Synthesis of 3-Nitro-2-arylimidazo[1,2-a]pyridines Using Sodium Dichloro­iodide

Abstract

Moderate to good yields of various 3-nitro-2-arylimidazo[1,2-a]pyridines have been easily achieved in the reaction of 2-aminopyridines and nitrostyrenes in the presence of sodium dichloriodide. The procedure is simple and various functional groups are tolerated in this reaction system.

Keywords

2-aminopyridine - nitrostyrene - iodine reagent - 3-nitro-2-arylimidazo[1,2-a]pyridines

• References and Notes

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• 10 Typical Procedure A mixture of nitrostyrene (1.2 equiv), 2-aminopyridine (1 equiv), and aq NaICl₂ (0.1 equiv) in DMF was stirred at 80 °C for 1.5 h. After completion of reaction (monitored by TLC), the reaction mixture was diluted with EtOAc and washed with brine. The organic layer was separated, dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to give the crude product. The product was then purified using silica gel column chromatography (EtOAc–hexane). 3-Nitro-2-phenylimidazo[1,2-a]pyridine (3a) Yellow solid; mp 170–172 °C (lit.^9a 172–174 °C). ¹H NMR (400 MHz, CDCl₃): δ = 9.52 (d, J = 7.2 Hz, 1 H, H-5), 7.92–7.89 (m, 2 H, H-2′ and H-6′-Ph), 7.84 (d, J = 8.8 Hz, 1 H, H-8), 7.68–7.64 (m, 1 H, H-7), 7.52 (t, J = 2.0 Hz, 3 H, H-3′, H-4′, and 5′-Ph), 7.28 (t, 1 H, H-6). IR (KBr): 3061, 3034, 1630, 1531, 1481, 1369, 1219, 929, 761, 694 cm^–1. 2-(4-Methoxyphenyl)-3-nitroimidazo[1,2-a]pyridine (3b) Yellow solid; mp 167–169 °C (lit.^9a 168–170 °C). ¹H NMR (400 MHz, CDCl₃): δ = 9.50 (d, J = 6.8 Hz, 1 H, H-5), 7.92 (d, J = 8.8 Hz, 2 H, H-2′ and 6′-Ph), 7.79 (d, J = 8.8 Hz, 1 H, H-8), 7.63 (t, J = 8.0 Hz, 1 H, H-7), 7.24 (d, J = 6.8 Hz, 1 H, H-6), 7.07 (d, J = 8.8 Hz, 2 H, H-3′ and 5′-Ph), 3.87 (s, 3 H, OCH₃). IR (KBr): 3016, 2922, 1608, 1541, 1481, 1369, 1211, 921, 758 cm^–1. 2-(4-Fluorophenyl)-3-nitroimidazo[1,2-a]pyridine (3d) Yellow solid; mp 224–226 °C (lit.^9c 227–228 °C). ¹H NMR (400 MHz, CDCl₃): δ = 9.52 (d, J = 6.8 Hz, 1 H, H-5), 7.88–7.82 (m, 3 H), 7.69–7.65 (m, 3 H), 7.31–7.27 (m, 1 H). IR (KBr): 3061, 3030, 1604, 1537, 1487, 1334, 1220, 837, 763 cm^–1. 3-Nitro-2-(4-nitrophenyl)imidazo[1,2-a]pyridine (3g) Yellow solid, mp 216–218 °C. ¹H NMR (400 MHz, CDCl₃): δ = 9.54 (d, J = 7.0 Hz, 1 H, H-5), 8.30 (d, J = 8.9 Hz, 2 H, H-2′ and 6′-Ph), 8.13 (d, J = 8.9 Hz, 2 H, H-3′ and 5′-Ph), 7.73 (t, J = 8.2 Hz, 1 H, H-7), 7.66 (d, J = 9.2 Hz, 1 H, H-8), 7.37 (t, J = 7.0 Hz, 1 H, H-6). IR (KBr): 3074, 3032, 1635, 1599, 1514, 1481, 1334, 856, 758 cm^–1. 2-(4-Methoxyphenyl)-8-methyl-3-nitroimidazo[1,2-a]pyridine (3j) Yellow solid; mp 148–150 °C. ¹H NMR (500 MHz, CDCl₃): δ = 9.37 (d, J = 7.2 Hz, 1 H, H-5), 7.94 (d, J = 8.8 Hz, 2 H, H-2′ and 6′-Ph), 7.43 (d, J = 6.8 Hz, 1 H, H-7), 7.15 (t, J = 6.8 Hz, 1 H, H-6), 7.03 (d, J = 8.8 Hz, 2 H, H-3′ and 5′-Ph), 3.84 (s, 3 H, OCH₃), 2.71 (s, 3 H, CH₃). IR (KBr): 3030, 2922, 1610, 1611, 1580, 1472, 1369, 1238, 1149, 1031, 827, 754 cm^–1. 2-(4-Fluorophenyl)-8-methyl-3-nitroimidazo[1,2-a]pyridine (3k) Yellow solid; mp 194–198 °C. ¹H NMR (500 MHz, CDCl₃): δ = 9.37 (d, J = 6.95 Hz, 1 H, H-5), 7.96–7.92 (m, 2 H, H-2′ and 6′-Ph), 7.46 (d, J = 7.2 Hz, 1 H, H-7), 7.20 (t, J = 7.1 Hz, 3 H, H-6, H-3′, and 5′-Ph) 2.73 (s, 3 H, CH₃). IR (KBr): 3053, 2918, 1607, 1539, 1479, 1366, 1238, 1157, 837, 746 cm^–1. 5-Methyl-3-nitro-2-phenylimidazo[1,2-a]pyridine (3l) Yellow viscous liquid. ¹H NMR (400 MHz, CDCl₃): δ = 7.99 (t, 2 H, H-2′ and 6′-Ph), 7.74 (s, 1 H, H-4′-Ph), 7.57 (d, J = 8.8 Hz, 1 H, H-8), 7.44 (t, 2 H, H-3′ and 5′-Ph), 7.37 (t, J = 7.4 Hz, 1 H, H-7), 7.15 (d, J = 6.8 Hz, 1 H, H-6), 2.61 (s, 3 H, CH₃). IR (KBr): 3061, 3030, 2920, 1674, 1537, 1483, 1344, 1226, 1153, 947, 825, 775 cm^–1.