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Synlett 2003(5): 0705-0707
DOI: 10.1055/s-2003-38352
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

The Synthesis of Naphtho[a]carbazoles and Benzo[c]carbazoles

Charles B. de Koning*, Joseph P. Michael, Johanna M. Nhlapo, Rakhi Pathak, Willem A. L. van Otterlo
Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, Johannesburg, South Africa
Further Information

Publication History

Received 6 December 2002
Publication Date:
28 March 2003 (online)

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Abstract

The synthesis of naphtho[a]carbazoles and benzo[c]carbazoles from indole precursors using a reaction mediated by potassium t-butoxide and light is described. The indole precursors were prepared utilizing Suzuki coupling methodology.

Key words

carbazoles - indoles - naphtho[a]carbazoles - benzo[c]carbazoles - Suzuki coupling

    References

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  • Typical Experimental Procedures: The preparation of the three boronic acids was accomplished as follows:
  • 12a

    2-Methyl-1-naphthylboronic Acid 5a. n-Butyllithium (1.2 M, 3.9 cm3, 4.7 mmol) was added dropwise to a solution of 1-bromo-2-methylnaphthalene (1.01 g, 4.57 mmol) in THF (30 cm3) at -78 °C. The reaction mixture was stirred for 30 min at -78 °C, then B(OMe)3 (1.39 g, 1.50 cm3, 13.4 mmol) was added. The resulting mixture was stirred at -78 °C for a further 30 min and then allowed to warm to r.t. The reaction mixture was acidified with aq 10% HCl solution and extracted with Et2O (3 ¥ 30 cm3). The organic layer was then dried with MgSO4 and concentrated under vacuum to afford an off-white crystalline material, 2-methyl-1-naphthyl-boronic acid 5a (0.74 g, 87%), which was used without further purification or characterization.
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  • 12c

    1-Methyl-2-naphthylboronic Acid 5b. n-Butyllithium (1.4 M, 2.1 cm3, 2.9 mmol) was added dropwise to a solution of 2-bromo-1-methylnaphthalene (0.50 g, 2.3 mmol) in THF (15 cm3) at
    -78 °C. The reaction mixture was then treated as described above and B(OMe)3 (0.70g, 0.75 cm3, 6.69 mmol) was added. An off-white crystalline material, 1-methyl-2-naphthylboronic acid 5b (0.39 g, 93%) was produced, which was used without further purification or characterization.
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13

1-Methyl-2-(2-methyl-1-naphthyl)-1 H -indole-3-carbaldehyde 6. A solution of 2-bromo-1-methyl-1H-indole-3-carbaldehyde 4a (see ref. [11] ) (0.10 g, 0.42 mmol) in DME (2 cm3) was deoxygenated by passing N2 through the mixture for 5 min. The deoxygenated mixture was added to Pd(PPh3)4 (10 mol%, 0.048 g, 0.04 mmol) and stirred under N2 for 10 min at r.t. A solution of 2-methyl-1-naphthyl-boronic acid 5a (0.11 g, 0.59 mmol) in EtOH (1.5 cm3) was deoxygenated and added to the reaction mixture. The mixture was stirred for a further 10 min. A deoxygenated 2 M aq Na2CO3 solution (3.0 cm3, 6.0 mmol) was added and the reaction mixture stirred at r.t. for 5 min before being heated at reflux for 2 d. The mixture was cooled to r.t. and quenched with H2O (20 cm3). The organic material was extracted with CH2Cl2 (3 ¥ 30 cm3) and the solvent was evaporated under reduced pressure. The crude product was subjected to column chromatography (2-10% EtOAc-hexane) to afford 1-methyl-2-(2-methyl-1-naphthyl)-1H-indole-3-carbaldehyde 6 as an off-white solid (0.13 g, 99%). Mp 146-147 °C. (Found: M+ 299.1307, C21H17NO requires M, 299.1310). IR (CHCl3): νmax =1655 (C=O) and 1579 (ArC=C) cm-1. 1H NMR (300 MHz, CDCl3, Me4Si): δ = 2.28 (3 H, s, ArCH3), 3.42 (3 H, s, NCH3), 7.23 (1 H, m, ArH), 7.35-7.51 (6 H, m, 6 ¥ ArH), 7.91 (1 H, d, J = 8.0 Hz, ArH), 7.96 (1 H, d, J = 8.5 Hz, ArH), 8.48 (1 H, m, Ar-H) and 9.45 (1 H, s, CHO). 13C NMR (75 MHz, CDCl3): δ = 20.5 (ArCH3), 30.2 (NCH3), 109.8, 122.3, 123.3, 123.8, 125.0, 125.7, 127.4, 128.1 (¥ 2) and 130.2 (ArCH), 116.4, 124.4, 125.3, 131.7, 133.6, 137.3, 137.6 and 149.4 (ArC), 186.0 (CHO). MS: m/z (%) = 299 (100) [M+], 284 (38), 282 (55), 254 (19), 127.

14

11-Methyl-11 H -naphtho[2,1- a ]carbazole 10. t-BuOK (0.12 g, 1.1 mmol), was added to 1-methyl-2-(1-methyl-2-naphthyl)-1H-indole-3-carbaldehyde 7 (0.085 g, 0.28 mmol) dissolved in dry DMF (10 cm3), and the mixture was heated under N2 at 80 °C while being irradiated with a high pressure mercury lamp through a quartz filter for 10 min. The reaction mixture was quenched with H2O (50 cm3) and extracted into Et2O (3 ¥ 50 cm3). The organic layer was dried with MgSO4 and filtered. It was then evaporated and subjected to column chromatography (5-20% EtOAc-hexane) to afford the product 10 (0.045 g, 56%) as an off-white solid. Mp 213-216 °C. (Found: M+ 281.1209, C21H15N requires 281.1204). IR (CHCl3): νmax = 1617 and 1572 (ArC=C) cm-1. 1H NMR (300 MHz, CDCl3, Me4Si): δ = 4.43 (3 H, s, NCH3), 7.33
(1 H, m, ArH), 7.50-7.71 (4 H, m, 4 ¥ ArH), 7.86 (1 H, d, J = 9.2 Hz, ArH), 7.94 (1 H, d, J = 7.6 Hz, ArH), 8.20 (1 H, d, J = 7.8 Hz, ArH), 8.35 (1 H, d, J = 8.7 Hz, ArH), 8.60 (1 H, d, J = 8.7 Hz, ArH), 8.71 (1 H, d, J = 9.2 Hz, ArH), 8.82 (1 H, d, J = 8.3 Hz, ArH). 13C NMR (75 MHz, CDCl3): δ = 34.4 (NCH3), 109.0, 114.8, 119.2, 119.5, 119.8, 121.0, 123.5, 125.3, 125.8, 126.1, 126.7 and 128.4 (ArCH), 120.7, 122.8, 129.7, 131.1, 131.2, 137.0 and 141.6 (ArC). MS: m/z (%) = 281 (100) [M+], 266 (22), 252 (3), 140(2).

15

This work is taken from the PhD of R. Pathak.

16

This work is taken from the MSc of J. M. Nhlapo.