Facile One-Pot Synthesis of Novel 6-Monosubstituted 5,11-Dihydroindolo[3,2-b]carbazoles and Preparation of Different Derivatives

Abstract

The synthesis of novel 6-monosubstituted 5,11-dihydroindolo[3,2-b]carbazoles was accomplished by a three-stage one-pot procedure involving condensation of indole and an aldehyde ­affording 3,3′-bis(indolyl)methanes, followed by isomerization to the 2,3′-analogues and acid-catalyzed intramolecular reaction with triethyl orthoformate to give the corresponding 6-monosubstituted indolo[3,2-b]carbazoles in good overall yield. Different substitution patterns, such as N-alkylation, N-arylation, formylation and bromination, were successfully introduced, leading to the formation of novel substituted 5,11-dihydroindolo[3,2-b]carbazole derivatives.

Key words

three-stage one-pot synthesis - 6-monosubstituted 5,11-dihydroindolo[3,2-b]carbazole - N-substitution - formylation - bromination

References and Notes

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8

Synthesis of Compound 4c.
To a solution of indole (4.6 g, 40 mmol) and n-hexanal (2.1 g, 20 mmol) in MeCN (10 mL) was added I₂ (1 g, 4 mmol). The reaction was stirred at r.t. for 14 h. Then, aq sat. Na₂SO₃ was added until the iodine color disappeared and the solution was extracted with EtOAc (3 × 20 mL). After concentration of the organic layers, the crude product and triethyl ortho-formate (2.9 g, 20 mmol) were dissolved in MeOH (4 mL). After the addition of methanesulfonic acid (0.3 mL, 4 mmol), the reaction was stirred overnight at r.t. The precipitate was filtered off and washed with MeOH. After drying the pure 4c (2.9 g, 45%) was obtained as a light yellow solid; mp 286-289 °C. IR (KBr): ν = 3405 (s), 2923 (m), 2860 (m), 1611 (m), 1527 (s), 1460 (s), 1422 (s) cm^-1. ¹H NMR (DMSO): δ = 0.85 (3 H, t, CH₃), 1.39 (2 H, m, CH₂), 1.56 (2 H, m, CH₂), 1.82 (2 H, m, CH₂), 3.50 (2 H, m, CH₂), 7.12 (2 H, m, 2 ICZ-H), 7.37 (2 H, m, 2 ICZ-H), 7.47 (2 H, m, 2 ICZ-H), 7.95 (1 H, s, H-12), 8.14 (dd, 2 H, 2 ICZ-H), 10.90 (1 H, s, NH), 11.05 (1 H, s, NH). ¹³C NMR (DMSO): δ = 14.9, 23.2, 29.3, 29.7, 32.5, 98.8, 111.2, 111.4, 118.4, 118.7, 119.1, 121.0, 121.1, 122.7, 123.1, 123.4, 123.7, 125.6, 126.3, 134.9, 136.4, 142.1. HRMS (EI):
m/z calcd for C₂₃H₂₂N₂ [M]⁺: 326.17833; found: 326.17801.