A New Preparative Route to Substituted Carbazoles by Benzannulation

Abstract

A new regioselective pathway to substituted carbazole derivatives is described here. According to this procedure substituted 2-alkoxycarbonyl-4-acetoxy-9-(p-toluenesulfonyl) carbazoles are obtained by treatment of substituted 6-[2-(p-toluenesulfonyl­amino)-aryl]-3-alkoxycarbonylhex-3-en-5-ynoic acids with acetic anhydride in the presence of sodium acetate. The latter acids are prepared from the easily available substituted o-iodo-anilines by Sonogashira coupling with propargylic alcohol and Wittig reaction as the key steps. The described benzannulation reaction proceeds in regiospecific fashion and a range of substituents are tolerated.

Key words

annulations - enynes - carbazoles - phenols - heterocycles

References

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• 12a

  2-Iodoaniline 8a is commercially available. The substituted 2-iodoanilines 8b, 8c and 8e were prepared from the commercially available 4-methylaniline, 2-nitro-4-methoxyaniline and 4-fluoroaniline, respectively, according to the procedure described by Ma et al. [12b] Ethyl 4-amino-3-iodobenzoate 8d and 4-nitro-2-iodoaniline 8f were prepared from commercially available ethyl 4-aminobenzoate and 4-nitroaniline, respectively by iodination according to the procedure described by Spivey et al. and Adimurthy et al., respectively. [12c] [d]

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14

The Wittig reaction between aldehydes 11a-f and ylide 12 was performed in toluene-CHCl₃ solution. The amount of CHCl₃ was adjusted depending on the solubility of the starting aldehydes. The above-mentioned reaction proceeds slowly at r.t. (typically 2 d). Notably, worse results have been obtained by heating the reaction mixture.

17

Acids 13a-f (50 mmol) were dissolved in acetic anhydride (48 mL, 0.5 mol). To this solution, anhyd NaOAc (8.2 g, 0.1 mol) and hydroquinone (275 mg, 2.5 mmol) were added in one portion. The obtained heterogeneous mixture was heated at reflux for 1 h under a nitrogen atmosphere. After cooling to r.t., the acetic anhydride was removed in vacuo and the residue was treated with EtOAc (300 mL) and H₂O (100 mL). The organic phase was separated, dried (Na₂SO₄) and concentrated under reduced pressure. The residue was purified by chromatography and crystallization to give carbazoles derivatives 14a-f.
All new compounds were fully characterized. Selected analytical data:
Compound 13e: Anal. Calcd for C₂₂H₂₀FNO₆S: C, 59.32; H, 4.53. Found: C, 59.45; H, 4.55. Mp 154 °C. FT-IR (nujol): 670, 954, 1030, 1100, 1189, 1280, 1363, 1448, 1466, 1539, 1594, 1633, 1697 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.40 (3 H, t, J = 7.2 Hz), 2.31 (3 H, s), 3.54 (2 H, s), 4.36 (2 H, q, J = 7.2 Hz), 6.75 (1 H, s), 7.06-7.20 (2 H, m), 7.16 (2 H, d, J = 8.3 Hz), 7.58 (2 H, d, J = 8.3 Hz), 8.18 (1 H, q, J = 4.4 Hz), 8.27 (1 H, s), 11.25 (1 H, br s). MS (EI): m/z = 446 [M⁺ + 1], 445 [M⁺], 290, 262, 246, 216, 200, 172, 155, 91, 65.
Compound 14e: Anal. Calcd for C₂₄H₂₀FNO₆S: C, 61.40; H, 4.29. Found: C, 61.50; H, 4.30. Mp 197-198 °C (hexane-CHCl₃). FT-IR (nujol): 666, 861, 1027, 1087, 1175, 1207, 1299, 1369, 1417, 1472, 1591, 1722, 1763 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.46 (3 H, t, J = 7.2 Hz), 2.27 (3 H, s), 2.49 (3 H, s), 4.47 (2 H, q, J = 7.2 Hz), 7.13 (2 H, d, J = 8.3 Hz), 7.27 (1 H, dt, J = 9.0, 2.5 Hz), 7.54 (1 H, dd, J = 8.2, 2.5 Hz), 7.69 (2 H, d, J = 8.3 Hz), 7.85 (1 H, s), 8.31 (1 H, dd, J = 9.0, 4.3 Hz), 8.86 (1 H, s). MS (EI): m/z = 470 [M⁺ + 1], 469 [M⁺], 427, 382, 354, 334, 315, 290, 272, 244, 227, 200, 171, 155, 139, 120, 91, 65.