Synthesis of 2,3-Disubstituted Carbazoles, Benzo[c]carbazoles, and Phenanthrenes Through FeCl₃-Mediated Cyclization of Triene Frameworks

Abstract

A facile synthesis of 2,3-disubstituted carbazoles through electrocyclization of 2,3-divinylindoles using FeCl₃ in DMF at reflux is reported. The methodology was found to be applicable for smooth transformation of 3-aryl-2-vinylindole as well as 2-styrylbiphenyl into the respective benzo[c]carbazole and phenanthrene.

Key words

carbazoles - electrocyclization - Iron(III) chloride - 2,3-di­vinylindole - benzocarbazole - phenanthrene

• References and Notes

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• 7 Representative procedure for 2a : To a stirred solution of 2,3-divinyl compound 1a (0.2 mmol) in anhydrous DMF (10 mL) at r.t., anhydrous FeCl₃ (0.4 mmol) was added and the reaction mixture was heated at reflux for 6 h. After completion of the reaction (monitored by TLC), the mixture was poured over crushed ice (50 g) containing conc. HCl (3 mL). The crude product was extracted with ethyl acetate (3 × 20 mL) and the combined organic layer was dried (Na₂SO₄). Removal of solvent followed by column chromatographic purification (1% EtOAc/hexane) afforded carbazole 2a (74 mg, 74%) as a colorless solid. Mp 220–222 °C; ¹H NMR (300 MHz_, CDCl₃): δ = 8.26 (s, 1 H), 8.23 (d, J = 7.2 Hz, 1 H), 8.15 (s, 1 H), 8.07 (d, J = 8.1 Hz, 1 H), 7.89 (d, J = 7.5 Hz, 1 H), 7.69 (d, J = 7.8 Hz, 2 H), 7.61 (m, 8 H), 4.05 (q, J = 6.5 Hz, 2 H), 1.01 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 166.1, 148.4, 140.1, 139.1, 138.9, 137.6, 137.1, 134.2, 132.6, 131.5, 129.2, 128.4, 128.3, 126.4, 126.1, 125.7, 125.1, 124.7, 124.0, 123.1, 120.5, 116.5, 115.3, 61.1, 13.8 ppm. Representative procedure for 3a : To a stirred solution of 3-aryl-2-vinylindole 6a (0.1 g, 0.21 mmol) in anhydrous 1,2-DCE (8 mL) at r.t., anhydrous FeCl₃ (18 mg, 0.10 mmol) was added and the reaction mixture was stirred at reflux for 3 h. After completion of the reaction (monitored by TLC), the mixture was poured over ice water (20 mL) and acidified with conc. HCl (2 mL). It was then extracted with CH₂Cl₂ (2 × 10 mL) and the combined organic layer was dried (Na₂SO₄). Removal of solvent followed by column chromatographic purification (Silica gel; EtOAc–hexane, 2:8) gave benzo[c]carbazole 3a as a colorless solid (79 mg, 79%). Mp 168–170 °C; ¹H NMR (300 MHz, CDCl₃): δ = 8.69 (d, J = 8.4 Hz, 1 H), 8.46–8.40 (m, 2 H), 7.97 (d, J = 8.4 Hz, 1 H), 7.73 (d, J = 7.8 Hz, 2 H), 7.60 (t, J = 7.2 Hz, 1 H), 7.42–7.32 (m, 7 H), 7.24–7.17 (m, 2 H), 7.00 (d, J = 8.4 Hz, 2 H), 3.84 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 159.2, 140.7, 138.2, 137.9, 136.1, 133.8, 133.0, 131.3, 129.8, 129.1, 129.0, 127.6, 127.1, 127.0, 126.3, 126.1, 124.8, 124.4, 123.7, 122.1, 119.0, 115.6, 115.3, 113.8, 55.4 ppm. Dept-135 (75 MHz, CDCl₃): δ = 133.8, 131.3, 129.0, 127.5, 127.1, 126.3, 126.0, 124.8, 124.4, 123.7, 122.0, 115.6, 115.3, 113.7, 55.3 ppm. HRMS (EI): m/z [M⁺] calcd for C₂₉H₂₁NO₃S: 463.1242; found: 463.1220. Representative procedure for 15a : To a stirred solution of 2-styrylbiphenyl compound biphenyl vinylene 14a (0.1 g, 0.26 mmol) in anhydrous 1,2-DCE (10 mL) at r.t., anhydrous FeCl₃ (21 mg, 0.13 mmol) was added and the reaction mixture was stirred at reflux for 3 h. Following a similar work up procedure to that for 6a afforded 2,3-dimethoxyphenanthrene 15a (62 mg, 62%) as a colorless solid. Mp 170–172 °C; ¹H NMR (300 MHz, CDCl₃): δ = 8.63 (d, J = 8.4 Hz, 1 H), 8.06 (s, 1 H), 7.97 (d, J = 8.4 Hz, 1 H), 7.68–7.62 (m, 2 H), 7.50 (t, J = 7.2 Hz, 1 H), 7.27 (d, J = 3.3 Hz, 1 H), 7.12–7.02 (m, 3 H), 4.17 (s, 3 H), 4.06 (s, 3 H), 4.00 (s, 3 H), 3.93 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 149.6, 149.3, 148.6, 148.3, 136.9, 133.7, 130.5, 130.0, 127.0, 126.7, 126.5, 126.0, 125.5, 124.4, 122.4, 122.3, 113.5, 111.0, 108.2, 103.2, 56.1, 56.0, 55.9, 55.8 ppm. HRMS (EI): m/z [M⁺] cacld for C₂₄H₂₂O₄: 374.1518; found: 374.1515.
• 8 Koufaki M, Theodorou E, Galaris D, Nousis L, Katsanou ES, Alexis MN. J. Med. Chem. 2006; 49: 300