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Synthesis 2003(11): 1661-1666
DOI: 10.1055/s-2003-40880
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Substituted Indoles and Carbazoles from 2-Fluorophenyl Imines

Linas V. Kudzma*
Baxter Healthcare Corporation, Anesthesia and Critical Care, 95 Spring Street, New Providence, NJ 07974, USA
Fax: +1(908)2867359; e-Mail: linas_kudzma@baxter.com;
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Publication History

Received 9 May 2003
Publication Date:
25 July 2003 (online)

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Abstract

The synthesis of a series of indole and carbazole derivatives from 2-fluorophenyl imines is reported. 2-Fluoroaniline-d 4 (13) is prepared and used to investigate the mechanism of this indolization. 2-Fluorophenyl enaminone 17 gives the synthetically useful carbazole 20 via a similar indolization and in situ alkylation.

Key words

indoles - imines - enaminone - benzyne - nucleophilic aromatic substitution

    References

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6

2,4-Diphenyl-3H-1-benzazepine(9), mp 129-30 °C. 1H NMR (CDCl3): δ = 7.86 (m 2 H), 7.60-7.31 (complex m, 11 H), 7.21 (m, 1 H), 7.07 (s, 1 H), 3.38 (s, 2 H). 13C NMR (CDCl3): δ = 157.33, 146.89, 139.93, 138.24, 134.94, 130.55, 130.15, 129.56, 128.78, 128.53, 128.04, 127.99, 127.90, 126.97, 126.86, 126.82, 123.98, 33.90. Anal. Calcd for C22H17N (295.38): C, 89.46; H, 5.80; N, 4.74. Found: C, 89.24 H, 5.68 N, 4.68.

7

Fluorobenzene-d 5, 97 atom%D was obtained from Aldrich Chemical Co., Milwaukee WI USA.

11

1,2,3,9-Tetrahydro-4H-carbazole-4-one(21) can be isolated as a tan solid; mp 219-221 °C; Rf 045 (EtOAc-hexanes, 2:1). 1H NMR (DMSO-d 6): δ = 11.85 (br s, 1 H), 7.96 (m, 1 H), 7.40 (m, 1 H), 7.15 (m, 2 H), 2.96 (t, J = 6.2 Hz, 2 H), 2.43 (t, J = 6.2 Hz, 2 H), 2.12 (m, 2 H). 13C NMR (DMSO-d 6): δ = 192.78, 152.17, 135.80, 124.49, 122.35, 121.43, 120.14, 111.72, 111.45, 37.77, 23.38, 22.68.

12

Longer reflux gives increasing amounts of the benzazepine side product discussed in the text.

13

If desired the crude imine 3 can be distilled under reduced pressure to give a colorless oil; bp 170-172 °C (0.25 mmHg).