Molecular Iodine-Catalyzed Imino-Diels-Alder Reactions: Efficient One-Pot Synthesis of Pyrano[3,2-c]quinolines

Abstract

The successful use of molecular iodine as a catalyst in the intermolecular imino-Diels-Alder reaction is described. A one-pot synthesis of pyrano[3,2-c]quinolines was achieved by three-component coupling of aldehydes and anilines with 2,3-dihydropyran catalyzed by iodine. The reactions could be carried out smoothly at room temperature within three to six hours to offer the target products in good yields. We also investigated solvent effect, sub­stituent effect, and the amount of iodine required.

Key words

Iodine - imino-Diels-Alder - one-pot - three-component - tetrahydroquinolines

References

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22

Pyrano[3,2-c]quinolines 3 and 4; General Procedure.
To a mixture of aldehyde 1 (2 mmol), aniline 2 (2 mmol), and 2,3-dihydropyran (4 mmol) in CH₃CN (10 mL) was added iodine (0.15 g, 30 mol%) and the solution was stirred at r.t. for the appropriate time (Table [3] ). To the reaction mixture was added 10% aq NaS₂O₃ soln (20 mL) and the product was extracted with CH₂Cl₂ (2 × 10 mL). The combined organic layers were washed with brine, dried (Na₂SO₄), filtered, and the solvent was evaporated. The residue was purified by silica gel column chromatography with petroleum ether (60-90 °C)-EtOAc (95:5) as the eluent to afford the pure compounds.
3a: white solid; mp 131-133 °C (Lit. [12] 130-132 °C).
IR (KBr): 3373, 3055, 3027, 2938, 2856, 1610, 1492, 1365, 1306, 1265, 1071, 913, 749, 702 cm^-1. ¹H NMR (400MHz, CDCl₃): δ = 1.27-1.53 (4 H, m), 2.18 (1 H, m), 3.61-3.88 (3 H, m), 4.66 (1 H, d, J = 2.6 Hz), 5.33 (1 H, d, J = 5.6 Hz), 6.58 (1 H, d, J = 7.8 Hz), 6.78 (1 H, t, J = 7.6 Hz), 7.03 (1 H, t, J = 7.6 Hz), 7.28-7.47 (6 H, m).
MS: m/z (%) = 265 (M⁺, 77), 206 (100).
4a: yellowish viscous liquid.
IR (neat film): 3378, 3061, 2945, 2857, 1612, 1499, 1366, 1271, 1072, 913, 756, 708 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.27 (1 H, m), 1.58 (1 H, m), 1.69 (1 H, m), 1.85 (1 H, m), 2.15 (1 H, m), 3.76 (1 H, dt, J = 2.5, 11.6 Hz), 4.11 (2 H, m), 4.43 (1 H, d, J = 2.7 Hz), 4.76 (1 H, d, J = 10.8 Hz), 6.59 (1 H, d, J = 7.4 Hz), 6.73 (1 H, t, J = 7.2 Hz), 7.11 (1 H, t, J = 7.2 Hz), 7.27 (1 H, d, J = 7.4 Hz), 7.39-7.46 (5 H, m).
MS: m/z (%) = 265 (M⁺, 100), 207 (69).
3b: white solid; mp 171-172 °C (Lit. [12] 170-172 °C).
IR (KBr): 3389, 3078, 3027, 2920, 2855, 1605, 1512, 1321, 1277, 818 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.26-1.31 (1 H, m), 1.42- 1.51 (3 H, m), 2.03-2.13 (1 H, m), 3.37-3.42 (1 H, m), 3.58-3.61 (1 H, m), 3.81-3.93 (1 H, br), 4.64 (1 H, d, J = 2.4 Hz), 5.25 (1 H, d, J = 5.6 Hz), 6.51 (1 H, d, J = 8 Hz), 7.02 (1 H, dd, J = 8.0, 2.4 Hz), 7.28-7.38 (6 H, m).
MS: m/z (%) = 299 (M⁺, 100), 241 (48). 4b: pale solid; mp 129-131 °C (Lit. [12] 125-126 °C).
IR (KBr): 3383, 3066, 3027, 2921, 2867, 1607, 151, 1366, 1265, 1079, 824 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.33-1.37 (1 H, m), 1.45-1.49 (1 H, m), 1.60-1.68 (1 H, m), 1.81-1.84 (1 H, m), 2.04-2.08 (1 H, m), 3.71 (1 H, dt, J = 2.6, 7.6 Hz), 4.06-4.10 (1 H, m), 4.34 (1 H, d, J = 2.8 Hz), 4.67 (1 H, d, J = 10.8 Hz), 6.46 (1 H, d, J = 8.4 Hz), 7.03 (1 H, dt, J = 8.4, 2.4 Hz), 7.21 (1 H, d, J = 2.4 Hz), 7.32-7.41 (5 H, m).
MS: m/z (%) = 299 (M⁺, 67), 241 (100).
3c: white solid; mp 146-147 °C (Lit. [12] 144-146 °C). IR (KBr): 3340, 3051, 2970, 2860, 1610, 1520, 1365, 1270, 1065, 837, 776 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.25-1.33 (1 H, m), 1.45-1.55 (3 H, m), 2.12-2.18 (1 H, m), 3.41-3.46 (1 H, m), 3.58 (1 H, m), 3.77 (3 H, s), 4.62 (1 H, d, J = 2.4 Hz), 5.30 (1 H, d, J = 5.6 Hz), 6.57 (1 H, d, J = 9.2 Hz), 6.71 (1 H, dd, J = 6.4, 1.8 Hz), 7.03 (1 H, dd, J = 2.9, 0.8 Hz), 7.29-7.43 (5 H, m).
MS: m/z (%) = 295 (M⁺, 100), 237 (33).
4c: pale solid; mp 97-99 °C (Lit. [12] 98-100 °C). IR (KBr):3340, 3021, 2975, 2845, 160, 1495, 1260, 1080, 845 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.31-1.35 (1 H, m), 1.45-1.48 (1 H, m), 1.62-1.67 (1 H, m), 1.78-1.85 (1 H, m), 2.06-2.11 (1 H, m), 3.46-3.55 (1 H, br), 3.70 (1 H, dt, J = 2.6, 7.0 Hz), 3.75 (3 H, s), 4.10 (1 H, dt, J = 11.2, 2.2 Hz), 4.36 (1 H, d, J = 2.8 Hz), 4.65 (1 H, d, J = 10.4 Hz), 6.49 (1 H, d, J = 8.8 Hz), 6.74 (1 H, dd, J = 8.8, 2.9 Hz), 6.81 (1 H, d, J = 2.8 Hz), 7.30-7.43 (5 H, m).
MS: m/z (%) = 295 (M⁺, 58), 237 (100).
3d: white solid; mp 143-144 °C (Lit. [21] 142-143 °C).
IR (KBr): 3366, 3023, 2933, 2859, 1617, 1499, 1454, 1352, 1307, 1258, 1082, 808, 698 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.27-1.32 (1 H, m), 1.42-1.55 (3 H, m), 2.15 (1 H, m), 2.27 (3 H, s), 3.44 (1 H, dt, J = 2.4, 7.0 Hz), 3.60 (1 H, m), 4.64 (1 H, d, J = 2.2 Hz), 5.30 (1 H, d, J = 5.6 Hz), 6.52 (1 H, d, J = 8.0 Hz), 6.91 (1 H, d, J = 8.0 Hz), 7.24 (1 H, s), 7.29-7.42 (5 H, m).
MS: m/z (%) = 279 (M⁺, 100), 220 (30).
4d: white solid; mp 89-91 °C.
IR (KBr): 3378, 3045, 2967, 2855, 1613, 1505, 1334, 1267, 1078, 826 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.24-1.27 (1 H, m), 1.30-1.34 (1 H, m), 1.43-1.50 (1 H, m), 1.61-1.69 (1 H, m), 2.06-2.09 (1 H, m), 2.23 (3 H, s), 3.69-3.74 (1 H, m), 4.08-4.11 (1 H, m), 4.36 (1 H, d, J = 2.7 Hz), 4.68 (1 H, d, J = 10.8 Hz), 6.45 (1 H, d, J = 8.0 Hz), 6.90 (1 H, dd, J = 8.0, 1.7 Hz), 7.04 (1 H, d, J = 1.0 Hz), 7.31-7.43 (5 H, m).
MS: m/z (%) = 279 (M⁺, 100), 221 (82).
3e: white solid; mp 147-148 °C (Lit. [12] 143-144 °C).
IR (KBr): 3338, 3023, 2933, 2864, 1601, 1474, 1348, 1303, 1270, 1086, 1037, 759, 702 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.24-1.33 (1 H, m), 1.40-1.55 (3 H, m), 2.14-2.17 (4 H, m), 3.42 (1 H, m), 3.55-3.59 (1 H, m), 3.69 (1 H, br), 4.70 (1 H, d, J = 2.4 Hz), 5.36 (1 H, d, J = 5.6 Hz), 6.74 (1 H, t, J = 7.2 Hz), 7.00 (1 H, d, J = 7.2 Hz), 7.32-7.47 (6 H, m).
MS: m/z (%) = 279 (M⁺, 100), 220 (52).
4e: white solid; mp 128-129 °C (Lit. [12] 130-132 °C).
IR (KBr): 3387, 3060, 3027, 2933, 2876, 2827, 1601, 1474, 1364, 1254, 1053, 747, 706 cm^-1. ¹H NMR (400MHz, CDCl₃): δ = 1.30-1.36 (1 H, m), 1.44-1.50 (1 H, m), 1.62-1.69 (1 H, m), 1.82-1.90 (1 H, m), 2.05 (3 H, s), 2.07-2.11 (1 H, m), 3.72 (1 H, dt, J = 2.4, 11.6 Hz), 4.11 (1 H, dt, J = 11.2, 2.2 Hz), 4.39 (1 H, d, J = 2.6 Hz), 4.75 (1 H, d, J = 11.2 Hz), 6.65 (1 H, t, J = 7.2 Hz), 7.00 (1 H, d, J = 7.2 Hz), 7.12 (1 H, d, J = 7.6 Hz), 7.33-7.46 (5 H, m).
MS: m/z (%) = 279 (M⁺, 100), 221 (80).
4g′: white solid; mp 155-156 °C.
IR (KBr): 3411, 3035, 2937, 2847, 1597, 1499, 1474, 1433, 1307, 1123, 1053, 918, 796, 735, 702 cm^-1.
¹H NMR (400 MHz, CDCl₃): δ = 1.33 (1 H, d, J = 13.2 Hz), 1.49 (1 H, dd, J = 13.8, 2 Hz), 1.66-1.73 (1 H, m), 1.89-1.95 (1 H, m), 2.02 (1 H, d, J = 11.5 Hz), 3.73 (1 H, dt, J = 2.4, 12 Hz), 4.13 (1 H, dd, J = 11.6, 4.8 Hz), 4.69 (1 H, s), 4.86 (1 H, d, J = 11.6 Hz), 6.65 (1 H, d, J = 8.0 Hz), 6.98 (1 H, d, J = 7.6 Hz), 7.13 (1 H, t, J = 8.0 Hz), 7.32-7.43 (5 H, m).
MS: m/z (%) = 333 (M⁺, 38), 275 (100).
3h: white solid; mp 126-128 °C.
IR (KBr): 3366, 3019, 2941, 2859, 1609, 1477, 1352, 1315, 1213, 1090, 1029, 927, 816, 751 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.29-1.34 (1 H, m), 1.42-1.55 (3 H, m), 2.13 (1 H, m), 2.36 (3 H, s), 3.43 (1 H, m), 3.56-3.60 (1 H, m), 4.65 (1 H, d, J = 2.4 Hz), 5.31 (1 H, d, J = 5.6 Hz), 6.58 (1 H, d, J = 8.0 Hz), 6.78 (1 H, t, J = 7.6 Hz), 7.08 (1 H, dt, J = 0.6, 8.0 Hz), 7.18 (2 H, d, J = 8.0 Hz), 7.29 (2 H, d, J = 8.0 Hz), 7.41 (1 H, d, J = 7.6 Hz).
MS: m/z (%) = 279 (M⁺, 100), 221 (73).
4h: white solid; mp 123-125 °C.
IR (KBr): 3370, 3019, 2937, 2855, 1609, 1491, 1372, 1307, 1262, 1078, 812, 743 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.33 (1 H, m), 1.50 (1 H, m), 1.63 (1 H, m), 1.88 (1 H, m), 2.08 (1 H, m), 2.36 (3 H, s), 3.70 (1 H, dt, J = 2.5, 11.6 Hz), 4.09 (1 H, dt, J = 10.8, 2.6 Hz), 4.37 (1 H, d, J = 2.7 Hz), 4.67 (1 H, d, J = 10.8 Hz), 6.50 (1 H, d, J = 8.0 Hz), 6.69 (1 H, dt, J = 1.0, 7.2 Hz), 7.06 (1 H, dt, J = 1.6, 8.0 Hz), 7.16-7.23 (3 H, m), 7.30 (2 H, d, J = 8.0 Hz).
MS: m/z (%) = 279 (M⁺, 100), 221 (35).
3i: white solid; mp 168-170 °C.
IR (KBr): 3346, 3051, 2941, 2859, 1605, 1482, 1315, 1262, 1060, 755, 620, 489 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.26-1.33 (1 H, m), 1.44-1.54 (3 H, m), 2.15 (1 H, m), 3.42 (1 H, m), 3.57-3.61 (1 H, m), 4.64 (1 H, d, J = 2.4 Hz), 5.30 (1 H, d, J = 5.5 Hz), 6.60 (1 H, d, J = 7.4 Hz), 6.80 (1 H, dt, J = 0.8, 7.4 Hz), 7.08 (1 H, t, J = 7.4 Hz), 7.29 (2 H, d, J = 8.4 Hz), 7.42 (1 H, d, J = 8.0 Hz), 7.50 (2 H, dd, J = 6.8, 1.8 Hz).
MS: m/z (%) = 235 (M + 1, 25), 286 (100).
4i: white solid; mp 131-133 °C.
IR (KBr): 3358, 3015, 2937, 2847, 1609, 1495, 1364, 1266, 1078, 1033, 1008, 841, 816, 747, 465 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.32-1.36 (1 H, m), 1.41-1.47 (1 H, m), 1.62-1.68 (1 H, m), 1.74-1.83 (1 H, m), 2.01-2.05 (1 H, m), 3.71 (1 H, dt, J = 2.4, 11.6 Hz), 4.09 (1 H, dt, J = 11.2, 2.1 Hz), 4.37 (1 H, d, J = 2.7 Hz), 4.67 (1 H, d, J = 10.8 Hz), 6.52 (1 H, d, J = 8.0 Hz), 6.71 (1 H, dt, J = 1.0, 7.6 Hz), 7.09 (1 H, t, J = 7.2 Hz), 7.21 (1 H, dd, J = 1.3, 7.6 Hz), 7.29 (2 H, dd, J = 1.6, 8.4 Hz), 7.48 (2 H, dd, J = 1.7, 8.4 Hz).
MS: m/z (%) = 235 (M + 1, 29), 286 (100).
3j: white solid; mp 165-167 °C.
IR (KBr): 3387, 3072, 3011, 2937, 2847, 1605, 1474, 1315, 1258, 1086, 1029, 743, 702 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.20-1.25 (1 H, m), 1.44-1.49 (1 H, m), 1.52-1.58 (2 H, m), 2.39-2.42 (1 H, m), 3.42 (1 H, dt, J = 2.3, 11.6 Hz), 3.56-3.61 (1 H, m), 5.06 (1 H, d, J = 2.1 Hz), 5.33 (1 H, d, J = 5.6 Hz), 6.61 (1 H, d, J = 7.6 Hz), 6.80 (1 H, t, J = 7.6 Hz), 7.09 (1 H, t, J = 7.6 Hz), 7.23-7.29 (2 H, m), 7.38-7.45 (2 H, m), 7.65 (1 H, dd, J = 1.5, 7.6 Hz).
MS: m/z (%) = 299 (M⁺, 70), 241 (100).
4j: colorless viscous liquid.
IR (neat film): 3358, 3056, 3019, 2941, 2855, 1613, 1491, 1364, 1319, 1260, 1082, 755 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.40-1.49 (2 H, m), 1.67-1.74 (1 H, m), 1.86-1.94 (1 H, m), 2.18-2.22 (1 H, m), 3.6 (1 H, dt, J = 2.8, 11.6 Hz), 3.96-4.00 (1 H, m), 4.43 (1 H, d, J = 3.1 Hz), 5.17 (1 H, d, J = 9.3 Hz), 6.52 (1 H, d, J = 8.0 Hz), 6.73 (1 H, t, J = 7.4 Hz), 7.20 (1 H, t, J = 8.0 Hz), 7.20-7.25 (3 H, m), 7.36 (1 H, dd, J = 1.2, 7.6 Hz), 7.48 (1 H, d, J = 7.6 Hz).
MS: m/z (%) = 299 (M⁺, 40), 241 (100).
3k: yellow solid; mp 181-183 °C.
IR (KBr): 3407, 3076, 3011, 2987, 2856, 1601, 1530, 1477, 1266, 1078, 886, 784, 698 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.20 (1 H, m), 1.44-1.60 (3 H, m), 2.19-2.22 (1 H, m), 3.44 (1 H, dt, J = 2.5, 11.2 Hz), 3.60 (1 H, dt, J = 11.6, 2.0 Hz), 3.83 (1 H, br), 4.80 (1 H, d, J = 2.3 Hz), 5.34 (1 H, d, J = 5.6 Hz), 6.66 (1 H, d, J = 8.0 Hz), 6.85 (1 H, t, J = 8.0 Hz), 7.13 (1 H, t, J = 7.6 Hz), 7.44 (1 H, d, J = 8.0 Hz), 7.56 (1 H, t, J = 8.0 Hz), 7.76 (1 H, d, J = 8.0 Hz), 8.17 (1 H, dd, J = 1.5, 8.0 Hz), 8.33 (1 H, s).
MS: m/z (%) = 310 (M⁺, 53), 251 (100).
4k: yellow solid; mp 159-161 °C.
IR (KBr): 3417, 3056, 2966, 2887, 1604, 1534, 1491, 1345, 1277, 1080, 874, 778, 702 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.40 (2 H, m), 1.67-1.74 (1 H, m), 1.79-1.86 (1 H, m), 2.12 (1 H, m), 3.74 (1 H, t, J = 11.2 Hz), 4.11 (1 H, d, J = 9.2 Hz), 4.40 (1 H, d, J = 2.5 Hz), 4.83 (1 H, d, J = 10.8 Hz), 6.57 (1 H, d, J = 8.0 Hz), 6.75 (1 H, t, J = 7.6 Hz), 7.12 (1 H, t, J = 7.6 Hz), 7.24 (1 H, d, J = 7.6 Hz), 7.55 (1 H, t, J = 8.0 Hz), 7.76 (1 H, d, J = 7.3 Hz), 8.18 (1 H, dd, J = 1.9, 8.0 Hz), 8.31 (1 H, s)
MS: m/z (%) = 310 (M⁺, 52), 251 (100).
4l: white solid; mp 134-135 °C.
IR (KBr): 3387, 3039, 2941, 2892, 2835, 1609, 1495, 1368, 1241, 1057, 767 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.30-1.33 (1 H, m), 1.47-1.52 (1 H, m), 1.61-1.67 (1 H, m), 1.78-1.85 (1 H, m), 2.06 (1 H, m), 3.71 (1 H, dt, J = 2.4, 11.6 Hz), 4.10 (1 H, dt, J = 11.2, 2.2 Hz), 4.38 (1 H, d, J = 2.6 Hz), 4.68 (1 H, d, J = 10.8 Hz), 6.51 (1 H, d, J = 8.0 Hz), 6.70 (1 H, t, J = 7.2 Hz), 6.90 (2 H, d, J = 8.4 Hz), 7.08 (1 H, dt, J = 1.4, 8.0 Hz), 7.21 (1, dd, J = 1.1, 7.6 Hz), 7.34 (2 H, d, J = 8.4 Hz)
MS: m/z (%) = 295 (M⁺, 100), 236 (182).
3m: white solid; mp 187-189 °C.
IR (KBr): 3382, 3068, 2941, 2868, 1601, 1486, 1274, 1082, 841, 808 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.25-1.28 (1 H, m), 1.44-1.50 (3 H, m), 2.10 (1 H, m), 3.40-3.46 (1 H, m), 3.59-3.63 (1 H, m), 4.63 (1 H, d, J = 2.4 Hz), 5.24 (1 H, d, J = 5.6 Hz), 6.53 (1 H, d, J = 8.6 Hz), 7.03 (1 H, dd, J = 2.2, 8.4 Hz), 7.31-7.36 (4 H, m), 7.38 (1 H, d, J = 1.4 Hz).
MS: m/z (%) = 333 (M⁺, 53), 274 (100).
4m: white solid; mp 154-156 °C.
IR (KBr): 3346, 2933, 2847, 1613, 1491, 1268, 1033, 882, 812 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.32-1.38 (1 H, m), 1.43-1.47 (1 H, m), 1.63-1.69 (1 H, m), 1.75-1.82 (1 H, m), 2.04 (1 H, m), 3.70 (1 H, dt, J = 2.4, 11.6 Hz), 4.07 (1 H, d, J = 11.6 Hz), 4.34 (1 H, d, J = 2.7 Hz), 4.67 (1 H, d, J = 10.8 Hz), 6.46 (1 H, d, J = 8.4 Hz), 7.04 (1 H, dd, J = 2.4, 8.8 Hz), 7.21 (1 H, d, J = 2.3 Hz), 7.35 (4 H, m).
MS: m/z (%) = 333 (M⁺, 55), 274 (100).
4n: white solid; mp 151-153 °C.
IR (KBr): 3346, 3035, 3002, 2970, 2941, 2884, 2839, 1609, 1511, 1462, 1298, 1241, 1172, 1045, 890, 824 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.33-1.38 (1 H, m), 1.45-1.52 (1 H, m), 1.63 (1 H, m), 1.78-1.84 (1 H, m), 2.05-2.11 (1 H, m), 3.71 (1 H, dt, J = 2.4, 11.2 Hz), 3.75 (3 H, s), 3.83 (3 H, s), 4.36 (1 H, d, J = 2.7 Hz), 4.62 (1 H, d, J = 10.8 Hz), 6.48 (1 H, d, J = 8.8 Hz), 6.72 (1 H, dd, J = 2.8, 8.8 Hz), 6.81 (1 H, d, J = 2.8 Hz), 6.90 (2 H, d, J = 8.4 Hz), 7.34 (2 H, d, J = 8.4 Hz).
MS: m/z (%) = 325 (M⁺, 100), 266 (30).