A Simple and Regioselective Synthesis of Dihydropyrido[2,3-c]carbazoles via Iodocyclization

Abstract

An efficient and simple method for the synthesis of various iodo-substituted dihydropyridocarbazole derivatives has been developed via iodocyclization of N-propargylated 3-aminocarbazoles.

iodocyclization - 3-aminocarbazole - dihydropyridocarbazole

References and Notes

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<A NAME="RG36410ST-12">12</A>

The CCDC deposition number for compound 6a is 800159. Formula: C₃₀H₂₅IN₂O₂S. Unit cell parameters: a = 9.8829 (15), b = 10.3179 (13), c = 14.554 (2), α = 80.103 (11), β = 72.103 (13), γ = 68.283 (13), space group P-1. The CCDC deposition number for compound 7a is 800160. Formula: C₂₃H₁₇IN₂. Unit cell parameters: a = 11.4798 (19), b = 10.4089 (15), c = 15.3963 (18), α = 90.00, β = 91.647 (12), γ = 90.00, space group P-1.

<A NAME="RG36410ST-13">13</A>

Preparation of 7-Ethyl-2-iodo-(4-methylphenylsulfonyl)-1-phenyl-4,7-dihydro-3 H -pyrido[2,3- c ]carbazole (6a) To a mixture of 9-ethyl-3-[4-methylphenyl(3-phenylpropyl)-
sulfonamido]-9H-carbazole (5a, 0.5 g, 1 mmol), iodine (0.8 g, 3 mmol), and NaHCO₃ (0.36 g, 2 mmol) was added MeCN (20 mL) at r.t. The reaction mixture was stirred for 4 h. The reaction mixture was then diluted with EtOAc, washed with sat. aq Na₂S₂O₃ (20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (25 mL). The combined organic layers were dried over Na₂CO₃, filtered, and concentrated under the reduced pressure. Product was purified by column chromatography on silica gel (eluent: hexane-EtOAc) afforded 6a (0.48 g, 80%).
Mp 172-174 ˚C. IR (KBr): 3043, 2976, 2926, 1608, 1593, 1440, 1346, 1163, 1087, 883 cm^-¹. ^¹H NMR (400 MHz, TMS, CDCl₃): δ = 8.16 (1 H, d, J = 8.8 Hz, ArCH), 7.55 (4 H, d, J = 7.2 Hz, ArCH), 7.26-7.16 (4 H, m, ArCH), 7.08 (2 H, m, ArCH), 6.95-6.93 (2 H, m, ArCH), 6.60-6.57 (2 H, m, ArCH), 5.00 (2 H, br s, CH₂), 2.15 (3 H, s, CH₃), 1.44 (3 H, t, J = 6.8 Hz, CH₃). ^¹³C NMR (100 MHz, TMS, CDCl₃): δ = 143.5, 141.0, 140.0, 139.8, 139.4, 135.6, 130.6, 129.9, 129.2, 128.1, 127.7, 127.1, 126.1, 125.2, 124.2, 124.0, 121.8, 118.4, 118.3, 109.2, 107.9, 91.7 (arom. C), 59.8, 37.5, 21.3, 13.6 (aliph. C). MS (positive mode): m/z = 604 [M + H]. Anal. Calcd (%) for C₃₀H₂₅IN₂O₂S: C, 59.61; H, 4.17; N, 4.63. Found: C, 59.58; H, 4.10; N, 4.56.

<A NAME="RG36410ST-14">14</A>

Preparation of 7-Ethyl-2-iodo-1-phenyl-7 H -pyrido[2,3- c ]carbazole (7a) In a round-bottom flask equipped with a magnetic stirring bar, 7-ethyl-2-iodo-(4-methylphenylsulfonyl)-1-phenyl-4,7-dihydro-3H-pyrido[2,3-c]carbazole (6a, 0.5 mmol) was dissolved in a mixture of THF (20 mL) and MeOH (10 mL) at r.t. Cs₂CO₃ (1.5 mmol) was added to the clear solution. The resulting mixture was stirred at 50 ˚C, and the progress of the reaction was monitored. When the reaction was complete (12 h), the mixture was evapourated under vacuum. To the residue was added H₂O (20 mL), and the mixture was stirred at r.t. for 10 min. Then the aqueous layer was extracted with EtOAc (3 × 20 mL). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Product was purified by column chromatography on silica gel (eluent: hexane-EtOAc) afforded 7a (0.2 g, 60%).
Mp 178-180 ˚C. IR (KBr): 3126, 3055, 2972, 1614, 1591, 1504, 1444, 1379, 1253, 952 cm^-¹. ^¹H NMR (400 MHz, TMS, CDCl₃): δ = 9.27 (1 H, s, ArCH), 8.21 (1 H, d, J = 8.0 Hz, ArCH), 7.95 (1 H, d, J = 8.0 Hz, ArCH), 7.58-7.40 (6 H, m, ArCH), 7.27 (1 H, t, J = 8.0 Hz, ArCH), 6.64 (1 H, t, J = 8.0 Hz, ArCH), 5.78 (1 H, d, J = 8.0 Hz, ArCH), 4.5
(2 H, q, J = 8.0 Hz, CH₂), 1.48 (3 H, t, J = 4.0 Hz, CH₃). ^¹³C NMR (100 MHz, TMS, CDCl₃): δ = 153.2, 148.4, 145.5, 144.6, 138.8, 138.7, 131.2, 129.4, 129.0, 128.9, 125.8, 124.6, 124.1, 123.4, 118.9, 114.5, 114.1, 108.2, 100.1 (arom. C), 37.6, 14.1 (aliph. C). MS (positive mode): m/z = 449
[M + H]. Anal. Calcd (%) for C₂₃H₁₇IN₂: C, 61.62; H, 3.82; N, 6.25. Found: C, 61.31; H, 3.78; N, 6.31.