Synlett 2005(5): 0809-0812  
DOI: 10.1055/s-2005-863741
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Preparative Route to Substituted Carbazoles by Benzannulation

Stefano Serra*, Claudio Fuganti
C.N.R. Istituto di Chimica del Riconoscimento Molecolare, Sezione ‘Adolfo Quilico’ presso Dipatimento di Chimica, Materiali ed Ingegneria Chimica ‘Giulio Natta’ del Politecnico, Via Mancinelli 7, 20133 Milano, Italy
Fax: +39(2)23993080; e-Mail: stefano.serra@polimi.it;
Further Information

Publication History

Received 17 January 2005
Publication Date:
09 March 2005 (online)

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.

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.