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Preparation method of indole compounds

A compound and indole technology, applied in the field of organic synthesis, can solve the problems of poor reaction regioselectivity, poor reactivity, high cost, etc.

Active Publication Date: 2019-03-22
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method needs to carry out under very high temperature, and reaction regioselectivity is poor (T. Nishida, Y. Tokuda, M. Tsuchiya, J. Chem. Soc., Perkin Trans. 2 1995, 823-830.)
Using oxirane compounds and arylamines as raw materials, the synthesis of 2-substituted indoles can also be realized under the co-catalysis of catalytic amounts of ruthenium and equivalent tin Co-catalysts make this process costly (C. S. Cho, J. H. Kim, H.-J. Choi, T.-J. Kim, S. C. Shim, Tetrahedron Lett. 2003, 44, 2975-2977.)
Through 7-oxabicyclo[4.1.0]heptane and arylamine in 1 mol% Ru 3 (CO) 12 , 3 mol% dppf and 10 mol% p-toluenesulfonic acid additive conditions can achieve the synthesis of the corresponding indole compounds, but for other stability-sensitive oxirane compounds, this method is poor Reactivity (M. Pena-Lopez, H. Neumann, M. Beller, Chem. -Eur. J. 2014, 20, 1818-1824.)

Method used

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  • Preparation method of indole compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] 2-(4-Bromophenyl)-1 H -Indole 1aa

[0071] Mix aniline (70 mg, 0.75 mmol) and 3-(4-bromophenyl)-2-cyanooxirane (112 mg, 0.5 mmol) in 5 mL of commercially available ethanol / trifluoroethanol 3:7 In the mixed solvent, boron trifluoride ether (11.3 µL, 0.08 mmol) was added and the reaction was refluxed for 20 h. After the solvent was spinned off, 86 mg, 63%, m.p. 207–209 was obtained as a beige solid by separation on a silica gel column o c. 1 H NMR (400 MHz, CDCl3 ) δ 8.27 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.57(d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.0 Hz, 1H),7.23–7.19 (m, 1H), 7.15–7.11 (m, 1H), 6.82 (s, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 136.9, 136.67, 132.2, 131.3, 129.2, 126.6, 122.7, 121.5, 120.8, 120.5, 110.9, 100.5.

Embodiment 2

[0073] 2-(4-Bromophenyl)-5-methyl-1 H -Indole 1ab

[0074] Mix 4-methylaniline (80 mg, 0.75 mmol) and 3-(4-bromophenyl)-2-cyanooxirane (112 mg, 0.5 mmol) in 5 mL of commercially available ethanol / trifluoro In a mixed solvent of ethanol 3:7, boron trifluoride ether (11.3 µL, 0.08 mmol) was added and the reaction was refluxed for 20 h. After the solvent was removed, the white solid 139 mg, 97%, m.p. 279-280 was obtained by silica gel column separation o c. 1 H NMR (400 MHz, CDCl 3 ) δ 8.17 (s, 1H), 7.56 (d, J = 8.4 Hz,2H), 7.51 (d, J = 8.4 Hz, 2H), 7.41 (s, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.04(d, J = 8.0 Hz, 1H), 6.74 (s, 1H), 2.45 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 136.7, 135.3, 132.1, 131.5, 129.7, 129.5, 126.5, 124.4, 121.3, 120.4, 110.6, 100.1, 21.4.

Embodiment 3

[0076] 2-(4-Bromophenyl)-6-methyl-1 H -indole 1ac

[0077] Mix 3-methylaniline (80 mg, 0.75 mmol) and 3-(4-bromophenyl)-2-cyanooxirane (112 mg, 0.5 mmol) in 5 mL of commercially available ethanol / trifluoroethylene In a mixed solvent of ethanol 3:7, boron trifluoride ether (11.3 µL, 0.08 mmol) was added and the reaction was refluxed for 20 h. After the solvent was removed, the beige solid was separated by silica gel column 127 mg, 89%, m.p. 241–243 o c. 1 H NMR (400 MHz, CDCl 3 ) δ 8.14 (s, 1H), 7.56–7.48 (m, 5H), 7.18 (s, 1H), 6.96 (dd, J = 8.0, 0.8 Hz, 1H), 6.77 (dd, J = 2.0, 0.8 Hz, 1H),2.47 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 137.4, 136.0, 132.7, 132.1, 131.5, 127.0, 126.4, 122.3, 121.2, 120.4, 110.9, 100.4, 21.8.

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Abstract

The invention provides a preparation method of indole compounds. 2-cyanoethylene oxide compounds and arylamine react under the catalysis effect of lewis acid (boron trifluoride diethyl etherate or aluminum trichloride) to obtain corresponding indole compounds. The preparation method of the compound has the advantages that the raw materials are simple and can be easily obtained; the operation is convenient; the reaction region selectivity is single. The prepared compounds are a type of very important organic intermediates and medicine intermediates, and have wide bioactivity.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of indole compounds. Background technique [0002] Indole compounds are a very important class of organic intermediates, which are widely used in the fields of medicinal chemistry and synthetic chemistry. Indole derivatives exhibit many biological activities in medicinal chemistry, such as anticancer (M.T. MacDonough, T.E. Strecker, E. Hamel, J.J. Hall, D.J. Chaplin, M.L. Trawick, K.G. Pinney, Bioorg. Med. Chem. 2013, 21, 6831-6843; A. Meric Koksal, Y. Mine Yarim, I. Durmaz, A. Rengul Cetin, Turk. J. Chem. 2012, 36, 515-525; N. Dalip Kumar, M. Kumar, B. Noel, K. Shah, Eur. J. Med. Chem. 2012, 55, 432-438; N. DalipKumar, M. Kumar, S. Sundaree, O. Emmanuel Johnson, K. Shah, Eur. J. Med. Chem. 2010, 45, 1244-1249.), antibacterial (E. Abele, R. Abele, O. Dzenitis, E.Lukevics, Chem. Heterocycl. Compd. 2003, 39, 3-35; T.C. Leboh...

Claims

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Application Information

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IPC IPC(8): C07D209/10C07D209/08
CPCC07D209/08C07D209/10
Inventor 许家喜徐闯闯
Owner BEIJING UNIV OF CHEM TECH