2H), 6.57 (dd, J = 7.3, 5.3 Hz, 2H), 3.31 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 153.7, 146.3, 138.0, 130.2, 126.7, 126.6, 125.7, 112.3, 40.5.

[0030]4-fluoro- N -methyl- N -(4-nitrophenyl) aniline: 3b

[0031] ...

Embodiment 2

[0051] Example 2: Preparation of 3i, 3j.

[0052] Will N -Ethylanilines 1i, 1j (0.5 mmol), t -BuONa (294 mg, 1.5 mmol), nitrobenzene 2a (184.5 mg, 1.5 mmol), added to 2.0 mL of dimethyl sulfoxide (DMSO), reacted at room temperature for 60 minutes to stop the reaction, quenched with water, dichloro Methane extraction, column chromatography separation (using silica gel column; eluent: petroleum ether / ethyl acetate = 20 / 1), to obtain pure product N -Methyldiphenyl derivatives 3i, 3j.

[0053] Its synthetic route is as follows:

[0054]

[0055] N -ethyl-4-nitro- N -phenylaniline: 3i

[0056] Yellow solid, yield 71%; 1 H NMR (400 MHz, CDCl 3 ) δ8.03 (d, J = 9.4 Hz, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H),7.26-7.15 (m, 2H), 6.64-6.55 (m, 2H), 3.82 (q, J = 7.1 Hz, 2H), 1.27 (t, J =7.1 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 153.1, 144.9, 137.8, 130.3, 127.8, 127.1, 126.0, 112.3, 47.2, 12.3.

[0057]N -ethyl-4-methyl- N -(4-nitrophenyl)anilin...

Embodiment 3

[0059] Example 3: Preparation of 3k, 3l.

[0060] Will N, N - diphenylamine compound 1k, 1l (0.5 mmol), t -BuONa (294 mg, 1.5 mmol), nitrobenzene 2a (184.5 mg, 1.5 mmol), added to 2.0 mL of dimethyl sulfoxide (DMSO), reacted at room temperature for 60 minutes to stop the reaction, quenched with water, dichloro Methane extraction, column chromatography separation (using silica gel column; eluent: petroleum ether / ethyl acetate=20 / 1), to obtain pure product N -Methyldiphenyl derivatives 3k, 3l.

[0061] Its synthetic route is as follows:

[0062]

[0063] 4-nitro- N,N -diphenylaniline: 3k

[0064]

[0065] Yellow solid, the yield is 67%; 1 H NMR (400 MHz, CDCl 3 ) δ 8.05 (t, J = 6.3 Hz, 2H), 7.39 (t, J = 7.8 Hz, 4H), 7.28 -7.18 (m, 6H), 6.94 (t, J = 6.3 Hz, 2H). 13 CNMR (100 MHz, CDCl 3 ) δ 153.6, 145.8, 140.3, 130.1, 126.7, 125.9, 125.6, 118.3.

[0066] 3-methyl- N -(4-nitrophenyl)- N -phenylaniline: 3l

[0067]

[0068] Yellow solid, yield 42%; 1 ...

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Abstract

The invention relates to the technical field of organic chemical synthesis, and relates to a preparation method of an N-aryl substituted heterocyclic compound. The method comprises the following steps: reacting an amine compound and a nitro derivative in a molar ratio of (1: 1)-(1: 3) for 30-60 minutes at normal temperature and normal pressure under the condition of an organic solvent by taking alkali as an accelerant; and after the reaction is finished, adding water for quenching, extracting with an organic solvent, and performing column chromatography separation (the ratio of V petroleum ether: V ethyl acetate is 40: 1 to 20: 1) to obtain the N-aryl substituted heterocyclic derivative. Nitrobenzene is used as an Ar-H source, N-methylaniline, N-ethylaniline, N-methyl heterocycle, tetrahydroquinoline and the like can be used as amine sources, and direct aromatic amination reaction of aromatic rings is realized in a t-BuONa / DMSO / O2 system. The method has the advantages of simplicity, high atom economy, avoiding of expensive transition metal and mild reaction conditions, and environment-friendly byproducts are generated.

Description

technical field [0001] The invention belongs to the technical field of organic chemical synthesis and relates to a N -Preparation method of aryl-substituted heterocyclic compound. Background technique [0002] N -Aryl-substituted heterocyclic compounds are important structural units of many natural products and drugs (Hili R, YudinA K. Nat. Chem. Boil. 2006, 2(6): 284-287), in addition, these compounds can be used to prepare ligands, artificial dyes, electronic materials and optical materials (Lawrence, S. A. Cambridge University Press, Cambridge, 2004; pp 265-305). Therefore, many synthetic N -A method for aryl-substituted heterocyclic compounds. Among these methods, the most classic method is Ullmann coupling (Ullmann F. Ueber eine neue Bildungsweise von Diphenylaminderrivaten[J]. Ber. Deut. Chem. Ges. 1903, 36(2):2382-2384) and Buchwald-Hartwig coupling (Guram A S, Buchwald S L. J. Am. Chem. Soc .1994, 116(17): 7901-7902; Paul F, Patt J, Hartwig J. F. J. Am. Che...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C211/56C07C209/02C07C213/00C07C217/92C07D215/06C07D213/74
CPCC07C209/02C07C213/00C07D213/74C07D215/06C07C211/56C07C217/92
Inventor 蔡琥谢永发张真阳如春张天奇严章强
Owner NANCHANG UNIV
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