Synlett 2022; 33(14): 1443-1447
DOI: 10.1055/a-1796-9647
cluster
Organic Chemistry in Thailand

One-Pot Synthesis of 2-Arylindole Derivatives under Transition-Metal-Free Conditions

Panitan Kraikruan
,
Intouch Rakchaya
,
Pattarapon Sang-aroon
,
,
The authors would like to thank National Research Council of Thailand (NRCT): NRCT5-RSA63002-10, the Graduate School, Kasetsart University (through the Graduate School Fellowship Program), Thailand Toray Science Foundation (TTSF), the Kasetsart University Research and Development Institute (KURDI), the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research and Innovation, the Department of Chemistry, and the Faculty of Science, Kasetsart University for financial support


Abstract

A new and simple method for preparing 2-arylindole derivatives under transition-metal-free conditions has been developed. When N-(2-methyl-3-nitrophenyl)acetamide was treated with 2-fluorobenzaldehydes in the presence of Cs2CO3 in DMF at 60 °C, the desired indoles were typically obtained in moderate to good yields (up to 83%). When other aniline substrates were employed, only a Knoevenagel condensation occurred, giving the corresponding diarylethenes in moderate to excellent yields.

Supporting Information



Publication History

Received: 11 February 2022

Accepted after revision: 14 March 2022

Accepted Manuscript online:
14 March 2022

Article published online:
12 April 2022

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  • References and Notes

  • 1 Gribble GW. Indole Ring Synthesis: From Natural Products to Drug Discovery. Wiley; Chichester: 2016
    • 2a Fischer E, Jourdan F. Ber. Dtsch. Chem. Ges. 1883; 16: 2241
    • 2b Robinson B. Chem. Rev. 1969; 69: 227
    • 2c Heravi MM, Rohani S, Zadsirjan V, Zahedi N. RSC Adv. 2017; 7: 52852
    • 4a Bartoli G, Palmieri G, Bosco M, Dalpozzo R. Tetrahedron Lett. 1989; 30: 2129
    • 4b Bartoli G, Dalpozzo R, Nardi M. Chem. Soc. Rev. 2014; 43: 4728
  • 5 Fouad MA, Ferretti F, Formenti D, Milani F, Ragaini F. Eur. J. Org. Chem. 2021; 2021: 4876
  • 6 Song H, Yang Z, Tung C.-H, Wang W. ACS Catal. 2020; 10: 276
  • 7 Li B, Ju Z, Zhou M, Su K, Yuan D. Angew. Chem. Int. Ed. 2019; 58: 7687
  • 8 Xia X.-D, Xuan J, Wang Q, Lu L.-Q, Chen J.-R, Xiao W.-J. Adv. Synth. Catal. 2014; 356: 2807
  • 9 Yan X, Ye R, Sun H, Zhong J, Xiang H, Zhou X. Org. Lett. 2019; 21: 7455
  • 10 Daniels M, de Jong F, Vandermeeren T, Van Meervelt L, Van der Auweraer M, Dehaen W. J. Org. Chem. 2019; 84: 13528
    • 11a Thanetchaiyakup A, Rattanarat H, Chuanopparat N, Ngernmeesri P. Tetrahedron Lett. 2018; 59: 1014
    • 11b Thongaram P, Borwornpinyo S, Kanjanasirirat P, Jearawuttanakul K, Kongsema M, Chuanopparat N, Ngernmeesri P. Tetrahedron 2020; 76: 131473
  • 12 Taweesak P, Thongaram P, Kraikruan P, Thanetchaiyakup A, Chuanopparat N, Hsieh H.-P, Uang B.-J, Ngernmeesri P. J. Org. Chem. 2021; 86: 1955
    • 13a Yao X, Sun X, Jin S, Yang L, Xu H, Rao Y. J. Med. Chem. 2019; 62: 6561
    • 13b Eberle C, Burkhard JA, Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. ChemMedChem 2009; 4: 2034
  • 14 2-(2-Fluorophenyl)-4-nitro-1H-indole(11a); Typical Procedure DMF (3 mL) and 2-fluorobenzaldehyde (10a) (170 μL, 1.60 mmol) were added sequentially to a mixture of N-(2-methyl-3-nitrophenyl)acetamide (9) (194 mg, 1.00 mmol) and Cs2CO3 (1.17 g, 3.60 mmol), and the mixture was stirred at 60 °C for 5 h then cooled to rt. The mixture was diluted with H2O (100 mL) and extracted with EtOAc (3 × 100 mL). The combined organic layer was dried (Na2SO4) and concentrated under reduced pressure, and the residue was purified by flash column chromatography [silica gel, EtOAc–hexanes (1:5)] to give a yellow solid; yield: 213 mg (83%); mp 190–191 °C. IR (neat): 3363, 1577, 1504, 1489, 1477, 1371, 1335 cm–1. 1H NMR (400 MHz, DMSO): δ = 12.36 (s, 1 H), 8.08 (dd, J = 8.0, 0.8 Hz, 1 H), 8.00 (td, J = 7.9, 1.7 Hz, 1 H), 7.93 (dt, J = 8.0, 0.9 Hz, 1 H), 7.51–7.46 (m, 1 H), 7.44–7.37 (m, 2 H), 7.35 (t, J = 8.0 Hz, 1 H). 13C NMR (100 MHz, DMSO): δ = 159.3 (d, J = 249.8 Hz), 139.1, 139.0, 136.6 (d, J = 2.5 Hz), 130.7 (d, J = 8.8 Hz), 128.6 (d, J = 3.0 Hz), 125.2 (d, J = 3.3 Hz), 122.00 (d, J = 1.4 Hz), 121.2, 119.1, 118.8 (d, J = 11.7 Hz), 117.9, 116.7 (d, J = 22.0 Hz), 102.0 (d, J = 9.6 Hz). HRMS (ESI): m/z [M + Na]+ calcd for C14H9FN2NaO2: 279.0540; found: 279.0558.
  • 15 Bergman J, Sand P. Tetrahedron 1990; 46: 6085