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Synlett 2004(7): 1306-1308  
DOI: 10.1055/s-2004-822923
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Imidazolo[5,4-b]carbazole-4,10-quinones

Gwénaëlle Desforges, Cécile Bossert, Cyril Montagne, Benoît Joseph*
Laboratoire de Chimie Organique 1, UMR-CNRS 5181, Université Claude Bernard - Lyon 1, CPE - Bâtiment 308, 43 Boulevard du 11 novembre 1918, 69622 Villeurbanne cedex, France
Fax: +33(0)472431214; e-Mail: benoit.joseph@univ-lyon1.fr;
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Publication History

Received 15 January 2004
Publication Date:
10 May 2004 (online)

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Abstract

The preparation of imidazolo[5,4-b]carbazole-4,10-quinones 9 is described. The key steps of the synthesis are selective halogen-metal exchanges on the imidazole 3 and subsequent addition to carbonyl groups of ethyl-3-formylindole-2-carboxylate 4.

Key words

quinone - imidazole - ellipticine - metalation

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Selected data for 3b: Yellow solid; mp 69-70 °C. IR (KBr): 1460, 1173, 1102 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.21 (t, J = 7.0 Hz, 3 H, CH3), 3.55 (q, J = 7.0 Hz, 2 H, CH2), 5.37 (s, 2 H, CH2). 13C NMR (75 MHz, CDCl3): δ = 14.9 (CH3), 65.0 (CH2), 77.2 (CH2), 83.2 (Cq), 94.8 (Cq), 134.3 (Cq). MS (ESI): m/z = 413 [M + H+] for 35Cl, 415 [M + H+] for 37Cl.

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Using standard conditions (esterification, Vilsmeier-Haack formylation, N-Boc-protection) the indole derivative 4 was prepared from commercially available indole-2-carboxylic acid in 94% overall yield.

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Typical Procedure for Cyclisation: To a solution of 7a (131 mg, 0.2 mmol) in anhyd THF (5 mL), was dropwise added at -78 °C a 2.24 M solution of BuLi in hexanes (103 µL, 0.2 mmol). After 1 h at -78 °C, the reaction mixture was allowed to warm to r.t. and was then hydrolysed by a sat. aq solution of NH4Cl. The solution was extracted with CH2Cl2 (3 ×), the combined organic layer was dried over MgSO4 and concentrated in vacuo. The crude residue was purified by flash chromatography on silica gel (CH2Cl2-MeOH, 98:2) to afford quinone 8a as a red solid in 48% yield. Mp >210 °C (MeOH). IR (KBr): 1676, 1649 cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 1.12 (t, J = 7.0 Hz, 3 H, CH3), 3.58 (q, J = 7.0 Hz, 2 H, CH2), 5.75 (s, 2 H, CH2), 7.28-7.38 (m, 2 H, HAr), 7.52 (d, J = 8.0 Hz, 1 H, HAr), 8.06 (d, J = 8.0 Hz, 1 H, HAr), 8.28 (s, 1 H, HAr), 12.99 (s, 1 H, NH). 13C NMR (75 MHz, DMSO-d 6): δ = 14.7 (CH3), 64.2 (CH2), 74.8 (CH2), 113.9 (CH), 115.3 (Cq), 121.4 (CH), 123.8 (Cq), 124.0 (CH), 125.9 (CH), 132.6 (Cq), 137.1 (Cq), 137.6 (Cq), 141.9 (Cq), 143.8 (CH), 173.6 (Cq), 174.6 (Cq). MS (ESI): m/z = 296 [M + H+]. HRMS (CI): m/z calcd for C16H14N3O3: 296.1035; found: 296.1035. Compound 8b was prepared similarly starting from 7b but was crystallised from MeOH after chromatography. Red solid; mp >210 °C (MeOH). IR (KBr): 1670, 1650 cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 1.20-1.27 (m, 3 H, CH3), 3.65-3.73 (m, 2 H, CH2), 5.83 (s, 2 H, CH2), 7.47-7.50 (m, 1 H, HAr), 7.98-8.05 (m, 2 H, HAr), 8.22 (d, J = 7.2 Hz, 1 H, HAr), 9.50 (s, 1 H, NH). 13C NMR (75 MHz, DMSO-d 6): δ = 14.8 (CH3), 64.6 (CH2), 74.0 (CH2), 114.1 (CH), 115.2 (Cq), 121.5 (CH), 123.9 (Cq), 124.4 (CH), 126.2 (CH), 133.7 (Cq), 136.5 (Cq), 137.7 (Cq), 139.2 (Cq), 139.8 (Cq), 172.6 (CO), 173.9 (CO). MS (ESI): m/z = 330 [M + H+] for 35Cl, 332 [M + H+] for 37Cl. HRMS (CI): m/z calcd for C16H13ClN3O3: 330.0645; found: 330.0645.

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Compounds 9 have been characterised by 1H NMR, 13C NMR (except carbonyl signals), IR, MS and HRMS.

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Selected data for 10: Mp >210 °C (MeOH). 1H NMR (acetone-d 6 ): δ = 1.12 (t, J = 7.0 Hz, 3 H, CH3), 2.81 (s, 3 H, CH3), 3.21 (s, 3 H, CH3), 3.56 (q, J = 7.0 Hz, 2 H, CH2), 5.84 (s, 2 H, CH2), 7.15 (t, J = 7.9 Hz, 1 H, HAr), 7.35 (t, J = 7.9 Hz, 1 H, HAr), 7.49 (d, J = 7.9 Hz, 1 H, HAr), 8.15 (s, 1 H, HAr), 8.29 (d, J = 7.9 Hz, 1 H, HAr), 10.05 (s, 1 H, NH). 13C NMR (acetone-d 6 ): δ = 11.5 (CH3), 15.0 (CH3), 15.2 (CH3), 63.6 (CH2), 76.4 (CH2), 107.0 (Cq), 111.2 (CH), 113.8 (Cq), 118.9 (CH), 120.6 (Cq), 123.3 (CH), 125.4 (Cq), 125.5 (CH), 128.3 (Cq), 137.5 (Cq), 142.6 (Cq), 144.7 (Cq), 146.5 (CH). MS (ESI): m/z = 294 [M + H+]. HRMS (CI): m/z calcd for C18H20N3O: 294.1606; found: 294.1606.